Therapeutic Role of Deep Eutectic Solvents Based on Menthol and Saturated Fatty Acids on Wound Healing
- Joana M. SilvaJoana M. Silva3B’s Research Group—Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark Barco, Guimarães 4805-017, PortugalICVS/3B’s PT Government Associated Laboratory, Braga/Guimarães 4806-909, PortugalMore by Joana M. Silva,
- Carolina V. PereiraCarolina V. PereiraNutraceuticals and Bioactives Process Technology Laboratory, Instituto de Biologia Experimental e Tecnológica, Oeiras 2780-157, PortugalMore by Carolina V. Pereira,
- Francisca ManoFrancisca ManoLAQV/REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516, PortugalMore by Francisca Mano,
- Eduardo SilvaEduardo Silva3B’s Research Group—Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark Barco, Guimarães 4805-017, PortugalICVS/3B’s PT Government Associated Laboratory, Braga/Guimarães 4806-909, PortugalMore by Eduardo Silva,
- Vânia I. B. CastroVânia I. B. Castro3B’s Research Group—Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark Barco, Guimarães 4805-017, PortugalICVS/3B’s PT Government Associated Laboratory, Braga/Guimarães 4806-909, PortugalMore by Vânia I. B. Castro,
- Isabel Sá-NogueiraIsabel Sá-NogueiraMicrobial Genetics Laboratory, UCIBIO/REQUIMTE, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516, PortugalMore by Isabel Sá-Nogueira,
- Rui L. ReisRui L. Reis3B’s Research Group—Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark Barco, Guimarães 4805-017, PortugalICVS/3B’s PT Government Associated Laboratory, Braga/Guimarães 4806-909, PortugalThe Discoveries Centre for Regenerative and Precision Medicine, Headquarters, University of Minho, Avepark Barco, Guimarães 4805-017, PortugalMore by Rui L. Reis,
- Alexandre PaivaAlexandre PaivaLAQV/REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516, PortugalMore by Alexandre Paiva,
- Ana A. MatiasAna A. MatiasNutraceuticals and Bioactives Process Technology Laboratory, Instituto de Biologia Experimental e Tecnológica, Oeiras 2780-157, PortugalInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2780-157, PortugalMore by Ana A. Matias, and
- Ana Rita C. Duarte*Ana Rita C. Duarte*E-mail: [email protected]3B’s Research Group—Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark Barco, Guimarães 4805-017, PortugalICVS/3B’s PT Government Associated Laboratory, Braga/Guimarães 4806-909, PortugalMore by Ana Rita C. Duarte
Copyright © 2019 American Chemical Society
Abstract
The breakthroughs achieved in green solvents promote the emergence of therapeutic deep eutectic solvents (THEDES), which possess intriguing possible applications in the biomedical field. Herein, the main aim was to unravel the biomedical potential of hydrophobic THEDES based in menthol and saturated fatty acids with different chain lengths (e.g., stearic acid (SA), myristic acid (MA), and lauric acid (LA)). Our comprehensive strategy resulted in the thermophysical characterization of different formulations, which allow one to identify the most suitable molar ratio, as well as the intermolecular interactions behind the successful formation of THEDES. The evaluation of their biological performance was also performed toward bacteria and HaCaT cells. Among the different formulations of THEDES, the one based on menthol and SA establishes stronger hydrogen bonding interactions, being also the most promising formulation because it did not elicit any relevant cytotoxicity, and potentiated wound healing, while presenting antibacterial properties against Staphylococcus epidermis and Staphylococcus aureus strains, some of which were methicillin resistant. This work provides clues on the future use of THEDES based on menthol:SA in wound dressings.
Introduction
ARTICLE SECTIONS
Introduced by Abbot and co-workers in a pioneering work, the interest in deep eutectic solvents (DES) has risen over the past decade due to their unique and attractive properties.(1−3) DES can easily be obtained by mixing at certain molar ratios the counterparts, which by self-association lead to a eutectic mixture with the lowest melting point when compared with the counterparts.(3−5) The depression on the melting point can be ascribed to hydrogen bond interactions between the hydrogen bond pairs.(1,2,6) Among the remarkable properties of DES are their low preparation costs, straightforward and green synthesis, no need of postsynthesis purification, environmental disposal, nonflammability, broad range of polarity, low volatility, dipolar nature, chemical and thermal stability, water compatibility, biodegradability, and negligible toxicity profiles.(6−9) Although DES present core characteristics similar to their analogues ionic liquids (ILs), DES fully represent the green chemistry metrics, which makes them highly desirable and a promising alternative to their former solvents.(1,6,7) One of the most attractive features of DES is the large numbers of possible combinations, up to 106, that turn them into an environmentally friendly designer solvent. The tailoring of DES properties can be performed by changing the hydrogen bond pairs, molar ratio, polarizability, temperature, and water content.(10−13)
DES have claimed attention in several fields, such as in organic synthesis, separation processes, biocatalysis, nanomaterials, electrochemistry, polymer fabrication, CO2 capture, foods, cosmetics, pharmaceutics, and biomedical applications.(14−17) In biomedical applications, DES can be used to improve solubility, permeation, and absorption of active pharmaceutical ingredients (APIs).(18−22) The APIs can be used as a DES counterpart, being hence called therapeutic deep eutectic systems (THEDES).(6,19,23) Herein, insights on therapeutic effects of the THEDES based on menthol and different saturated fatty acids will be addressed. Even though the THEDES herein reported have been mentioned in previously published works,(11,24) their biological and pharmaceutical activity was not evaluated and their use in biomedical applications not explored. Menthol is a terpene that can been extracted from Mentha species, and it has been already used for THEDES preparation in combination with a wide range of compounds including ibuprofen, lidocaine, fluconazole, and captopril, among others.(19,23−26) In this work, it was mostly used due to their effectiveness as permeation enhancer together with their well-known anti-inflammatory and antimicrobial properties.(27−29) On the other side, fatty acids are commonly extracted from vegetal and animal fats and their potent antimicrobial properties have been extensively reported, including their important role of self-disinfection power of human skin.(30−32) The preparation of THEDES from fatty acid blends was reported by Silva and co-workers, who evaluated the biological performance of the systems, namely the antimicrobial activity and the possibility to prepare gauzes loaded with the blend.(33) Thereby, our interests have mainly focused on the study of the physicochemical and biological activity of THEDES based on menthol and fatty acids. This study will provide clues and relevant information on the thermophysical properties of these THEDES as well as on their potential use for therapeutic purposes, namely, in wound treatment.
Materials and Methods
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THEDES Production and Characterization
During the preparation of the THEDES, menthol (Sigma-Aldrich, ref M2772) was mixed with different saturated fatty acids, including lauric acid (LA; Sigma-Aldrich, ref. W261408-SAMPLE-K), stearic acid (SA; Sigma-Aldrich, ref 175366), and myristic acid (MA; Sigma-Aldrich, ref. 70082). The systems were constantly stirred and heated to 70 °C during 30 min, until formation of a clear liquid solution. Optical characterization of different formulations of THEDES was carried out at room temperature (RT) by polarized optical microscopy (POM), as elsewhere reported.(20,33) The viscosity was measured under controlled stress (shear rate, 10 s–1) using a Kinexus Prot rheometer (Malvern, MaL 1097376). A temperature scan was performed from 50 to 15 °C, adapting previous methodology in the literature.(20,33) The differential scanning calorimetry (DSC; thermal analysis and analyzers) experiments of the powders and THEDES were also performed. The formulations were equilibrated at 40 °C, followed by cooling to −40 °C, an isothermal period of 5 min, and a heating to 100 °C at 5 °C/min. NMR experiments were recorded when the systems were in equilibrium, and no further change in their properties were observed, as elsewhere reported.(34)
Assessment of Cytotoxicity
HaCaT cell line (German Cancer Research Center (DKFZ), Germany) was cultured according to the manufacturer’s instructions in supplemented Dulbecco’s modified Eagle’s medium (Sigma-Aldrich). The assay was made using confluent and differentiated HaCaT cells, which represent 80% epidermal cells. HaCaT cells were seeded at a density of 4.5 × 104 cells/well and allowed to grow during 72 h. The cytotoxic effect of the individual counterparts and THEDES was performed by analyzing the effects of each formulation extract on the cellular metabolism, as established in ISO/EN 10993 and usually performed with THEDES.(20,33−35) The extracts were prepared by overnight incubation of THEDES and powders at concentrations ranging from 0 to 32 mM. Then, cells were washed and cell viability was assessed using MTS colorimetric assay, cell viability being expressed in terms of percentage of living cells relative to the control. The half-maximal effective concentration (EC50) was also obtained using best-fitted trend lines.
Wound Healing Assay
HaCaT cells were seeded cells at a density of 1 × 105 cell/cm2 in a 12-well plate and allowed to grow until 100% confluence (48 h). Afterward, the wound was formed with a 200 μL pipet tip and each well washed twice with warm PBS in order to remove the nonadherent cells. Then, menthol:SA (8:1), menthol, and SA were incubated for 24 h. Micrographs were taken by optic microscopy (Leica DM6000, Germany) at two different time points: 0 and 24 h. Image analysis was performed using ImageJ software and the wound area measured between borderlines. The wound area recovered was expressed in terms of percentage with the following equation using six isolated experiments performed in duplicate:
Antibacterial Assay
THEDES antimicrobial activity was tested by applying the agar diffusion assay. The antibacterial activity of eutectic blends was determined using Staphylococcus aureus (S. aureus) ATCC 25923 and ATCC 700698 (methicillin-resistant strain), S. epidermis ATCC 35984 (methicillin-resistant strain), Pseudomonas aeruginosa (P. aeruginosa) ATCC 27853, and Escherichia coli (E. coli) ATCC 25922, according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI), adapting a methodology previously reported(33) with slight modifications, namely, the use of DMSO at 1% (v/v) concentration to help solubilize the compounds without affecting microbial growth significantly. Furthermore, due to the inherent volatility of menthol for MIC/MBC determination instead of the traditional 96-well plate, microtubes were used and volumes up-scaled accordingly (500 μL of formulations + 500 μL of bacterial suspension) for optimal conditions.
Statistical Analysis
The data were expressed as mean ± standard errors (SD). GraphPad Prism 6 software was used to calculate EC50 values and to analyze significant differences between data sets through one-way analysis of variance (ANOVA) followed by Tukey post hoc test. A p-value < 0.05 was considered significant.
Results and Discussion
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THEDES Production and Characterization
In this work, THEDES were prepared from readily available materials, such as menthol and saturated fatty acids. Different molar ratios of the compounds in their solid state have been prepared, by simple mixing of the constituents at either equimolar or imbalanced ratios (Table 1). The liquid phase is dependent on several factors, including the chemical nature of the counterparts and also the molar ratio used, which impair the eutectic point.(36) The eutectic point is the point in the phase diagram with the lowest melting when compared with the counterparts.(2,37) Thereby, DSC analysis was also performed to assess thermal events (Figure 1), namely, the variations on the melting point of THEDES when compared with the parent species, as a depression on the melting point of counterparts is a strong indicator of the successful formation of THEDES. The thermogram of racemic menthol presents two melting points at ≈28 and ≈33 °C, which have been ascribed to α and β polymorphs and is in good agreement with previous reported data.(24,38,39) In the thermogram of each saturated fatty acid a well-defined and sharp endothermic peak was obtained at ≈46.6, ≈58.6, and ≈73 °C, for LA, MA, and SA, respectively. The thermograms of the individual starting materials corroborated previous data in the literature.(24,38−41)
Table 1. Different THEDES Formulations, Their Respective Visual Aspects, and POM Micrographsa
a
The scale bar is 200 μm.
Figure 1
Figure 1. DSC thermograms obtained for powders (A) and THEDES, including menthol:LA (B) menthol:MA (C) and menthol:SA (D). Peaks arising above the baseline represent endothermic peaks.
The peaks obtained in THEDES are different from the ones of the parent species, which further suggests the supramolecular rearrangement while the compounds are in THEDES form. Additionally, a clear depression on the melting point of the parent species can be observed. The thermograms of THEDES indicate that the molar ratio strongly affects the intensity and shift of the peaks, which was previously reported for other THEDES.(20,26,42,43) The DSC data together with POM were both used as easily accessible tools to assess the potential of particular molar ratios to originate THEDES. After this initial assessment, menthol was combined with LA, MA, and SA at 4:1, 8:1, and 8:1, respectively. In each case, a full black background was obtained and a thermogram with an endothermic peak was also achieved.
The establishment of hydrogen bonding between each parent species was then assessed by using NMR spectroscopy. NMR is commonly used to elucidate the types of interactions, as well as the atoms of each counterpart involved, allowing one to get insights into the hydrogen bonding network.(10,44) In Figures 2 and 3, the 1 H NMR spectra of powders and THEDES are presented, as well as the integrals of different signals.
Figure 2
Figure 2. 1H NMR spectra of the powders; (A) menthol, (B) LA, (C) MA, and (D) SA. All of the resonances are attributed.
Figure 3
Figure 3. 1H NMR spectra of the THEDES: (A) menthol:LA (4:1), (B) menthol:MA (8:1), and (C) menthol:SA (8:1). All of the resonances are attributed.
One of the differences between the spectrum of powders and the one of THEDES is the chemical signals ascribed to the hydroxyl groups of menthol. The powder spectrum (Figure 2A) of menthol presents a well-defined doublet (δ = 3.9 ppm), whereas in the THEDES spectrum (Figure 3) a larger singlet was obtained, without any further upfield or downfield chemical displacement. Additionally, the other evidence of the establishment of hydrogen bonding is the signal from proton (H9) bonded to the same carbon (C9) of the hydroxyl group from menthol. In the 1H NMR spectrum of the powder, this signal presents -H- resonance at a chemical shift of 3.14–3.22 ppm, being, as expected, a multiplet. However, in the THEDES 1H NMR spectra, besides no detectable shift, the signals are not anymore a well-defined multiplet, which further suggests that the H9 of menthol is affected by hydrogen bond interactions between the parent molecules. The establishment of hydrogen bonding is further proven by the disappearance of the hydroxyl group of saturated fatty acids in the THEDES spectrum comparison, while in the powder’s spectrum of fatty acids the sharp and defined signals were obtained in the expected chemical shift (δ = 11.5–11.8 ppm). Since these systems are viscous, at the bottom of the peaks in NMR spectra the line width is slightly broad due to the inter- and intradipolar interactions. The overall data indicate that the hydrogen bonds are established between the hydroxyl groups from menthol (hydrogen bond donor) and the carboxyl group from saturated fatty acids (hydrogen bond acceptor). The NMR data support the POM and DSC, as an extensive hydrogen bonding network was observed for the evaluated molar ratios.
After this initial screening, the viscosity of the different THEDES was evaluated at constant shear rate and as a function of temperature (Figure 4). As expected, as the temperature increases, the viscosity of the systems decreases, which is in accordance with the Arrhenius equation.(26,43,45) The menthol systems with lower viscosity were the one with LA, followed by those with MA and SA. Thereby, one can conclude that it highly depends on the chain length of saturated fatty acids. In menthol:SA, it was only possible to evaluate the viscosity until 30 °C; at lower temperatures the system is in solid phase, as shown in the DSC thermogram. The higher viscosity of menthol:SA can be attributed to their extensive hydrogen bonding interactions, which corroborated 1H NMR data.
Figure 4
Figure 4. Variation of the shear viscosity of the different formulations of THEDES as a function of the temperature.
The data obtained also corroborated the one in the literature, where the ability to tune the viscosity of THEDES by the nature of starting compounds and temperature has been described.(11,21,46−49) Additionally, the values of viscosity of these THEDES are relatively low, which is a valuable feature as it allows their manipulation and facilitates their potential applications without the need to, for example, add water in the formulations. The tailoring of viscosity of THEDES is recurrently performed by water content, chemical nature, and working temperature.(12,35,48,50−52)
The main advantage of using THEDES concerns in the formation of a supramolecular arrangement established due to intermolecular interactions, including hydrogen bonding interactions and van der Waals ones. Thereby, the solubility of these poorly water-soluble compounds is strongly increased by a phenomenon known as hydrotropy, where hydrotopes are capable of enhancing the solubility of hydrophobic molecules by means other than micellar solubilization.(53−56) This is in fact a major advantage of the THEDES which can be further explored in biomedical/pharmaceutical field.(18−21,23,26,57,58) Thereby, when using a physical mixture of compounds, different behaviors are obtained, as in that situation a simple dissolution of each compound in a certain medium occurred without any supramolecular arrangement of THEDES.
Bioactivity of THEDES
Menthol-based THEDES were initially tested in terms of cytotoxicity effect in order to select the range of concentrations that will be used in further assays. Comparing the effect of isolated compounds, none of the saturated fatty acids showed cytotoxicity in the range of concentration evaluated, as Figure 5 shows. Assessing THEDES cytotoxicity, menthol:LA (4:1) showed higher cytotoxicity with EC50 value of 5.569 ± 0.326 mM of equivalent menthol (Figure 5A). Moreover, this system showed cytotoxicity similar to that of pure menthol. Comparing menthol with other formulations of THEDES (menthol:MA (8:1) and menthol:SA (8:1)), the isolated compound had higher cytotoxic activity (Figure 5B,C). The presence of MA and SA compounds in the systems decreases the cytotoxicity, which further suggests the supramolecular arrangement between both counterparts while in THEDES form. These data corroborated several studies in the literature where it has been reported that hydrogen-bonded supramolecular arrangements established in DES may lead to synergetic or additive effects between the counterparts. .(35,59−62) However, the synergetic/additivity effects may lead in some cases in more or less toxic systems in comparison with their constituents.(13)
Figure 5
Figure 5. Cytotoxic effect of menthol:LA (4:1) (A), menthol:MA (8:1) (B), and menthol:SA (8:1) (C) with use of HaCaT cell model treated for 24 h. Results were expressed relative to the control as mean ± SD of three independent experiments performed in triplicate.
THEDES based on menthol:SA (8:1) present the lowest cytotoxicity, being the system selected to evaluate its wound healing properties. The bioactive properties of fatty acids and menthol have been reported,(63−65) but from the best of our knowledge there is no information while in THEDES form. Three noncytotoxic concentrations of menthol:SA (8:1) were selected, and the ability of HaCaT cells to migrate was assessed using the wound healing assay. As panels A and B of Figure 6 show, the two highest menthol:SA (8:1) concentrations significantly induce cell migration, leading to higher wound enclosure (areas of 66.00 ± 5.92% and 70.50 ± 4.28%) compared to that of the control (53.23 ± 5.35%), representing an increase of nearly 40%. Moreover, isolated menthol and SA did not show a strong effect on cell migration, with the exception of menthol at a concentration of 0.75 mM. The THEDES (0.75 menthol + 0.09 SA mM) were more effective than isolated menthol, which might suggest that the hydrogen bonding interaction of SA with menthol potentiates its activity. Menthol is a terpene highly explored as anti-inflammatory, antiseptic, and antipruritic, therefore having a strong application in skin disorders.(66) These results may reflect the potential bioactive properties of menthol:SA (8:1) over menthol for topical applications by its high capacity of inducing cell migration.
Figure 6
Figure 6. Wound healing assay. (A) Migration assessment of HaCaT cells after the treatment with menthol:SA (8:1) and menthol and SA at 0 and 24 h postscratch. The lines indicated the boundary lines of the scratch at 0 h. (B) Results were expressed in terms of percentage of wound closure relative to the control using the mean ± SD of six independent experiments performed in duplicate.
Antibacterial Properties
After confirming the biological activity of menthol:SA in wound healing by migration of HaCaT cells, the antibacterial properties were screened out against several microorganisms with disk diffusion assay (DDA). The results obtained for each bacteria and compounds are presented in Table 2. For both, the tested THEDES and pure compounds, no significant inhibition halo was observed in either the E. coli or P. aeruginosa strains tested, with instances of deposit being observable in menthol:SA plates which deterred correct assessment of inhibition halo diameter. Nevertheless, since for both isolated menthol and SA no inhibition halo was observable, these strains were deemed resistant. These results are not surprising, as several instances in literature report greater difficulty in dealing with Gram-negative bacteria due to their more complex membrane structure.(31,67,68) Regarding the Gram-positive strains tested, SA showed no apparent inhibition and deposit formation was observed in menthol:SA, once again interfered with correct determination of inhibition halo. However, isolated menthol showed a significant inhibition halo in all cases.
Table 2. Representative Images of Disk Diffusion Assay Plates Obtained for Individual Counterparts, THEDES, and Controlsa
a
Plates are presented by bacterial strains tested.
It should be noted that the lack of antibacterial activity of SA, as well as, the formation of deposit in all cases for menthol:SA is most likely a consequence of this fatty acid’s low solubility and, consequently, low diffusion rate. However, since the major component of the tested THEDES is menthol which showed relevant antibacterial activity in the DDA against the Gram-positive bacteria strains tested, these were subjected to MIC/MBC determination to try and accurately assess THEDES antibacterial potential. According to the performed experiments, menthol has a MIC value for S. aureus of 4 mM. Once again, SA did not show any antibacterial activity, which might be due to its low solubility, which hinders the complete dissolution of the compound in the selected conditions. Except for SA, all compositions demonstrate antimicrobial activity, being more efficient at higher concentrations, as expected. The methicillin-resistant strains tested show greater resilience, having a higher resistance to both menthol and the THEDES than S. aureus ATCC 25923. Nevertheless, MIC/MBC values for the methicillin-resistant strains are still within noncytotoxic values shown to promote wound healing. These results are presented in Table 3.
Table 3. MIC/MBC Values of Individual Counterparts and THEDESa
| MIC (mM) | MBC (mM) | |||||
|---|---|---|---|---|---|---|
| microbial strain | menthol | SA | menthol:SA | menthol | SA | menthol:SA |
| S. aureus | 4 | ND | 3.26 + 1.79 | 8 | ND | 6.52 + 3.58 |
| MRSA | 8 | ND | 6.52 + 3.58 | 16 | ND | 13.03 + 7.16 |
| MRSE | 8 | ND | 6.52 + 3.58 | 16 | ND | 13.03 + 7.16 |
a
Results are presented by bacterial strains tested. ND, not dissolved.
A point of note in the results obtained lies in the fact that, in all cases, the MIC/MBC values of menthol:SA match those of its major component menthol. However, as already mentioned previously according to the molar ratio, 1 mol of menthol:SA (8:1) is composed of about 0.82 mol of menthol and 0.18 mol of stearic acid. As such, even though the MIC/MBC values of menthol:SA and menthol overlap, the THEDES effectively contains, in all cases, a lower amount of menthol per defect which strongly suggests a synergistic interaction between menthol and SA that potentiates antibacterial activity, highlighting the advantages of the studied THEDES.
Conclusion
ARTICLE SECTIONS
Herein, the potential of THEDES based on menthol and fatty acid were unveiled, starting from comprehensive data on the thermophysical properties of these solvents and going up to their potential therapeutic application. The fundamental knowledge provides clues for a deeper understanding of these solvents, being crucial to understanding their properties at different operating conditions. The fundamental characterization is hence essential for choosing the right system for a certain application. The thermophysical characterization of THEDES was followed by the evaluation of their biological performance in terms of toxicity toward HaCaT cells and also by their antibacterial properties. Remarkably, among the different formulations, menthol:SA was the most promising formulation and the wound healing assay further suggests their ability to promote the migration of HaCaT. Thereby, the generated data in this work will fulfill gaps in the fundamental knowledge and biological performance of the THEDES based on menthol and fatty acids which fasten the pace to predicting their positive effects in biomedical applications. On the whole, we envisage that the present work opens new intriguing possibilities on the use of these THEDES in wound treatments. Additionally, these results emphasize the huge versatility of THEDES as a new approach toward the development of more effective therapies.
○Author Present Address
LAQV-REQUIMTE, Chemistry Department, Faculty of Science and Technology, Nova University of Lisbon, 2829-516 Caparica, Portugal.
The authors declare no competing financial interest.
Author Information
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- Ana Rita C. Duarte - 3B’s Research Group—Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark Barco, Guimarães 4805-017, Portugal; ICVS/3B’s PT Government Associated Laboratory, Braga/Guimarães 4806-909, Portugal; Present Address: LAQV-REQUIMTE, Chemistry Department, Faculty of Science and Technology, Nova University of Lisbon, 2829-516 Caparica, Portugal;
http://orcid.org/0000-0003-0800-0112;
Email: [email protected]
The authors declare no competing financial interest.
Acknowledgments
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The research leading to these results has received funding from Horizon 2020 through ERC-2016-CoG-725034 Des.Solve (ERC Consolidator Grant). We also acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through the postdoctoral grant with Reference No. SFRH/BPD/116779/2016, the PTDC/BBB-490 EBB/1676/2014 Project, the PEst-OE/EQB/LA0004/2011 Grant, iNOVA4Health-UID/Multi/04462/2013, IF Starting Grant GRAPHYT (IF/00723/2014), FCT/MCTES (UID/QUI/50006/2019), FCT/MCTES (UID/Multi/04378/2019) and IF Starting Grant IF/01146/2015.
References
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This article references 68 other publications.
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- 2Smith, E. L.; Abbott, A. P.; Ryder, K. S. Deep eutectic solvents (DESs) and their applications. Chem. Rev. 2014, 114 (21), 11060– 11082, DOI: 10.1021/cr300162p[ACS Full Text
], [CAS], Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsleksrzM&md5=23e782e87410fb1014857dd350ee5146Deep Eutectic Solvents (DESs) and Their ApplicationsSmith, Emma L.; Abbott, Andrew P.; Ryder, Karl S.Chemical Reviews (Washington, DC, United States) (2014), 114 (21), 11060-11082CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)This article describes the phys. and chem. properties of deep eutectic solvents (DESs) and ionic liq. (ILs), and how their applications differ. DESs are now widely acknowledged as a new class of IL analogs because they share many characteristics and properties with ILs. The terms DES and IL have been used interchangeably in the literature, though it is necessary to point out that these are actually two different types of solvent. DESs are systems formed from a eutectic mixt. of Lewis or Bronsted acids and bases which can contain a variety of anionic and/or cationic species; in contrast, ILs are formed from systems composed primarily of one type of discrete anion and cation. - 3Tang, B.; Row, K. H. Recent developments in deep eutectic solvents in chemical sciences. Monatsh. Chem. 2013, 144 (10), 1427– 1454, DOI: 10.1007/s00706-013-1050-3[Crossref], [CAS], Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlCqsrvE&md5=43278104871b5ce32b062bd1ccb8f1a6Recent developments in deep eutectic solvents in chemical sciencesTang, Baokun; Row, Kyung HoMonatshefte fuer Chemie (2013), 144 (10), 1427-1454CODEN: MOCMB7; ISSN:0026-9247. (Springer-Verlag GmbH)A review. In recent years, deep eutectic solvents (DESs) were considered green solvent alternatives to conventional solvents and have attracted considerable attention. With an in-depth understanding of the common and novel properties of DESs, many of them were prepd. and applied to various areas of chem. To summarize the full-scale development of DESs, this field is reviewed from its inception. This review summarizes the general trends in the development of DESs and evaluates the major aspects of DESs, such as their properties, prepns., and applications. This work is expected to be helpful for the further development of DESs based on a summary of the fundamental research in the field.
- 4Xu, P.; Zheng, G.-W.; Zong, M.-H.; Li, N.; Lou, W.-Y. Recent progress on deep eutectic solvents in biocatalysis. Bioresour. Bioprocess. 2017, 4 (1), 34, DOI: 10.1186/s40643-017-0165-5[Crossref], [PubMed], [CAS], Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cfmt1Kjuw%253D%253D&md5=82948b79c4ad39132300e7b8b40ce9fdRecent progress on deep eutectic solvents in biocatalysisXu Pei; Zong Min-Hua; Li Ning; Lou Wen-Yong; Xu Pei; Zong Min-Hua; Lou Wen-Yong; Zheng Gao-WeiBioresources and bioprocessing (2017), 4 (1), 34 ISSN:2197-4365.Deep eutectic solvents (DESs) are eutectic mixtures of salts and hydrogen bond donors with melting points low enough to be used as solvents. DESs have proved to be a good alternative to traditional organic solvents and ionic liquids (ILs) in many biocatalytic processes. Apart from the benign characteristics similar to those of ILs (e.g., low volatility, low inflammability and low melting point), DESs have their unique merits of easy preparation and low cost owing to their renewable and available raw materials. To better apply such solvents in green and sustainable chemistry, this review firstly describes some basic properties, mainly the toxicity and biodegradability of DESs. Secondly, it presents several valuable applications of DES as solvent/co-solvent in biocatalytic reactions, such as lipase-catalyzed transesterification and ester hydrolysis reactions. The roles, serving as extractive reagent for an enzymatic product and pretreatment solvent of enzymatic biomass hydrolysis, are also discussed. Further understanding how DESs affect biocatalytic reaction will facilitate the design of novel solvents and contribute to the discovery of new reactions in these solvents.
- 5Zhang, Q.; De Oliveira Vigier, K.; Royer, S.; Jerome, F. Deep eutectic solvents: syntheses, properties and applications. Chem. Soc. Rev. 2012, 41 (21), 7108– 7146, DOI: 10.1039/c2cs35178a[Crossref], [PubMed], [CAS], Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVOnurjF&md5=b2e43b5e7332276be1699afe9ddd561fDeep eutectic solvents: Syntheses, properties and applicationsZhang, Qinghua; De Oliveira Vigier, Karine; Royer, Sebastien; Jerome, FrancoisChemical Society Reviews (2012), 41 (21), 7108-7146CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Within the framework of green chem., solvents occupy a strategic place. To be qualified as a green medium, these solvents have to meet different criteria such as availability, non-toxicity, biodegradability, recyclability, flammability, and low price among others. Up to now, the no. of available green solvents are rather limited. Here we wish to discuss a new family of ionic fluids, so-called Deep Eutectic Solvents (DES), that are now rapidly emerging in the current literature. A DES is a fluid generally composed of two or three cheap and safe components that are capable of self-assocn., often through hydrogen bond interactions, to form a eutectic mixt. with a m.p. lower than that of each individual component. DESs are generally liq. at temps. lower than 100 °C. These DESs exhibit similar physico-chem. properties to the traditionally used ionic liqs., while being much cheaper and environmentally friendlier. Owing to these remarkable advantages, DESs are now of growing interest in many fields of research. In this review, we report the major contributions of DESs in catalysis, org. synthesis, dissoln. and extn. processes, electrochem. and material chem. All works discussed in this review aim at demonstrating that DESs not only allow the design of eco-efficient processes but also open a straightforward access to new chems. and materials.
- 6Paiva, A.; Craveiro, R.; Aroso, I.; Martins, M.; Reis, R. L.; Duarte, A. R. C. Natural deep eutectic solvents–solvents for the 21st century. ACS Sustainable Chem. Eng. 2014, 2 (5), 1063– 1071, DOI: 10.1021/sc500096j[ACS Full Text], [CAS], Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktlSqsLc%253D&md5=4e0b6d730b233beea8404df78f0dced5Natural Deep Eutectic Solvents - Solvents for the 21st CenturyPaiva, Alexandre; Craveiro, Rita; Aroso, Ivo; Martins, Marta; Reis, Rui L.; Duarte, Ana Rita C.ACS Sustainable Chemistry & Engineering (2014), 2 (5), 1063-1071CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)A review. Green technol. actively seeks new solvents to replace common org. solvents that present inherent toxicity and have high volatility, leading to evapn. of volatile org. compds. to the atm. Over the past two decades, ionic liqs. (ILs) have gained enormous attention from the scientific community, and the no. of reported articles in the literature has grown exponentially. Nevertheless, IL "greenness" is often challenged, mainly due to their poor biodegradability, biocompatibility, and sustainability. An alternative to ILs are deep eutectic solvents (DES). Deep eutectic solvents are defined as a mixt. of two or more components, which may be solid or liq. and that at a particular compn. present a high m.p. depression becoming liqs. at room temp. When the compds. that constitute the DES are primary metabolites, namely, aminoacids, org. acids, sugars, or choline derivs., the DES are so called natural deep eutectic solvents (NADES). NADES fully represent green chem. principles. Can natural deep eutectic solvents be foreseen as the next generation solvents and can a similar path to ionic liqs. be outlined. The current state of the art concerning the advances made on these solvents in the past few years is reviewed in this paper, which is more than an overview on the different applications for which they have been suggested, particularly, biocatalysis, electrochem., and extn. of new data. Citotoxicity of different NADES was evaluated and compared to conventional imidazolium-based ionic liqs., and hints at the extn. of phenolic compds. from green coffee beans and on the foaming effect of NADES are revealed. Future perspectives on the major directions toward which the research on NADES is envisaged are here discussed, and these comprised undoubtedly a wide range of chem. related subjects.
- 7Mbous, Y. P.; Hayyan, M.; Hayyan, A.; Wong, W. F.; Hashim, M. A.; Looi, C. Y. Applications of deep eutectic solvents in biotechnology and bioengineering—promises and challenges. Biotechnol. Adv. 2017, 35 (2), 105– 134, DOI: 10.1016/j.biotechadv.2016.11.006[Crossref], [PubMed], [CAS], Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1Wltr4%253D&md5=33e403fa0e22c0416948931fa3cd50bdApplications of deep eutectic solvents in biotechnology and bioengineering-Promises and challengesMbous, Yves Paul; Hayyan, Maan; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd. Ali; Looi, Chung YengBiotechnology Advances (2017), 35 (2), 105-134CODEN: BIADDD; ISSN:0734-9750. (Elsevier)Deep eutectic solvents (DESs) have been touted recently as potential alternatives to ionic liqs. (ILs). Although they possess core characteristics that are similar to those of ILs (e.g., low volatility, non-flammability, low m.ps., low vapor pressure, dipolar nature, chem. and thermal stability, high soly., and tuneability), DESs are superior in terms of the availability of raw materials, the ease of storage and synthesis, and the low cost of their starting materials. As such, they have become the subject of intensive research in various sectors, notably the chem., electrochem., and biol. sectors. To date, the applications of DESs have shown great promise, esp. in the medical and biotechnol. fields. In spite of these various achievements, the safety concern for these mixts. must be sufficiently addressed. Indeed, in order to exploit the vast array of opportunities that DESs offer to the biol. industry, first, they must be established as safe mixts. Hence, the biotechnol. applications of DESs only can be implemented if they are proven to have negligible or low toxicity profiles. This review is the first of its kind, and it discusses two current aspects of DES-based research. First, it describes the properties of these mixts. with ample focus on their toxicity profiles. Second, it provides an overview of the breakthroughs that have occurred and the foreseeable prospects of the use of DESs in various biotechnol. and biol. applications.
- 8Mouden, S.; Klinkhamer, P. G.; Choi, Y. H.; Leiss, K. A. Towards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolites. Phytochem. Rev. 2017, 16 (5), 935– 951, DOI: 10.1007/s11101-017-9502-8[Crossref], [PubMed], [CAS], Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlt1Smtrs%253D&md5=2ced8d68a88399b32c03ced3592aae1fTowards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolitesMouden, Sanae; Klinkhamer, Peter G. L.; Choi, Young Hae; Leiss, Kirsten A.Phytochemistry Reviews (2017), 16 (5), 935-951CODEN: PRHEBS; ISSN:1568-7767. (Springer)A review. With mounting concerns over health and environmental effects of pesticides, the search for environmentally acceptable substitutes has amplified. Plant secondary metabolites appear in the horizon as an attractive soln. for green crop protection. This paper reviews the need for changes in the techniques and compds. that, until recently, have been the mainstay for dealing with pest insects. Here we describe and discuss main strategies for selecting plant-derived metabolites as candidates for sustainable agriculture. The second part surveys ten important insecticidal compds., with special emphasis on those involved in human health. Many of these insecticidal metabolites, however, are cryst. solids with limited soly. which might potentially hamper com. formulation. As such, we introduce the concept of natural deep eutectic solvents for enhancing soly. and stability of such compds. The concept, principles and examples of green pest control discussed here offer a new suite of environmental-friendly tools designed to promote and adopt sustainable agriculture.
- 9Radošević, K.; Ćurko, N.; Gaurina Srček, V.; Cvjetko Bubalo, M.; Tomašević, M.; Kovačević Ganić, K. K.; Radojčić Redovniković, I. R. Natural deep eutectic solvents as beneficial extractants for enhancement of plant extracts bioactivity. LWT-Food Sci. Technol. 2016, 73, 45– 51, DOI: 10.1016/j.lwt.2016.05.037[Crossref], [CAS], Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XptVWitbg%253D&md5=fc0d624856aba0d1ed821b6df9820242Natural deep eutectic solvents as beneficial extractants for enhancement of plant extracts bioactivityRadosevic, Kristina; Curko, Natka; Gaurina Srcek, Visnja; Cvjetko Bubalo, Marina; Tomasevic, Marina; Kovacevic Ganic, Karin; Radojcic Redovnikovic, IvanaLWT--Food Science and Technology (2016), 73 (), 45-51CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)In the present study phenolic grape skin exts. were prepd. by using five choline chloride based natural deep eutectic solvents (NADESs) contg. glucose, fructose, xylose, glycerol, malic acid and valorised by testing their biol. activity in vitro using two human tumor cell lines (HeLa and MCF-7). Initially, used NADESs were investigated regard to their toxicity and low cytotoxicity of solvents was obsd. toward HeLa and MCF-7 cells (EC50 values > 2000 mg/L). Among used choline chloride based NADESs, the one contg. malic acid showed the best performance concerning extn. efficiency (total phenolic and total anthocyanin were 91 and 24 mg/g dw), as well as antioxidant (ORAC values were 371 μmol TE/g dw) and antiproliferative activity (percentage of cell viability were about 20%). Herein, for the first time it was showed that NADES components could be chosen not only to fine-tune solvent physicochem. characteristics but also to enhance biol. activity of exts. prepd. in NADESs. Therefore, our research confirmed that NADESs are excellent and promising choice of solvents for sustainable and green extn., which will lead to its novel application in food and pharmaceutical industry.
- 10Florindo, C.; McIntosh, A.; Welton, T.; Branco, L.; Marrucho, I. A closer look into deep eutectic solvents: exploring intermolecular interactions using solvatochromic probes. Phys. Chem. Chem. Phys. 2018, 20 (1), 206– 213, DOI: 10.1039/C7CP06471C[Crossref], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvVKgtL%252FN&md5=9503fa9f92f53cce74cedb6cda235a4aA closer look into deep eutectic solvents: exploring intermolecular interactions using solvatochromic probesFlorindo, C.; McIntosh, A. J. S.; Welton, T.; Branco, L. C.; Marrucho, I. M.Physical Chemistry Chemical Physics (2018), 20 (1), 206-213CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Deep eutectic solvents (DESs) constitute a new class of ionic solvents that was developing at a fast pace in recent years. Since these solvents are commonly suggested as green alternatives to org. solvents, it is important to understand their phys. properties. In particular, polarity plays an important role in solvation phenomena. In this work, the polarity of different families of DESs was studied through solvatochromic responses of UV-vis absorption probes. Kamlet-Taft α, β, π* and ETN parameters were evaluated using different solvatochromic probes, as 2,6-dichloro-4-(2,4,6-triphenyl-N-pyridino)-phenolate (Reichardt's betaine dye 33), 4-nitroaniline, and N,N-diethyl-4-nitroaniline for several families of DESs based on cholinium chloride, DL-menthol and a quaternary ammonium salt ([N4444]Cl). In addn., a study to understand the difference in polarity properties between DESs and the corresponding ILs, namely ILs based on cholinium cation and carboxylic acids as anions ([Ch][Lev], [Ch][Gly] and [Ch][Mal]), was carried out. The chem. structure of the hydrogen bond acceptor (HBA) in a DES clearly controls the dipolarity/polarizability afforded by the DES. Moreover, Kamlet-Taft parameters do not vary much within the family, but they differ among families based on different HBA, either for DESs contg. salts ([Ch]Cl or [N4444]Cl) or neutral compds. (DL-menthol). A substitution of the HBD was also found to play an important role in solvatochromic probe behavior for all the studied systems.
- 11Martins, M. A. R.; Crespo, E. A.; Pontes, P. V.; Silva, L. P.; Bülow, M.; Maximo, G. J.; Batista, E. A. C.; Held, C.; Pinho, S. P.; Coutinho, J. A. Tunable hydrophobic eutectic solvents based on terpenes and monocarboxylic acids. ACS Sustainable Chem. Eng. 2018, 6 (7), 8836– 8846, DOI: 10.1021/acssuschemeng.8b01203[ACS Full Text], [CAS], Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtVags7zN&md5=87ef83987b5a9d8f59e9b370b3fe65ccTunable Hydrophobic Eutectic Solvents Based on Terpenes and Monocarboxylic AcidsMartins, Monia A. R.; Crespo, Emanuel A.; Pontes, Paula V. A.; Silva, Liliana P.; Bulow, Mark; Maximo, Guilherme J.; Batista, Eduardo A. C.; Held, Christoph; Pinho, Simao P.; Coutinho, Joao A. P.ACS Sustainable Chemistry & Engineering (2018), 6 (7), 8836-8846CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Recently, some works claim that hydrophobic deep eutectic solvents could be prepd. based on menthol and monocarboxylic acids. Despite of some promising potential applications, these systems were poorly understood, and this work addresses this issue. Here, the characterization of eutectic solvents composed of the terpenes thymol or L(-)-menthol and monocarboxylic acids is studied aiming the design of these solvents. Their solid-liq. phase diagrams were measured by differential scanning calorimetry in the whole compn. range, showing that a broader compn. range, and not only fixed stoichiometric proportions, can be used as solvents at low temps. Addnl., solvent densities and viscosities close to the eutectic compns. were measured, showing low viscosity and lower d. than water. The solvatochromic parameters at the eutectic compn. were also investigated aiming at better understanding their polarity. The high acidity is mainly provided by the presence of thymol in the mixt., while L(-)-menthol plays the major role on the hydrogen-bond basicity. The measured mutual solubilities with water attest to the hydrophobic character of the mixts. investigated. The exptl. solid-liq. phase diagrams were described using the PC-SAFT equation of state that is shown to accurately describe the exptl. data and quantify the small deviations from ideality.
- 12Dai, Y.; Witkamp, G.-J.; Verpoorte, R.; Choi, Y. H. Tailoring properties of natural deep eutectic solvents with water to facilitate their applications. Food Chem. 2015, 187, 14– 19, DOI: 10.1016/j.foodchem.2015.03.123[Crossref], [PubMed], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXlvVChur0%253D&md5=5e9f1f5fdd6fbf71562e1c0c1504e5d3Tailoring properties of natural deep eutectic solvents with water to facilitate their applicationsDai, Yuntao; Witkamp, Geert-Jan; Verpoorte, Robert; Choi, Young HaeFood Chemistry (2015), 187 (), 14-19CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)Previously it was demonstrated that natural deep eutectic solvents (NADES) are promising green solvents for the extn. of natural products. However, despite their potential, an obvious disadvantage of NADES is the high viscosity. Here we explored the diln. effect on the structures and physicochem. properties of NADES and their improvements of applications using quercetin and carthamin. The results of FT-IR and 1H NMR expts. demonstrated that there are intensive H-bonding interactions between the two components of NADES and diln. with water caused the interactions weaken gradually and even disappeared completely at around 50% (vol./vol.) water addn. A small amt. of water could reduce the viscosity of NADES to the range of water and increase the cond. by up to 100 times for some NADES. This study provides the basis for modulating NADES in a controllable way for their applications in food processing, enzyme reactions, pharmaceuticals and cosmetics.
- 13van Osch, D. J.; Zubeir, L. F.; van den Bruinhorst, A.; Rocha, M. A.; Kroon, M. C. Hydrophobic deep eutectic solvents as water-immiscible extractants. Green Chem. 2015, 17 (9), 4518– 4521, DOI: 10.1039/C5GC01451D[Crossref], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2hsbvE&md5=1864bab4fcef1077c5219b3db77668deHydrophobic deep eutectic solvents as water-immiscible extractantsvan Osch, Dannie J. G. P.; Zubeir, Lawien F.; van den Bruinhorst, Adriaan; Rocha, Marisa A. A.; Kroon, Maaike C.Green Chemistry (2015), 17 (9), 4518-4521CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Hydrophobic deep eutectic solvents (DESs) are presented for the first time. They consist of decanoic acid and various quaternary ammonium salts. The effect of the alkyl chains on the hydrophobicity and the equil. of the two-phase DES-water system were investigated. These new DESs were successfully evaluated for the recovery of volatile fatty acids from dild. aq. solns.
- 14Abo-Hamad, A.; Hayyan, M.; AlSaadi, M. A.; Hashim, M. A. Potential applications of deep eutectic solvents in nanotechnology. Chem. Eng. J. 2015, 273, 551– 567, DOI: 10.1016/j.cej.2015.03.091[Crossref], [CAS], Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXlsV2ntLc%253D&md5=d65a40cb9afeb09424d581a40ec62b59Potential applications of deep eutectic solvents in nanotechnologyAbo-Hamad, Ali; Hayyan, Maan; AlSaadi, Mohammed AbdulHakim; Hashim, Mohd AliChemical Engineering Journal (Amsterdam, Netherlands) (2015), 273 (), 551-567CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)A review. Deep eutectic solvents (DESs) have recently received a great interest in diverse fields including nanotechnol. due to their unique properties as new green solvents, efficient dispersants and as large-scale media for chem. and electrochem. synthesis of advanced functional nanomaterials. DESs have also an active role in improving the size and morphol. of nanomaterials during synthesis stage. Moreover, DESs confined in nano-size pores or tubes show distinct behavior from those in the same types but in larger scales. Therefore, a numerous studies sprung up to expose the importance of the synergy between DESs and nanomaterials. This review revealed the recent studies that devoted to the impact of involving DESs in nanotechnol. and potential applications.
- 15Alonso, D. A.; Baeza, A.; Chinchilla, R.; Guillena, G.; Pastor, I. M.; Ramón, D. J. Deep eutectic solvents: the organic reaction medium of the century. Eur. J. Org. Chem. 2016, 2016 (4), 612– 632, DOI: 10.1002/ejoc.201501197[Crossref], [CAS], Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XislamtA%253D%253D&md5=2a5804acb485c86f357e36300e0e238bDeep Eutectic Solvents: The Organic Reaction Medium of the CenturyAlonso, Diego A.; Baeza, Alejandro; Chinchilla, Rafael; Guillena, Gabriela; Pastor, Isidro M.; Ramon, Diego J.European Journal of Organic Chemistry (2016), 2016 (4), 612-632CODEN: EJOCFK; ISSN:1099-0690. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. This microreview summarizes the use of deep eutectic solvents (DESs) and related melts in org. synthesis. Solvents of this type combine the great advantages of other proposed environmentally benign alternative solvents, such as low toxicity, high availability, low inflammability, high recyclability, low volatility, and low price, avoiding many disadvantages of the more modern media. The fact that many of the components of these mixts. come directly from nature assures their biodegradability and renewability. The classification and distribution of the reactions into different sections in this microreview, as well as the emphasis paid to their scope, easily allow a general reader to understand the actual state of the art and the great opportunities opened, not only for academic purposes but also for industry.
- 16Dai, Y.; van Spronsen, J.; Witkamp, G.-J.; Verpoorte, R.; Choi, Y. H. Natural deep eutectic solvents as new potential media for green technology. Anal. Chim. Acta 2013, 766, 61– 68, DOI: 10.1016/j.aca.2012.12.019[Crossref], [PubMed], [CAS], Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1Ggsrw%253D&md5=9d549b112fed92d496cc14f3d70ba9beNatural deep eutectic solvents as new potential media for green technologyDai, Yuntao; van Spronsen, Jaap; Witkamp, Geert-Jan; Verpoorte, Robert; Choi, Young HaeAnalytica Chimica Acta (2013), 766 (), 61-68CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Developing new green solvents is one of the key subjects in Green Chem. Ionic liqs. (ILs) and deep eutectic solvents, thus, have been paid great attention to replace current harsh org. solvents and have been applied to many chem. processing such as extn. and synthesis. However, current ionic liqs. and deep eutectic solvents have still limitations to be applied to a real chem. industry due to toxicity against human and environment and high cost of ILs and solid state of most deep eutectic solvents at room temp. Recently we discovered that many plant abundant primary metabolites changed their state from solid to liq. when they were mixed in proper ratio. This finding made us hypothesize that natural deep eutectic solvents (NADES) play a role as alternative media to water in living organisms and tested a wide range of natural products, which resulted in discovery of over 100 NADES from nature. In order to prove deep eutectic feature the interaction between the mols. was investigated by NMR spectroscopy. All the tested NADES show clear hydrogen bonding between components. As next step phys. properties of NADES such as water activity, d., viscosity, polarity and thermal properties were measured as well as the effect of water on the phys. properties. In the last stage the novel NADES were applied to the solubilization of wide range of biomols. such as non-water sol. bioactive natural products, gluten, starch, and DNA. In most cases the soly. of the biomols. evaluated in this study was greatly higher than water. Based on the results the novel NADES may be expected as potential green solvents at room temp. in diverse fields of chem.
- 17Tang, B.; Zhang, H.; Row, K. H. Application of deep eutectic solvents in the extraction and separation of target compounds from various samples. J. Sep. Sci. 2015, 38 (6), 1053– 1064, DOI: 10.1002/jssc.201401347[Crossref], [PubMed], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvVeku7c%253D&md5=4beea05995228911980de57d4c2d94d9Application of deep eutectic solvents in the extraction and separation of target compounds from various samplesTang, Baokun; Zhang, Heng; Row, Kyung HoJournal of Separation Science (2015), 38 (6), 1053-1064CODEN: JSSCCJ; ISSN:1615-9314. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Deep eutectic solvents, as a new type of eco-friendly solvent, have attracted increasing attention in chem. for the extn. and sepn. of target compds. from various samples. To summarize the application of deep eutectic solvents, this review highlights some of the unique properties of deep eutectic solvents and deep-eutectic-solvent-based materials, as well as their applications in extn. and sepn. In this paper, the available data and refs. in this field are reviewed to summarize the application developments of deep eutectic solvents. Based on the development of deep eutectic solvents, the exploitation of new deep eutectic solvents and deep-eutectic-solvent-based materials are expected to diversify into extn. and sepn.
- 18Stott, P. W.; Williams, A. C.; Barry, B. W. Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. J. Controlled Release 1998, 50 (1–3), 297– 308, DOI: 10.1016/S0168-3659(97)00153-3[Crossref], [PubMed], [CAS], Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnvFSnsrc%253D&md5=0ffc946fc451f5d4917573e78fbdd34bTransdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofenStott, Paul W.; Williams, Adrian C.; Barry, Brian W.Journal of Controlled Release (1998), 50 (1-3), 297-308CODEN: JCREEC; ISSN:0168-3659. (Elsevier Science B.V.)The formation of eutectic systems between ibuprofen (Ibu) and 7 terpene skin penetration enhancers was studied and, by using the eutectic systems as donors, the effects of m.p. depression of the delivery system on transdermal delivery were investigated. A range of Ibu:terpene binary mixts. were melted together, cooled, and recrystd. Compn./m.p. phase diagrams detd. by DSC and FT-IR anal. was used to investigate the nature of the interaction. Permeation of Ibu across human epidermal membranes from the eutectic systems was measured and compared to the flux from a satd. aq. soln. across skin and skin pretreated with the terpenes. The eutectic, i.e. min., m.p. of these systems ranged from 32° for Ibu:thymol 40:60 to -13° for Ibu:1,8-cineole 40:60 ( wt./wt.) compared to 76° for Ibu alone. FT-IR studies indicated that only the terpenes which formed hydrogen bonds with Ibu produced eutectic systems. Each set of Ibu:terpene eutectic systems produced a significant increase in flux compared to a satd. aq. soln. applied to untreated and to terpene pretreated skin. For example, Ibu:thymol 40:60 ( wt./wt.) produced a flux of 150 μg/cm2/h, 5.9-fold the flux from a satd. aq. soln. with thymol pretreated skin and 12.7-fold the flux from a satd. aq. soln. across non-pretreated skin. A hydrogen bonding interaction is the primary mechanism by which some terpenes form binary eutectic mixts. with Ibu. The resultant m.p. depression of the delivery system is correlated with a significant increase in transdermal permeation.
- 19Duarte, A. R. C.; Ferreira, A. S. D.; Barreiros, S.; Cabrita, E.; Reis, R. L.; Paiva, A. A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies. Eur. J. Pharm. Biopharm. 2017, 114, 296– 304, DOI: 10.1016/j.ejpb.2017.02.003[Crossref], [PubMed], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisFSit78%253D&md5=6b902e17189ec5c601aeba97bb825d98A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studiesDuarte, Ana Rita C.; Ferreira, Ana Sofia D.; Barreiros, Susana; Cabrita, Eurico; Reis, Rui L.; Paiva, AlexandreEuropean Journal of Pharmaceutics and Biopharmaceutics (2017), 114 (), 296-304CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)THEDES, so called therapeutic deep eutectic solvents are here defined as a mixt. of two components, which at a particular molar compn. become liq. at room temp. and in which one of them is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepd. The interactions between the components that constitute the THEDES were studied by NMR, confirming that the eutectic system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was studied by PFGSE NMR spectroscopy. It was detd. that the self-diffusion of the species followed the same behavior as obsd. previously for ionic liqs., in which the components migrate via jumping between voids in the suprastructure created by punctual thermal fluctuations. The soly. and permeability of the systems in an isotonic soln. was evaluated and a comparison with the pure APIs was established through diffusion and permeability studies carried out in a Franz cell. The soly. of the APIs when in the THEDES system can be improved up to 12 fold, namely for the system contg. ibu. Furthermore, for this system the permeability was calcd. to be 14 × 10-5 cm/s representing a 3 fold increase in comparison with the pure API. With the exception of the systems contg. PA an increase in the soly., coupled with an increase in permeability was obsd. In this work, we hence demonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability of APIs by changing the phys. state of the mols. from a solid dosage to a liq. system.
- 20Silva, J. M.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Design of functional therapeutic deep eutectic solvents based on choline chloride and ascorbic acid. ACS Sustainable Chem. Eng. 2018, 6 (8), 10355– 10363, DOI: 10.1021/acssuschemeng.8b01687[ACS Full Text], [CAS], Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFCrsr3M&md5=a89eb5656e918e621c17bf49a53e1657Design of Functional Therapeutic Deep Eutectic Solvents Based on Choline Chloride and Ascorbic AcidSilva, Joana M.; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.ACS Sustainable Chemistry & Engineering (2018), 6 (8), 10355-10363CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)In this work, we report the prepn. of novel therapeutic deep eutectic solvents (THEDES) based on choline chloride (CC) and ascorbic acid (AA), in which dexamethasone (DEX) was successfully solubilized. THEDES were synthesized and characterized for thermal behavior and polarized optic microscopy to confirm the formation of a eutectic mixt. The soly. profile of DEX solubilized in THEDES was greatly improved when compared with DEX in powder form. Addnl., the diffusion and permeability of DEX were also slightly increased. The antioxidant properties of AA were maintained up to 6 mo when the compd. is in THEDES form. Biol. tests were also performed, and the results indicate that cell viability varies in a dose-dependent manner. After the half maximal effective concn. (EC50) was detd., a controlled drug delivery system was successfully developed by supercrit. fluid sintering of a starch:poly-ε-caprolactone blend doped with THEDES contg. solubilized DEX. The present study highlights the potential applicability of THEDES based on CC and AA in the pharmaceutical industry and/or tissue engineering (TE) applications.
- 21Morrison, H. G.; Sun, C. C.; Neervannan, S. Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehicles. Int. J. Pharm. 2009, 378 (1–2), 136– 139, DOI: 10.1016/j.ijpharm.2009.05.039[Crossref], [PubMed], [CAS], Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXovFKqtbw%253D&md5=cbd7b0b69611417b3be6d8b6e1f2a3e0Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehiclesMorrison, Henry G.; Sun, Changquan C.; Neervannan, SeshaInternational Journal of Pharmaceutics (2009), 378 (1-2), 136-139CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)Deep eutectic solvent (DES) is a new class of solvents typically formed by mixing choline chloride with hydrogen bond donors such as amines, acids, and alcs. Most DES's are non-reactive with water, biodegradable, and have acceptable toxicity profiles. Urea-choline chloride and malonic acid-choline chloride eutectic systems were characterized using differential scanning calorimetry (DSC) and thermal microscopy. A potential new 2:1 urea-choline chloride cocrystal with a m.p. of 25° was characterized at the eutectic compn. The formation of this cocrystal suggests that DES should not be universally explained by simple eutectic melting, and may be useful in guiding the search for new DES systems. The lack of nucleation of the malonic acid-choline chloride system prohibited the construction of a phase diagram for this system using DSC. We also investigated possible uses of DES in solubilizing poorly sol. compds. for enhanced bioavailability in early drug development such as toxicol. studies. For five poorly sol. model compds., soly. in DES is 5 to 22,000 folds more than that in water. Thus, DES can be a promising vehicle for increasing exposure of poorly sol. compds. in preclin. studies.
- 22Santos, F.; P. S. Leitão, M.; C. Duarte, A. Properties of Therapeutic Deep Eutectic Solvents of L-Arginine and Ethambutol for Tuberculosis Treatment. Molecules 2019, 24 (55), 55, DOI: 10.3390/molecules24010055[Crossref], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXntlCqsLc%253D&md5=eb5e1e06bd4202c3954bbcbe3545f99dProperties of therapeutic deep eutectic solvents of l-arginine and ethambutol for tuberculosis treatmentSantos, Filipa; Leitao, Maria Ines P. S.; Duarte, Ana Rita C.Molecules (2019), 24 (1), 55/1-55/12CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)The treatment for tuberculosis infection usually involves a prolonged regimen of multiple antibacterial drugs, which might lead to various secondary effects. For preventing drug resistance and side-effects of anti-tuberculosis drugs, new methods for improving the bioavailability of APIs were investigated. The strategy proposed consists of the prepn. of therapeutic deep eutectic solvents (THEDES), that incorporate L-arginine and ethambutol. The eutectic mixts. were prepd. by mixing the components at a certain molar ratio, until a clear liq. soln. was formed. The prepd. mixts. were characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and NMR spectroscopy (1H and 13C-NMR). The soly. and permeability of the drugs when they are in the THEDES form was evaluated at 37 °C, in phosphate buffered saline (PBS). Soly. studies showed an increase of the soly. of ethambutol when incorporated in the eutectic system. The cytotoxicity was evaluated using a model cell line (Caco-2), comparing the cytotoxicity of the API incorporated in the eutectic system. We obsd. that the cell viability in the THEDES was affected by the presence of citric acid, and higher cytotoxicity values were obsd. Nonetheless, these findings do not compromise the possibility to use these systems as new delivery systems for ethambutol and arginine.
- 23Aroso, I. M.; Craveiro, R.; Rocha, Â.; Dionísio, M.; Barreiros, S.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Design of controlled release systems for THEDES—therapeutic deep eutectic solvents, using supercritical fluid technology. Int. J. Pharm. 2015, 492 (1–2), 73– 79, DOI: 10.1016/j.ijpharm.2015.06.038[Crossref], [PubMed], [CAS], Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1eksLvI&md5=8dfc9a754f4fda96582dc01e5698fc85Design of controlled release systems for THEDES-Therapeutic deep eutectic solvents, using supercritical fluid technologyAroso, Ivo M.; Craveiro, Rita; Rocha, Angelo; Dionisio, Madalena; Barreiros, Susana; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.International Journal of Pharmaceutics (Amsterdam, Netherlands) (2015), 492 (1-2), 73-79CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)Deep eutectic solvents (DES) can be formed by bioactive compds. or pharmaceutical ingredients. A therapeutic DES (THEDES) based on ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and menthol was synthesized and its thermal behavior was analyzed by differential scanning calorimetry (DSC). A controlled drug delivery system was developed by impregnating a starch:poly-ε-caprolactone polymeric blend (SPCL 30:70) with the menthol:ibuprofen THEDES in different ratios (10 and 20 wt%), after supercrit. fluid sintering at 20 MPa and 50 °C. The morphol. characterization of SPCL matrixes impregnated with THEDES was performed by SEM (SEM) and micro-computed tomog. (micro-CT). Drug release studies were carried out in a phosphate buffered saline. The results obtained provide important clues for the development of carriers for the sustainable delivery of bioactive compds.
- 24Ribeiro, B. D.; Florindo, C.; Iff, L. C.; Coelho, M. A.; Marrucho, I. M. Menthol-based eutectic mixtures: hydrophobic low viscosity solvents. ACS Sustainable Chem. Eng. 2015, 3 (10), 2469– 2477, DOI: 10.1021/acssuschemeng.5b00532[ACS Full Text], [CAS], Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVKlsLjE&md5=c8fd66ce9a6782940808fa5c9c44d1acMenthol-based Eutectic Mixtures: Hydrophobic Low Viscosity SolventsRibeiro, Bernardo D.; Florindo, Catarina; Iff, Lucas C.; Coelho, Maria A. Z.; Marrucho, Isabel M.ACS Sustainable Chemistry & Engineering (2015), 3 (10), 2469-2477CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Inspired by one of the major problems in the pharmaceutical industry, we advantageously used the formation of eutectic mixts. to synthesize new solvents. The aim of this work is to identify low viscosity, cheap, biodegradable and hydrophobic eutectic solvents from natural resources. Consequently, novel eutectic mixts. based on DL-menthol and naturally occurring acids, namely pyruvic acid, acetic acid, L-lactic acid, and lauric acid, were synthesized and are here reported for the first time. The obtained DL-menthol-based eutectic mixts. were analyzed using NMR and FTIR spectroscopy in order to check their structures and purities and to confirm the interaction of the two compds. leading to the eutectic formation. Important solvent thermophys. properties, such as d. and viscosity, of the prepd. eutectic solvents with different water contents (dried and water-satd.) were measured. Finally, taking advantage of their hydrophobic character, namely the formation of two phases with water at room temp., four different biomols., caffeine, tryptophan, isophthalic acid, and vanillin, were extd. and the extn. efficiencies of the prepd. eutectic solvents compared.
- 25Jeevan, R.; Venkat, R.; Khan, M. A.; Kunta; Goskonda; Brotherton, H. O.; Reddy, I. K. Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin. J. Pharm. Sci. 1997, 86 (12), 1369– 1373, DOI: 10.1021/js970161+
- 26Aroso, I. M.; Silva, J. C.; Mano, F.; Ferreira, A. S.; Dionísio, M.; Sá-Nogueira, I.; Barreiros, S.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems. Eur. J. Pharm. Biopharm. 2016, 98, 57– 66, DOI: 10.1016/j.ejpb.2015.11.002[Crossref], [PubMed], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVGnur3K&md5=f8f24c25c624df40e9abee321426ad28Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systemsAroso, Ivo M.; Silva, Joao C.; Mano, Francisca; Ferreira, Ana S. D.; Dionisio, Madalena; Sa-Nogueira, Isabel; Barreiros, Susana; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.European Journal of Pharmaceutics and Biopharmaceutics (2016), 98 (), 57-66CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive mols. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behavior, structural features, dissoln. rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liq. at room temp. Dissoln. studies in PBS led to increased dissoln. rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissoln. rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-pos. and Gram-neg. model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissoln. enhancers in the development of novel and more effective drug delivery systems.
- 27Juergens, U.; Stöber, M.; Vetter, H. The anti-inflammatory activity of L-menthol compared to mint oil in human monocytes in vitro: a novel perspective for its therapeutic use in inflammatory diseases. Eur. J. Med. Res. 1998, 3 (12), 539– 545[PubMed], [CAS], Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXosVSj&md5=5a7fd9948d836b2565a8c82b982ac404The anti-inflammatory activity of L-menthol compared to mint oil in human monocytes in vitro. A novel perspective for its therapeutic use in inflammatory diseasesJuergens, Uwe R.; Stoeber, M.; Vetter, H.European Journal of Medical Research (1998), 3 (12), 539-545CODEN: EJMRFL; ISSN:0949-2321. (I. Holzapfel Publishers)The anti-inflammatory efficacy was studied of L-menthol and mint oil in LPS-stimulated monocytes. Arachidonic acid metab. was assessed by measuring leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) as indicators for lipoxygenase and the cyclooxygenase pathway, resp. The anti-inflammatory effects on interleukin 1β (IL-1β) prodn. were analyzed. L-Menthol suppressed the prodn. of each mediator. LTB4 decreased by 64.4%, PGE2 by 56.6%, and IL-1β by 64.2% at L-menthol concns. within the presumed therapeutic range of about 10-7 g/mL. Mint oil had a bimodal effect on PGE2 prodn. with 10-10-10-8 g/mL increasing PGE2 <6-fold and 10-7 g/mL suppressing PGE2 prodn. app. by 50%. It had similar effects on LTB4 and IL-1β as L-menthol, the suppression being less at lower concns. The authors suggest preferable anti-inflammatory effects of L-menthol compared to mint oil at therapeutically relevant concns. supplied in enteric coated capsules.
- 28Patel, T.; Ishiuji, Y.; Yosipovitch, G. Menthol: a refreshing look at this ancient compound. J. Am. Acad. Dermatol. 2007, 57 (5), 873– 878, DOI: 10.1016/j.jaad.2007.04.008[Crossref], [PubMed], [CAS], Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2snhsVyitg%253D%253D&md5=d752190d04fbd0337412b5b70b10ac12Menthol: a refreshing look at this ancient compoundPatel Tejesh; Ishiuji Yozo; Yosipovitch GilJournal of the American Academy of Dermatology (2007), 57 (5), 873-8 ISSN:.Menthol is a naturally occurring cyclic terpene alcohol of plant origin, which has been used since antiquity for medicinal purposes. Its use in dermatology is ubiquitous, where it is frequently part of topical antipruritic, antiseptic, analgesic, and cooling formulations. Despite its widespread use, it was only recently that the mechanism by which menthol elicits the same cool sensation as low temperature was elucidated upon, with the discovery of the TRPM8 receptor. Although almost 5 years have passed since the discovery of this receptor, many dermatologists are still unaware of menthol's underlying target. The purpose of this review is to highlight the recent advances in the mechanism of action of menthol and to provide an overview of its dermatologic applications.
- 29Tsuk, A. G. Menthol enhancement of transdermal drug delivery. U.S. Pat. Appl. US 07/031,077, 1990.Google ScholarThere is no corresponding record for this reference.
- 30Nakatsuji, T.; Kao, M. C.; Fang, J.-Y.; Zouboulis, C. C.; Zhang, L.; Gallo, R. L.; Huang, C.-M. Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J. Invest. Dermatol. 2009, 129 (10), 2480– 2488, DOI: 10.1038/jid.2009.93[Crossref], [PubMed], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFWqurjF&md5=20f52224bd9284a920b142973dd62b32Antimicrobial Property of Lauric Acid Against Propionibacterium Acnes: Its Therapeutic Potential for Inflammatory Acne VulgarisNakatsuji, Teruaki; Kao, Mandy C.; Fang, Jia-You; Zouboulis, Christos C.; Zhang, Liangfang; Gallo, Richard L.; Huang, Chun-MingJournal of Investigative Dermatology (2009), 129 (10), 2480-2488CODEN: JIDEAE; ISSN:0022-202X. (Nature Publishing Group)The strong bactericidal properties of lauric acid (C12:0), a middle chain-free fatty acid commonly found in natural products, have been shown in a no. of studies. However, it has not been demonstrated whether lauric acid can be used for acne treatment as a natural antibiotic against Propionibacterium acnes (P. acnes), which promotes follicular inflammation (inflammatory acne). This study evaluated the antimicrobial property of lauric acid against P. acnes both in vitro and in vivo. Incubation of the skin bacteria P. acnes, Staphylococcus aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis) with lauric acid yielded minimal inhibitory concn. (MIC) values against the bacterial growth over 15 times lower than those of benzoyl peroxide (BPO). The lower MIC values of lauric acid indicate stronger antimicrobial properties than that of BPO. The detected values of half maximal effective concn. (EC50) of lauric acid on P. acnes, S. aureus, and S. epidermidis growth indicate that P. acnes is the most sensitive to lauric acid among these bacteria. In addn., lauric acid did not induce cytotoxicity to human sebocytes. Notably, both intradermal injection and epicutaneous application of lauric acid effectively decreased the no. of P. acnes colonized with mouse ears, thereby relieving P. acnes-induced ear swelling and granulomatous inflammation. The obtained data highlight the potential of using lauric acid as an alternative treatment for antibiotic therapy of acne vulgaris.
- 31McGaw, L.; Jäger, A.; Van Staden, J.; Houghton, P. Antibacterial effects of fatty acids and related compounds from plants. S. Afr. J. Bot. 2002, 68 (4), 417– 423, DOI: 10.1016/S0254-6299(15)30367-7[Crossref], [CAS], Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXis1GmtLk%253D&md5=675d4354805646a48fd0209fc38e4879Antibacterial effects of fatty acids and related compounds from plantsMcGaw, L. J.; Jager, A. K.; van Staden, J.South African Journal of Botany (2002), 68 (4), 417-423CODEN: SAJBDD; ISSN:0254-6299. (NISC Pty Ltd.)A review. Fatty acids are important constituents of plants and are commonly known to possess antimicrobial activities. The structure-activity relationship of fatty acids, including the effects of hydrocarbon chain length, unsatn. and presence of functional groups, is reviewed. The biol. activity of fatty acids is significant as they are often isolated following bioassay-guided fractionation of plant exts. The possibility of the therapeutic use of fatty acids as antimicrobial agents is worthy of note.
- 32Desbois, A. P.; Smith, V. J. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl. Microbiol. Biotechnol. 2010, 85 (6), 1629– 1642, DOI: 10.1007/s00253-009-2355-3[Crossref], [PubMed], [CAS], Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtVaqu7s%253D&md5=79f2088f5eaa7c30d26dd6876020aceeAntibacterial free fatty acids: activities, mechanisms of action and biotechnological potentialDesbois, Andrew P.; Smith, Valerie J.Applied Microbiology and Biotechnology (2010), 85 (6), 1629-1642CODEN: AMBIDG; ISSN:0175-7598. (Springer)A review. Amongst the diverse and potent biol. activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. While their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy prodn., FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidn. and auto-oxidn. degrdn. products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, esp. where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for com. or biomedical exploitation of antibacterial FFAs, esp. for those from natural sources, is discussed.
- 33Silva, J. M.; Akkache, S.; Araújo, A. C.; Masmoudi, Y.; Reis, R. L.; Badens, E.; Duarte, A. R. C. Development of innovative medical devices by dispersing fatty acid eutectic blend on gauzes using supercritical particle generation processes. Mater. Sci. Eng., C 2019, 99, 599– 610, DOI: 10.1016/j.msec.2019.02.012[Crossref], [PubMed], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXivFyhtLo%253D&md5=5d29a8224cfbc34e2805367eb80c70eeDevelopment of innovative medical devices by dispersing fatty acid eutectic blend on gauzes using supercritical particle generation processesSilva, Joana M.; Akkache, Salah; Araujo, Ana C.; Masmoudi, Yasmine; Reis, Rui L.; Badens, Elisabeth; Duarte, Ana Rita C.Materials Science & Engineering, C: Materials for Biological Applications (2019), 99 (), 599-610CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)In order to limit bacterial infections during wound treatment, it is interesting to consider the concept of loading medical devices with antibacterial agents. With this in mind, an innovative system with thermosensitive properties was produced: loading a com. available gauze with a fatty acid eutectic blend based on lauric acid (LA) and myristic acid (MA). This eutectic blend presents a m.p. near physiol. temp., which together with its antibacterial properties make an appealing alternative in biomedical applications. At room temp., the properties and the efficacy of the eutectic blend loaded onto gauzes are preserved, whereas at physiol. temp. the eutectic blend undergoes a phase change that facilitates its diffusion from the gauze. The loading of the eutectic blend onto gauzes was performed using two different supercrit. fluid technologies, namely, particle from gas satd. solns. (PGSS) and a derived version of rapid expansion of supercrit. soln. (D-RESS). The PGSS led to a heterogeneous dispersion of the eutectic blend in the gauze, whereas the D-RESS process led to the formation of a homogeneous dispersion along the surface of the gauze. Addnl., with D-RESS no phase sepn. of the eutectic blend occurred and the cytotoxicity was greatly improved compared with PGSS without compromising the antibacterial properties of the fatty acid eutectic blend. Hence, the present study highlights the potential use of the flexible D-RESS process to load the fatty acid eutectic blend with antibacterial properties onto medical devices in a controllable way. Overall, the effects produced by the loaded gauzes suggest the enormous potential of the developed technol. in health-related areas.
- 34Castro, V. I.; Craveiro, R.; Silva, J. M.; Reis, R. L.; Paiva, A.; C. Duarte, A. R. Natural deep eutectic systems as alternative nontoxic cryoprotective agents. Cryobiology 2018, 83, 15– 26, DOI: 10.1016/j.cryobiol.2018.06.010[Crossref], [PubMed], [CAS], Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXht1ejtL%252FE&md5=9911b1ac7128af94798e8e1fd33ce15fNatural deep eutectic systems as alternative nontoxic cryoprotective agentsCastro, Vania I. B.; Craveiro, Rita; Silva, Joana M.; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.Cryobiology (2018), 83 (), 15-26CODEN: CRYBAS; ISSN:0011-2240. (Elsevier Ltd.)Natural deep eutectic systems (NADES) are mostly composed of natural primary metabolites such as sugars, sugar alcs., org. acids, amino acids and amines. These simple mols. have been identified in animals living in environments with extreme temp. amplitudes, being responsible for their survival at neg. temps. during winter. Herein, we report for the first time the use of NADES based on trehalose (Treh) and glycerol (Gly) in cryopreservation, as cryoprotective agents (CPA). The evaluation of the thermal behavior of these eutectic systems, showed that NADES have a strong effect on the water crystn./freezing and melting process, being able to reduce the no. of ice crystals and hence ice crystal damage in cells, which is a crucial parameter for their survival, upon freezing. Using this NADES as CPA, it is possible to achieve similar or even better cellular performance when compared with the gold std. for cryopreservation DMSO (DMSO). In this sense, this work relates the phys. properties of the NADES with their biol. performance in cryopreservation. Our comprehensive strategy results in the demonstration of NADES as a promising nontoxic green alternative to the conventional CPA's used in cryopreservation methods.
- 35Hayyan, M.; Looi, C. Y.; Hayyan, A.; Wong, W. F.; Hashim, M. A. In vitro and in vivo toxicity profiling of ammonium-based deep eutectic solvents. PLoS One 2015, 10 (2), e0117934 DOI: 10.1371/journal.pone.0117934[Crossref], [PubMed], [CAS], Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFymsbzE&md5=d326f5a659c28dd15e3c7085e0897bfdIn Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solventsHayyan, Maan; Looi, Chung Yeng; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd. AliPLoS One (2015), 10 (2), e0117934/1-e0117934/18CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerin (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examd. using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were detd. for the DESs, their individual components and their combinations as aq. solns. for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, resp. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS prodn. and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examd. DESs showed less cytotoxicity compared with ionic liqs. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixts. and their potential applicability to be used for therapeutic purposes.
- 36Parnham, E. R.; Drylie, E. A.; Wheatley, P. S.; Slawin, A. M.; Morris, R. E. Ionothermal materials synthesis using unstable deep-eutectic solvents as template-delivery agents. Angew. Chem. 2006, 118 (30), 5084– 5088, DOI: 10.1002/ange.200600290
- 37Abbott, A. P.; Capper, G.; Gray, S. Design of improved deep eutectic solvents using hole theory. ChemPhysChem 2006, 7 (4), 803– 806, DOI: 10.1002/cphc.200500489[Crossref], [PubMed], [CAS], Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XjvVCgtbk%253D&md5=7ffc74a1bbfad12db923f25de253fc9dDesign of improved deep eutectic solvents using hole theoryAbbott, Andrew P.; Capper, Glen; Gray, StephenChemPhysChem (2006), 7 (4), 803-806CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)Ambient temp. ionic liqs. have attracted a great deal of interest owing to their potential as environmentally benign solvents and their unusual solvent properties. An alternative approach to the formation of ionic liqs. is to start with a quaternary ammonium halide and shield the charge on the anion by complexing it with hydrogen-bond donors such as carboxylic acids or amides. These liqs., termed deep eutectic solvents (DESs), have phys. and solvent properties that are similar to ionic liqs. formed with discrete ions, but they are easy to produce by simply mixing common commodity chems. such as choline chloride and urea. In this study, less viscous liqs. with higher conductivities were obtained using small quaternary ammonium cations such as ethylammonium and fluorinated hydrogen-bond donors such as trifluoroacetamide. The fluidity and transport of DESs are both affected by small changes in chem. structure. Thus, the hole theory can be used to design DESs with decreased viscosity and increased cond. by using small cations or fluorinated hydrogen-bond donors. These changes can be quite significant particularly at ambient temp. where the differences in viscosity and cond. can be up to 4 orders of magnitude.
- 38Corvis, Y.; Négrier, P.; Massip, S.; Leger, J.-M.; Espeau, P. Insights into the crystal structure, polymorphism and thermal behavior of menthol optical isomers and racemates. CrystEngComm 2012, 14 (20), 7055– 7064, DOI: 10.1039/c2ce26025e[Crossref], [CAS], Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlGgurnL&md5=3b2492710fd2224b423be4166ed1af7eInsights into the crystal structure, polymorphism and thermal behavior of menthol optical isomers and racematesCorvis, Yohann; Negrier, Philippe; Massip, Stephane; Leger, Jean-Michel; Espeau, PhilippeCrystEngComm (2012), 14 (20), 7055-7064CODEN: CRECF4; ISSN:1466-8033. (Royal Society of Chemistry)The physico-chem. properties of the levo- and dextrorotatory menthol isomers as well as the corresponding racemic compd. were studied using X-ray single-crystal or powder diffraction and differential scanning calorimetry expts. As a result, the not yet detd. crystal structure of dl-menthol was solved. Moreover, the stable and metastable exptl. temp.-compn. phase diagrams of the l-menthol/d-menthol binary system were detd. The thermodn. relative stability of the different menthol polymorphs was also established. The present paper provides new phys., chem. and thermodn. data of l-, d- and dl-menthol and offers new insight into their polymorphism as well as into the levorotatory-dextrorotatory menthol interactions. Both the thermodn. and crystallog. approaches demonstrate unambiguously that racemic menthol is a racemate.
- 39Corvis, Y.; Wurm, A.; Schick, C.; Espeau, P. New menthol polymorphs identified by flash scanning calorimetry. CrystEngComm 2015, 17 (29), 5357– 5359, DOI: 10.1039/C5CE00697J[Crossref], [CAS], Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXps1Wmt7Y%253D&md5=e66eb8e4f82f5535da68748b5eb68a65New menthol polymorphs identified by flash scanning calorimetryCorvis, Yohann; Wurm, Andreas; Schick, Christoph; Espeau, PhilippeCrystEngComm (2015), 17 (29), 5357-5359CODEN: CRECF4; ISSN:1466-8033. (Royal Society of Chemistry)Menthol, which is used in the food, pharmaceutical and cosmetics industries, was studied by flash scanning calorimetry. New levorotatory and racemic menthol polymorphs were thus identified. This study is also forward-looking regarding the use of org. mols. in flash scanning calorimetry, which is frequently used for polymer studies.
- 40Wang, L.; Meng, D. Fatty acid eutectic/polymethyl methacrylate composite as form-stable phase change material for thermal energy storage. Appl. Energy 2010, 87 (8), 2660– 2665, DOI: 10.1016/j.apenergy.2010.01.010[Crossref], [CAS], Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmtFKqsb8%253D&md5=7a07c6f84ba214c13f72d630a8e16fcaFatty acid eutectic/polymethyl methacrylate composite as form-stable phase change material for thermal energy storageWang, Lijiu; Meng, DuoApplied Energy (2010), 87 (8), 2660-2665CODEN: APENDX; ISSN:0306-2619. (Elsevier Ltd.)This work is focused on the prepn. and characterization of fatty acid eutectic/polymethyl methacrylate (PMMA) form-stable phase change material (PCM). Capric acid (CA), lauric acid (LA), myristic acid (MA) and stearic acid (SA) were selected to prep. binary fatty acid eutectic for the sake of decreasing the phase change temp. Using the method of self-polymn., CA-LA, CA-MA, CA-SA and LA-MA eutectics acting as the heat-absorbing materials and PMMA serving as the supporting material were compounded in the ratio of 50/50 wt.%. The relations between mass fraction of LA-MA eutectic and latent heat and compressive strength of LA-MA/PMMA composite were discussed, and the feasible max. mass fraction of LA-MA eutectic was detd. to be 70%. CA-LA/PMMA, CA-MA/PMMA, CA-SA/PMMA and LA-MA/PMMA composites were examd. to investigate their potential application in building energy conservation. Scanning electron microscope and polarizing optical microscope observations showed that fatty acid eutectic was coated by PMMA thus the composite remained solid when the sample was heated above the melted point of the fatty acid. Fourier-transform IR results indicated that fatty acid and PMMA had no chem. reaction and exhibited good compatibility with each other. According to the differential scanning calorimetry results, phase change temps. of CA-LA/PMMA, CA-MA/PMMA, CA-SA/PMMA and LA-MA/PMMA composites were 21.11 °C, 25.16 °C, 26.38 °C and 34.81 °C and their latent heat values were detd. to be 76.3 kJ/kg, 69.32 kJ/kg, 59.29 kJ/kg and 80.75 kJ/kg, resp. Moreover, thermal stability and expansibility of the form-stable PCMs were characterized by thermogravimetric anal. and vol. expansion coeff. resp., and the results indicated that the composites were available for building energy conservation.
- 41Yuan, Y.; Zhang, N.; Tao, W.; Cao, X.; He, Y. Fatty acids as phase change materials: a review. Renewable Sustainable Energy Rev. 2014, 29, 482– 498, DOI: 10.1016/j.rser.2013.08.107[Crossref], [CAS], Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslGmtbnP&md5=098eed70762a6febe5c9c2f6d2d02baaFatty acids as phase change materials: A reviewYuan, Yanping; Zhang, Nan; Tao, Wenquan; Cao, Xiaoling; He, YalingRenewable & Sustainable Energy Reviews (2014), 29 (), 482-498CODEN: RSERFH; ISSN:1364-0321. (Elsevier Ltd.)A review. Fatty acids as phase change materials have attracted much attention for their various applications in building energy efficiency, solar heating systems and air-conditioning systems. After summarizing the basic characteristics of fatty acids, eutectic mixts. of fatty acids and fatty acid esters, as well as the prepn. and characteristics of fatty acid composites as phase change materials (PCMs), this paper analyzes the thermal reliability and stability of fatty acids as PCMs and their heat transfer characteristics in a unit which is followed by an introduction to the energy storage systems of three kinds of fatty acids as PCMs. Besides, it also points out the future research direction of fatty acids as PCMs as a soln. of the insufficiency and flaws of current researches.
- 42Castro, V. n. I.; Mano, F.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Synthesis and Physical and Thermodynamic Properties of Lactic Acid and Malic Acid-Based Natural Deep Eutectic Solvents. J. Chem. Eng. Data 2018, 63 (7), 2548– 2556, DOI: 10.1021/acs.jced.7b01037[ACS Full Text], [CAS], Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFGisr3M&md5=2aae9c5b5d25c8ab4a051799b5d4d69fSynthesis and Physical and Thermodynamic Properties of Lactic Acid and Malic Acid-Based Natural Deep Eutectic SolventsCastro, Vania I. B.; Mano, Francisca; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.Journal of Chemical & Engineering Data (2018), 63 (7), 2548-2556CODEN: JCEAAX; ISSN:0021-9568. (American Chemical Society)In this paper, four natural deep eutectic solvents (NADES) systems were prepd. at specific molar ratios, La:Bet (2:1) (lactic acid/betaine), La:Hist (9:1) (lactic acid/histidine), Ma:Bet:H2O (1:2:3) (malic acid/betaine/water) and Ma:Bet:Pro:H2O (1:1:1:2) (malic acid/betaine/proline/water). Their phys. and thermodn. properties were studied, namely viscosity, elec. cond., and heat capacity. The viscosity and elec. cond. were detd. as a function of temp. and the correlation for the temp. dependence was obtained and discussed based on Arrhenius theory. The heat capacity for all eutectic systems was measured by differential scanning calorimetry (DSC) over a temp. range of 293.15-363.15 K. The ability of these NADES to reduce cellulose crystallinity was evaluated. Cellulose crystallinity after suspension in these NADES was studied by x-ray diffraction. Cellulose suspended in Ma/Bet/H2O (1:2:3) suffer the highest crystallinity redn. among the systems studied and was about of 20%.
- 43Craveiro, R.; Aroso, I.; Flammia, V.; Carvalho, T.; Viciosa, M.; Dionísio, M.; Barreiros, S.; Reis, R.; Duarte, A. R. C.; Paiva, A. Properties and thermal behavior of natural deep eutectic solvents. J. Mol. Liq. 2016, 215, 534– 540, DOI: 10.1016/j.molliq.2016.01.038[Crossref], [CAS], Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XovVGnsA%253D%253D&md5=cd995f4b423b7e9205d4269b3967392cProperties and thermal behavior of natural deep eutectic solventsCraveiro, R.; Aroso, I.; Flammia, V.; Carvalho, T.; Viciosa, M. T.; Dionisio, M.; Barreiros, S.; Reis, R. L.; Duarte, A. R. C.; Paiva, A.Journal of Molecular Liquids (2016), 215 (), 534-540CODEN: JMLIDT; ISSN:0167-7322. (Elsevier B.V.)Natural deep eutectic solvents (NADES) have shown to be promising sustainable media for a wide range of applications. Nonetheless, very limited data is available on the properties of these solvents. A more comprehensive body of data on NADES is required for a deeper understanding of these solvents at mol. level, which will undoubtedly foster the development of new applications. NADES based on choline chloride, org. acids, amino acids and sugars were prepd., and their d., thermal behavior, cond. and polarity were assessed, for different NADES compns. The NADES studied can be stable up to 170 °C, depending on their compn. The thermal characterization revealed that all the NADES are glass formers and some, after water removal, exhibit crystallinity. The morphol. characterization of the crystallizable materials was performed using polarized optical microscopy which also provided evidence of homogeneity/phase sepn. The cond. of the NADES was also assessed from 0 to 40 °C. The more polar, org. acid-based NADES presented the highest conductivities. The cond. dependence on temp. was well described by the Vogel-Fulcher-Tammann equation for some of the NADES studied.
- 44D’Agostino, C.; Harris, R. C.; Abbott, A. P.; Gladden, L. F.; Mantle, M. D. Molecular motion and ion diffusion in choline chloride based deep eutectic solvents studied by 1 H pulsed field gradient NMR spectroscopy. Phys. Chem. Chem. Phys. 2011, 13 (48), 21383– 21391, DOI: 10.1039/c1cp22554e[Crossref], [PubMed], [CAS], Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFeru7fO&md5=73dd737a1d32443513ef41074fcabbd6Molecular motion and ion diffusion in choline chloride based deep eutectic solvents studied by 1H pulsed field gradient NMR spectroscopyD'Agostino, Carmine; Harris, Robert C.; Abbott, Andrew P.; Gladden, Lynn F.; Mantle, Mick D.Physical Chemistry Chemical Physics (2011), 13 (48), 21383-21391CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Deep Eutectic Solvents (DESs) are a novel class of solvents with potential industrial applications in sepn. processes, chem. reactions, metal recovery and metal finishing processes such as electrodeposition and electropolishing. Macroscopic phys. properties such as viscosity, cond., eutectic compn. and surface tension are already available for several DESs, but the microscopic transport properties for this class of compds. are not well understood and the literature lacks exptl. data that could give a better insight into the understanding of such properties. This paper presents the first pulsed field gradient NMR (PFG-NMR) study of DESs. Several choline chloride based DESs were chosen as exptl. samples, each of them with a different assocd. hydrogen bond donor. The mol. equil. self-diffusion coeff. of both the choline cation and hydrogen bond donor was probed using a std. stimulated echo PFG-NMR pulse sequence. The increasing temp. leads to a weaker interaction between the choline cation and the correspondent hydrogen bond donor. The self-diffusion coeffs. of the samples obey an Arrhenius law temp.-dependence, with values of self-diffusivity in the range of [10-10-10-13 m2 s-1]. The results also highlight that the mol. structure of the hydrogen bond donor can greatly affect the mobility of the whole system. While for ethaline, glyceline and reline the choline cation diffuses slower than the assocd. hydrogen bond donor, reflecting the trend of mol. size and mol. wt., the opposite behavior is obsd. for maline, in which the hydrogen bond donor, i.e. malonic acid, diffuses slower than the choline cation, with self-diffusion coeffs. values of the order of 10-13 m2 s-1 at room temp., which are remarkably low values for a liq. This is believed to be due to the formation of extensive dimer chains between malonic acid mols., which restricts the mobility of the whole system at low temp. (<30 °C), with malonic acid and choline chloride having almost identical diffusivity values. Diffusion and viscosity data were combined together to gain insights into the diffusion mechanism, which is the same as for ionic liqs. with discrete anions.
- 45Aroso, I. M.; Paiva, A.; Reis, R. L.; Duarte, A. R. C. Natural deep eutectic solvents from choline chloride and betaine–Physicochemical properties. J. Mol. Liq. 2017, 241, 654– 661, DOI: 10.1016/j.molliq.2017.06.051[Crossref], [CAS], Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVChsLfP&md5=46a512a98ee7daf0b1327984eb1ee47fNatural deep eutectic solvents from choline chloride and betaine - Physicochemical propertiesAroso, Ivo M.; Paiva, Alexandre; Reis, Rui L.; Duarte, Ana Rita C.Journal of Molecular Liquids (2017), 241 (), 654-661CODEN: JMLIDT; ISSN:0167-7322. (Elsevier B.V.)The prepn. of natural deep eutectic solvents (NADESs) from cheap and readily available raw materials is reported. In this work, we have considered mixts. of choline chloride (CC) or betaine (Bet) with 3 sugar mols. (glucose (Glu), xylose (Xyl) and sucrose (Suc)) and 2 carboxylic acids (citric (CA) and tartaric (Tart) acids). The formation of NADESs was investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The CC mixts. give origin to NADESs for 1:1 M ratio with the sugar mols. and for 2:1, 1:1 and 1:2 with the carboxylic acids, while Bet mixts. only formed NADES with the carboxylic acids. The effect of water content (up to 5% (wt.%)) and temp. in cond. and rheol. were characterized. The NADESs were found to be non-thixotropic, Newtonian liqs. with high viscosity, decreasing with increasing temp. and water content. The cond. is limited by charge carrier mobility, thus increasing with water content and temp.
- 46Passos, H.; Tavares, D. J.; Ferreira, A. M.; Freire, M. G.; Coutinho, J. o. A. Are aqueous biphasic systems composed of deep eutectic solvents ternary or quaternary systems?. ACS Sustainable Chem. Eng. 2016, 4 (5), 2881– 2886, DOI: 10.1021/acssuschemeng.6b00485[ACS Full Text], [CAS], Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xls1KisbY%253D&md5=6a1c4e540c1c2ca0053cd3b4b0c19a78Are Aqueous Biphasic Systems Composed of Deep Eutectic Solvents Ternary or Quaternary Systems?Passos, Helena; Tavares, Daniel J. P.; Ferreira, Ana M.; Freire, Mara G.; Coutinho, Joao A. P.ACS Sustainable Chemistry & Engineering (2016), 4 (5), 2881-2886CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Deep eutectic solvents (DES) have emerged in the past few years as a new class of solvents with promising applications in several fields. In the present work, the application of DES (formed by binary mixts. of cholinium chloride and carboxylic acids or urea) as phase-forming components of aq. biphasic systems (ABS) is investigated. The mechanisms assocd. with the phases demixing of ABS composed of DES, as well as the DES stability in aq. solns., are investigated to address the crit. question whether DES-based ABS are in fact ternary or quaternary mixts. The DES integrity is destroyed in ABS by the disruption of the hydrogen-bonding interactions of the complex (a result of the isolated components preferential solvation by water), and as confirmed by a nonstoichiometric partition of the DES components between the coexisting phases. As a result, there are no "real" DES-based ABS; instead, there is the formation of ABS composed of four components, where the carboxylic acid used as the hydrogen-bond donor species seems to act as an additive. Finally, these ABS have an outstanding potential to be used in extn. processes, as it is here demonstrated with the complete sepn. of two dyes. However, the volatile nature of short chain carboxylic acids and the nonstoichiometric partition of the DES components in ABS make the development of recovery and recycling steps more difficult to accomplish.
- 47Yadav, A.; Pandey, S. Densities and viscosities of (choline chloride+ urea) deep eutectic solvent and its aqueous mixtures in the temperature range 293.15 to 363.15 K. J. Chem. Eng. Data 2014, 59 (7), 2221– 2229, DOI: 10.1021/je5001796[ACS Full Text], [CAS], Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXps1Kls7w%253D&md5=2529220f983049b3a020918bc2dd95bfDensities and Viscosities of (Choline Chloride + Urea) Deep Eutectic Solvent and Its Aqueous Mixtures in the Temperature Range 293.15 K to 363.15 KYadav, Anita; Pandey, SiddharthJournal of Chemical & Engineering Data (2014), 59 (7), 2221-2229CODEN: JCEAAX; ISSN:0021-9568. (American Chemical Society)Deep eutectic solvents (DESs) have been regarded as one of the most promising environmentally benign and cost-effective alternatives to conventional ionic liqs. and volatile org. solvents. Aq. mixts. of DESs have the potential to afford modified properties for specific applications. Densities and dynamic viscosities of a common and popular DES composed of choline chloride and urea in 1:2 molar ratio, named reline, and its aq. mixts. in the temp. range 293.15 K to 363.15 K are reported. A decrease in d. with increasing temp. is found to follow a quadratic expression. Excess molar volumes of the aq. mixts. of reline are found to be neg. at all temps. and compns. The abs. excess molar volume is found to decrease, in general, as the temp. is increased from 293.15 K to 323.15 K. For temps. above 323.15 K, the excess molar volume does not change much with further increase in temp. to 363.15 K. The temp. dependence of dynamic viscosity of aq. mixts. of reline in the temp. range 293.15 K to 363.15 K at all compns. is found to be better described by a Vogel-Fulcher-Tamman (VFT) model as opposed to an Arrhenius expression. Excess logarithmic viscosities for aq. mixts. of reline are found to be neg. at most temps. and compns.; however, they become pos. at 353.15 K and 363.15 K. The excess logarithmic viscosities of aq. reline mixts. are in Stark contrast to that reported for aq. mixts. of DES glyceline, composed of choline chloride and glycerol in the same mole ratio, where the excess logarithmic viscosities are pos. Facile interstitial accommodation of water within H-bonded reline network as opposed to formation of extensive H-bonding is proposed to be the reason for this exptl. observation. The important role of the H-bond donor as a constituent of DES is amply highlighted as it controls the interactions present in a DES and its aq. mixts.
- 48Abbott, A. P.; Ahmed, E. I.; Harris, R. C.; Ryder, K. S. Evaluating water miscible deep eutectic solvents (DESs) and ionic liquids as potential lubricants. Green Chem. 2014, 16 (9), 4156– 4161, DOI: 10.1039/C4GC00952E[Crossref], [CAS], Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVGjs7nO&md5=8a52073321744b382abc17414a5819c4Evaluating water miscible deep eutectic solvents (DESs) and ionic liquids as potential lubricantsAbbott, Andrew P.; Ahmed, Essa I.; Harris, Robert C.; Ryder, Karl S.Green Chemistry (2014), 16 (9), 4156-4161CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Although mineral oils are commonly used as lubricants their emission particularly in marine environments can cause significant impact. In the current study the properties of water miscible deep eutectic solvents and ionic liqs. are compared with a typical mineral base oil to ascertain their efficacy for potential marine lubricants. The environmental compatibility of some of the liqs., particularly choline chloride and glycerol, makes it an interesting potential base lubricant. Surprisingly some DESs showed very low corrosion rates with steel, nickel and aluminum even when the liqs. contained water. This is a surprising result given that the chloride ion concn. is approx. 5 mol dm-3.
- 49AlOmar, M. K.; Hayyan, M.; Alsaadi, M. A.; Akib, S.; Hayyan, A.; Hashim, M. A. Glycerol-based deep eutectic solvents: physical properties. J. Mol. Liq. 2016, 215, 98– 103, DOI: 10.1016/j.molliq.2015.11.032[Crossref], [CAS], Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvFKgsrjM&md5=7faef94e14f157fd449341aa93c8a802Glycerol-based deep eutectic solvents: Physical propertiesAlOmar, Mohamed Khalid; Hayyan, Maan; Alsaadi, Mohammed Abdulhakim; Akib, Shatirah; Hayyan, Adeeb; Hashim, Mohd AliJournal of Molecular Liquids (2016), 215 (), 98-103CODEN: JMLIDT; ISSN:0167-7322. (Elsevier B.V.)Deep eutectic solvents (DESs) have been used in many industrial applications. DES is a mixt. of a salt and a hydrogen bond donor (HBD). In this study, 70 DESs were synthesized successfully based on glycerol (Gly) as the HBD with different phosphonium and ammonium salts, namely Me tri-Ph phosphonium bromide (MTPB), benzyl tri-Ph phosphonium chloride (BTPC), allyl tri-Ph phosphonium bromide (ATPB), choline chloride (ChCl), N,N-diethylethanolammonium chloride (DAC), and tetra-n-butylammonium bromide (TBAB). The DESs were prepd. using different molar ratios of the HBD to the salts. The f.p. of each DES was detd. using Differential Scanning Calorimetry (DSC). The phys. properties of these DESs, including d., viscosity, cond., and surface tension, were investigated as functions of temp. In addn., the functional groups were analyzed utilizing Fourier transform IR (FTIR) spectroscopy. It is worth noting that these systems have a wide variety of phys. properties, which implies that these DESs would be suitable for diverse applications.
- 50Jeong, K. M.; Lee, M. S.; Nam, M. W.; Zhao, J.; Jin, Y.; Lee, D.-K.; Kwon, S. W.; Jeong, J. H.; Lee, J. Tailoring and recycling of deep eutectic solvents as sustainable and efficient extraction media. Journal of Chromatography A 2015, 1424, 10– 17, DOI: 10.1016/j.chroma.2015.10.083[Crossref], [PubMed], [CAS], Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslKkt7rF&md5=86b657d59a24245771f0b79561a489a5Tailoring and recycling of deep eutectic solvents as sustainable and efficient extraction mediaJeong, Kyung Min; Lee, Min Sang; Nam, Min Woo; Zhao, Jing; Jin, Yan; Lee, Dong-Kyu; Kwon, Sung Won; Jeong, Ji Hoon; Lee, JeongmiJournal of Chromatography A (2015), 1424 (), 10-17CODEN: JCRAEY; ISSN:0021-9673. (Elsevier B.V.)The present study demonstrates that deep eutectic solvents (DESs) with the highest extractability can be designed by combining effective DES components from screening diverse DESs. The extn. of polar ginseng saponins from white ginseng was used as a way to demonstrate the tuneability as well as recyclability of DESs. A newly designed ternary DES (GPS-5) composed of glycerol, L-proline, and sucrose at 9:4:1 was used as a sustainable and efficient extn. medium. Based on the anti-tumor activity on HCT-116 cancer cells, it was confirmed that GPS-5 was merely an extn. solvent with no influence of the bioactivity of the ginsenosides extd. Excellent recovery of the extd. saponins was easily achieved through solid-phase extn. (SPE). Recycling of the DES was accomplished by simple freeze-drying of the washed solns. from the SPE. The extn. efficiencies of the DESs recycled once, twice, and thrice were 92%, 85%, and 83% of that of the freshly synthesized solvent.
- 51AlOmar, M. K.; Alsaadi, M. A.; Hayyan, M.; Akib, S.; Ibrahim, R. K.; Hashim, M. A. Lead removal from water by choline chloride based deep eutectic solvents functionalized carbon nanotubes. J. Mol. Liq. 2016, 222, 883– 894, DOI: 10.1016/j.molliq.2016.07.074
- 52Zhekenov, T.; Toksanbayev, N.; Kazakbayeva, Z.; Shah, D.; Mjalli, F. S. Formation of type III Deep Eutectic Solvents and effect of water on their intermolecular interactions. Fluid Phase Equilib. 2017, 441, 43– 48, DOI: 10.1016/j.fluid.2017.01.022[Crossref], [CAS], Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1equr0%253D&md5=7f756b90831e7fce99c4cd1aab56037aFormation of type III Deep Eutectic Solvents and effect of water on their intermolecular interactionsZhekenov, Temirlan; Toksanbayev, Nursultan; Kazakbayeva, Zhanna; Shah, Dhawal; Mjalli, Farouq S.Fluid Phase Equilibria (2017), 441 (), 43-48CODEN: FPEQDT; ISSN:0378-3812. (Elsevier B.V.)Several novel applications of Deep Eutectic Solvents (DESs) have emerged recently. With a growing interest in the field, there is an urge to understand formation and functioning of these solvents at mol. level, which in turn would assist in further designing of DESs. We herein performed mol. dynamics simulations on three of the commonly used type III DES, viz, reline, ethaline, and glyceline, which are mixts. of urea, ethylene glycol, and glycerol with choline chloride at eutectic compn. Our results explain the role of inter-mol. and intra-mol. hydrogen bonding and energies on formation of these DESs. Furthermore, the ability of these DESs to be altered in a desired way through a simple addn. of water makes it versatile soln. for several other applications. Hence, simulations are also performed on the aq. DES solns., which reveal the effect of water on intermol. network of interaction existing within these DESs.
- 53Cláudio, A. F. M.; Neves, M. C.; Shimizu, K.; Canongia Lopes, J. N.; Freire, M. G.; Coutinho, J. A. The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropes. Green Chem. 2015, 17, 3948– 3963, DOI: 10.1039/C5GC00712G[Crossref], [PubMed], [CAS], Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXoslCku7s%253D&md5=07ca34afff9fee7ac3b86eb0500989a3The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropesClaudio, Ana Filipa M.; Neves, Marcia C.; Shimizu, Karina; Canongia Lopes, Jose N.; Freire, Mara G.; Coutinho, Joao A. P.Green Chemistry (2015), 17 (7), 3948-3963CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Hydrotropes are compds. able to enhance the soly. of hydrophobic substances in aq. media and therefore are widely used in the formulation of drugs, cleaning and personal care products. Ionic liqs. are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the soly. of biomols. in water. The effects of the ionic liq. chem. structures, their concn. and the temp. on the soly. of two model biomols., vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The soly. of these two biomols. was studied in the entire compn. range, from pure water to pure ionic liqs., and an increase in the soly. of up to 40-fold was obsd., confirming the potential of ionic liqs. to act as hydrotropes. Using dynamic light scattering, NMR and mol. dynamics simulations, it was possible to infer that the enhanced soly. of the biomol. in the IL aq. solns. is related to the formation of ionic-liq.-biomols. aggregates. Finally, hydrotropy induced by ionic liqs. can be used to recover solutes from aq. media by pptn., simply by using water as an anti-solvent. The results reported here have a significant impact on the understanding of the role of ionic liq. aq. solns. in the extn. of value-added compds. from biomass as well as in the design of novel processes for their recovery from aq. media.
- 54Cláudio, A. F. M.; Neves, M. C.; Shimizu, K.; Canongia Lopes, J. N.; Freire, M. G.; Coutinho, J. A. The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropes. Green Chem. 2015, 17 (7), 3948– 3963, DOI: 10.1039/C5GC00712G[Crossref], [PubMed], [CAS], Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXoslCku7s%253D&md5=07ca34afff9fee7ac3b86eb0500989a3The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropesClaudio, Ana Filipa M.; Neves, Marcia C.; Shimizu, Karina; Canongia Lopes, Jose N.; Freire, Mara G.; Coutinho, Joao A. P.Green Chemistry (2015), 17 (7), 3948-3963CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Hydrotropes are compds. able to enhance the soly. of hydrophobic substances in aq. media and therefore are widely used in the formulation of drugs, cleaning and personal care products. Ionic liqs. are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the soly. of biomols. in water. The effects of the ionic liq. chem. structures, their concn. and the temp. on the soly. of two model biomols., vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The soly. of these two biomols. was studied in the entire compn. range, from pure water to pure ionic liqs., and an increase in the soly. of up to 40-fold was obsd., confirming the potential of ionic liqs. to act as hydrotropes. Using dynamic light scattering, NMR and mol. dynamics simulations, it was possible to infer that the enhanced soly. of the biomol. in the IL aq. solns. is related to the formation of ionic-liq.-biomols. aggregates. Finally, hydrotropy induced by ionic liqs. can be used to recover solutes from aq. media by pptn., simply by using water as an anti-solvent. The results reported here have a significant impact on the understanding of the role of ionic liq. aq. solns. in the extn. of value-added compds. from biomass as well as in the design of novel processes for their recovery from aq. media.
- 55Sintra, T. E.; Shimizu, K.; Ventura, S. P.; Shimizu, S.; Canongia Lopes, J. N.; Coutinho, J. A. Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes. Phys. Chem. Chem. Phys. 2018, 20 (3), 2094– 2103, DOI: 10.1039/C7CP07569C[Crossref], [PubMed], [CAS], Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitVShsr3O&md5=cead2b4e2adb88454484b11548164dfeEnhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropesSintra, T. E.; Shimizu, K.; Ventura, S. P. M.; Shimizu, S.; Canongia Lopes, J. N.; Coutinho, J. A. P.Physical Chemistry Chemical Physics (2018), 20 (3), 2094-2103CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The therapeutic effectiveness of a drug largely depends on its bioavailability, and thus ultimately on its aq. soly. Hydrotropes are compds. able to enhance the soly. of hydrophobic substances in aq. media and therefore are extensively used in the formulation of drugs and personal care products. Recently, some ionic liqs. were shown to display a strong ability to enhance the soly. of biomols. through hydrotropy. In this work, the impact of the ionic liq. chem. structures and their concn. on the soly. of ibuprofen was evaluated and compared with the performance of conventional hydrotropes. The results obtained clearly evidence the exceptional capacity of ionic liqs. to enhance the soly. of ibuprofen. [C4C1i.m.][SCN] and [C4C1i.m.][N(CN)2] seem to be the most promising ionic liqs. for ibuprofen solubilization, where an increase in the soly. of 60- and 120-fold was obsd. with ionic liq. concns. of circa 1 mol kg-1, resp. Dynamic light scattering and mol. dynamics simulations were used to investigate the mechanism of the IL-mediated drug soly. and the results obtained indicate that the structure of aq. solns. of ionic liqs. and the role it plays in the formation of ionic liq.-drug aggregates is the mechanism driving the hydrotropic dissoln.
- 56Soares, B.; Tavares, D. J.; Amaral, J. L.; Silvestre, A. J.; Freire, C. S.; Coutinho, J. A. Enhanced solubility of lignin monomeric model compounds and technical lignins in aqueous solutions of deep eutectic solvents. ACS Sustainable Chem. Eng. 2017, 5 (5), 4056– 4065, DOI: 10.1021/acssuschemeng.7b00053[ACS Full Text], [CAS], Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXls1SmsLg%253D&md5=dc8d99eaacda307e165c5b7b5ddb595dEnhanced Solubility of Lignin Monomeric Model Compounds and Technical Lignins in Aqueous Solutions of Deep Eutectic SolventsSoares, Belinda; Tavares, Daniel J. P.; Amaral, Jose Luis; Silvestre, Armando J. D.; Freire, Carmen S. R.; Coutinho, Joao A. P.ACS Sustainable Chemistry & Engineering (2017), 5 (5), 4056-4065CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)The solubilities of lignin monomeric model compds. and tech. lignins (organosolv and kraft) in aq. solns. of several deep eutectic solvents (DES) were here investigated. The effects of DES components, temp. and concn., were evaluated. The results show aq. solns. of DES to be a new class of powerful solvents where both the hydrogen bond donor and the hydrogen bond acceptor synergistically contribute to increase the soly. of the lignin model compds., being the dispersive interactions with lignin the driving force behind the good performance of DES. The soly. of the model compds. is shown to be a good guide for the selection of the best DES for tech. lignins soly., leading to identifying an aq. soln. of DES allowing a soly. enhancement of 1181.7 ± 29.2 and 228.5 ± 9.7 times for kraft and organosolv lignin, resp. The results indicate that the soly. of the tech. lignins and their monomers in DES aq. solns. is driven by a hydrotropic mechanism, here confirmed by dynamic light scattering that is here obsd. for the first time with DES as hydrotropes.
- 57Mano, F.; Aroso, I. M.; Barreiros, S.; Borges, J. o. P.; Reis, R. L.; Duarte, A. R. C.; Paiva, A. Production of poly (vinyl alcohol)(PVA) fibers with encapsulated natural deep eutectic solvent (NADES) using electrospinning. ACS Sustainable Chem. Eng. 2015, 3 (10), 2504– 2509, DOI: 10.1021/acssuschemeng.5b00613[ACS Full Text], [CAS], Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFWhs7%252FO&md5=4078991f8d30de7c5cfa5bdc94b3805bProduction of poly(vinyl alcohol) (PVA) fibers with encapsulated natural deep eutectic solvent (NADES) using electrospinningMano, Francisca; Aroso, Ivo M.; Barreiros, Susana; Borges, Joao Paulo; Reis, Rui L.; Duarte, Ana Rita C.; Paiva, AlexandreACS Sustainable Chemistry & Engineering (2015), 3 (10), 2504-2509CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Functionalized electrospun fibers are of great interest for biomedical applications such as in the design of drug delivery systems. Nevertheless, in some cases the mols. of interest have poor soly. in water or have high melting temps. These drawbacks can be overcome using deep eutectic solvents. In this work, poly(vinyl alc.) (PVA), a common biodegradable biopolymer, was used to produce new functionalized fibers with the eutectic mixt. choline chloride:citric acid in a molar ratio of (1:1) ChCl:CA (1:1), which was used as a model system. Fibers were produced from an aq. soln. with 7.8% (w/v) and 9.8% (w/v) of 95% hydrolyzed PVA and a 2% (vol./vol.) of ChCl:CA (1:1). Smooth, uniform fibers with an av. diam. of 0.4 μm were obtained with a content of 19.8 wt % of ChCl:CA (1:1) encapsulated.
- 58Yong, C. S.; Jung, S. H.; Rhee, J.-D.; Choi, H.-G.; Lee, B.-J.; Kim, D.-C.; Choi, Y. W.; Kim, C.-K. Improved solubility and in vitro dissolution of Ibuprofen from poloxamer gel using eutectic mixture with menthol. Drug Delivery 2003, 10 (3), 179– 183, DOI: 10.1080/713840406[Crossref], [PubMed], [CAS], Google Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmslClsrc%253D&md5=faf7f2b8213001218b84573818fa804bImproved Solubility and In Vitro Dissolution of Ibuprofen from Poloxamer Gel Using Eutectic Mixture with MentholYong, Chul Soon; Jung, Se Hyun; Rhee, Jong-Dal; Choi, Han-Gon; Lee, Beom-Jin; Kim, Dong-Chool; Choi, Young Wook; Kim, Chong-KookDrug Delivery (2003), 10 (3), 179-183CODEN: DDELEB; ISSN:1071-7544. (Taylor & Francis, Inc.)To improve the soly. and in vitro dissoln. of poorly water-sol. ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aq. soly. of ibuprofen were investigated. The dissoln. study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, the soly. of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6, followed by an abrupt decrease in soly. above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutectic mixt. with 6 parts of menthol. In the presence of poloxamer 188, the solns. with the same ratio of menthol to ibuprofen showed abrupt increase in the soly. of ibuprofen. Furthermore, the soln. with ratio of 4:6 showed more than 2.5- and 6-fold increase in the soly. of ibuprofen compared with that without poloxamer and that without menthol, resp. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the max. soly. of ibuprofen, 1.2 mg/mL. Menthol improved the dissoln. rates of ibuprofen from poloxamer gels. Dissoln. mechanism showed that the dissoln. rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixt. with menthol, which gave the improved soly. and dissoln. of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.
- 59Hayyan, M.; Mbous, Y. P.; Looi, C. Y.; Wong, W. F.; Hayyan, A.; Salleh, Z.; Mohd-Ali, O. Natural deep eutectic solvents: cytotoxic profile. SpringerPlus 2016, 5 (1), 913, DOI: 10.1186/s40064-016-2575-9[Crossref], [PubMed], [CAS], Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7nslGmtA%253D%253D&md5=c4aabcb10c8ceda288a8dd72b93a637aNatural deep eutectic solvents: cytotoxic profileHayyan Maan; Mbous Yves Paul; Salleh Zulhaziman; Looi Chung Yeng; Wong Won Fen; Hayyan Adeeb; Mohd-Ali OzairSpringerPlus (2016), 5 (1), 913 ISSN:2193-1801.The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures.
- 60Juneidi, I.; Hayyan, M.; Hashim, M. A. Evaluation of toxicity and biodegradability for cholinium-based deep eutectic solvents. RSC Adv. 2015, 5 (102), 83636– 83647, DOI: 10.1039/C5RA12425E[Crossref], [CAS], Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFGkurbM&md5=8bbeafa30ad9e4b1096df73eff95f7a8Evaluation of toxicity and biodegradability for cholinium-based deep eutectic solventsJuneidi, Ibrahim; Hayyan, Maan; Hashim, Mohd AliRSC Advances (2015), 5 (102), 83636-83647CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)This study presented the toxicol. and biodegradable assessment of different cholinium-based deep eutectic solvents (DESs). They were formed from choline chloride (ChCl) and N,N-di-Et ethanol ammonium chloride (EAC) as salts and four hydrogen bond donors, namely ethylene glycol (EG), glycerol (Gly), urea (U), malonic acid (MA), in addn. to a metal salt, i.e. zinc chloride (ZnCl2), and a hydrated metal salt, i.e. zinc nitrate hexahydrate (ZnN). The toxicity towards Aspergillus niger of pure and aq. DESs was evaluated by observing the inhibition zone using an agar well diffusion assay, and the min. inhibition concn. (MIC) using a broth diln. assay, resp. The MIC values of the DESs varied from 1 to 650 mg mL-1, whereas the inhibition zones changed according to the DES dose amt. Another test for acute toxicity was performed by evaluating the lethal concn. at 50% (LC50) of the same DESs on Cyprinus carpio fish. The LC50 of DESs ranged from practically harmless (e.g. ChCl : EG-DESaq) to highly toxic (e.g. EAC : ZnCl2-DESaq). The toxicity profile of the DESs depended on their concn., type of individual components, and interaction with living organisms. Moreover, the DESs recorded higher toxicity compared to their individual components on fungi. However, lower toxicity was found for the DESs tested on Cyprinus carpio. Types I (org. salts and metal salt) and II (org. salt and hydrate metal salt) eutectics exhibited significantly higher toxicity than type III (org. salts and HBD). This was due to the presence of the innate toxicity of the metal salts. The biodegradability was appraised by a closed bottle test in which all the DESs were found to be readily biodegradable. To the best of our knowledge, there are no previous studies reported regarding the toxicity of cholinium-based DESs on freshwater fish or fungi and the biodegradability of EAC-based DESs. Therefore, this investigation can be used as a benchmark for future development of DESs.
- 61Radošević, K.; Cvjetko Bubalo, M. C.; Gaurina Srček, V. G.; Grgas, D.; Landeka Dragičević, T. L.; Radojčić Redovniković, I. R. Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solvents. Ecotoxicol. Environ. Saf. 2015, 112, 46– 53, DOI: 10.1016/j.ecoenv.2014.09.034[Crossref], [PubMed], [CAS], Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVGitrbE&md5=8d768400367b3c378f845636e00da992Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solventsRadosevic, Kristina; Cvjetko Bubalo, Marina; Gaurina Srcek, Visnje; Grgas, Dijana; Landeka Dragicevic, Tibela; Radojcic Redovnikovic, IvanaEcotoxicology and Environmental Safety (2015), 112 (), 46-53CODEN: EESADV; ISSN:0147-6513. (Elsevier B.V.)Deep eutectic solvents (DESs) have been dramatically expanding in popularity as a new generation of environmentally friendly solvents with possible applications in various industrial fields, but their ecol. footprint has not yet been thoroughly investigated. In the present study, three choline chloride-based DESs with glucose, glycerol and oxalic acid as hydrogen bond donors were evaluated for in vitro toxicity using fish and human cell line, phytotoxicity using wheat and biodegradability using wastewater microorganisms through closed bottle test. Obtained in vitro toxicity data on cell lines indicate that choline chloride: glucose and choline chloride:glycerol possess low cytotoxicity (EC50>10 mM for both cell lines) while choline chloride:oxalic acid possess moderate cytotoxicity (EC50 value 1.64 mM and 4.19 mM for fish and human cell line, resp.). Results on phytotoxicity imply that tested DESs are non-toxic with seed germination EC50 values higher than 5000 mg L-1. All tested DESs were classified as'readily biodegradable' based on their high levels of mineralization (68-96%). These findings indicate that DESs have a green profile and a good prospect for a wider use in the field of green technologies.
- 62Radošević, K.; Ćanak, I.; Panić, M.; Markov, K.; Bubalo, M. C.; Frece, J.; Srček, V. G.; Redovniković, I. R. Antimicrobial, cytotoxic and antioxidative evaluation of natural deep eutectic solvents. Environ. Sci. Pollut. Res. 2018, 25 (14), 14188– 14196, DOI: 10.1007/s11356-018-1669-z[Crossref], [PubMed], [CAS], Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkslWktLg%253D&md5=6eb369173ee63b1998ea37ef993af0f9Antimicrobial, cytotoxic and antioxidative evaluation of natural deep eutectic solventsRadosevic, Kristina; Canak, Iva; Panic, Manuela; Markov, Ksenija; Bubalo, Marina Cvjetko; Frece, Jadranka; Srcek, Visnja Gaurina; Redovnikovic, Ivana RadojcicEnvironmental Science and Pollution Research (2018), 25 (14), 14188-14196CODEN: ESPLEC; ISSN:0944-1344. (Springer)Natural deep eutectic solvents (NADES) are a new generation of green solvents. They are mixts. of two or three compds. such as choline chloride as a cationic salt and alcs., acids, amides, amines or sugars as hydrogen-bond donors. Although the majority of NADES' components are of natural origin and therefore NADES are often presumed to be non-toxic, the evaluation of their toxicity and biodegradability must accompany the research on their synthesis and application. Therefore, the aim of this work was to investigate the effect of ten synthesized NADES towards bacteria (i.e., Escherichia coli, Proteus mirabilis, Salmonella typhimurium, Pseudomonas aeruginosa, Staphylococcus aureus), yeast (i.e., Candida albicans) and human cell lines (i.e., HeLa, MCF-7 and HEK293T). In addn., oxygen radical absorbance capacity (ORAC) method was used to det. the antioxidative activity of the tested NADES. Differences in toxicity response between microorganisms and cell lines were obsd., and only NADES that contained org. acid showed toxicity towards the test systems. Furthermore, the NADES contg. compds. that possess antioxidative activity also showed antioxidative activity. However, research whose primary purpose is the synthesis and application of NADES must be followed by an evaluation of their biol. properties (e.g., antimicrobial activity, toxicity towards animal cells and antioxidative or other biol. activity) to find the solvent with the best profile for wider industrial applications.
- 63Hou, C. T. New bioactive fatty acids. Asia Pac. J. Clin. Nutr. 2008, 17 (S1), 192– 195[PubMed], [CAS], Google Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtFymsrc%253D&md5=06356a55e22f0b25def4ae3be9ac31e1New bioactive fatty acidsHou, Ching T.Asia Pacific Journal of Clinical Nutrition (2008), 17 (Suppl. 1), 192-195CODEN: APJNFQ; ISSN:0964-7058. (HEC Press)A review. Many oxygenated fatty acids are bioactive compds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compds., 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) through 10-hydroxy-8-octadecenoic acid, and racinoleic acid to 7,10,12-trihydroxy-8-octadecenoic acid. DOD showed antibacterial activity including against food-borne pathogens. Bacillus megaterium ALA2 converted n-6 and n-3 PUFAs to many new oxygenated fatty acids. For example: linoleic acid was converted to 12,13-epoxy-9-octadecenoic acid and then to 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOA). From here, there are two bioconversion pathways. The major pathway is: 12,13-DHOA → 12,13,17-trihydroxy-9(S)-octadecenoic acid (THOA) → 12,17;13,17-diepoxy-16-hydroxy-9(Z)-octadecenoic acid (DEOA) → 7-hydroxy-DEOA. The minor pathway is: 12,13-DHOA → 12,13,16-THOA → 12-hydroxy-13,16-epoxy-9(Z)-octadecenoic acid. 12,13,17-THOA has anti-plant pathogenic fungal activity. The tetrahydrofuranyl moiety is known in anti cancer drugs. Strain ALA2 also converts other n-3 and n-6 PUFAs such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) to many new oxygenated unsatd. fatty acid products. All of these new products have high potential for antimicrobial agents or biomedical applications. We also screened 12 Mortierella fungal strains from the ARS Culture Collection for the prodn. of bioactive fatty acids such as dihomo-gama-linolenic acid (DGLA) and arachidonic acid. All of the strains tested produced AA and DGLA from glucose or glycerol. The top five AA producers (mg AA/g CDW) were in the following order: M. alpina > M. zychae > M. hygrophila > M. minutissima > M. parvispora. Both AA and DGLA are important natural precursors of a large family of prostaglandin and thromboxane groups.
- 64McKay, D. L.; Blumberg, J. B. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.). Phytother. Res. 2006, 20 (8), 619– 633, DOI: 10.1002/ptr.1936[Crossref], [PubMed], [CAS], Google Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xps1Sisro%253D&md5=d2c9bcda4e0e14a3e364ad6b642b8f18A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.)McKay, Diane L.; Blumberg, Jeffrey B.Phytotherapy Research (2006), 20 (8), 619-633CODEN: PHYREH; ISSN:0951-418X. (John Wiley & Sons Ltd.)A review. Peppermint (Mentha piperita L.) is one of the most widely consumed single ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant leaves, and the essential oil of peppermint are used in traditional medicines. Evidence-based research regarding the bioactivity of this herb is reviewed. The phenolic constituents of the leaves include rosmarinic acid and several flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile components of the essential oil are menthol and menthone. In vitro, peppermint has significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential. Human studies on the GI, respiratory tract and analgesic effects of peppermint oil and its constituents have been reported. Several clin. trials examg. the effects of peppermint oil on irritable bowel syndrome (IBS) symptoms have been conducted. However, human studies of peppermint leaf are limited and clin. trials of peppermint tea are absent. Adverse reactions to peppermint tea have not been reported, although caution has been urged for peppermint oil therapy in patients with GI reflux, hiatal hernia or kidney stones.
- 65Muniyan, R.; Gurunathan, J. Lauric acid and myristic acid from Allium sativum inhibit the growth of Mycobacterium tuberculosis H37Ra: in silico analysis reveals possible binding to protein kinase B. Pharm. Biol. 2016, 54 (12), 2814– 2821, DOI: 10.1080/13880209.2016.1184691[Crossref], [PubMed], [CAS], Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtVSrsrvE&md5=6e3b89732a449e0bdd16796357a6dae4Lauric acid and myristic acid from Allium sativum inhibit the growth of Mycobacterium tuberculosis H37Ra: in silico analysis reveals possible binding to protein kinase BMuniyan, Rajiniraja; Gurunathan, JayaramanPharmaceutical Biology (Abingdon, United Kingdom) (2016), 54 (12), 2814-2821CODEN: PHBIFC; ISSN:1388-0209. (Taylor & Francis Ltd.)The bulb of Allium sativum Linn (Alliaceae) has numerous medicinal values. Though the petroleum ether ext. of the bulb has shown to exhibit antimycobacterial activity, the phytochem.(s) responsible for this inhibitory activity is not known. To characterize the bioactive compds. in the petroleum ether ext. of Allium sativum (garlic) that inhibit the growth of Mycobacterium tuberculosis H37Ra. Bioactivity-guided fractionation was employed to isolate the bioactive compds. Antimycobacterial activity was evaluated by well-diffusion method and microplate alamar blue assay (MABA). IR spectroscopy, mass spectrometry and NMR spectroscopy were used to characterize the bioactive compds. Autodock was used to obtain information on mol. recognition, and mol. dynamics simulation was performed using GROMACS. The bioactive compds. that inhibited the growth of M. tuberculosis H37Ra were found to be lauric acid (LA) and myristic acid (MA). The minimal inhibitory concn. of LA and MA was found to be 22.2 and 66.7 μg/mL, resp. In silico anal. revealed that these fatty acids could bind at the cleft between the N-terminal and C-terminal lobes of the cytosolic domain of serine/threonine protein kinase B (PknB). The inhibition activity was dependent on the alkyl chain length of the fatty acid, and the amino acid residues involved in binding to fatty acid was found to be conserved across the Pkn family of proteins. The study indicates the possibility of using fatty acid derivs., involving Pkn family of proteins, to inhibit the signal transduction processes in M. tuberculosis.
- 66Barros, A. A.; Silva, J. M.; Craveiro, R.; Paiva, A.; Reis, R. L.; Duarte, A. R. C. Green solvents for enhanced impregnation processes in biomedicine. Current Opinion in Green and Sustainable Chemistry 2017, 5, 82– 87, DOI: 10.1016/j.cogsc.2017.03.014
- 67Kitahara, T.; Koyama, N.; Matsuda, J.; Aoyama, Y.; Hirakata, Y.; Kamihira, S.; Kohno, S.; Nakashima, M.; Sasaki, H. Antimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus. Biol. Pharm. Bull. 2004, 27 (9), 1321– 1326, DOI: 10.1248/bpb.27.1321[Crossref], [PubMed], [CAS], Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXptFWqsrs%253D&md5=5af1a49553a048f3cdf01a7a7ca9021cAntimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureusKitahara, Takashi; Koyama, Nao; Matsuda, Junichi; Aoyama, Yuko; Hirakata, Yoichi; Kamihira, Shimeru; Kohno, Shigeru; Nakashima, Mikiro; Sasaki, HitoshiBiological & Pharmaceutical Bulletin (2004), 27 (9), 1321-1326CODEN: BPBLEO; ISSN:0918-6158. (Pharmaceutical Society of Japan)The objective of this study was to investigate the antimicrobial activities of satd. fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of satd. fatty acids and fatty amines was detd. by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the satd. fatty acids, showed antimicrobial activity at 400 μg/mL against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concn. (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 μg/mL; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, resp. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 satd. fatty acids and 3 fatty amines was examd. in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of satd. fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, esp. in the case of insol. substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.
- 68Ouattara, B.; Simard, R. E.; Holley, R. A.; Piette, G. J.-P.; Bégin, A. Antibacterial activity of selected fatty acids and essential oils against six meat spoilage organisms. Int. J. Food Microbiol. 1997, 37 (2–3), 155– 162, DOI: 10.1016/S0168-1605(97)00070-6[Crossref], [PubMed], [CAS], Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmtl2jsbs%253D&md5=b0ef65b7ed8e6fce942c463a883295c6Antibacterial activity of selected fatty acids and essential oils against six meat spoilage organismsOuattara, Blaise; Simard, Ronald E.; Holley, Richard A.; Piette, Gabriel J. P.; Begin, AndreInternational Journal of Food Microbiology (1997), 37 (2,3), 155-162CODEN: IJFMDD; ISSN:0168-1605. (Elsevier)The antibacterial activity of selected fatty acids and essential oils was examd. against 2 gram-neg. (Pseudomonas fluorescens and Serratia liquefaciens), and 4 gram-pos. (Brochothrix thermosphacta, Carnobacterium piscicola, Lactobacillus curvatus, and Lactobacillus sake) bacteria involved in meat spoilage. Various amts. of each preservative were added to brain heart infusion or MRS agars, and the min. inhibitory concn. was detd. for each organism. Essential oils were analyzed by gas-liq. chromatog. to det. the concn. of selected components commonly found in spices. B. thermosphacta, P. fluorescens, and S. liquefaciens were not affected by fatty acids and generally overcame the inhibitory effect of essential oils after 24 h of exposure. Among the fatty acids, lauric and palmitoleic acids exhibited the greatest inhibitory effect with MICs of 250-500 μg/mL, while myristic, palmitic, stearic, and oleic acids were completely ineffective. For essential oils, clove, cinnamon, pimento, and rosemary were the most active. The 1/100 diln. of those oils inhibited ≥5 of the 6 tested organisms. A relation was found between the inhibitory effect of essential oils and the presence of eugenol and cinnamaldehyde.
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Abstract
Figure 1
Figure 1. DSC thermograms obtained for powders (A) and THEDES, including menthol:LA (B) menthol:MA (C) and menthol:SA (D). Peaks arising above the baseline represent endothermic peaks.
Figure 2
Figure 2. 1H NMR spectra of the powders; (A) menthol, (B) LA, (C) MA, and (D) SA. All of the resonances are attributed.
Figure 3
Figure 3. 1H NMR spectra of the THEDES: (A) menthol:LA (4:1), (B) menthol:MA (8:1), and (C) menthol:SA (8:1). All of the resonances are attributed.
Figure 4
Figure 4. Variation of the shear viscosity of the different formulations of THEDES as a function of the temperature.
Figure 5
Figure 5. Cytotoxic effect of menthol:LA (4:1) (A), menthol:MA (8:1) (B), and menthol:SA (8:1) (C) with use of HaCaT cell model treated for 24 h. Results were expressed relative to the control as mean ± SD of three independent experiments performed in triplicate.
Figure 6
Figure 6. Wound healing assay. (A) Migration assessment of HaCaT cells after the treatment with menthol:SA (8:1) and menthol and SA at 0 and 24 h postscratch. The lines indicated the boundary lines of the scratch at 0 h. (B) Results were expressed in terms of percentage of wound closure relative to the control using the mean ± SD of six independent experiments performed in duplicate.
References
ARTICLE SECTIONSThis article references 68 other publications.
- 1Domínguez de María, P. D.; Maugeri, Z. Ionic liquids in biotransformations: from proof-of-concept to emerging deep-eutectic-solvents. Curr. Opin. Chem. Biol. 2011, 15 (2), 220– 225, DOI: 10.1016/j.cbpa.2010.11.008[Crossref], [PubMed], [CAS], Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXksFKnt7o%253D&md5=d095cf4a47bfdb0b2c28f3602e02a538Ionic liquids in biotransformations: from proof-of-concept to emerging deep-eutectic-solventsDominguez de Maria, Pablo; Maugeri, ZairaCurrent Opinion in Chemical Biology (2011), 15 (2), 220-225CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Ionic liqs. (ILs) have been extensively assessed in biotransformations with different purposes, for example, non-conventional (co-)solvents, performance additives, coating agents for immobilizing/stabilizing enzymes, and IL-membrane-based processes. Fuelled by their premature labeling as green solvents', academic research has flourished. However, in recent years environmental aspects related to ILs have been strongly addressed, stating that many ILs commonly used cannot be regarded as green derivs.'. Likewise, ILs costs are still a barrier for practical uses. Attempting to combine sustainability with the promising added-values of ILs, the third generation of ILs is currently under development. Likewise, deep-eutectic-solvents (DESs) appear in the horizon as an attractive and cost-effective option for using ionic solvents in biotransformations. DESs are often produced by gently warming and stirring two (bio-based and cheap) salts (e.g. choline chloride and urea). First successful uses of DES in biotransformations were reported recently. It may be expected that knowledge accumulated in (second generation) ILs and biotransformations could be turned into real applications by using these DESs, and third generation ILs, in the coming years.
- 2Smith, E. L.; Abbott, A. P.; Ryder, K. S. Deep eutectic solvents (DESs) and their applications. Chem. Rev. 2014, 114 (21), 11060– 11082, DOI: 10.1021/cr300162p[ACS Full Text], [CAS], Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsleksrzM&md5=23e782e87410fb1014857dd350ee5146Deep Eutectic Solvents (DESs) and Their ApplicationsSmith, Emma L.; Abbott, Andrew P.; Ryder, Karl S.Chemical Reviews (Washington, DC, United States) (2014), 114 (21), 11060-11082CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)This article describes the phys. and chem. properties of deep eutectic solvents (DESs) and ionic liq. (ILs), and how their applications differ. DESs are now widely acknowledged as a new class of IL analogs because they share many characteristics and properties with ILs. The terms DES and IL have been used interchangeably in the literature, though it is necessary to point out that these are actually two different types of solvent. DESs are systems formed from a eutectic mixt. of Lewis or Bronsted acids and bases which can contain a variety of anionic and/or cationic species; in contrast, ILs are formed from systems composed primarily of one type of discrete anion and cation.
- 3Tang, B.; Row, K. H. Recent developments in deep eutectic solvents in chemical sciences. Monatsh. Chem. 2013, 144 (10), 1427– 1454, DOI: 10.1007/s00706-013-1050-3[Crossref], [CAS], Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlCqsrvE&md5=43278104871b5ce32b062bd1ccb8f1a6Recent developments in deep eutectic solvents in chemical sciencesTang, Baokun; Row, Kyung HoMonatshefte fuer Chemie (2013), 144 (10), 1427-1454CODEN: MOCMB7; ISSN:0026-9247. (Springer-Verlag GmbH)A review. In recent years, deep eutectic solvents (DESs) were considered green solvent alternatives to conventional solvents and have attracted considerable attention. With an in-depth understanding of the common and novel properties of DESs, many of them were prepd. and applied to various areas of chem. To summarize the full-scale development of DESs, this field is reviewed from its inception. This review summarizes the general trends in the development of DESs and evaluates the major aspects of DESs, such as their properties, prepns., and applications. This work is expected to be helpful for the further development of DESs based on a summary of the fundamental research in the field.
- 4Xu, P.; Zheng, G.-W.; Zong, M.-H.; Li, N.; Lou, W.-Y. Recent progress on deep eutectic solvents in biocatalysis. Bioresour. Bioprocess. 2017, 4 (1), 34, DOI: 10.1186/s40643-017-0165-5[Crossref], [PubMed], [CAS], Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cfmt1Kjuw%253D%253D&md5=82948b79c4ad39132300e7b8b40ce9fdRecent progress on deep eutectic solvents in biocatalysisXu Pei; Zong Min-Hua; Li Ning; Lou Wen-Yong; Xu Pei; Zong Min-Hua; Lou Wen-Yong; Zheng Gao-WeiBioresources and bioprocessing (2017), 4 (1), 34 ISSN:2197-4365.Deep eutectic solvents (DESs) are eutectic mixtures of salts and hydrogen bond donors with melting points low enough to be used as solvents. DESs have proved to be a good alternative to traditional organic solvents and ionic liquids (ILs) in many biocatalytic processes. Apart from the benign characteristics similar to those of ILs (e.g., low volatility, low inflammability and low melting point), DESs have their unique merits of easy preparation and low cost owing to their renewable and available raw materials. To better apply such solvents in green and sustainable chemistry, this review firstly describes some basic properties, mainly the toxicity and biodegradability of DESs. Secondly, it presents several valuable applications of DES as solvent/co-solvent in biocatalytic reactions, such as lipase-catalyzed transesterification and ester hydrolysis reactions. The roles, serving as extractive reagent for an enzymatic product and pretreatment solvent of enzymatic biomass hydrolysis, are also discussed. Further understanding how DESs affect biocatalytic reaction will facilitate the design of novel solvents and contribute to the discovery of new reactions in these solvents.
- 5Zhang, Q.; De Oliveira Vigier, K.; Royer, S.; Jerome, F. Deep eutectic solvents: syntheses, properties and applications. Chem. Soc. Rev. 2012, 41 (21), 7108– 7146, DOI: 10.1039/c2cs35178a[Crossref], [PubMed], [CAS], Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVOnurjF&md5=b2e43b5e7332276be1699afe9ddd561fDeep eutectic solvents: Syntheses, properties and applicationsZhang, Qinghua; De Oliveira Vigier, Karine; Royer, Sebastien; Jerome, FrancoisChemical Society Reviews (2012), 41 (21), 7108-7146CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Within the framework of green chem., solvents occupy a strategic place. To be qualified as a green medium, these solvents have to meet different criteria such as availability, non-toxicity, biodegradability, recyclability, flammability, and low price among others. Up to now, the no. of available green solvents are rather limited. Here we wish to discuss a new family of ionic fluids, so-called Deep Eutectic Solvents (DES), that are now rapidly emerging in the current literature. A DES is a fluid generally composed of two or three cheap and safe components that are capable of self-assocn., often through hydrogen bond interactions, to form a eutectic mixt. with a m.p. lower than that of each individual component. DESs are generally liq. at temps. lower than 100 °C. These DESs exhibit similar physico-chem. properties to the traditionally used ionic liqs., while being much cheaper and environmentally friendlier. Owing to these remarkable advantages, DESs are now of growing interest in many fields of research. In this review, we report the major contributions of DESs in catalysis, org. synthesis, dissoln. and extn. processes, electrochem. and material chem. All works discussed in this review aim at demonstrating that DESs not only allow the design of eco-efficient processes but also open a straightforward access to new chems. and materials.
- 6Paiva, A.; Craveiro, R.; Aroso, I.; Martins, M.; Reis, R. L.; Duarte, A. R. C. Natural deep eutectic solvents–solvents for the 21st century. ACS Sustainable Chem. Eng. 2014, 2 (5), 1063– 1071, DOI: 10.1021/sc500096j[ACS Full Text], [CAS], Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktlSqsLc%253D&md5=4e0b6d730b233beea8404df78f0dced5Natural Deep Eutectic Solvents - Solvents for the 21st CenturyPaiva, Alexandre; Craveiro, Rita; Aroso, Ivo; Martins, Marta; Reis, Rui L.; Duarte, Ana Rita C.ACS Sustainable Chemistry & Engineering (2014), 2 (5), 1063-1071CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)A review. Green technol. actively seeks new solvents to replace common org. solvents that present inherent toxicity and have high volatility, leading to evapn. of volatile org. compds. to the atm. Over the past two decades, ionic liqs. (ILs) have gained enormous attention from the scientific community, and the no. of reported articles in the literature has grown exponentially. Nevertheless, IL "greenness" is often challenged, mainly due to their poor biodegradability, biocompatibility, and sustainability. An alternative to ILs are deep eutectic solvents (DES). Deep eutectic solvents are defined as a mixt. of two or more components, which may be solid or liq. and that at a particular compn. present a high m.p. depression becoming liqs. at room temp. When the compds. that constitute the DES are primary metabolites, namely, aminoacids, org. acids, sugars, or choline derivs., the DES are so called natural deep eutectic solvents (NADES). NADES fully represent green chem. principles. Can natural deep eutectic solvents be foreseen as the next generation solvents and can a similar path to ionic liqs. be outlined. The current state of the art concerning the advances made on these solvents in the past few years is reviewed in this paper, which is more than an overview on the different applications for which they have been suggested, particularly, biocatalysis, electrochem., and extn. of new data. Citotoxicity of different NADES was evaluated and compared to conventional imidazolium-based ionic liqs., and hints at the extn. of phenolic compds. from green coffee beans and on the foaming effect of NADES are revealed. Future perspectives on the major directions toward which the research on NADES is envisaged are here discussed, and these comprised undoubtedly a wide range of chem. related subjects.
- 7Mbous, Y. P.; Hayyan, M.; Hayyan, A.; Wong, W. F.; Hashim, M. A.; Looi, C. Y. Applications of deep eutectic solvents in biotechnology and bioengineering—promises and challenges. Biotechnol. Adv. 2017, 35 (2), 105– 134, DOI: 10.1016/j.biotechadv.2016.11.006[Crossref], [PubMed], [CAS], Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1Wltr4%253D&md5=33e403fa0e22c0416948931fa3cd50bdApplications of deep eutectic solvents in biotechnology and bioengineering-Promises and challengesMbous, Yves Paul; Hayyan, Maan; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd. Ali; Looi, Chung YengBiotechnology Advances (2017), 35 (2), 105-134CODEN: BIADDD; ISSN:0734-9750. (Elsevier)Deep eutectic solvents (DESs) have been touted recently as potential alternatives to ionic liqs. (ILs). Although they possess core characteristics that are similar to those of ILs (e.g., low volatility, non-flammability, low m.ps., low vapor pressure, dipolar nature, chem. and thermal stability, high soly., and tuneability), DESs are superior in terms of the availability of raw materials, the ease of storage and synthesis, and the low cost of their starting materials. As such, they have become the subject of intensive research in various sectors, notably the chem., electrochem., and biol. sectors. To date, the applications of DESs have shown great promise, esp. in the medical and biotechnol. fields. In spite of these various achievements, the safety concern for these mixts. must be sufficiently addressed. Indeed, in order to exploit the vast array of opportunities that DESs offer to the biol. industry, first, they must be established as safe mixts. Hence, the biotechnol. applications of DESs only can be implemented if they are proven to have negligible or low toxicity profiles. This review is the first of its kind, and it discusses two current aspects of DES-based research. First, it describes the properties of these mixts. with ample focus on their toxicity profiles. Second, it provides an overview of the breakthroughs that have occurred and the foreseeable prospects of the use of DESs in various biotechnol. and biol. applications.
- 8Mouden, S.; Klinkhamer, P. G.; Choi, Y. H.; Leiss, K. A. Towards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolites. Phytochem. Rev. 2017, 16 (5), 935– 951, DOI: 10.1007/s11101-017-9502-8[Crossref], [PubMed], [CAS], Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlt1Smtrs%253D&md5=2ced8d68a88399b32c03ced3592aae1fTowards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolitesMouden, Sanae; Klinkhamer, Peter G. L.; Choi, Young Hae; Leiss, Kirsten A.Phytochemistry Reviews (2017), 16 (5), 935-951CODEN: PRHEBS; ISSN:1568-7767. (Springer)A review. With mounting concerns over health and environmental effects of pesticides, the search for environmentally acceptable substitutes has amplified. Plant secondary metabolites appear in the horizon as an attractive soln. for green crop protection. This paper reviews the need for changes in the techniques and compds. that, until recently, have been the mainstay for dealing with pest insects. Here we describe and discuss main strategies for selecting plant-derived metabolites as candidates for sustainable agriculture. The second part surveys ten important insecticidal compds., with special emphasis on those involved in human health. Many of these insecticidal metabolites, however, are cryst. solids with limited soly. which might potentially hamper com. formulation. As such, we introduce the concept of natural deep eutectic solvents for enhancing soly. and stability of such compds. The concept, principles and examples of green pest control discussed here offer a new suite of environmental-friendly tools designed to promote and adopt sustainable agriculture.
- 9Radošević, K.; Ćurko, N.; Gaurina Srček, V.; Cvjetko Bubalo, M.; Tomašević, M.; Kovačević Ganić, K. K.; Radojčić Redovniković, I. R. Natural deep eutectic solvents as beneficial extractants for enhancement of plant extracts bioactivity. LWT-Food Sci. Technol. 2016, 73, 45– 51, DOI: 10.1016/j.lwt.2016.05.037[Crossref], [CAS], Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XptVWitbg%253D&md5=fc0d624856aba0d1ed821b6df9820242Natural deep eutectic solvents as beneficial extractants for enhancement of plant extracts bioactivityRadosevic, Kristina; Curko, Natka; Gaurina Srcek, Visnja; Cvjetko Bubalo, Marina; Tomasevic, Marina; Kovacevic Ganic, Karin; Radojcic Redovnikovic, IvanaLWT--Food Science and Technology (2016), 73 (), 45-51CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)In the present study phenolic grape skin exts. were prepd. by using five choline chloride based natural deep eutectic solvents (NADESs) contg. glucose, fructose, xylose, glycerol, malic acid and valorised by testing their biol. activity in vitro using two human tumor cell lines (HeLa and MCF-7). Initially, used NADESs were investigated regard to their toxicity and low cytotoxicity of solvents was obsd. toward HeLa and MCF-7 cells (EC50 values > 2000 mg/L). Among used choline chloride based NADESs, the one contg. malic acid showed the best performance concerning extn. efficiency (total phenolic and total anthocyanin were 91 and 24 mg/g dw), as well as antioxidant (ORAC values were 371 μmol TE/g dw) and antiproliferative activity (percentage of cell viability were about 20%). Herein, for the first time it was showed that NADES components could be chosen not only to fine-tune solvent physicochem. characteristics but also to enhance biol. activity of exts. prepd. in NADESs. Therefore, our research confirmed that NADESs are excellent and promising choice of solvents for sustainable and green extn., which will lead to its novel application in food and pharmaceutical industry.
- 10Florindo, C.; McIntosh, A.; Welton, T.; Branco, L.; Marrucho, I. A closer look into deep eutectic solvents: exploring intermolecular interactions using solvatochromic probes. Phys. Chem. Chem. Phys. 2018, 20 (1), 206– 213, DOI: 10.1039/C7CP06471C[Crossref], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvVKgtL%252FN&md5=9503fa9f92f53cce74cedb6cda235a4aA closer look into deep eutectic solvents: exploring intermolecular interactions using solvatochromic probesFlorindo, C.; McIntosh, A. J. S.; Welton, T.; Branco, L. C.; Marrucho, I. M.Physical Chemistry Chemical Physics (2018), 20 (1), 206-213CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Deep eutectic solvents (DESs) constitute a new class of ionic solvents that was developing at a fast pace in recent years. Since these solvents are commonly suggested as green alternatives to org. solvents, it is important to understand their phys. properties. In particular, polarity plays an important role in solvation phenomena. In this work, the polarity of different families of DESs was studied through solvatochromic responses of UV-vis absorption probes. Kamlet-Taft α, β, π* and ETN parameters were evaluated using different solvatochromic probes, as 2,6-dichloro-4-(2,4,6-triphenyl-N-pyridino)-phenolate (Reichardt's betaine dye 33), 4-nitroaniline, and N,N-diethyl-4-nitroaniline for several families of DESs based on cholinium chloride, DL-menthol and a quaternary ammonium salt ([N4444]Cl). In addn., a study to understand the difference in polarity properties between DESs and the corresponding ILs, namely ILs based on cholinium cation and carboxylic acids as anions ([Ch][Lev], [Ch][Gly] and [Ch][Mal]), was carried out. The chem. structure of the hydrogen bond acceptor (HBA) in a DES clearly controls the dipolarity/polarizability afforded by the DES. Moreover, Kamlet-Taft parameters do not vary much within the family, but they differ among families based on different HBA, either for DESs contg. salts ([Ch]Cl or [N4444]Cl) or neutral compds. (DL-menthol). A substitution of the HBD was also found to play an important role in solvatochromic probe behavior for all the studied systems.
- 11Martins, M. A. R.; Crespo, E. A.; Pontes, P. V.; Silva, L. P.; Bülow, M.; Maximo, G. J.; Batista, E. A. C.; Held, C.; Pinho, S. P.; Coutinho, J. A. Tunable hydrophobic eutectic solvents based on terpenes and monocarboxylic acids. ACS Sustainable Chem. Eng. 2018, 6 (7), 8836– 8846, DOI: 10.1021/acssuschemeng.8b01203[ACS Full Text], [CAS], Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtVags7zN&md5=87ef83987b5a9d8f59e9b370b3fe65ccTunable Hydrophobic Eutectic Solvents Based on Terpenes and Monocarboxylic AcidsMartins, Monia A. R.; Crespo, Emanuel A.; Pontes, Paula V. A.; Silva, Liliana P.; Bulow, Mark; Maximo, Guilherme J.; Batista, Eduardo A. C.; Held, Christoph; Pinho, Simao P.; Coutinho, Joao A. P.ACS Sustainable Chemistry & Engineering (2018), 6 (7), 8836-8846CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Recently, some works claim that hydrophobic deep eutectic solvents could be prepd. based on menthol and monocarboxylic acids. Despite of some promising potential applications, these systems were poorly understood, and this work addresses this issue. Here, the characterization of eutectic solvents composed of the terpenes thymol or L(-)-menthol and monocarboxylic acids is studied aiming the design of these solvents. Their solid-liq. phase diagrams were measured by differential scanning calorimetry in the whole compn. range, showing that a broader compn. range, and not only fixed stoichiometric proportions, can be used as solvents at low temps. Addnl., solvent densities and viscosities close to the eutectic compns. were measured, showing low viscosity and lower d. than water. The solvatochromic parameters at the eutectic compn. were also investigated aiming at better understanding their polarity. The high acidity is mainly provided by the presence of thymol in the mixt., while L(-)-menthol plays the major role on the hydrogen-bond basicity. The measured mutual solubilities with water attest to the hydrophobic character of the mixts. investigated. The exptl. solid-liq. phase diagrams were described using the PC-SAFT equation of state that is shown to accurately describe the exptl. data and quantify the small deviations from ideality.
- 12Dai, Y.; Witkamp, G.-J.; Verpoorte, R.; Choi, Y. H. Tailoring properties of natural deep eutectic solvents with water to facilitate their applications. Food Chem. 2015, 187, 14– 19, DOI: 10.1016/j.foodchem.2015.03.123[Crossref], [PubMed], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXlvVChur0%253D&md5=5e9f1f5fdd6fbf71562e1c0c1504e5d3Tailoring properties of natural deep eutectic solvents with water to facilitate their applicationsDai, Yuntao; Witkamp, Geert-Jan; Verpoorte, Robert; Choi, Young HaeFood Chemistry (2015), 187 (), 14-19CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)Previously it was demonstrated that natural deep eutectic solvents (NADES) are promising green solvents for the extn. of natural products. However, despite their potential, an obvious disadvantage of NADES is the high viscosity. Here we explored the diln. effect on the structures and physicochem. properties of NADES and their improvements of applications using quercetin and carthamin. The results of FT-IR and 1H NMR expts. demonstrated that there are intensive H-bonding interactions between the two components of NADES and diln. with water caused the interactions weaken gradually and even disappeared completely at around 50% (vol./vol.) water addn. A small amt. of water could reduce the viscosity of NADES to the range of water and increase the cond. by up to 100 times for some NADES. This study provides the basis for modulating NADES in a controllable way for their applications in food processing, enzyme reactions, pharmaceuticals and cosmetics.
- 13van Osch, D. J.; Zubeir, L. F.; van den Bruinhorst, A.; Rocha, M. A.; Kroon, M. C. Hydrophobic deep eutectic solvents as water-immiscible extractants. Green Chem. 2015, 17 (9), 4518– 4521, DOI: 10.1039/C5GC01451D[Crossref], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2hsbvE&md5=1864bab4fcef1077c5219b3db77668deHydrophobic deep eutectic solvents as water-immiscible extractantsvan Osch, Dannie J. G. P.; Zubeir, Lawien F.; van den Bruinhorst, Adriaan; Rocha, Marisa A. A.; Kroon, Maaike C.Green Chemistry (2015), 17 (9), 4518-4521CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Hydrophobic deep eutectic solvents (DESs) are presented for the first time. They consist of decanoic acid and various quaternary ammonium salts. The effect of the alkyl chains on the hydrophobicity and the equil. of the two-phase DES-water system were investigated. These new DESs were successfully evaluated for the recovery of volatile fatty acids from dild. aq. solns.
- 14Abo-Hamad, A.; Hayyan, M.; AlSaadi, M. A.; Hashim, M. A. Potential applications of deep eutectic solvents in nanotechnology. Chem. Eng. J. 2015, 273, 551– 567, DOI: 10.1016/j.cej.2015.03.091[Crossref], [CAS], Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXlsV2ntLc%253D&md5=d65a40cb9afeb09424d581a40ec62b59Potential applications of deep eutectic solvents in nanotechnologyAbo-Hamad, Ali; Hayyan, Maan; AlSaadi, Mohammed AbdulHakim; Hashim, Mohd AliChemical Engineering Journal (Amsterdam, Netherlands) (2015), 273 (), 551-567CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)A review. Deep eutectic solvents (DESs) have recently received a great interest in diverse fields including nanotechnol. due to their unique properties as new green solvents, efficient dispersants and as large-scale media for chem. and electrochem. synthesis of advanced functional nanomaterials. DESs have also an active role in improving the size and morphol. of nanomaterials during synthesis stage. Moreover, DESs confined in nano-size pores or tubes show distinct behavior from those in the same types but in larger scales. Therefore, a numerous studies sprung up to expose the importance of the synergy between DESs and nanomaterials. This review revealed the recent studies that devoted to the impact of involving DESs in nanotechnol. and potential applications.
- 15Alonso, D. A.; Baeza, A.; Chinchilla, R.; Guillena, G.; Pastor, I. M.; Ramón, D. J. Deep eutectic solvents: the organic reaction medium of the century. Eur. J. Org. Chem. 2016, 2016 (4), 612– 632, DOI: 10.1002/ejoc.201501197[Crossref], [CAS], Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XislamtA%253D%253D&md5=2a5804acb485c86f357e36300e0e238bDeep Eutectic Solvents: The Organic Reaction Medium of the CenturyAlonso, Diego A.; Baeza, Alejandro; Chinchilla, Rafael; Guillena, Gabriela; Pastor, Isidro M.; Ramon, Diego J.European Journal of Organic Chemistry (2016), 2016 (4), 612-632CODEN: EJOCFK; ISSN:1099-0690. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. This microreview summarizes the use of deep eutectic solvents (DESs) and related melts in org. synthesis. Solvents of this type combine the great advantages of other proposed environmentally benign alternative solvents, such as low toxicity, high availability, low inflammability, high recyclability, low volatility, and low price, avoiding many disadvantages of the more modern media. The fact that many of the components of these mixts. come directly from nature assures their biodegradability and renewability. The classification and distribution of the reactions into different sections in this microreview, as well as the emphasis paid to their scope, easily allow a general reader to understand the actual state of the art and the great opportunities opened, not only for academic purposes but also for industry.
- 16Dai, Y.; van Spronsen, J.; Witkamp, G.-J.; Verpoorte, R.; Choi, Y. H. Natural deep eutectic solvents as new potential media for green technology. Anal. Chim. Acta 2013, 766, 61– 68, DOI: 10.1016/j.aca.2012.12.019[Crossref], [PubMed], [CAS], Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1Ggsrw%253D&md5=9d549b112fed92d496cc14f3d70ba9beNatural deep eutectic solvents as new potential media for green technologyDai, Yuntao; van Spronsen, Jaap; Witkamp, Geert-Jan; Verpoorte, Robert; Choi, Young HaeAnalytica Chimica Acta (2013), 766 (), 61-68CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Developing new green solvents is one of the key subjects in Green Chem. Ionic liqs. (ILs) and deep eutectic solvents, thus, have been paid great attention to replace current harsh org. solvents and have been applied to many chem. processing such as extn. and synthesis. However, current ionic liqs. and deep eutectic solvents have still limitations to be applied to a real chem. industry due to toxicity against human and environment and high cost of ILs and solid state of most deep eutectic solvents at room temp. Recently we discovered that many plant abundant primary metabolites changed their state from solid to liq. when they were mixed in proper ratio. This finding made us hypothesize that natural deep eutectic solvents (NADES) play a role as alternative media to water in living organisms and tested a wide range of natural products, which resulted in discovery of over 100 NADES from nature. In order to prove deep eutectic feature the interaction between the mols. was investigated by NMR spectroscopy. All the tested NADES show clear hydrogen bonding between components. As next step phys. properties of NADES such as water activity, d., viscosity, polarity and thermal properties were measured as well as the effect of water on the phys. properties. In the last stage the novel NADES were applied to the solubilization of wide range of biomols. such as non-water sol. bioactive natural products, gluten, starch, and DNA. In most cases the soly. of the biomols. evaluated in this study was greatly higher than water. Based on the results the novel NADES may be expected as potential green solvents at room temp. in diverse fields of chem.
- 17Tang, B.; Zhang, H.; Row, K. H. Application of deep eutectic solvents in the extraction and separation of target compounds from various samples. J. Sep. Sci. 2015, 38 (6), 1053– 1064, DOI: 10.1002/jssc.201401347[Crossref], [PubMed], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvVeku7c%253D&md5=4beea05995228911980de57d4c2d94d9Application of deep eutectic solvents in the extraction and separation of target compounds from various samplesTang, Baokun; Zhang, Heng; Row, Kyung HoJournal of Separation Science (2015), 38 (6), 1053-1064CODEN: JSSCCJ; ISSN:1615-9314. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Deep eutectic solvents, as a new type of eco-friendly solvent, have attracted increasing attention in chem. for the extn. and sepn. of target compds. from various samples. To summarize the application of deep eutectic solvents, this review highlights some of the unique properties of deep eutectic solvents and deep-eutectic-solvent-based materials, as well as their applications in extn. and sepn. In this paper, the available data and refs. in this field are reviewed to summarize the application developments of deep eutectic solvents. Based on the development of deep eutectic solvents, the exploitation of new deep eutectic solvents and deep-eutectic-solvent-based materials are expected to diversify into extn. and sepn.
- 18Stott, P. W.; Williams, A. C.; Barry, B. W. Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. J. Controlled Release 1998, 50 (1–3), 297– 308, DOI: 10.1016/S0168-3659(97)00153-3[Crossref], [PubMed], [CAS], Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnvFSnsrc%253D&md5=0ffc946fc451f5d4917573e78fbdd34bTransdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofenStott, Paul W.; Williams, Adrian C.; Barry, Brian W.Journal of Controlled Release (1998), 50 (1-3), 297-308CODEN: JCREEC; ISSN:0168-3659. (Elsevier Science B.V.)The formation of eutectic systems between ibuprofen (Ibu) and 7 terpene skin penetration enhancers was studied and, by using the eutectic systems as donors, the effects of m.p. depression of the delivery system on transdermal delivery were investigated. A range of Ibu:terpene binary mixts. were melted together, cooled, and recrystd. Compn./m.p. phase diagrams detd. by DSC and FT-IR anal. was used to investigate the nature of the interaction. Permeation of Ibu across human epidermal membranes from the eutectic systems was measured and compared to the flux from a satd. aq. soln. across skin and skin pretreated with the terpenes. The eutectic, i.e. min., m.p. of these systems ranged from 32° for Ibu:thymol 40:60 to -13° for Ibu:1,8-cineole 40:60 ( wt./wt.) compared to 76° for Ibu alone. FT-IR studies indicated that only the terpenes which formed hydrogen bonds with Ibu produced eutectic systems. Each set of Ibu:terpene eutectic systems produced a significant increase in flux compared to a satd. aq. soln. applied to untreated and to terpene pretreated skin. For example, Ibu:thymol 40:60 ( wt./wt.) produced a flux of 150 μg/cm2/h, 5.9-fold the flux from a satd. aq. soln. with thymol pretreated skin and 12.7-fold the flux from a satd. aq. soln. across non-pretreated skin. A hydrogen bonding interaction is the primary mechanism by which some terpenes form binary eutectic mixts. with Ibu. The resultant m.p. depression of the delivery system is correlated with a significant increase in transdermal permeation.
- 19Duarte, A. R. C.; Ferreira, A. S. D.; Barreiros, S.; Cabrita, E.; Reis, R. L.; Paiva, A. A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies. Eur. J. Pharm. Biopharm. 2017, 114, 296– 304, DOI: 10.1016/j.ejpb.2017.02.003[Crossref], [PubMed], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisFSit78%253D&md5=6b902e17189ec5c601aeba97bb825d98A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studiesDuarte, Ana Rita C.; Ferreira, Ana Sofia D.; Barreiros, Susana; Cabrita, Eurico; Reis, Rui L.; Paiva, AlexandreEuropean Journal of Pharmaceutics and Biopharmaceutics (2017), 114 (), 296-304CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)THEDES, so called therapeutic deep eutectic solvents are here defined as a mixt. of two components, which at a particular molar compn. become liq. at room temp. and in which one of them is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepd. The interactions between the components that constitute the THEDES were studied by NMR, confirming that the eutectic system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was studied by PFGSE NMR spectroscopy. It was detd. that the self-diffusion of the species followed the same behavior as obsd. previously for ionic liqs., in which the components migrate via jumping between voids in the suprastructure created by punctual thermal fluctuations. The soly. and permeability of the systems in an isotonic soln. was evaluated and a comparison with the pure APIs was established through diffusion and permeability studies carried out in a Franz cell. The soly. of the APIs when in the THEDES system can be improved up to 12 fold, namely for the system contg. ibu. Furthermore, for this system the permeability was calcd. to be 14 × 10-5 cm/s representing a 3 fold increase in comparison with the pure API. With the exception of the systems contg. PA an increase in the soly., coupled with an increase in permeability was obsd. In this work, we hence demonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability of APIs by changing the phys. state of the mols. from a solid dosage to a liq. system.
- 20Silva, J. M.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Design of functional therapeutic deep eutectic solvents based on choline chloride and ascorbic acid. ACS Sustainable Chem. Eng. 2018, 6 (8), 10355– 10363, DOI: 10.1021/acssuschemeng.8b01687[ACS Full Text], [CAS], Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFCrsr3M&md5=a89eb5656e918e621c17bf49a53e1657Design of Functional Therapeutic Deep Eutectic Solvents Based on Choline Chloride and Ascorbic AcidSilva, Joana M.; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.ACS Sustainable Chemistry & Engineering (2018), 6 (8), 10355-10363CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)In this work, we report the prepn. of novel therapeutic deep eutectic solvents (THEDES) based on choline chloride (CC) and ascorbic acid (AA), in which dexamethasone (DEX) was successfully solubilized. THEDES were synthesized and characterized for thermal behavior and polarized optic microscopy to confirm the formation of a eutectic mixt. The soly. profile of DEX solubilized in THEDES was greatly improved when compared with DEX in powder form. Addnl., the diffusion and permeability of DEX were also slightly increased. The antioxidant properties of AA were maintained up to 6 mo when the compd. is in THEDES form. Biol. tests were also performed, and the results indicate that cell viability varies in a dose-dependent manner. After the half maximal effective concn. (EC50) was detd., a controlled drug delivery system was successfully developed by supercrit. fluid sintering of a starch:poly-ε-caprolactone blend doped with THEDES contg. solubilized DEX. The present study highlights the potential applicability of THEDES based on CC and AA in the pharmaceutical industry and/or tissue engineering (TE) applications.
- 21Morrison, H. G.; Sun, C. C.; Neervannan, S. Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehicles. Int. J. Pharm. 2009, 378 (1–2), 136– 139, DOI: 10.1016/j.ijpharm.2009.05.039[Crossref], [PubMed], [CAS], Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXovFKqtbw%253D&md5=cbd7b0b69611417b3be6d8b6e1f2a3e0Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehiclesMorrison, Henry G.; Sun, Changquan C.; Neervannan, SeshaInternational Journal of Pharmaceutics (2009), 378 (1-2), 136-139CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)Deep eutectic solvent (DES) is a new class of solvents typically formed by mixing choline chloride with hydrogen bond donors such as amines, acids, and alcs. Most DES's are non-reactive with water, biodegradable, and have acceptable toxicity profiles. Urea-choline chloride and malonic acid-choline chloride eutectic systems were characterized using differential scanning calorimetry (DSC) and thermal microscopy. A potential new 2:1 urea-choline chloride cocrystal with a m.p. of 25° was characterized at the eutectic compn. The formation of this cocrystal suggests that DES should not be universally explained by simple eutectic melting, and may be useful in guiding the search for new DES systems. The lack of nucleation of the malonic acid-choline chloride system prohibited the construction of a phase diagram for this system using DSC. We also investigated possible uses of DES in solubilizing poorly sol. compds. for enhanced bioavailability in early drug development such as toxicol. studies. For five poorly sol. model compds., soly. in DES is 5 to 22,000 folds more than that in water. Thus, DES can be a promising vehicle for increasing exposure of poorly sol. compds. in preclin. studies.
- 22Santos, F.; P. S. Leitão, M.; C. Duarte, A. Properties of Therapeutic Deep Eutectic Solvents of L-Arginine and Ethambutol for Tuberculosis Treatment. Molecules 2019, 24 (55), 55, DOI: 10.3390/molecules24010055[Crossref], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXntlCqsLc%253D&md5=eb5e1e06bd4202c3954bbcbe3545f99dProperties of therapeutic deep eutectic solvents of l-arginine and ethambutol for tuberculosis treatmentSantos, Filipa; Leitao, Maria Ines P. S.; Duarte, Ana Rita C.Molecules (2019), 24 (1), 55/1-55/12CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)The treatment for tuberculosis infection usually involves a prolonged regimen of multiple antibacterial drugs, which might lead to various secondary effects. For preventing drug resistance and side-effects of anti-tuberculosis drugs, new methods for improving the bioavailability of APIs were investigated. The strategy proposed consists of the prepn. of therapeutic deep eutectic solvents (THEDES), that incorporate L-arginine and ethambutol. The eutectic mixts. were prepd. by mixing the components at a certain molar ratio, until a clear liq. soln. was formed. The prepd. mixts. were characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and NMR spectroscopy (1H and 13C-NMR). The soly. and permeability of the drugs when they are in the THEDES form was evaluated at 37 °C, in phosphate buffered saline (PBS). Soly. studies showed an increase of the soly. of ethambutol when incorporated in the eutectic system. The cytotoxicity was evaluated using a model cell line (Caco-2), comparing the cytotoxicity of the API incorporated in the eutectic system. We obsd. that the cell viability in the THEDES was affected by the presence of citric acid, and higher cytotoxicity values were obsd. Nonetheless, these findings do not compromise the possibility to use these systems as new delivery systems for ethambutol and arginine.
- 23Aroso, I. M.; Craveiro, R.; Rocha, Â.; Dionísio, M.; Barreiros, S.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Design of controlled release systems for THEDES—therapeutic deep eutectic solvents, using supercritical fluid technology. Int. J. Pharm. 2015, 492 (1–2), 73– 79, DOI: 10.1016/j.ijpharm.2015.06.038[Crossref], [PubMed], [CAS], Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1eksLvI&md5=8dfc9a754f4fda96582dc01e5698fc85Design of controlled release systems for THEDES-Therapeutic deep eutectic solvents, using supercritical fluid technologyAroso, Ivo M.; Craveiro, Rita; Rocha, Angelo; Dionisio, Madalena; Barreiros, Susana; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.International Journal of Pharmaceutics (Amsterdam, Netherlands) (2015), 492 (1-2), 73-79CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)Deep eutectic solvents (DES) can be formed by bioactive compds. or pharmaceutical ingredients. A therapeutic DES (THEDES) based on ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and menthol was synthesized and its thermal behavior was analyzed by differential scanning calorimetry (DSC). A controlled drug delivery system was developed by impregnating a starch:poly-ε-caprolactone polymeric blend (SPCL 30:70) with the menthol:ibuprofen THEDES in different ratios (10 and 20 wt%), after supercrit. fluid sintering at 20 MPa and 50 °C. The morphol. characterization of SPCL matrixes impregnated with THEDES was performed by SEM (SEM) and micro-computed tomog. (micro-CT). Drug release studies were carried out in a phosphate buffered saline. The results obtained provide important clues for the development of carriers for the sustainable delivery of bioactive compds.
- 24Ribeiro, B. D.; Florindo, C.; Iff, L. C.; Coelho, M. A.; Marrucho, I. M. Menthol-based eutectic mixtures: hydrophobic low viscosity solvents. ACS Sustainable Chem. Eng. 2015, 3 (10), 2469– 2477, DOI: 10.1021/acssuschemeng.5b00532[ACS Full Text], [CAS], Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVKlsLjE&md5=c8fd66ce9a6782940808fa5c9c44d1acMenthol-based Eutectic Mixtures: Hydrophobic Low Viscosity SolventsRibeiro, Bernardo D.; Florindo, Catarina; Iff, Lucas C.; Coelho, Maria A. Z.; Marrucho, Isabel M.ACS Sustainable Chemistry & Engineering (2015), 3 (10), 2469-2477CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Inspired by one of the major problems in the pharmaceutical industry, we advantageously used the formation of eutectic mixts. to synthesize new solvents. The aim of this work is to identify low viscosity, cheap, biodegradable and hydrophobic eutectic solvents from natural resources. Consequently, novel eutectic mixts. based on DL-menthol and naturally occurring acids, namely pyruvic acid, acetic acid, L-lactic acid, and lauric acid, were synthesized and are here reported for the first time. The obtained DL-menthol-based eutectic mixts. were analyzed using NMR and FTIR spectroscopy in order to check their structures and purities and to confirm the interaction of the two compds. leading to the eutectic formation. Important solvent thermophys. properties, such as d. and viscosity, of the prepd. eutectic solvents with different water contents (dried and water-satd.) were measured. Finally, taking advantage of their hydrophobic character, namely the formation of two phases with water at room temp., four different biomols., caffeine, tryptophan, isophthalic acid, and vanillin, were extd. and the extn. efficiencies of the prepd. eutectic solvents compared.
- 25Jeevan, R.; Venkat, R.; Khan, M. A.; Kunta; Goskonda; Brotherton, H. O.; Reddy, I. K. Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin. J. Pharm. Sci. 1997, 86 (12), 1369– 1373, DOI: 10.1021/js970161+
- 26Aroso, I. M.; Silva, J. C.; Mano, F.; Ferreira, A. S.; Dionísio, M.; Sá-Nogueira, I.; Barreiros, S.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems. Eur. J. Pharm. Biopharm. 2016, 98, 57– 66, DOI: 10.1016/j.ejpb.2015.11.002[Crossref], [PubMed], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVGnur3K&md5=f8f24c25c624df40e9abee321426ad28Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systemsAroso, Ivo M.; Silva, Joao C.; Mano, Francisca; Ferreira, Ana S. D.; Dionisio, Madalena; Sa-Nogueira, Isabel; Barreiros, Susana; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.European Journal of Pharmaceutics and Biopharmaceutics (2016), 98 (), 57-66CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive mols. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behavior, structural features, dissoln. rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liq. at room temp. Dissoln. studies in PBS led to increased dissoln. rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissoln. rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-pos. and Gram-neg. model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissoln. enhancers in the development of novel and more effective drug delivery systems.
- 27Juergens, U.; Stöber, M.; Vetter, H. The anti-inflammatory activity of L-menthol compared to mint oil in human monocytes in vitro: a novel perspective for its therapeutic use in inflammatory diseases. Eur. J. Med. Res. 1998, 3 (12), 539– 545[PubMed], [CAS], Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXosVSj&md5=5a7fd9948d836b2565a8c82b982ac404The anti-inflammatory activity of L-menthol compared to mint oil in human monocytes in vitro. A novel perspective for its therapeutic use in inflammatory diseasesJuergens, Uwe R.; Stoeber, M.; Vetter, H.European Journal of Medical Research (1998), 3 (12), 539-545CODEN: EJMRFL; ISSN:0949-2321. (I. Holzapfel Publishers)The anti-inflammatory efficacy was studied of L-menthol and mint oil in LPS-stimulated monocytes. Arachidonic acid metab. was assessed by measuring leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) as indicators for lipoxygenase and the cyclooxygenase pathway, resp. The anti-inflammatory effects on interleukin 1β (IL-1β) prodn. were analyzed. L-Menthol suppressed the prodn. of each mediator. LTB4 decreased by 64.4%, PGE2 by 56.6%, and IL-1β by 64.2% at L-menthol concns. within the presumed therapeutic range of about 10-7 g/mL. Mint oil had a bimodal effect on PGE2 prodn. with 10-10-10-8 g/mL increasing PGE2 <6-fold and 10-7 g/mL suppressing PGE2 prodn. app. by 50%. It had similar effects on LTB4 and IL-1β as L-menthol, the suppression being less at lower concns. The authors suggest preferable anti-inflammatory effects of L-menthol compared to mint oil at therapeutically relevant concns. supplied in enteric coated capsules.
- 28Patel, T.; Ishiuji, Y.; Yosipovitch, G. Menthol: a refreshing look at this ancient compound. J. Am. Acad. Dermatol. 2007, 57 (5), 873– 878, DOI: 10.1016/j.jaad.2007.04.008[Crossref], [PubMed], [CAS], Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2snhsVyitg%253D%253D&md5=d752190d04fbd0337412b5b70b10ac12Menthol: a refreshing look at this ancient compoundPatel Tejesh; Ishiuji Yozo; Yosipovitch GilJournal of the American Academy of Dermatology (2007), 57 (5), 873-8 ISSN:.Menthol is a naturally occurring cyclic terpene alcohol of plant origin, which has been used since antiquity for medicinal purposes. Its use in dermatology is ubiquitous, where it is frequently part of topical antipruritic, antiseptic, analgesic, and cooling formulations. Despite its widespread use, it was only recently that the mechanism by which menthol elicits the same cool sensation as low temperature was elucidated upon, with the discovery of the TRPM8 receptor. Although almost 5 years have passed since the discovery of this receptor, many dermatologists are still unaware of menthol's underlying target. The purpose of this review is to highlight the recent advances in the mechanism of action of menthol and to provide an overview of its dermatologic applications.
- 29Tsuk, A. G. Menthol enhancement of transdermal drug delivery. U.S. Pat. Appl. US 07/031,077, 1990.Google ScholarThere is no corresponding record for this reference.
- 30Nakatsuji, T.; Kao, M. C.; Fang, J.-Y.; Zouboulis, C. C.; Zhang, L.; Gallo, R. L.; Huang, C.-M. Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J. Invest. Dermatol. 2009, 129 (10), 2480– 2488, DOI: 10.1038/jid.2009.93[Crossref], [PubMed], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFWqurjF&md5=20f52224bd9284a920b142973dd62b32Antimicrobial Property of Lauric Acid Against Propionibacterium Acnes: Its Therapeutic Potential for Inflammatory Acne VulgarisNakatsuji, Teruaki; Kao, Mandy C.; Fang, Jia-You; Zouboulis, Christos C.; Zhang, Liangfang; Gallo, Richard L.; Huang, Chun-MingJournal of Investigative Dermatology (2009), 129 (10), 2480-2488CODEN: JIDEAE; ISSN:0022-202X. (Nature Publishing Group)The strong bactericidal properties of lauric acid (C12:0), a middle chain-free fatty acid commonly found in natural products, have been shown in a no. of studies. However, it has not been demonstrated whether lauric acid can be used for acne treatment as a natural antibiotic against Propionibacterium acnes (P. acnes), which promotes follicular inflammation (inflammatory acne). This study evaluated the antimicrobial property of lauric acid against P. acnes both in vitro and in vivo. Incubation of the skin bacteria P. acnes, Staphylococcus aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis) with lauric acid yielded minimal inhibitory concn. (MIC) values against the bacterial growth over 15 times lower than those of benzoyl peroxide (BPO). The lower MIC values of lauric acid indicate stronger antimicrobial properties than that of BPO. The detected values of half maximal effective concn. (EC50) of lauric acid on P. acnes, S. aureus, and S. epidermidis growth indicate that P. acnes is the most sensitive to lauric acid among these bacteria. In addn., lauric acid did not induce cytotoxicity to human sebocytes. Notably, both intradermal injection and epicutaneous application of lauric acid effectively decreased the no. of P. acnes colonized with mouse ears, thereby relieving P. acnes-induced ear swelling and granulomatous inflammation. The obtained data highlight the potential of using lauric acid as an alternative treatment for antibiotic therapy of acne vulgaris.
- 31McGaw, L.; Jäger, A.; Van Staden, J.; Houghton, P. Antibacterial effects of fatty acids and related compounds from plants. S. Afr. J. Bot. 2002, 68 (4), 417– 423, DOI: 10.1016/S0254-6299(15)30367-7[Crossref], [CAS], Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXis1GmtLk%253D&md5=675d4354805646a48fd0209fc38e4879Antibacterial effects of fatty acids and related compounds from plantsMcGaw, L. J.; Jager, A. K.; van Staden, J.South African Journal of Botany (2002), 68 (4), 417-423CODEN: SAJBDD; ISSN:0254-6299. (NISC Pty Ltd.)A review. Fatty acids are important constituents of plants and are commonly known to possess antimicrobial activities. The structure-activity relationship of fatty acids, including the effects of hydrocarbon chain length, unsatn. and presence of functional groups, is reviewed. The biol. activity of fatty acids is significant as they are often isolated following bioassay-guided fractionation of plant exts. The possibility of the therapeutic use of fatty acids as antimicrobial agents is worthy of note.
- 32Desbois, A. P.; Smith, V. J. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl. Microbiol. Biotechnol. 2010, 85 (6), 1629– 1642, DOI: 10.1007/s00253-009-2355-3[Crossref], [PubMed], [CAS], Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtVaqu7s%253D&md5=79f2088f5eaa7c30d26dd6876020aceeAntibacterial free fatty acids: activities, mechanisms of action and biotechnological potentialDesbois, Andrew P.; Smith, Valerie J.Applied Microbiology and Biotechnology (2010), 85 (6), 1629-1642CODEN: AMBIDG; ISSN:0175-7598. (Springer)A review. Amongst the diverse and potent biol. activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. While their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy prodn., FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidn. and auto-oxidn. degrdn. products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, esp. where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for com. or biomedical exploitation of antibacterial FFAs, esp. for those from natural sources, is discussed.
- 33Silva, J. M.; Akkache, S.; Araújo, A. C.; Masmoudi, Y.; Reis, R. L.; Badens, E.; Duarte, A. R. C. Development of innovative medical devices by dispersing fatty acid eutectic blend on gauzes using supercritical particle generation processes. Mater. Sci. Eng., C 2019, 99, 599– 610, DOI: 10.1016/j.msec.2019.02.012[Crossref], [PubMed], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXivFyhtLo%253D&md5=5d29a8224cfbc34e2805367eb80c70eeDevelopment of innovative medical devices by dispersing fatty acid eutectic blend on gauzes using supercritical particle generation processesSilva, Joana M.; Akkache, Salah; Araujo, Ana C.; Masmoudi, Yasmine; Reis, Rui L.; Badens, Elisabeth; Duarte, Ana Rita C.Materials Science & Engineering, C: Materials for Biological Applications (2019), 99 (), 599-610CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)In order to limit bacterial infections during wound treatment, it is interesting to consider the concept of loading medical devices with antibacterial agents. With this in mind, an innovative system with thermosensitive properties was produced: loading a com. available gauze with a fatty acid eutectic blend based on lauric acid (LA) and myristic acid (MA). This eutectic blend presents a m.p. near physiol. temp., which together with its antibacterial properties make an appealing alternative in biomedical applications. At room temp., the properties and the efficacy of the eutectic blend loaded onto gauzes are preserved, whereas at physiol. temp. the eutectic blend undergoes a phase change that facilitates its diffusion from the gauze. The loading of the eutectic blend onto gauzes was performed using two different supercrit. fluid technologies, namely, particle from gas satd. solns. (PGSS) and a derived version of rapid expansion of supercrit. soln. (D-RESS). The PGSS led to a heterogeneous dispersion of the eutectic blend in the gauze, whereas the D-RESS process led to the formation of a homogeneous dispersion along the surface of the gauze. Addnl., with D-RESS no phase sepn. of the eutectic blend occurred and the cytotoxicity was greatly improved compared with PGSS without compromising the antibacterial properties of the fatty acid eutectic blend. Hence, the present study highlights the potential use of the flexible D-RESS process to load the fatty acid eutectic blend with antibacterial properties onto medical devices in a controllable way. Overall, the effects produced by the loaded gauzes suggest the enormous potential of the developed technol. in health-related areas.
- 34Castro, V. I.; Craveiro, R.; Silva, J. M.; Reis, R. L.; Paiva, A.; C. Duarte, A. R. Natural deep eutectic systems as alternative nontoxic cryoprotective agents. Cryobiology 2018, 83, 15– 26, DOI: 10.1016/j.cryobiol.2018.06.010[Crossref], [PubMed], [CAS], Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXht1ejtL%252FE&md5=9911b1ac7128af94798e8e1fd33ce15fNatural deep eutectic systems as alternative nontoxic cryoprotective agentsCastro, Vania I. B.; Craveiro, Rita; Silva, Joana M.; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.Cryobiology (2018), 83 (), 15-26CODEN: CRYBAS; ISSN:0011-2240. (Elsevier Ltd.)Natural deep eutectic systems (NADES) are mostly composed of natural primary metabolites such as sugars, sugar alcs., org. acids, amino acids and amines. These simple mols. have been identified in animals living in environments with extreme temp. amplitudes, being responsible for their survival at neg. temps. during winter. Herein, we report for the first time the use of NADES based on trehalose (Treh) and glycerol (Gly) in cryopreservation, as cryoprotective agents (CPA). The evaluation of the thermal behavior of these eutectic systems, showed that NADES have a strong effect on the water crystn./freezing and melting process, being able to reduce the no. of ice crystals and hence ice crystal damage in cells, which is a crucial parameter for their survival, upon freezing. Using this NADES as CPA, it is possible to achieve similar or even better cellular performance when compared with the gold std. for cryopreservation DMSO (DMSO). In this sense, this work relates the phys. properties of the NADES with their biol. performance in cryopreservation. Our comprehensive strategy results in the demonstration of NADES as a promising nontoxic green alternative to the conventional CPA's used in cryopreservation methods.
- 35Hayyan, M.; Looi, C. Y.; Hayyan, A.; Wong, W. F.; Hashim, M. A. In vitro and in vivo toxicity profiling of ammonium-based deep eutectic solvents. PLoS One 2015, 10 (2), e0117934 DOI: 10.1371/journal.pone.0117934[Crossref], [PubMed], [CAS], Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFymsbzE&md5=d326f5a659c28dd15e3c7085e0897bfdIn Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solventsHayyan, Maan; Looi, Chung Yeng; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd. AliPLoS One (2015), 10 (2), e0117934/1-e0117934/18CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerin (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examd. using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were detd. for the DESs, their individual components and their combinations as aq. solns. for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, resp. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS prodn. and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examd. DESs showed less cytotoxicity compared with ionic liqs. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixts. and their potential applicability to be used for therapeutic purposes.
- 36Parnham, E. R.; Drylie, E. A.; Wheatley, P. S.; Slawin, A. M.; Morris, R. E. Ionothermal materials synthesis using unstable deep-eutectic solvents as template-delivery agents. Angew. Chem. 2006, 118 (30), 5084– 5088, DOI: 10.1002/ange.200600290
- 37Abbott, A. P.; Capper, G.; Gray, S. Design of improved deep eutectic solvents using hole theory. ChemPhysChem 2006, 7 (4), 803– 806, DOI: 10.1002/cphc.200500489[Crossref], [PubMed], [CAS], Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XjvVCgtbk%253D&md5=7ffc74a1bbfad12db923f25de253fc9dDesign of improved deep eutectic solvents using hole theoryAbbott, Andrew P.; Capper, Glen; Gray, StephenChemPhysChem (2006), 7 (4), 803-806CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)Ambient temp. ionic liqs. have attracted a great deal of interest owing to their potential as environmentally benign solvents and their unusual solvent properties. An alternative approach to the formation of ionic liqs. is to start with a quaternary ammonium halide and shield the charge on the anion by complexing it with hydrogen-bond donors such as carboxylic acids or amides. These liqs., termed deep eutectic solvents (DESs), have phys. and solvent properties that are similar to ionic liqs. formed with discrete ions, but they are easy to produce by simply mixing common commodity chems. such as choline chloride and urea. In this study, less viscous liqs. with higher conductivities were obtained using small quaternary ammonium cations such as ethylammonium and fluorinated hydrogen-bond donors such as trifluoroacetamide. The fluidity and transport of DESs are both affected by small changes in chem. structure. Thus, the hole theory can be used to design DESs with decreased viscosity and increased cond. by using small cations or fluorinated hydrogen-bond donors. These changes can be quite significant particularly at ambient temp. where the differences in viscosity and cond. can be up to 4 orders of magnitude.
- 38Corvis, Y.; Négrier, P.; Massip, S.; Leger, J.-M.; Espeau, P. Insights into the crystal structure, polymorphism and thermal behavior of menthol optical isomers and racemates. CrystEngComm 2012, 14 (20), 7055– 7064, DOI: 10.1039/c2ce26025e[Crossref], [CAS], Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlGgurnL&md5=3b2492710fd2224b423be4166ed1af7eInsights into the crystal structure, polymorphism and thermal behavior of menthol optical isomers and racematesCorvis, Yohann; Negrier, Philippe; Massip, Stephane; Leger, Jean-Michel; Espeau, PhilippeCrystEngComm (2012), 14 (20), 7055-7064CODEN: CRECF4; ISSN:1466-8033. (Royal Society of Chemistry)The physico-chem. properties of the levo- and dextrorotatory menthol isomers as well as the corresponding racemic compd. were studied using X-ray single-crystal or powder diffraction and differential scanning calorimetry expts. As a result, the not yet detd. crystal structure of dl-menthol was solved. Moreover, the stable and metastable exptl. temp.-compn. phase diagrams of the l-menthol/d-menthol binary system were detd. The thermodn. relative stability of the different menthol polymorphs was also established. The present paper provides new phys., chem. and thermodn. data of l-, d- and dl-menthol and offers new insight into their polymorphism as well as into the levorotatory-dextrorotatory menthol interactions. Both the thermodn. and crystallog. approaches demonstrate unambiguously that racemic menthol is a racemate.
- 39Corvis, Y.; Wurm, A.; Schick, C.; Espeau, P. New menthol polymorphs identified by flash scanning calorimetry. CrystEngComm 2015, 17 (29), 5357– 5359, DOI: 10.1039/C5CE00697J[Crossref], [CAS], Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXps1Wmt7Y%253D&md5=e66eb8e4f82f5535da68748b5eb68a65New menthol polymorphs identified by flash scanning calorimetryCorvis, Yohann; Wurm, Andreas; Schick, Christoph; Espeau, PhilippeCrystEngComm (2015), 17 (29), 5357-5359CODEN: CRECF4; ISSN:1466-8033. (Royal Society of Chemistry)Menthol, which is used in the food, pharmaceutical and cosmetics industries, was studied by flash scanning calorimetry. New levorotatory and racemic menthol polymorphs were thus identified. This study is also forward-looking regarding the use of org. mols. in flash scanning calorimetry, which is frequently used for polymer studies.
- 40Wang, L.; Meng, D. Fatty acid eutectic/polymethyl methacrylate composite as form-stable phase change material for thermal energy storage. Appl. Energy 2010, 87 (8), 2660– 2665, DOI: 10.1016/j.apenergy.2010.01.010[Crossref], [CAS], Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmtFKqsb8%253D&md5=7a07c6f84ba214c13f72d630a8e16fcaFatty acid eutectic/polymethyl methacrylate composite as form-stable phase change material for thermal energy storageWang, Lijiu; Meng, DuoApplied Energy (2010), 87 (8), 2660-2665CODEN: APENDX; ISSN:0306-2619. (Elsevier Ltd.)This work is focused on the prepn. and characterization of fatty acid eutectic/polymethyl methacrylate (PMMA) form-stable phase change material (PCM). Capric acid (CA), lauric acid (LA), myristic acid (MA) and stearic acid (SA) were selected to prep. binary fatty acid eutectic for the sake of decreasing the phase change temp. Using the method of self-polymn., CA-LA, CA-MA, CA-SA and LA-MA eutectics acting as the heat-absorbing materials and PMMA serving as the supporting material were compounded in the ratio of 50/50 wt.%. The relations between mass fraction of LA-MA eutectic and latent heat and compressive strength of LA-MA/PMMA composite were discussed, and the feasible max. mass fraction of LA-MA eutectic was detd. to be 70%. CA-LA/PMMA, CA-MA/PMMA, CA-SA/PMMA and LA-MA/PMMA composites were examd. to investigate their potential application in building energy conservation. Scanning electron microscope and polarizing optical microscope observations showed that fatty acid eutectic was coated by PMMA thus the composite remained solid when the sample was heated above the melted point of the fatty acid. Fourier-transform IR results indicated that fatty acid and PMMA had no chem. reaction and exhibited good compatibility with each other. According to the differential scanning calorimetry results, phase change temps. of CA-LA/PMMA, CA-MA/PMMA, CA-SA/PMMA and LA-MA/PMMA composites were 21.11 °C, 25.16 °C, 26.38 °C and 34.81 °C and their latent heat values were detd. to be 76.3 kJ/kg, 69.32 kJ/kg, 59.29 kJ/kg and 80.75 kJ/kg, resp. Moreover, thermal stability and expansibility of the form-stable PCMs were characterized by thermogravimetric anal. and vol. expansion coeff. resp., and the results indicated that the composites were available for building energy conservation.
- 41Yuan, Y.; Zhang, N.; Tao, W.; Cao, X.; He, Y. Fatty acids as phase change materials: a review. Renewable Sustainable Energy Rev. 2014, 29, 482– 498, DOI: 10.1016/j.rser.2013.08.107[Crossref], [CAS], Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslGmtbnP&md5=098eed70762a6febe5c9c2f6d2d02baaFatty acids as phase change materials: A reviewYuan, Yanping; Zhang, Nan; Tao, Wenquan; Cao, Xiaoling; He, YalingRenewable & Sustainable Energy Reviews (2014), 29 (), 482-498CODEN: RSERFH; ISSN:1364-0321. (Elsevier Ltd.)A review. Fatty acids as phase change materials have attracted much attention for their various applications in building energy efficiency, solar heating systems and air-conditioning systems. After summarizing the basic characteristics of fatty acids, eutectic mixts. of fatty acids and fatty acid esters, as well as the prepn. and characteristics of fatty acid composites as phase change materials (PCMs), this paper analyzes the thermal reliability and stability of fatty acids as PCMs and their heat transfer characteristics in a unit which is followed by an introduction to the energy storage systems of three kinds of fatty acids as PCMs. Besides, it also points out the future research direction of fatty acids as PCMs as a soln. of the insufficiency and flaws of current researches.
- 42Castro, V. n. I.; Mano, F.; Reis, R. L.; Paiva, A.; Duarte, A. R. C. Synthesis and Physical and Thermodynamic Properties of Lactic Acid and Malic Acid-Based Natural Deep Eutectic Solvents. J. Chem. Eng. Data 2018, 63 (7), 2548– 2556, DOI: 10.1021/acs.jced.7b01037[ACS Full Text], [CAS], Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFGisr3M&md5=2aae9c5b5d25c8ab4a051799b5d4d69fSynthesis and Physical and Thermodynamic Properties of Lactic Acid and Malic Acid-Based Natural Deep Eutectic SolventsCastro, Vania I. B.; Mano, Francisca; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.Journal of Chemical & Engineering Data (2018), 63 (7), 2548-2556CODEN: JCEAAX; ISSN:0021-9568. (American Chemical Society)In this paper, four natural deep eutectic solvents (NADES) systems were prepd. at specific molar ratios, La:Bet (2:1) (lactic acid/betaine), La:Hist (9:1) (lactic acid/histidine), Ma:Bet:H2O (1:2:3) (malic acid/betaine/water) and Ma:Bet:Pro:H2O (1:1:1:2) (malic acid/betaine/proline/water). Their phys. and thermodn. properties were studied, namely viscosity, elec. cond., and heat capacity. The viscosity and elec. cond. were detd. as a function of temp. and the correlation for the temp. dependence was obtained and discussed based on Arrhenius theory. The heat capacity for all eutectic systems was measured by differential scanning calorimetry (DSC) over a temp. range of 293.15-363.15 K. The ability of these NADES to reduce cellulose crystallinity was evaluated. Cellulose crystallinity after suspension in these NADES was studied by x-ray diffraction. Cellulose suspended in Ma/Bet/H2O (1:2:3) suffer the highest crystallinity redn. among the systems studied and was about of 20%.
- 43Craveiro, R.; Aroso, I.; Flammia, V.; Carvalho, T.; Viciosa, M.; Dionísio, M.; Barreiros, S.; Reis, R.; Duarte, A. R. C.; Paiva, A. Properties and thermal behavior of natural deep eutectic solvents. J. Mol. Liq. 2016, 215, 534– 540, DOI: 10.1016/j.molliq.2016.01.038[Crossref], [CAS], Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XovVGnsA%253D%253D&md5=cd995f4b423b7e9205d4269b3967392cProperties and thermal behavior of natural deep eutectic solventsCraveiro, R.; Aroso, I.; Flammia, V.; Carvalho, T.; Viciosa, M. T.; Dionisio, M.; Barreiros, S.; Reis, R. L.; Duarte, A. R. C.; Paiva, A.Journal of Molecular Liquids (2016), 215 (), 534-540CODEN: JMLIDT; ISSN:0167-7322. (Elsevier B.V.)Natural deep eutectic solvents (NADES) have shown to be promising sustainable media for a wide range of applications. Nonetheless, very limited data is available on the properties of these solvents. A more comprehensive body of data on NADES is required for a deeper understanding of these solvents at mol. level, which will undoubtedly foster the development of new applications. NADES based on choline chloride, org. acids, amino acids and sugars were prepd., and their d., thermal behavior, cond. and polarity were assessed, for different NADES compns. The NADES studied can be stable up to 170 °C, depending on their compn. The thermal characterization revealed that all the NADES are glass formers and some, after water removal, exhibit crystallinity. The morphol. characterization of the crystallizable materials was performed using polarized optical microscopy which also provided evidence of homogeneity/phase sepn. The cond. of the NADES was also assessed from 0 to 40 °C. The more polar, org. acid-based NADES presented the highest conductivities. The cond. dependence on temp. was well described by the Vogel-Fulcher-Tammann equation for some of the NADES studied.
- 44D’Agostino, C.; Harris, R. C.; Abbott, A. P.; Gladden, L. F.; Mantle, M. D. Molecular motion and ion diffusion in choline chloride based deep eutectic solvents studied by 1 H pulsed field gradient NMR spectroscopy. Phys. Chem. Chem. Phys. 2011, 13 (48), 21383– 21391, DOI: 10.1039/c1cp22554e[Crossref], [PubMed], [CAS], Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFeru7fO&md5=73dd737a1d32443513ef41074fcabbd6Molecular motion and ion diffusion in choline chloride based deep eutectic solvents studied by 1H pulsed field gradient NMR spectroscopyD'Agostino, Carmine; Harris, Robert C.; Abbott, Andrew P.; Gladden, Lynn F.; Mantle, Mick D.Physical Chemistry Chemical Physics (2011), 13 (48), 21383-21391CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Deep Eutectic Solvents (DESs) are a novel class of solvents with potential industrial applications in sepn. processes, chem. reactions, metal recovery and metal finishing processes such as electrodeposition and electropolishing. Macroscopic phys. properties such as viscosity, cond., eutectic compn. and surface tension are already available for several DESs, but the microscopic transport properties for this class of compds. are not well understood and the literature lacks exptl. data that could give a better insight into the understanding of such properties. This paper presents the first pulsed field gradient NMR (PFG-NMR) study of DESs. Several choline chloride based DESs were chosen as exptl. samples, each of them with a different assocd. hydrogen bond donor. The mol. equil. self-diffusion coeff. of both the choline cation and hydrogen bond donor was probed using a std. stimulated echo PFG-NMR pulse sequence. The increasing temp. leads to a weaker interaction between the choline cation and the correspondent hydrogen bond donor. The self-diffusion coeffs. of the samples obey an Arrhenius law temp.-dependence, with values of self-diffusivity in the range of [10-10-10-13 m2 s-1]. The results also highlight that the mol. structure of the hydrogen bond donor can greatly affect the mobility of the whole system. While for ethaline, glyceline and reline the choline cation diffuses slower than the assocd. hydrogen bond donor, reflecting the trend of mol. size and mol. wt., the opposite behavior is obsd. for maline, in which the hydrogen bond donor, i.e. malonic acid, diffuses slower than the choline cation, with self-diffusion coeffs. values of the order of 10-13 m2 s-1 at room temp., which are remarkably low values for a liq. This is believed to be due to the formation of extensive dimer chains between malonic acid mols., which restricts the mobility of the whole system at low temp. (<30 °C), with malonic acid and choline chloride having almost identical diffusivity values. Diffusion and viscosity data were combined together to gain insights into the diffusion mechanism, which is the same as for ionic liqs. with discrete anions.
- 45Aroso, I. M.; Paiva, A.; Reis, R. L.; Duarte, A. R. C. Natural deep eutectic solvents from choline chloride and betaine–Physicochemical properties. J. Mol. Liq. 2017, 241, 654– 661, DOI: 10.1016/j.molliq.2017.06.051[Crossref], [CAS], Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVChsLfP&md5=46a512a98ee7daf0b1327984eb1ee47fNatural deep eutectic solvents from choline chloride and betaine - Physicochemical propertiesAroso, Ivo M.; Paiva, Alexandre; Reis, Rui L.; Duarte, Ana Rita C.Journal of Molecular Liquids (2017), 241 (), 654-661CODEN: JMLIDT; ISSN:0167-7322. (Elsevier B.V.)The prepn. of natural deep eutectic solvents (NADESs) from cheap and readily available raw materials is reported. In this work, we have considered mixts. of choline chloride (CC) or betaine (Bet) with 3 sugar mols. (glucose (Glu), xylose (Xyl) and sucrose (Suc)) and 2 carboxylic acids (citric (CA) and tartaric (Tart) acids). The formation of NADESs was investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The CC mixts. give origin to NADESs for 1:1 M ratio with the sugar mols. and for 2:1, 1:1 and 1:2 with the carboxylic acids, while Bet mixts. only formed NADES with the carboxylic acids. The effect of water content (up to 5% (wt.%)) and temp. in cond. and rheol. were characterized. The NADESs were found to be non-thixotropic, Newtonian liqs. with high viscosity, decreasing with increasing temp. and water content. The cond. is limited by charge carrier mobility, thus increasing with water content and temp.
- 46Passos, H.; Tavares, D. J.; Ferreira, A. M.; Freire, M. G.; Coutinho, J. o. A. Are aqueous biphasic systems composed of deep eutectic solvents ternary or quaternary systems?. ACS Sustainable Chem. Eng. 2016, 4 (5), 2881– 2886, DOI: 10.1021/acssuschemeng.6b00485[ACS Full Text], [CAS], Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xls1KisbY%253D&md5=6a1c4e540c1c2ca0053cd3b4b0c19a78Are Aqueous Biphasic Systems Composed of Deep Eutectic Solvents Ternary or Quaternary Systems?Passos, Helena; Tavares, Daniel J. P.; Ferreira, Ana M.; Freire, Mara G.; Coutinho, Joao A. P.ACS Sustainable Chemistry & Engineering (2016), 4 (5), 2881-2886CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Deep eutectic solvents (DES) have emerged in the past few years as a new class of solvents with promising applications in several fields. In the present work, the application of DES (formed by binary mixts. of cholinium chloride and carboxylic acids or urea) as phase-forming components of aq. biphasic systems (ABS) is investigated. The mechanisms assocd. with the phases demixing of ABS composed of DES, as well as the DES stability in aq. solns., are investigated to address the crit. question whether DES-based ABS are in fact ternary or quaternary mixts. The DES integrity is destroyed in ABS by the disruption of the hydrogen-bonding interactions of the complex (a result of the isolated components preferential solvation by water), and as confirmed by a nonstoichiometric partition of the DES components between the coexisting phases. As a result, there are no "real" DES-based ABS; instead, there is the formation of ABS composed of four components, where the carboxylic acid used as the hydrogen-bond donor species seems to act as an additive. Finally, these ABS have an outstanding potential to be used in extn. processes, as it is here demonstrated with the complete sepn. of two dyes. However, the volatile nature of short chain carboxylic acids and the nonstoichiometric partition of the DES components in ABS make the development of recovery and recycling steps more difficult to accomplish.
- 47Yadav, A.; Pandey, S. Densities and viscosities of (choline chloride+ urea) deep eutectic solvent and its aqueous mixtures in the temperature range 293.15 to 363.15 K. J. Chem. Eng. Data 2014, 59 (7), 2221– 2229, DOI: 10.1021/je5001796[ACS Full Text], [CAS], Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXps1Kls7w%253D&md5=2529220f983049b3a020918bc2dd95bfDensities and Viscosities of (Choline Chloride + Urea) Deep Eutectic Solvent and Its Aqueous Mixtures in the Temperature Range 293.15 K to 363.15 KYadav, Anita; Pandey, SiddharthJournal of Chemical & Engineering Data (2014), 59 (7), 2221-2229CODEN: JCEAAX; ISSN:0021-9568. (American Chemical Society)Deep eutectic solvents (DESs) have been regarded as one of the most promising environmentally benign and cost-effective alternatives to conventional ionic liqs. and volatile org. solvents. Aq. mixts. of DESs have the potential to afford modified properties for specific applications. Densities and dynamic viscosities of a common and popular DES composed of choline chloride and urea in 1:2 molar ratio, named reline, and its aq. mixts. in the temp. range 293.15 K to 363.15 K are reported. A decrease in d. with increasing temp. is found to follow a quadratic expression. Excess molar volumes of the aq. mixts. of reline are found to be neg. at all temps. and compns. The abs. excess molar volume is found to decrease, in general, as the temp. is increased from 293.15 K to 323.15 K. For temps. above 323.15 K, the excess molar volume does not change much with further increase in temp. to 363.15 K. The temp. dependence of dynamic viscosity of aq. mixts. of reline in the temp. range 293.15 K to 363.15 K at all compns. is found to be better described by a Vogel-Fulcher-Tamman (VFT) model as opposed to an Arrhenius expression. Excess logarithmic viscosities for aq. mixts. of reline are found to be neg. at most temps. and compns.; however, they become pos. at 353.15 K and 363.15 K. The excess logarithmic viscosities of aq. reline mixts. are in Stark contrast to that reported for aq. mixts. of DES glyceline, composed of choline chloride and glycerol in the same mole ratio, where the excess logarithmic viscosities are pos. Facile interstitial accommodation of water within H-bonded reline network as opposed to formation of extensive H-bonding is proposed to be the reason for this exptl. observation. The important role of the H-bond donor as a constituent of DES is amply highlighted as it controls the interactions present in a DES and its aq. mixts.
- 48Abbott, A. P.; Ahmed, E. I.; Harris, R. C.; Ryder, K. S. Evaluating water miscible deep eutectic solvents (DESs) and ionic liquids as potential lubricants. Green Chem. 2014, 16 (9), 4156– 4161, DOI: 10.1039/C4GC00952E[Crossref], [CAS], Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVGjs7nO&md5=8a52073321744b382abc17414a5819c4Evaluating water miscible deep eutectic solvents (DESs) and ionic liquids as potential lubricantsAbbott, Andrew P.; Ahmed, Essa I.; Harris, Robert C.; Ryder, Karl S.Green Chemistry (2014), 16 (9), 4156-4161CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Although mineral oils are commonly used as lubricants their emission particularly in marine environments can cause significant impact. In the current study the properties of water miscible deep eutectic solvents and ionic liqs. are compared with a typical mineral base oil to ascertain their efficacy for potential marine lubricants. The environmental compatibility of some of the liqs., particularly choline chloride and glycerol, makes it an interesting potential base lubricant. Surprisingly some DESs showed very low corrosion rates with steel, nickel and aluminum even when the liqs. contained water. This is a surprising result given that the chloride ion concn. is approx. 5 mol dm-3.
- 49AlOmar, M. K.; Hayyan, M.; Alsaadi, M. A.; Akib, S.; Hayyan, A.; Hashim, M. A. Glycerol-based deep eutectic solvents: physical properties. J. Mol. Liq. 2016, 215, 98– 103, DOI: 10.1016/j.molliq.2015.11.032[Crossref], [CAS], Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvFKgsrjM&md5=7faef94e14f157fd449341aa93c8a802Glycerol-based deep eutectic solvents: Physical propertiesAlOmar, Mohamed Khalid; Hayyan, Maan; Alsaadi, Mohammed Abdulhakim; Akib, Shatirah; Hayyan, Adeeb; Hashim, Mohd AliJournal of Molecular Liquids (2016), 215 (), 98-103CODEN: JMLIDT; ISSN:0167-7322. (Elsevier B.V.)Deep eutectic solvents (DESs) have been used in many industrial applications. DES is a mixt. of a salt and a hydrogen bond donor (HBD). In this study, 70 DESs were synthesized successfully based on glycerol (Gly) as the HBD with different phosphonium and ammonium salts, namely Me tri-Ph phosphonium bromide (MTPB), benzyl tri-Ph phosphonium chloride (BTPC), allyl tri-Ph phosphonium bromide (ATPB), choline chloride (ChCl), N,N-diethylethanolammonium chloride (DAC), and tetra-n-butylammonium bromide (TBAB). The DESs were prepd. using different molar ratios of the HBD to the salts. The f.p. of each DES was detd. using Differential Scanning Calorimetry (DSC). The phys. properties of these DESs, including d., viscosity, cond., and surface tension, were investigated as functions of temp. In addn., the functional groups were analyzed utilizing Fourier transform IR (FTIR) spectroscopy. It is worth noting that these systems have a wide variety of phys. properties, which implies that these DESs would be suitable for diverse applications.
- 50Jeong, K. M.; Lee, M. S.; Nam, M. W.; Zhao, J.; Jin, Y.; Lee, D.-K.; Kwon, S. W.; Jeong, J. H.; Lee, J. Tailoring and recycling of deep eutectic solvents as sustainable and efficient extraction media. Journal of Chromatography A 2015, 1424, 10– 17, DOI: 10.1016/j.chroma.2015.10.083[Crossref], [PubMed], [CAS], Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslKkt7rF&md5=86b657d59a24245771f0b79561a489a5Tailoring and recycling of deep eutectic solvents as sustainable and efficient extraction mediaJeong, Kyung Min; Lee, Min Sang; Nam, Min Woo; Zhao, Jing; Jin, Yan; Lee, Dong-Kyu; Kwon, Sung Won; Jeong, Ji Hoon; Lee, JeongmiJournal of Chromatography A (2015), 1424 (), 10-17CODEN: JCRAEY; ISSN:0021-9673. (Elsevier B.V.)The present study demonstrates that deep eutectic solvents (DESs) with the highest extractability can be designed by combining effective DES components from screening diverse DESs. The extn. of polar ginseng saponins from white ginseng was used as a way to demonstrate the tuneability as well as recyclability of DESs. A newly designed ternary DES (GPS-5) composed of glycerol, L-proline, and sucrose at 9:4:1 was used as a sustainable and efficient extn. medium. Based on the anti-tumor activity on HCT-116 cancer cells, it was confirmed that GPS-5 was merely an extn. solvent with no influence of the bioactivity of the ginsenosides extd. Excellent recovery of the extd. saponins was easily achieved through solid-phase extn. (SPE). Recycling of the DES was accomplished by simple freeze-drying of the washed solns. from the SPE. The extn. efficiencies of the DESs recycled once, twice, and thrice were 92%, 85%, and 83% of that of the freshly synthesized solvent.
- 51AlOmar, M. K.; Alsaadi, M. A.; Hayyan, M.; Akib, S.; Ibrahim, R. K.; Hashim, M. A. Lead removal from water by choline chloride based deep eutectic solvents functionalized carbon nanotubes. J. Mol. Liq. 2016, 222, 883– 894, DOI: 10.1016/j.molliq.2016.07.074
- 52Zhekenov, T.; Toksanbayev, N.; Kazakbayeva, Z.; Shah, D.; Mjalli, F. S. Formation of type III Deep Eutectic Solvents and effect of water on their intermolecular interactions. Fluid Phase Equilib. 2017, 441, 43– 48, DOI: 10.1016/j.fluid.2017.01.022[Crossref], [CAS], Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1equr0%253D&md5=7f756b90831e7fce99c4cd1aab56037aFormation of type III Deep Eutectic Solvents and effect of water on their intermolecular interactionsZhekenov, Temirlan; Toksanbayev, Nursultan; Kazakbayeva, Zhanna; Shah, Dhawal; Mjalli, Farouq S.Fluid Phase Equilibria (2017), 441 (), 43-48CODEN: FPEQDT; ISSN:0378-3812. (Elsevier B.V.)Several novel applications of Deep Eutectic Solvents (DESs) have emerged recently. With a growing interest in the field, there is an urge to understand formation and functioning of these solvents at mol. level, which in turn would assist in further designing of DESs. We herein performed mol. dynamics simulations on three of the commonly used type III DES, viz, reline, ethaline, and glyceline, which are mixts. of urea, ethylene glycol, and glycerol with choline chloride at eutectic compn. Our results explain the role of inter-mol. and intra-mol. hydrogen bonding and energies on formation of these DESs. Furthermore, the ability of these DESs to be altered in a desired way through a simple addn. of water makes it versatile soln. for several other applications. Hence, simulations are also performed on the aq. DES solns., which reveal the effect of water on intermol. network of interaction existing within these DESs.
- 53Cláudio, A. F. M.; Neves, M. C.; Shimizu, K.; Canongia Lopes, J. N.; Freire, M. G.; Coutinho, J. A. The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropes. Green Chem. 2015, 17, 3948– 3963, DOI: 10.1039/C5GC00712G[Crossref], [PubMed], [CAS], Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXoslCku7s%253D&md5=07ca34afff9fee7ac3b86eb0500989a3The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropesClaudio, Ana Filipa M.; Neves, Marcia C.; Shimizu, Karina; Canongia Lopes, Jose N.; Freire, Mara G.; Coutinho, Joao A. P.Green Chemistry (2015), 17 (7), 3948-3963CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Hydrotropes are compds. able to enhance the soly. of hydrophobic substances in aq. media and therefore are widely used in the formulation of drugs, cleaning and personal care products. Ionic liqs. are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the soly. of biomols. in water. The effects of the ionic liq. chem. structures, their concn. and the temp. on the soly. of two model biomols., vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The soly. of these two biomols. was studied in the entire compn. range, from pure water to pure ionic liqs., and an increase in the soly. of up to 40-fold was obsd., confirming the potential of ionic liqs. to act as hydrotropes. Using dynamic light scattering, NMR and mol. dynamics simulations, it was possible to infer that the enhanced soly. of the biomol. in the IL aq. solns. is related to the formation of ionic-liq.-biomols. aggregates. Finally, hydrotropy induced by ionic liqs. can be used to recover solutes from aq. media by pptn., simply by using water as an anti-solvent. The results reported here have a significant impact on the understanding of the role of ionic liq. aq. solns. in the extn. of value-added compds. from biomass as well as in the design of novel processes for their recovery from aq. media.
- 54Cláudio, A. F. M.; Neves, M. C.; Shimizu, K.; Canongia Lopes, J. N.; Freire, M. G.; Coutinho, J. A. The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropes. Green Chem. 2015, 17 (7), 3948– 3963, DOI: 10.1039/C5GC00712G[Crossref], [PubMed], [CAS], Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXoslCku7s%253D&md5=07ca34afff9fee7ac3b86eb0500989a3The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropesClaudio, Ana Filipa M.; Neves, Marcia C.; Shimizu, Karina; Canongia Lopes, Jose N.; Freire, Mara G.; Coutinho, Joao A. P.Green Chemistry (2015), 17 (7), 3948-3963CODEN: GRCHFJ; ISSN:1463-9262. (Royal Society of Chemistry)Hydrotropes are compds. able to enhance the soly. of hydrophobic substances in aq. media and therefore are widely used in the formulation of drugs, cleaning and personal care products. Ionic liqs. are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the soly. of biomols. in water. The effects of the ionic liq. chem. structures, their concn. and the temp. on the soly. of two model biomols., vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The soly. of these two biomols. was studied in the entire compn. range, from pure water to pure ionic liqs., and an increase in the soly. of up to 40-fold was obsd., confirming the potential of ionic liqs. to act as hydrotropes. Using dynamic light scattering, NMR and mol. dynamics simulations, it was possible to infer that the enhanced soly. of the biomol. in the IL aq. solns. is related to the formation of ionic-liq.-biomols. aggregates. Finally, hydrotropy induced by ionic liqs. can be used to recover solutes from aq. media by pptn., simply by using water as an anti-solvent. The results reported here have a significant impact on the understanding of the role of ionic liq. aq. solns. in the extn. of value-added compds. from biomass as well as in the design of novel processes for their recovery from aq. media.
- 55Sintra, T. E.; Shimizu, K.; Ventura, S. P.; Shimizu, S.; Canongia Lopes, J. N.; Coutinho, J. A. Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes. Phys. Chem. Chem. Phys. 2018, 20 (3), 2094– 2103, DOI: 10.1039/C7CP07569C[Crossref], [PubMed], [CAS], Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitVShsr3O&md5=cead2b4e2adb88454484b11548164dfeEnhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropesSintra, T. E.; Shimizu, K.; Ventura, S. P. M.; Shimizu, S.; Canongia Lopes, J. N.; Coutinho, J. A. P.Physical Chemistry Chemical Physics (2018), 20 (3), 2094-2103CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The therapeutic effectiveness of a drug largely depends on its bioavailability, and thus ultimately on its aq. soly. Hydrotropes are compds. able to enhance the soly. of hydrophobic substances in aq. media and therefore are extensively used in the formulation of drugs and personal care products. Recently, some ionic liqs. were shown to display a strong ability to enhance the soly. of biomols. through hydrotropy. In this work, the impact of the ionic liq. chem. structures and their concn. on the soly. of ibuprofen was evaluated and compared with the performance of conventional hydrotropes. The results obtained clearly evidence the exceptional capacity of ionic liqs. to enhance the soly. of ibuprofen. [C4C1i.m.][SCN] and [C4C1i.m.][N(CN)2] seem to be the most promising ionic liqs. for ibuprofen solubilization, where an increase in the soly. of 60- and 120-fold was obsd. with ionic liq. concns. of circa 1 mol kg-1, resp. Dynamic light scattering and mol. dynamics simulations were used to investigate the mechanism of the IL-mediated drug soly. and the results obtained indicate that the structure of aq. solns. of ionic liqs. and the role it plays in the formation of ionic liq.-drug aggregates is the mechanism driving the hydrotropic dissoln.
- 56Soares, B.; Tavares, D. J.; Amaral, J. L.; Silvestre, A. J.; Freire, C. S.; Coutinho, J. A. Enhanced solubility of lignin monomeric model compounds and technical lignins in aqueous solutions of deep eutectic solvents. ACS Sustainable Chem. Eng. 2017, 5 (5), 4056– 4065, DOI: 10.1021/acssuschemeng.7b00053[ACS Full Text], [CAS], Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXls1SmsLg%253D&md5=dc8d99eaacda307e165c5b7b5ddb595dEnhanced Solubility of Lignin Monomeric Model Compounds and Technical Lignins in Aqueous Solutions of Deep Eutectic SolventsSoares, Belinda; Tavares, Daniel J. P.; Amaral, Jose Luis; Silvestre, Armando J. D.; Freire, Carmen S. R.; Coutinho, Joao A. P.ACS Sustainable Chemistry & Engineering (2017), 5 (5), 4056-4065CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)The solubilities of lignin monomeric model compds. and tech. lignins (organosolv and kraft) in aq. solns. of several deep eutectic solvents (DES) were here investigated. The effects of DES components, temp. and concn., were evaluated. The results show aq. solns. of DES to be a new class of powerful solvents where both the hydrogen bond donor and the hydrogen bond acceptor synergistically contribute to increase the soly. of the lignin model compds., being the dispersive interactions with lignin the driving force behind the good performance of DES. The soly. of the model compds. is shown to be a good guide for the selection of the best DES for tech. lignins soly., leading to identifying an aq. soln. of DES allowing a soly. enhancement of 1181.7 ± 29.2 and 228.5 ± 9.7 times for kraft and organosolv lignin, resp. The results indicate that the soly. of the tech. lignins and their monomers in DES aq. solns. is driven by a hydrotropic mechanism, here confirmed by dynamic light scattering that is here obsd. for the first time with DES as hydrotropes.
- 57Mano, F.; Aroso, I. M.; Barreiros, S.; Borges, J. o. P.; Reis, R. L.; Duarte, A. R. C.; Paiva, A. Production of poly (vinyl alcohol)(PVA) fibers with encapsulated natural deep eutectic solvent (NADES) using electrospinning. ACS Sustainable Chem. Eng. 2015, 3 (10), 2504– 2509, DOI: 10.1021/acssuschemeng.5b00613[ACS Full Text], [CAS], Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFWhs7%252FO&md5=4078991f8d30de7c5cfa5bdc94b3805bProduction of poly(vinyl alcohol) (PVA) fibers with encapsulated natural deep eutectic solvent (NADES) using electrospinningMano, Francisca; Aroso, Ivo M.; Barreiros, Susana; Borges, Joao Paulo; Reis, Rui L.; Duarte, Ana Rita C.; Paiva, AlexandreACS Sustainable Chemistry & Engineering (2015), 3 (10), 2504-2509CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Functionalized electrospun fibers are of great interest for biomedical applications such as in the design of drug delivery systems. Nevertheless, in some cases the mols. of interest have poor soly. in water or have high melting temps. These drawbacks can be overcome using deep eutectic solvents. In this work, poly(vinyl alc.) (PVA), a common biodegradable biopolymer, was used to produce new functionalized fibers with the eutectic mixt. choline chloride:citric acid in a molar ratio of (1:1) ChCl:CA (1:1), which was used as a model system. Fibers were produced from an aq. soln. with 7.8% (w/v) and 9.8% (w/v) of 95% hydrolyzed PVA and a 2% (vol./vol.) of ChCl:CA (1:1). Smooth, uniform fibers with an av. diam. of 0.4 μm were obtained with a content of 19.8 wt % of ChCl:CA (1:1) encapsulated.
- 58Yong, C. S.; Jung, S. H.; Rhee, J.-D.; Choi, H.-G.; Lee, B.-J.; Kim, D.-C.; Choi, Y. W.; Kim, C.-K. Improved solubility and in vitro dissolution of Ibuprofen from poloxamer gel using eutectic mixture with menthol. Drug Delivery 2003, 10 (3), 179– 183, DOI: 10.1080/713840406[Crossref], [PubMed], [CAS], Google Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmslClsrc%253D&md5=faf7f2b8213001218b84573818fa804bImproved Solubility and In Vitro Dissolution of Ibuprofen from Poloxamer Gel Using Eutectic Mixture with MentholYong, Chul Soon; Jung, Se Hyun; Rhee, Jong-Dal; Choi, Han-Gon; Lee, Beom-Jin; Kim, Dong-Chool; Choi, Young Wook; Kim, Chong-KookDrug Delivery (2003), 10 (3), 179-183CODEN: DDELEB; ISSN:1071-7544. (Taylor & Francis, Inc.)To improve the soly. and in vitro dissoln. of poorly water-sol. ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aq. soly. of ibuprofen were investigated. The dissoln. study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, the soly. of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6, followed by an abrupt decrease in soly. above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutectic mixt. with 6 parts of menthol. In the presence of poloxamer 188, the solns. with the same ratio of menthol to ibuprofen showed abrupt increase in the soly. of ibuprofen. Furthermore, the soln. with ratio of 4:6 showed more than 2.5- and 6-fold increase in the soly. of ibuprofen compared with that without poloxamer and that without menthol, resp. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the max. soly. of ibuprofen, 1.2 mg/mL. Menthol improved the dissoln. rates of ibuprofen from poloxamer gels. Dissoln. mechanism showed that the dissoln. rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixt. with menthol, which gave the improved soly. and dissoln. of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.
- 59Hayyan, M.; Mbous, Y. P.; Looi, C. Y.; Wong, W. F.; Hayyan, A.; Salleh, Z.; Mohd-Ali, O. Natural deep eutectic solvents: cytotoxic profile. SpringerPlus 2016, 5 (1), 913, DOI: 10.1186/s40064-016-2575-9[Crossref], [PubMed], [CAS], Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7nslGmtA%253D%253D&md5=c4aabcb10c8ceda288a8dd72b93a637aNatural deep eutectic solvents: cytotoxic profileHayyan Maan; Mbous Yves Paul; Salleh Zulhaziman; Looi Chung Yeng; Wong Won Fen; Hayyan Adeeb; Mohd-Ali OzairSpringerPlus (2016), 5 (1), 913 ISSN:2193-1801.The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures.
- 60Juneidi, I.; Hayyan, M.; Hashim, M. A. Evaluation of toxicity and biodegradability for cholinium-based deep eutectic solvents. RSC Adv. 2015, 5 (102), 83636– 83647, DOI: 10.1039/C5RA12425E[Crossref], [CAS], Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFGkurbM&md5=8bbeafa30ad9e4b1096df73eff95f7a8Evaluation of toxicity and biodegradability for cholinium-based deep eutectic solventsJuneidi, Ibrahim; Hayyan, Maan; Hashim, Mohd AliRSC Advances (2015), 5 (102), 83636-83647CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)This study presented the toxicol. and biodegradable assessment of different cholinium-based deep eutectic solvents (DESs). They were formed from choline chloride (ChCl) and N,N-di-Et ethanol ammonium chloride (EAC) as salts and four hydrogen bond donors, namely ethylene glycol (EG), glycerol (Gly), urea (U), malonic acid (MA), in addn. to a metal salt, i.e. zinc chloride (ZnCl2), and a hydrated metal salt, i.e. zinc nitrate hexahydrate (ZnN). The toxicity towards Aspergillus niger of pure and aq. DESs was evaluated by observing the inhibition zone using an agar well diffusion assay, and the min. inhibition concn. (MIC) using a broth diln. assay, resp. The MIC values of the DESs varied from 1 to 650 mg mL-1, whereas the inhibition zones changed according to the DES dose amt. Another test for acute toxicity was performed by evaluating the lethal concn. at 50% (LC50) of the same DESs on Cyprinus carpio fish. The LC50 of DESs ranged from practically harmless (e.g. ChCl : EG-DESaq) to highly toxic (e.g. EAC : ZnCl2-DESaq). The toxicity profile of the DESs depended on their concn., type of individual components, and interaction with living organisms. Moreover, the DESs recorded higher toxicity compared to their individual components on fungi. However, lower toxicity was found for the DESs tested on Cyprinus carpio. Types I (org. salts and metal salt) and II (org. salt and hydrate metal salt) eutectics exhibited significantly higher toxicity than type III (org. salts and HBD). This was due to the presence of the innate toxicity of the metal salts. The biodegradability was appraised by a closed bottle test in which all the DESs were found to be readily biodegradable. To the best of our knowledge, there are no previous studies reported regarding the toxicity of cholinium-based DESs on freshwater fish or fungi and the biodegradability of EAC-based DESs. Therefore, this investigation can be used as a benchmark for future development of DESs.
- 61Radošević, K.; Cvjetko Bubalo, M. C.; Gaurina Srček, V. G.; Grgas, D.; Landeka Dragičević, T. L.; Radojčić Redovniković, I. R. Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solvents. Ecotoxicol. Environ. Saf. 2015, 112, 46– 53, DOI: 10.1016/j.ecoenv.2014.09.034[Crossref], [PubMed], [CAS], Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVGitrbE&md5=8d768400367b3c378f845636e00da992Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solventsRadosevic, Kristina; Cvjetko Bubalo, Marina; Gaurina Srcek, Visnje; Grgas, Dijana; Landeka Dragicevic, Tibela; Radojcic Redovnikovic, IvanaEcotoxicology and Environmental Safety (2015), 112 (), 46-53CODEN: EESADV; ISSN:0147-6513. (Elsevier B.V.)Deep eutectic solvents (DESs) have been dramatically expanding in popularity as a new generation of environmentally friendly solvents with possible applications in various industrial fields, but their ecol. footprint has not yet been thoroughly investigated. In the present study, three choline chloride-based DESs with glucose, glycerol and oxalic acid as hydrogen bond donors were evaluated for in vitro toxicity using fish and human cell line, phytotoxicity using wheat and biodegradability using wastewater microorganisms through closed bottle test. Obtained in vitro toxicity data on cell lines indicate that choline chloride: glucose and choline chloride:glycerol possess low cytotoxicity (EC50>10 mM for both cell lines) while choline chloride:oxalic acid possess moderate cytotoxicity (EC50 value 1.64 mM and 4.19 mM for fish and human cell line, resp.). Results on phytotoxicity imply that tested DESs are non-toxic with seed germination EC50 values higher than 5000 mg L-1. All tested DESs were classified as'readily biodegradable' based on their high levels of mineralization (68-96%). These findings indicate that DESs have a green profile and a good prospect for a wider use in the field of green technologies.
- 62Radošević, K.; Ćanak, I.; Panić, M.; Markov, K.; Bubalo, M. C.; Frece, J.; Srček, V. G.; Redovniković, I. R. Antimicrobial, cytotoxic and antioxidative evaluation of natural deep eutectic solvents. Environ. Sci. Pollut. Res. 2018, 25 (14), 14188– 14196, DOI: 10.1007/s11356-018-1669-z[Crossref], [PubMed], [CAS], Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkslWktLg%253D&md5=6eb369173ee63b1998ea37ef993af0f9Antimicrobial, cytotoxic and antioxidative evaluation of natural deep eutectic solventsRadosevic, Kristina; Canak, Iva; Panic, Manuela; Markov, Ksenija; Bubalo, Marina Cvjetko; Frece, Jadranka; Srcek, Visnja Gaurina; Redovnikovic, Ivana RadojcicEnvironmental Science and Pollution Research (2018), 25 (14), 14188-14196CODEN: ESPLEC; ISSN:0944-1344. (Springer)Natural deep eutectic solvents (NADES) are a new generation of green solvents. They are mixts. of two or three compds. such as choline chloride as a cationic salt and alcs., acids, amides, amines or sugars as hydrogen-bond donors. Although the majority of NADES' components are of natural origin and therefore NADES are often presumed to be non-toxic, the evaluation of their toxicity and biodegradability must accompany the research on their synthesis and application. Therefore, the aim of this work was to investigate the effect of ten synthesized NADES towards bacteria (i.e., Escherichia coli, Proteus mirabilis, Salmonella typhimurium, Pseudomonas aeruginosa, Staphylococcus aureus), yeast (i.e., Candida albicans) and human cell lines (i.e., HeLa, MCF-7 and HEK293T). In addn., oxygen radical absorbance capacity (ORAC) method was used to det. the antioxidative activity of the tested NADES. Differences in toxicity response between microorganisms and cell lines were obsd., and only NADES that contained org. acid showed toxicity towards the test systems. Furthermore, the NADES contg. compds. that possess antioxidative activity also showed antioxidative activity. However, research whose primary purpose is the synthesis and application of NADES must be followed by an evaluation of their biol. properties (e.g., antimicrobial activity, toxicity towards animal cells and antioxidative or other biol. activity) to find the solvent with the best profile for wider industrial applications.
- 63Hou, C. T. New bioactive fatty acids. Asia Pac. J. Clin. Nutr. 2008, 17 (S1), 192– 195[PubMed], [CAS], Google Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtFymsrc%253D&md5=06356a55e22f0b25def4ae3be9ac31e1New bioactive fatty acidsHou, Ching T.Asia Pacific Journal of Clinical Nutrition (2008), 17 (Suppl. 1), 192-195CODEN: APJNFQ; ISSN:0964-7058. (HEC Press)A review. Many oxygenated fatty acids are bioactive compds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compds., 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) through 10-hydroxy-8-octadecenoic acid, and racinoleic acid to 7,10,12-trihydroxy-8-octadecenoic acid. DOD showed antibacterial activity including against food-borne pathogens. Bacillus megaterium ALA2 converted n-6 and n-3 PUFAs to many new oxygenated fatty acids. For example: linoleic acid was converted to 12,13-epoxy-9-octadecenoic acid and then to 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOA). From here, there are two bioconversion pathways. The major pathway is: 12,13-DHOA → 12,13,17-trihydroxy-9(S)-octadecenoic acid (THOA) → 12,17;13,17-diepoxy-16-hydroxy-9(Z)-octadecenoic acid (DEOA) → 7-hydroxy-DEOA. The minor pathway is: 12,13-DHOA → 12,13,16-THOA → 12-hydroxy-13,16-epoxy-9(Z)-octadecenoic acid. 12,13,17-THOA has anti-plant pathogenic fungal activity. The tetrahydrofuranyl moiety is known in anti cancer drugs. Strain ALA2 also converts other n-3 and n-6 PUFAs such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) to many new oxygenated unsatd. fatty acid products. All of these new products have high potential for antimicrobial agents or biomedical applications. We also screened 12 Mortierella fungal strains from the ARS Culture Collection for the prodn. of bioactive fatty acids such as dihomo-gama-linolenic acid (DGLA) and arachidonic acid. All of the strains tested produced AA and DGLA from glucose or glycerol. The top five AA producers (mg AA/g CDW) were in the following order: M. alpina > M. zychae > M. hygrophila > M. minutissima > M. parvispora. Both AA and DGLA are important natural precursors of a large family of prostaglandin and thromboxane groups.
- 64McKay, D. L.; Blumberg, J. B. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.). Phytother. Res. 2006, 20 (8), 619– 633, DOI: 10.1002/ptr.1936[Crossref], [PubMed], [CAS], Google Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xps1Sisro%253D&md5=d2c9bcda4e0e14a3e364ad6b642b8f18A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.)McKay, Diane L.; Blumberg, Jeffrey B.Phytotherapy Research (2006), 20 (8), 619-633CODEN: PHYREH; ISSN:0951-418X. (John Wiley & Sons Ltd.)A review. Peppermint (Mentha piperita L.) is one of the most widely consumed single ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant leaves, and the essential oil of peppermint are used in traditional medicines. Evidence-based research regarding the bioactivity of this herb is reviewed. The phenolic constituents of the leaves include rosmarinic acid and several flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile components of the essential oil are menthol and menthone. In vitro, peppermint has significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential. Human studies on the GI, respiratory tract and analgesic effects of peppermint oil and its constituents have been reported. Several clin. trials examg. the effects of peppermint oil on irritable bowel syndrome (IBS) symptoms have been conducted. However, human studies of peppermint leaf are limited and clin. trials of peppermint tea are absent. Adverse reactions to peppermint tea have not been reported, although caution has been urged for peppermint oil therapy in patients with GI reflux, hiatal hernia or kidney stones.
- 65Muniyan, R.; Gurunathan, J. Lauric acid and myristic acid from Allium sativum inhibit the growth of Mycobacterium tuberculosis H37Ra: in silico analysis reveals possible binding to protein kinase B. Pharm. Biol. 2016, 54 (12), 2814– 2821, DOI: 10.1080/13880209.2016.1184691[Crossref], [PubMed], [CAS], Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtVSrsrvE&md5=6e3b89732a449e0bdd16796357a6dae4Lauric acid and myristic acid from Allium sativum inhibit the growth of Mycobacterium tuberculosis H37Ra: in silico analysis reveals possible binding to protein kinase BMuniyan, Rajiniraja; Gurunathan, JayaramanPharmaceutical Biology (Abingdon, United Kingdom) (2016), 54 (12), 2814-2821CODEN: PHBIFC; ISSN:1388-0209. (Taylor & Francis Ltd.)The bulb of Allium sativum Linn (Alliaceae) has numerous medicinal values. Though the petroleum ether ext. of the bulb has shown to exhibit antimycobacterial activity, the phytochem.(s) responsible for this inhibitory activity is not known. To characterize the bioactive compds. in the petroleum ether ext. of Allium sativum (garlic) that inhibit the growth of Mycobacterium tuberculosis H37Ra. Bioactivity-guided fractionation was employed to isolate the bioactive compds. Antimycobacterial activity was evaluated by well-diffusion method and microplate alamar blue assay (MABA). IR spectroscopy, mass spectrometry and NMR spectroscopy were used to characterize the bioactive compds. Autodock was used to obtain information on mol. recognition, and mol. dynamics simulation was performed using GROMACS. The bioactive compds. that inhibited the growth of M. tuberculosis H37Ra were found to be lauric acid (LA) and myristic acid (MA). The minimal inhibitory concn. of LA and MA was found to be 22.2 and 66.7 μg/mL, resp. In silico anal. revealed that these fatty acids could bind at the cleft between the N-terminal and C-terminal lobes of the cytosolic domain of serine/threonine protein kinase B (PknB). The inhibition activity was dependent on the alkyl chain length of the fatty acid, and the amino acid residues involved in binding to fatty acid was found to be conserved across the Pkn family of proteins. The study indicates the possibility of using fatty acid derivs., involving Pkn family of proteins, to inhibit the signal transduction processes in M. tuberculosis.
- 66Barros, A. A.; Silva, J. M.; Craveiro, R.; Paiva, A.; Reis, R. L.; Duarte, A. R. C. Green solvents for enhanced impregnation processes in biomedicine. Current Opinion in Green and Sustainable Chemistry 2017, 5, 82– 87, DOI: 10.1016/j.cogsc.2017.03.014
- 67Kitahara, T.; Koyama, N.; Matsuda, J.; Aoyama, Y.; Hirakata, Y.; Kamihira, S.; Kohno, S.; Nakashima, M.; Sasaki, H. Antimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus. Biol. Pharm. Bull. 2004, 27 (9), 1321– 1326, DOI: 10.1248/bpb.27.1321[Crossref], [PubMed], [CAS], Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXptFWqsrs%253D&md5=5af1a49553a048f3cdf01a7a7ca9021cAntimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureusKitahara, Takashi; Koyama, Nao; Matsuda, Junichi; Aoyama, Yuko; Hirakata, Yoichi; Kamihira, Shimeru; Kohno, Shigeru; Nakashima, Mikiro; Sasaki, HitoshiBiological & Pharmaceutical Bulletin (2004), 27 (9), 1321-1326CODEN: BPBLEO; ISSN:0918-6158. (Pharmaceutical Society of Japan)The objective of this study was to investigate the antimicrobial activities of satd. fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of satd. fatty acids and fatty amines was detd. by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the satd. fatty acids, showed antimicrobial activity at 400 μg/mL against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concn. (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 μg/mL; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, resp. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 satd. fatty acids and 3 fatty amines was examd. in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of satd. fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, esp. in the case of insol. substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.
- 68Ouattara, B.; Simard, R. E.; Holley, R. A.; Piette, G. J.-P.; Bégin, A. Antibacterial activity of selected fatty acids and essential oils against six meat spoilage organisms. Int. J. Food Microbiol. 1997, 37 (2–3), 155– 162, DOI: 10.1016/S0168-1605(97)00070-6[Crossref], [PubMed], [CAS], Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmtl2jsbs%253D&md5=b0ef65b7ed8e6fce942c463a883295c6Antibacterial activity of selected fatty acids and essential oils against six meat spoilage organismsOuattara, Blaise; Simard, Ronald E.; Holley, Richard A.; Piette, Gabriel J. P.; Begin, AndreInternational Journal of Food Microbiology (1997), 37 (2,3), 155-162CODEN: IJFMDD; ISSN:0168-1605. (Elsevier)The antibacterial activity of selected fatty acids and essential oils was examd. against 2 gram-neg. (Pseudomonas fluorescens and Serratia liquefaciens), and 4 gram-pos. (Brochothrix thermosphacta, Carnobacterium piscicola, Lactobacillus curvatus, and Lactobacillus sake) bacteria involved in meat spoilage. Various amts. of each preservative were added to brain heart infusion or MRS agars, and the min. inhibitory concn. was detd. for each organism. Essential oils were analyzed by gas-liq. chromatog. to det. the concn. of selected components commonly found in spices. B. thermosphacta, P. fluorescens, and S. liquefaciens were not affected by fatty acids and generally overcame the inhibitory effect of essential oils after 24 h of exposure. Among the fatty acids, lauric and palmitoleic acids exhibited the greatest inhibitory effect with MICs of 250-500 μg/mL, while myristic, palmitic, stearic, and oleic acids were completely ineffective. For essential oils, clove, cinnamon, pimento, and rosemary were the most active. The 1/100 diln. of those oils inhibited ≥5 of the 6 tested organisms. A relation was found between the inhibitory effect of essential oils and the presence of eugenol and cinnamaldehyde.