Log Poct/SA Predicts the Thermoresponsive Behavior of P(DMA-co-RA) Statistical Copolymers
- Irem AkarIrem AkarSchool of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Irem Akar,
- Jeffrey C. FosterJeffrey C. FosterSchool of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Jeffrey C. Foster,
- Xiyue LengXiyue LengSchool of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Xiyue Leng,
- Amanda K. PearceAmanda K. PearceSchool of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Amanda K. Pearce,
- Robert T. Mathers*Robert T. Mathers*E-mail: [email protected]Department of Chemistry, Pennsylvania State University, New Kensington, Pennsylvania 15068, United StatesMore by Robert T. Mathers, and
- Rachel K. O’Reilly*Rachel K. O’Reilly*E-mail: [email protected]School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Rachel K. O’Reilly
Copyright © 2022 The Authors. Published by American Chemical Society
Abstract
Polymers that exhibit a lower critical solution temperature (LCST) have been of great interest for various biological applications such as drug or gene delivery, controlled release systems, and biosensing. Tuning the LCST behavior through control over polymer composition (e.g., upon copolymerization of monomers with different hydrophobicity) is a widely used method, as the phase transition is greatly affected by the hydrophilic/hydrophobic balance of the copolymers. However, the lack of a general method that relates copolymer hydrophobicity to their temperature response leads to exhaustive experiments when seeking to obtain polymers with desired properties. This is particularly challenging when the target copolymers are comprised of monomers that individually form nonresponsive homopolymers, that is, only when copolymerized do they display thermoresponsive behavior. In this study, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temperature (TCP). A series of statistical copolymers were synthesized based on hydrophilic N,N-dimethyl acrylamide (DMA) and hydrophobic alkyl acrylate monomers, and their hydrophobicity was compared using surface area-normalized octanol/water partition coefficients (Log Poct/SA). Interestingly, a correlation between the Log Poct/SA of the copolymers and their TCPs was observed for the P(DMA-co-RA) copolymers, which allowed TCP prediction of a demonstrative copolymer P(DMA-co-MMA). These results highlight the strong potential of this computational tool to improve the rational design of copolymers with desired temperature responses prior to synthesis.
“Smart” polymers that change their physical or chemical structures upon exposure to external stimuli such as light, pH, redox state, ultrasound, and temperature have been used extensively in a range of applications from biosensors to drug delivery systems. (1−5) Among these stimuli, temperature has been the most widely studied on account of its easy external applicability and the abundance of methods to tune thermoresponsive behavior within the desired range. (6) Thermoresponsive polymers display either a lower critical solution temperature (LCST) or an upper critical solution temperature (UCST) behavior in water, where they undergo structural changes and thus changes in their solubility upon heating up above or cooling down below a specific temperature, respectively. (3,7) In general, LCST-based systems are more preferable than UCST-based systems, particularly for biological applications, because of the high-temperature requirements of the latter. (8,9) In an LCST-based system, polymers are soluble below their LCST on account of strong interactions between polymer chains and the solvent (water); however, upon heating above a specific temperature, they undergo a phase transition where they become immiscible as a consequence of the weakening of the polymer–solvent interactions. (10)
It is desirable to be able to tune polymer LCST temperatures in order to suit the requirements of a particular application. Several methods have been studied toward this, such as changing the polymer molecular weight, hydrophobicity, or solution concentration. (11−16) In particular, tuning polymer hydrophobicity is an interesting strategy, as changes to overall hydrophobicity can readily modulate polymer–solvent interactions. (17) For example, Sumerlin and Vogt reported a method to decrease poly(N-isopropylacrylamide) (PNIPAM) LCST by moving from a linear to branched architecture, which increased polymer hydrophobicity through an increase in hydrophobic end groups. They confirmed that the hydrophobic end groups had the greatest impact on polymer LCST (rather than branching) by showing that polymer LCSTs increased significantly upon removal of the end groups. (18) Another route to tune polymer hydrophobicity is via copolymerization of a high LCST monomer with monomers of lower LCST. (19−24) For example, Lutz and Hoth reported copolymers of oligoethylene glycol monomethyl ether methacrylate (OEGMA) and diethylene glycol methacrylate (DEGMA) where they showed that the cloud point temperature (TCP) of the copolymers decreased from 90 to 28 °C as the molar quantity of DEGMA increased. (25) Additionally, previous work has shown linear correlations of TCP to hydrophobic mole fraction for copolymers of N-isopropylacrylamide (NiPA) and N-isopropylmethacrylamide (NiPMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA) and methyl methacrylate (MMA); (26,27) however, nonlinear TCP behavior has also been reported. (28) These inconsistencies could be due to differences in experimentation, chain end effects, or the type of polymerization employed. Thus, despite some work in the field to date, there are still fundamental gaps in our understanding of how LCST behavior can be tuned using copolymerization, such as isolating the effect of polymer structure and specific monomer chemistry. Specifically, the ability to generate overall design rules for achieving desired thermoresponsive behavior would contribute essential knowledge toward the design of copolymers for many given applications.
Hydrophobicity is one of the most important phenomena that has been investigated to explain polymer behavior in bulk or solution; however, the influence of polymer hydrophobicity on solution behavior from a theoretical perspective is relatively underexplored. (29) In medicinal chemistry, hydrophobicity of small molecules can be quantified via octanol–water partition coefficient (Log Poct) calculations, which describes the partitioning of a substance between octanol and water. (30,31) Inspired by this, Mathers and co-workers sought to adapt this method to computationally predict the hydrophobicity of macromolecules, developing a surface-area-normalized method (Log Poct/SA). Subsequent studies have shown that the addition of the surface area normalization improves the predictive power for polymers compared to standard small molecule methods. (32−36)
In our previous study we were interested in correlating the polymer hydrophobicity to its LCST behavior by investigating the relationship between the Log Poct/SA of a series of statistical copolymers of hydrophilic OEGMA with different hydrophobic methacrylate comonomers (Figure 1A). We aimed to determine a correlation between a polymer hydrophobicity and its TCP, thereby reducing the experimental workload by predicting the TCP of new copolymers prior to synthesis. However, we found that the strongest influence of the copolymer TCP was the hydrophobic comonomer mol %, that is, the grafting density rather than the chemical identity of the comonomers, as the brushy nature of the OEGMA dominated the phase transition. (21) This finding inspired us to investigate whether a correlation could be found between polymer hydrophobicity and the TCP when using nonbrushy monomers; thus, providing a route to uniquely tune polymer LCST behavior using specific monomer chemistry (Figure 1B).
Figure 1
Figure 1. Our studies on how hydrophobicity influences thermoresponsive behavior of (A) brushy polymers and (B) nonbrushy polymers.
With the goal of realizing this, we selected hydrophilic N,N-dimethyl acrylamide (DMA) as our nonbrushy monomer of interest, due to its simple chain structure and commercial availability, and alkyl acrylates such as n-butyl acrylate (nBuA), benzyl acrylate (BA), tetrahydrofurfuryl acrylate (THFA), and tert-butyl acrylate (tBuA) for the hydrophobic component on account of their commercial availability and compatibility with polymerization conditions. Interestingly, to the best of our knowledge, no literature studies report DMA homopolymers displaying LCST behaviors under the dilute conditions that are typically employed during TCP measurements (ca. 1–10 mg mL–1 polymer), with only one study by Fischer et al. reporting a DMA homopolymer with a very high TCP at a solution concentration of 20 mg mL–1. (37) Thus, our aim was two-fold: to not only establish correlations for polymer hydrophobicity and TCP, but to investigate the intriguing LCST behavior of this largely nonthermoresponsive monomer at lower concentrations and temperature windows.
To this end, we initially synthesized a library of copolymers based on DMA and various hydrophobic alkyl acrylates (RA, R = n-butyl, benzyl, tetrahydrofurfuryl, and tert-butyl) in order to observe the effect of monomer chemistry and copolymer composition and studied their LCST response. TCP was used as a proxy of the LCST behavior as it is a macroscopic effect that can be detected easily via dynamic light scattering, (38) differential scanning calorimetry, (39) microdifferential scanning calorimetry, (21) and UV–vis spectroscopy. (21) Then, we attempted to correlate the TCP of the copolymers to their hydrophobicity, which was determined by calculating the Log Poct/SA of oligomeric models representative of the final copolymers. Overall, copolymer MW and the targeted hydrophobic mol % were maintained as consistently as possible across each series. The copolymers were prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization in 1,4-dioxane for 4 h until targeted DPs were reached (Figure 2A). The final molar composition of the purified copolymers was determined using 1H NMR spectroscopy by relative integration of resonances corresponding to each monomer (Figures 2B and S1–S4). Kinetic analysis showed that both DMA and RA monomers were consumed at an approximately equal rate, confirming the statistical nature of the copolymerizations (Figures S5–S8). Molecular weight distributions (MWDs) for the P(DMA-co-RA) copolymers were determined using size-exclusion chromatography (SEC). Copolymers were obtained with narrow and symmetrical MWDs (Figures 2D and S6–S8). Variations in number-average MW (Mn) and dispersity (ĐM) values were determined by calculating the coefficients of variance. Using this measure, Mn varied by only 2% across the entire data set, while ĐM varied by 0.04% with all values <1.36. Turbidity measurements were conducted using UV–vis spectroscopy in order to measure the TCP of the copolymers. Changes in the percentage transmittance were recorded at λ = 550 nm within the temperature range of 0 to 90 °C. Temperature points that correspond to 50% transmittance values were taken as the TCP of polymers (see Supporting Information for a detailed method). In general, an inverse relationship was observed between the TCP of P(DMA-co-RA) copolymers and the RA content (Figures 2E and S9).
Figure 2
Figure 2. (A) Synthetic scheme for the preparation of P(DMA-co-RA) statistical copolymers. THFA is used as the comonomer in this example. (B) Molar composition (determined by 1H NMR spectroscopy), number-average MW (Mn), and dispersity (ĐM; determined by SEC) of P(DMA-co-THFA) copolymers. (C) 1H NMR spectra of P(DMA-co-THFA) copolymers in CDCl3 (300 MHz). (D) Normalized SEC molecular weight distributions for the P(DMA-co-THFA) series (eluent: CHCl3 + 0.5 v/v% NEt3, PMMA standards). (E) Percent transmittance as a function of temperature for the P(DMA-co-THFA) copolymers dissolved in H2O at 10 mg/mL as measured by UV–vis spectroscopy (λ = 550 nm, 0–90 °C, 1 °C min–1).
Log Poct values of short oligomer models that represent each P(DMA-co-RA) copolymer were calculated (at T = 298 K) for quantifying hydrophobicity. Then, the Log Poct value of each representative model was normalized by surface area using Molecular Dynamics (MD) simulations (see Supporting Information for a detailed model). Normalizing a thermodynamic parameter (i.e., Log Poct) with a structural parameter (i.e., SA) facilitates comparison of architectural differences resulting from monomer size and functionality as well as oligomer length. (36,40,41) Furthermore, this strategy conforms to the Lum–Chandler–Weeks theory, which states that above a critical length scale, hydrophobicity scales with surface area rather than volume. (29,42) Consequently, Log Poct/SA values provide a general method for correlating hydrophobicity to TCP that accommodates models with enough repeating units to represent the actual polymer. Figure 3A shows the repeating units for each of the P(DMA-co-RA) copolymers that were used to build oligomer models to calculate the Log Poct/SA values. The length of the oligomer models varied between 17 and 27 units and the models were built based on the hydrophobic mol % that each copolymer contains (see Supporting Information for detailed model). Log Poct/SA increased as the hydrophobic mol % in the copolymers increased, confirming the relationship between hydrophobicity and Log Poct (Figure 3B). (36) Comonomers nBuA, BA, and tBuA produced copolymers with similar slopes, while P(DMA-co-THFA) copolymers differed from the others. The ether oxygen in the tetrahydrofuran ring of THFA had a significant influence on Log Poct/SA values. Importantly, this data demonstrates that the comonomer chemistry plays an important role in overall hydrophobicity of P(DMA-co-RA) copolymers. Figure 3C shows the inverse linear relationships between the hydrophobic mol % and TCP of the copolymers for each series. Linear regression data for each series is shown in Table S3. This clearly illustrates that the increase in the hydrophobic comonomer content results in an increase in the overall copolymer hydrophobicity, causing the copolymer TCP to decrease. Motivated by this, we next plotted the calculated Log Poct/SA values against the measured TCPs in order to see if any correlation could be built. Figure 3D shows the inverse relationship between the Log Poct/SA (polymer hydrophobicity) and the TCP of P(DMA-co-RA) copolymers with each series possessing a similar slope. This indicates that copolymer hydrophobicity can be directly correlated to its TCP for these nonbrushy copolymers, unlike the OEGMA-based brushy copolymers we studied in our previous work. Of importance, the data shown in Figure 3D was fitted using linear, exponential, and polynomial fits. We found that the prediction capability of the linear fit was superior to the polynomial fit and very similar to the exponential fit in terms of the similarity of the measured and calculated TCP of the P(DMA-co-RA) copolymers. Therefore, we chose the linear fit for the TCP prediction due to its greater simplicity. Comparison of the measured and predicted TCP for P(DMA-co-RA) copolymers showed a reasonably strong correlation, suggesting that this tool could be used for predicting the TCP of new nonbrushy copolymers (Figure 3E). Thus, we suggest that the experimental TCP of new copolymers can be reliably predicted using this computational method.
Figure 3
Figure 3. (A) Chemical structures of the repeating units for the P(DMA-co-nBuA), P(DMA-co-BA), P(DMA-co-THFA), and P(DMA-co-tBuA) copolymers, respectively. (B) Calculated Log Poct/SA values for P(DMA-co-RA) copolymer oligomers as a function of the mol % of the hydrophobic comonomer. (C) Plot of TCP as measured by UV–vis spectroscopy vs the mol % of hydrophobic comonomer. (D) Plot of TCP as measured by UV–vis spectroscopy vs the calculated Log Poct/SA values for P(DMA-co-RA) copolymer oligomers. The solid line represents a linear fit of these data. (E) Comparison between measured TCP values of P(DMA-co-RA) copolymers and those predicted from their Log Poct/SA. The solid line represents a linear fit of these data. The equation was generated using the linear fit of the data in the plot of Figure 3D.
It is important to note the significance of these findings in the context of facilitating the targeted design of new copolymers based on monomers known to produce nonresponsive homopolymers. In such cases, conventional methods like the Flory–Fox equation, which determines the thermal properties of polymers based on both weight fraction and thermoresponse of the two homopolymers, cannot be used. Therefore, the predictive tool developed in this work significantly increases ease of access to new thermoresponsive copolymers with varied chemistries and tunable on-demand temperature responses.
Finally, to prove this hypothesis, we chose to design a new copolymer of DMA and the well-known hydrophobic monomer methyl methacrylate (MMA), which was one of the hydrophobic comonomers used in our previous work.
Log Poct/SA of the P(DMA-co-MMA) copolymer with 31% hydrophobic mol % was calculated prior to synthesis, giving a predicted TCP of 41 °C when using the equation generated based on the relationship between Log Poct/SA and measured TCP. Following the polymer synthesis, the measured TCP of the copolymer was determined as 42 °C using UV–vis spectroscopy. This confirmed that the TCP of new copolymers could be predicted using this guidance with only minor deviations from the targeted TCP. Interestingly, unlike the P(DMA-co-RA) polymerizations, the copolymerization of DMA and MMA yielded a copolymer with a gradient topology (Figure S10). Based on the fact that Log Poct/SA could still predict TCP for this copolymer, it was hypothesized that the exact copolymer sequence may not be a critical determinant of thermoresponsiveness. Further investigation is warranted to test this hypothesis.
To conclude, we report the synthesis of a series of thermoresponsive P(DMA-co-RA) copolymers via copolymerization of DMA and different alkyl acrylate monomers and the investigation of their LCST behavior by measuring the copolymer TCPs using UV–vis spectroscopy. Analysis of our experimental data using computational modeling of Log Poct/SA revealed that the thermoresponsive behavior of nonbrushy P(DMA-co-RA) copolymers could be related to their hydrophobicity. We validated this method by predicting the TCP of a P(DMA-co-MMA), which showed good correlation with the experimentally measured TCP (1 °C difference from targeted TCP). Overall, this study demonstrates the strength of the Log Poct/SA computational modeling tool for the prediction of copolymer interactions in solution. We envisage this to be particularly powerful in the study of thermoresponsive copolymers comprised of monomers that produce nonresponsive homopolymers, thus, widening access to new monomer chemistries that can be used in the rational design of polymers with thermoresponsive behavior.
Supporting Information
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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmacrolett.1c00776.
Materials, characterization techniques, experimental procedures, and additional data (SEC, 1H NMR, and UV–vis spectra) (PDF)
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Author Information
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- Robert T. Mathers - Department of Chemistry, Pennsylvania State University, New Kensington, Pennsylvania 15068, United States;
https://orcid.org/0000-0002-0503-4571;
- Rachel K. O’Reilly - School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;https://orcid.org/0000-0002-1043-7172;
- Jeffrey C. Foster - School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;https://orcid.org/0000-0002-9097-8680
- Amanda K. Pearce - School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;https://orcid.org/0000-0003-3372-7380
The manuscript was written through contributions of all authors.
Acknowledgments
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This work is supported by the Turkish Ministry of National Education, the Engineering and Physical Sciences Research Council, EPSRC, (EP/S00338X/1), and the University of Birmingham.
References
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- 8Vanparijs, N.; Nuhn, L.; De Geest, B. G. Transiently thermoresponsive polymers and their applications in biomedicine. Chem. Soc. Rev. 2017, 46 (4), 1193– 1239, DOI: 10.1039/C6CS00748A[Crossref], [PubMed], [CAS], Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitFektbc%253D&md5=f0a3888358a833de232d6b2d7aa7ecc7Transiently thermoresponsive polymers and their applications in biomedicineVanparijs, Nane; Nuhn, Lutz; De Geest, Bruno G.Chemical Society Reviews (2017), 46 (4), 1193-1239CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)The focus of this review is on the class of transiently thermoresponsive polymers. These polymers are thermoresponsive, but gradually lose this property upon chem. transformation - often a hydrolysis reaction - in the polymer side chain or backbone. An overview of the different approaches used for the design of these polymers along with their physicochem. properties is given. Their amphiphilic properties and degradability into fully sol. compds. make this class of responsive polymers attractive for drug delivery and tissue engineering applications. Examples of these are also provided in this review.
- 9Doberenz, F.; Zeng, K.; Willems, C.; Zhang, K.; Groth, T. Thermoresponsive polymers and their biomedical application in tissue engineering - a review. J. Mater. Chem. B 2020, 8 (4), 607– 628, DOI: 10.1039/C9TB02052G[Crossref], [PubMed], [CAS], Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjvVWjtg%253D%253D&md5=a0ebe5ab84d7dd6e8d5c929584170d45Thermoresponsive polymers and their biomedical application in tissue engineering - a reviewDoberenz, Falko; Zeng, Kui; Willems, Christian; Zhang, Kai; Groth, ThomasJournal of Materials Chemistry B: Materials for Biology and Medicine (2020), 8 (4), 607-628CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)A review. Thermoresponsive polymers hold great potential in the biomedical field, since they enable the fabrication of cell sheets, in situ drug delivery and 3D-printing under physiol. conditions. In this review we provide an overview of several thermoresponsive polymers and their application, with focus on poly(N-isopropylacrylamide)-surfaces for cell sheet engineering. Basic knowledge of important processes like protein adsorption on surfaces and cell adhesion is provided. For different thermoresponsive polymers, namely PNIPAm, Pluronics, elastin-like polypeptides (ELP) and poly(N-vinylcaprolactam) (PNVCL), synthesis and basic chem. and phys. properties have been described and the mechanism of their thermoresponsive behavior highlighted. Fabrication methods of thermoresponsive surfaces have been discussed, focusing on PNIPAm, and describing several methods in detail. The latter part of this review is dedicated to the application of the thermoresponsive polymers and with regard to cell sheet engineering, the process of temp.-dependent cell sheet detachment is explained. We provide insight into several applications of PNIPAm surfaces in cell sheet engineering. For Pluronics, ELP and PNVCL we show their application in the field of drug delivery and tissue engineering. We conclude, that research of thermoresponsive polymers has made big progress in recent years, esp. for PNIPAm since the 1990s. However, manifold research possibilities, e.g. in surface fabrication and 3D-printing and further translational applications are conceivable in near future.
- 10Zhang, Q.; Weber, C.; Schubert, U. S.; Hoogenboom, R. Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditions. Mater. Horiz. 2017, 4 (2), 109– 116, DOI: 10.1039/C7MH00016B[Crossref], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1yjtb8%253D&md5=0b3b67a706a7ee1f549bbb03a734b0e0Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditionsZhang, Qilu; Weber, Christine; Schubert, Ulrich S.; Hoogenboom, RichardMaterials Horizons (2017), 4 (2), 109-116CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)Thermoresponsive polymers that undergo reversible phase transition by responding to an environmental temp. change, in particular polymers showing lower crit. soln. temp. (LCST), are frequently used as smart materials that have found increasing applications. Recently, there has been a rapid growth in interest on LCST polymers and many new research groups are entering the field from a wide range of application areas. While it is great to see more researchers working on LCST polymers, the downside of this rapid growth is that the fundamentals of the LCST phase transition behavior are not always clearly known and respected. Hence, this focus article provides a systematic discussion of the key aspects of the LCST behavior of polymers starting from fundamentals of LCST behavior to practical detn. of cloud point temp. (Tcp). Finally, we offer a basic set of recommended measuring conditions for detn. of Tcp (10 mg mL-1; 0.5°C min-1; 600 nm) to facilitate the comparison of the LCST behavior and Tcp values of polymers developed and studied in different labs. around the globe, which is nowadays nearly impossible since various techniques and parameters are being utilized for the measurements. It should be noted that these recommended conditions serve as a robust tool for turbidimetry, which is one out of the many characterization techniques one should utilize to fully understand LCST behavior of polymers.
- 11Ieong, N. S.; Hasan, M.; Phillips, D. J.; Saaka, Y.; O’Reilly, R. K.; Gibson, M. I. Polymers with molecular weight dependent LCSTs are essential for cooperative behaviour. Polym. Chem. 2012, 3 (3), 794– 799, DOI: 10.1039/c2py00604a[Crossref], [CAS], Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvFaltbY%253D&md5=141c23b5a069a98f4df6b8d74273a72cPolymers with molecular weight dependent LCSTs are essential for cooperative behaviorIeong, Nga Sze; Hasan, Muhammad; Phillips, Daniel J.; Saaka, Yussif; O'Reilly, Rachel K.; Gibson, Matthew I.Polymer Chemistry (2012), 3 (3), 794-799CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)The potential to fine-tune the transition temps. of polymers displaying lower-crit. soln. temps. (LCST) by a simple mixing strategy is investigated. Using a panel of four distinct polymer classes (poly[oligo(ethyleneglycol)methacrylate], poly(N-vinylpiperidone), poly(N-vinylcaprolactam) poly(N-isopropylacrylamide)) it was shown that only those with strong mol. wt. dependent LCSTs produced a single, cooperative, transition when blended together. Furthermore, the actual transition temp. was linked to the wt. av. not the no. av. mol. wt. The only polymer which did not show strong mol.-wt.-LCST correlation was poly(oligo(ethyleneglycol)methacrylate), which showed two independent transitions, one for each polymer.
- 12Liu, Z.; Guo, Y.; Inomata, K. LCST-type phase behavior of poly(2-chloroethyl vinyl ether-alt-maleic anhydride) in n-butyl acetate. Polym. J. 2011, 43 (8), 676– 682, DOI: 10.1038/pj.2011.41[Crossref], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpvV2itrc%253D&md5=accf8daccd588b9101ad3e7d5bdf5747LCST-type phase behavior of poly(2-chloroethyl vinyl ether-alt-maleic anhydride) in n-butyl acetateLiu, Zhenjie; Guo, Yongliang; Inomata, KatsuhiroPolymer Journal (Tokyo, Japan) (2011), 43 (8), 676-682CODEN: POLJB8; ISSN:0032-3896. (NPG Nature Asia-Pacific)Novel polymer solns. exhibiting lower crit. soln. temps. (LCSTs) have been studied. An alternating copolymer of 2-chloroethyl vinyl ether and maleic anhydride was synthesized through free-radical soln. polymn. This copolymer can exhibit LCST-type phase behavior in Bu acetate (BuAc) under relatively mild conditions at temps. sufficiently below its b.p. The effects of mol. wt., polymer concn. and addn. of cosolvent on the polymer soln.'s cloud point temp. (Tcp) were investigated. The Tcp value was nearly const. over a wide range of concns. and increased when the polymer concn. was reduced below a certain value. The exptl. LCST-type phase diagram can be reasonably described by Flory-Huggins theory. The addn. of non-solvents could reduce the Tcp of the polymer soln. in BuAc, whereas the addn. of good solvents could increase the Tcp. These LCST-type phase behaviors may be attributed to specific polar interactions between the polymer and the solvent.
- 13Keogh, R.; Blackman, L. D.; Foster, J. C.; Varlas, S.; O’Reilly, R. K. The Importance of Cooperativity in Polymer Blending: Toward Controlling the Thermoresponsive Behavior of Blended Block Copolymer Micelles. Macromol. Rapid Commun. 2020, 41 (6), 1900599, DOI: 10.1002/marc.201900599[Crossref], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFGjsL4%253D&md5=abeced61e31d53497d8dbe65c95f0fa2The Importance of Cooperativity in Polymer Blending: Toward Controlling the Thermoresponsive Behavior of Blended Block Copolymer MicellesKeogh, Robert; Blackman, Lewis D.; Foster, Jeffrey C.; Varlas, Spyridon; O'Reilly, Rachel K.Macromolecular Rapid Communications (2020), 41 (6), 1900599CODEN: MRCOE3; ISSN:1022-1336. (Wiley-VCH Verlag GmbH & Co. KGaA)Understanding, predicting, and controlling the self-assembly behavior of stimuli-responsive block copolymers remains a pertinent challenge. Copolymer blending protocol provides an accessible methodol. for obtaining a range of intermediate polymeric nanostructures simply by blending two or more block copolymers in desired molar ratio to target specific stimuli-responsiveness. Herein, thermoresponsive amphiphilic diblock copolymers are blended in various combinations that composed of statistical poly(Bu acrylate-co-N,N-dimethylacrylamide) core-forming blocks and four different thermoresponsive corona-forming blocks, namely poly(diethylene glycol monomethyl ether methacrylate) (p(DEGMA)), poly(N-isopropylacrylamide), poly(N,N-diethylacrylamide), and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (p(OEGMA)) are selected for evaluation. Using variable temp. turbidimetry, the thermoresponsive behavior of blended diblock copolymer self-assemblies is assessed and compared to thermoresponsive behavior of the constituent pure diblock copolymer micelles to det. whether comicellization is achieved or whether the two blended corona-forming thermoresponsive blocks exhibit cooperative behavior. Blended diblock copolymer micelles composed of p(DEGMA)/p(OEGMA) mixed coronae display cooperative behavior, highlighting the potential of copolymer blending for the prepn. of stimuli-responsive nanomaterials in applications such as oil recovery, drug delivery, biosensing, and catalysis.
- 14Miclotte, M. P. J.; Lawrenson, S. B.; Varlas, S.; Rashid, B.; Chapman, E.; O’Reilly, R. K. Tuning the Cloud-Point and Flocculation Temperature of Poly(2-(diethylamino)ethyl methacrylate)-Based Nanoparticles via a Postpolymerization Betainization Approach. ACS Polym. Au 2021, 1 (1), 47– 58, DOI: 10.1021/acspolymersau.1c00010[ACS Full Text
], [CAS], Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsVyrsrrP&md5=a138208f5fd78b638defdf2d979d790fTuning the Cloud-Point and Flocculation Temperature of Poly(2-(diethylamino)ethyl methacrylate)-Based Nanoparticles via a Postpolymerization Betainization ApproachMiclotte, Matthieu P. J.; Lawrenson, Stefan B.; Varlas, Spyridon; Rashid, Bilal; Chapman, Emma; O'Reilly, Rachel K.ACS Polymers Au (2021), 1 (1), 47-58CODEN: APACCD; ISSN:2694-2453. (American Chemical Society)The ability to tune the behavior of temp.-responsive polymers and self-assembled nanostructures has attracted significant interest in recent years, particularly in regard to their use in biotechnol. applications. Herein, well-defined poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA)-based core-shell particles were prepd. by RAFT-mediated emulsion polymn., which displayed a lower-crit. soln. temp. (LCST) phase transition in aq. media. The tertiary amine groups of PDEAEMA units were then utilized as functional handles to modify the core-forming block chem. via a postpolymn. betainization approach for tuning both the cloud-point temp. (TCP) and flocculation temp. (TCFT) of these particles. In particular, four different sulfonate salts were explored aiming to investigate the effect of the carbon chain length and the presence of hydroxyl functionalities alongside the carbon spacer on the particle's thermoresponsiveness. In all cases, it was possible to regulate both TCP and TCFT of these nanoparticles upon varying the degree of betainization. Although TCP was found to be dependent on the type of betainization reagent utilized, it only significantly increased for particles betainized using sodium 3-chloro-2-hydroxy-1-propanesulfonate, while varying the aliph. chain length of the sulfobetaine only provided limited temp. variation. In comparison, the onset of flocculation for betainized particles varied over a much broader temp. range when varying the degree of betainization with no real correlation identified between TCFT and the sulfobetaine structure. Moreover, exptl. results were shown to partially correlate to computational oligomer hydrophobicity calcns. Overall, the innovative postpolymn. betainization approach utilizing various sulfonate salts reported herein provides a straightforward methodol. for modifying the thermoresponsive behavior of soft polymeric particles with potential applications in drug delivery, sensing, and oil/lubricant viscosity modification. - 15Ramírez-Jiménez, A.; Montoya-Villegas, K. A.; Licea-Claverie, A.; Gónzalez-Ayón, M. A. Tunable Thermo-Responsive Copolymers from DEGMA and OEGMA Synthesized by RAFT Polymerization and the Effect of the Concentration and Saline Phosphate Buffer on Its Phase Transition. Polymer 2019, 11 (10), 1657, DOI: 10.3390/polym11101657
- 16Van Guyse, J. F. R.; Bera, D.; Hoogenboom, R. Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition. Polymer 2021, 13 (3), 374, DOI: 10.3390/polym13030374
- 17Eggenhuisen, T. M.; Becer, C. R.; Fijten, M. W. M.; Eckardt, R.; Hoogenboom, R.; Schubert, U. S. Libraries of Statistical Hydroxypropyl Acrylate Containing Copolymers with LCST Properties Prepared by NMP. Macromolecules. 2008, 41 (14), 5132– 5140, DOI: 10.1021/ma800469p[ACS Full Text], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXns1Cltbg%253D&md5=e5693c726708252bb4cfb43e3376d692Libraries of Statistical Hydroxypropyl Acrylate Containing Copolymers with LCST Properties Prepared by NMPEggenhuisen, Tamara M.; Becer, C. Remzi; Fijten, Martin W. M.; Eckardt, Rebecca; Hoogenboom, Richard; Schubert, Ulrich S.Macromolecules (Washington, DC, United States) (2008), 41 (14), 5132-5140CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)The nitroxide-mediated copolymn. of 2-hydroxypropyl acrylate (HPA) with N-acryloylmorpholine (Amor) or N,N-dimethylacrylamide (DMA) was studied using N-tert-butyl-N-(1'-diethylphosphono-2,2'-dimethylpropyl)-O-(2-carboxyl-prop-2-yl) (BlocBuilder) alkoxyamine initiator and addnl. free nitroxide (SG1). Different reaction conditions, such as the concn. of addnl. SG-1, were tested to optimize the homopolymns. using a Chemspeed ASW2000 automated parallel synthesizer. Best control for the homopolymns. (polydispersity indexes of 1.2-1.3) of all three monomers was achieved using 20% addnl. SG-1 (relative to the initiator) at a reaction temp. of 110 °C for 2 M solns. in N,N-dimethylformamide and a monomer/initiator ratio of 100/1. Libraries of P(Amor-stat-HPA) and P(DMA-stat-HPA) were synthesized with 0-100 mol % HPA with 10 mol % increments using the optimized conditions obtained for the homopolymns. The resulting polymers had narrow mol. wt. distributions, and their compns., detd. using 1H NMR spectroscopy and elemental anal., were close to the theor. compns. In addn., all copolymers of both libraries had single glass transition temps. (Tg), and the transition temps. decreased from the Tg of P(Amor) (147 °C) and P(DMA) (111 °C) to the Tg of P(HPA) (22 °C) with increasing HPA content. The cloud point of P(HPA) showed concn. dependence and a concn. dependent hysteresis. The cloud points of aq. solns. of the copolymer libraries could be tuned from 21.4 to 88.0 °C and to 82.9 °C for P(Amor-stat-HPA) and P(DMA-stat-HPA), resp., at a concn. of 1 wt. %. LCST behavior was obsd. for copolymers with >40 wt. % HPA in P(Amor-stat-HPA) and >55 wt. % HPA in the P(DMA-stat-HPA) library.
- 18Vogt, A. P.; Sumerlin, B. S. Tuning the Temperature Response of Branched Poly(N-isopropylacrylamide) Prepared by RAFT Polymerization. Macromolecules. 2008, 41 (20), 7368– 7373, DOI: 10.1021/ma801256k[ACS Full Text], [CAS], Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtFGjsLzJ&md5=d963455a09cb6258be16397a0043c390Tuning the Temperature Response of Branched Poly(N-isopropylacrylamide) Prepared by RAFT PolymerizationVogt, Andrew P.; Sumerlin, Brent S.Macromolecules (Washington, DC, United States) (2008), 41 (20), 7368-7373CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Reversible addn.-fragmentation chain transfer (RAFT) polymn. in the presence of a compd. capable of both reversible chain transfer through a thiocarbonylthio moiety and propagation via a vinyl group led to highly branched copolymers by a method analogous to self-condensing vinyl copolymn. An acryloyl trithiocarbonate prepd. by copper-catalyzed azide-alkyne cycloaddn. was copolymd. with N-isopropylacrylamide (NIPAM) in ratios selected to tune the distribution and length of branches in the resulting thermoresponsive polymers. The degree of branching increased with chain transfer agent (CTA) concn., as proven by NMR spectroscopy, size exclusion chromatog., and viscometry. Retention of the thiocarbonylthio compd. during the polymn. was evidenced by successful chain extension of a branched N-isopropylacrylamide (PNIPAM) macroCTA by RAFT polymn. of N,N-dimethylacrylamide. The branched polymers led to reduced lower crit. soln. temps. as compared to linear PNIPAM, an effect attributed primarily to an increased contribution of hydrophobic end groups. End group cleavage by radical-induced redn. resulted in an increased transition temp. more similar to that expected for linear PNIPAM.
- 19Smith, A. A. A.; Maikawa, C. L.; Lopez Hernandez, H.; Appel, E. A. Controlling properties of thermogels by tuning critical solution behaviour of ternary copolymers. Polym. Chem. 2021, 12 (13), 1918– 1923, DOI: 10.1039/D0PY01696A[Crossref], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXntlSjsb0%253D&md5=f85fc853b87c6d842ca10b34dc934d2bControlling properties of thermo-gels by tuning critical solution behavior of ternary copolymersSmith, Anton A. A.; Maikawa, Caitlin L.; Lopez Hernandez, Hector; Appel, Eric A.Polymer Chemistry (2021), 12 (13), 1918-1923CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)Thermoresponsive hydrogel materials show promise as biomaterials as their properties can be widely tuned to fit engineering requirements for an array of important applications. Here we show that the properties of thermo-gelling tri-block copolymers consisting of a central poly(ethylene glycol) block and pendant N-substituted polyacrylamides can be tuned by altering the random terpolymer compns. The heterogeneity of the pendant terpolymer blocks is reflected in the concn. dependence of their crit. soln. behavior. The lower crit. soln. temp. (LCST) of the pendant blocks can be finely tuned, enabling controlled modulation of thermo-gel properties. Altering terpolymer compn. to control LCST behavior, therefore, provides a facile approach to design thermo-gel properties.
- 20Luzon, M.; Boyer, C.; Peinado, C.; Corrales, T.; Whittaker, M.; Tao, L.; Davis, T. P. Water-soluble, thermoresponsive, hyperbranched copolymers based on PEG-methacrylates: Synthesis, characterization, and LCST behavior. J. Polym. Sci. A: Polym. Chem. 2010, 48 (13), 2783– 2792, DOI: 10.1002/pola.24027[Crossref], [CAS], Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXms1yhsbk%253D&md5=8754e2a808b5b0094971af9bf8913201Water-soluble, thermoresponsive, hyperbranched copolymers based on PEG-methacrylates: synthesis, characterization, and LCST behaviorLuzon, Mario; Boyer, Cyrille; Peinado, Carmen; Corrales, Teresa; Whittaker, Michael; Tao, Lei; Davis, Thomas P.Journal of Polymer Science, Part A: Polymer Chemistry (2010), 48 (13), 2783-2792CODEN: JPACEC; ISSN:0887-624X. (John Wiley & Sons, Inc.)A series of water-sol. thermoresponsive hyperbranched copoly(oligoethylene glycol)s were synthesized by copolymn. of di(ethylene glycol) methacrylate (DEG-MA) and oligo(ethylene glycol) methacrylate (OEG-MA, Mw = 475 g/mol), with ethylene glycol dimethacrylate (EGD-MA) used as the crosslinker, via reversible addn. fragmentation chain transfer polymn. Polymers were characterized by size exclusion chromatog. and NMR analyses. According to the monomer compn., i.e., the ratio of OEG-MA: DEG-MA: EGD-MA, the lower crit. soln. temp. (LCST) could be tuned from 25 °C to 90 °C. The thermoresponsive properties of these hyperbranched copolymers were studied carefully and compared with their linear analogs. It was found that mol. architecture influences thermoresponsive behavior, with a decrease of around 5-10 °C in the LCST of the hyperbranched polymers compared with the LCST of linear chains. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2783-2792, 2010.
- 21Akar, I.; Keogh, R.; Blackman, L. D.; Foster, J. C.; Mathers, R. T.; O’Reilly, R. K. Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical Copolymers. ACS Macro Lett. 2020, 9 (8), 1149– 1154, DOI: 10.1021/acsmacrolett.0c00461[ACS Full Text], [CAS], Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVChsrzP&md5=664a1eb64b5f92e900508e4e37b95a19Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical CopolymersAkar, Irem; Keogh, Robert; Blackman, Lewis D.; Foster, Jeffrey C.; Mathers, Robert T.; O'Reilly, Rachel K.ACS Macro Letters (2020), 9 (8), 1149-1154CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Thermoresponsive copolymers that exhibit a lower crit. soln. temp. (LCST) have been exploited to prep. stimuli-responsive materials for a broad range of applications. It is well understood that the LCST of such copolymers can be controlled by tuning mol. wt. or through copolymn. of two known thermoresponsive monomers. However, no general methodol. has been established to relate polymer properties to their temp. response in soln. Herein, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temp. (TCP). A series of statistical copolymers were synthesized based on hydrophilic oligoethylene glycol monomethyl ether methacrylate (OEGMA) and hydrophobic alkyl methacrylate monomers and their hydrophobicity was compared using surface area-normalized partition coeffs. (log Poct/SA). However, while some insight was gained by comparing TCP and hydrophobicity values, further statistical anal. on both exptl. and literature data showed that the molar percentage of comonomer (i.e., grafting d.) was the strongest influencer of TCP, regardless of the comonomer used. The lack of dependence of TCP on comonomer chem. implies that a broad range of functional, thermoresponsive materials can be prepd. based on OEGMA by simply tuning grafting d.
- 22Fournier, D.; Hoogenboom, R.; Thijs, H. M. L.; Paulus, R. M.; Schubert, U. S. Tunable pH- and Temperature-Sensitive Copolymer Libraries by Reversible Addition-Fragmentation Chain Transfer Copolymerizations of Methacrylates. Macromolecules 2007, 40 (4), 915– 920, DOI: 10.1021/ma062199r[ACS Full Text], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXlsl2gtg%253D%253D&md5=e750ef29e45f0b16be51ac313e30dbf2Tunable pH- and Temperature-Sensitive Copolymer Libraries by Reversible Addition-Fragmentation Chain Transfer Copolymerizations of MethacrylatesFournier, David; Hoogenboom, Richard; Thijs, Hanneke M. L.; Paulus, Renzo M.; Schubert, Ulrich S.Macromolecules (2007), 40 (4), 915-920CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Reversible addn.-fragmentation chain transfer (RAFT) polymns. were performed on a Chemspeed Accelerator SLT100 automated synthesizer to polymerize N,N-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) Me ether methacrylate (PEGMA) at 70 °C. Azobis(isobutyronitrile) (AIBN) was used as source of radicals and 2-cyano-2-Bu dithiobenzoate (CBDB) as RAFT agent. A complete screening in compn. of P(DMAEMA-stat-PEGMA) copolymers was elaborated from 0% of PEGMA to 100% of PEGMA. All polydispersity indexes of the obtained copolymers are comprised between 1.11 and 1.30. The reactivity ratios were detd. by the extended Kelen-Tuedoes method (rDMAEMA = 0.93 and rPEGMA = 0.66). The behavior of the pH- and temp.-sensitive copolymers was studied in aq. soln. by measuring the lower crit. soln. temp. (LCST) by UV/vis spectroscopy. The measurements were performed at three different pH values (4, 7, and 10). At pH 7 and pH 10 the LCST is increasing linearly with the wt. % PEGMA in the copolymer feed. On the contrary, at pH 4, the hydrophilicity of the P(DMAEMA-stat-PEGMA) copolymers is too high due to the protonation of the DMAEMA units. Thus, no LCST was detected for most of them. By varying the pH and the compn. of the P(DMAEMA-stat-PEGMA) copolymers, the LCST can be easily tuned between 34.7 and 82.0 °C.
- 23Bebis, K.; Jones, M. W.; Haddleton, D. M.; Gibson, M. I. Thermoresponsive behaviour of poly[(oligo(ethyleneglycol methacrylate)]s and their protein conjugates: importance of concentration and solvent system. Polym. Chem. 2011, 2 (4), 975– 982, DOI: 10.1039/c0py00408a[Crossref], [CAS], Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjvFWntr0%253D&md5=828ec2802f065d18f87c4021fe536c01Thermoresponsive behaviour of poly[(oligo(ethyleneglycol) methacrylate)]s and their protein conjugates: importance of concentration and solvent systemBebis, Konstantinos; Jones, Mathew W.; Haddleton, David M.; Gibson, Matthew I.Polymer Chemistry (2011), 2 (4), 975-982CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)Thermoresponsive poly[oligo(ethyleneglycol) methacrylate]s with a variety of different oligo(ethyleneglycol) graft lengths were synthesized by reversible-addn. fragmentation chain transfer (RAFT) polymn. The lower crit. soln. temp. (LCST) behavior of these polymers was evaluated as a function of polymer concn. and concn. of dissolved solutes, to understand their applicability for in vitro and in vivo expts. In the relevant dil. (<1 mg mL-1) concn. range, the obsd. LCSTs increased by approx. 6° compared to higher concns. This was confirmed by complimentary dynamic light scattering and differential scanning calorimetry measurements. The impact of biol. solns. on the LCST was detd. using bovine blood plasma, which resulted in obsd. LCSTs lower than what is found in traditional buffer or pure aq. solns. A well-defined polymer-protein conjugate was synthesized by the grafting from procedure, using single-electron transfer (SET) polymn. This model polymer-protein therapeutic also displayed similar concn. dependent behavior, highlighting the importance of testing novel smart materials and conjugates at both relevant concn. ranges and in appropriate solvent systems to use them in biotechnol. applications.
- 24Porsch, C.; Hansson, S.; Nordgren, N.; Malmström, E. Thermo-responsive cellulose-based architectures: tailoring LCST using poly(ethylene glycol) methacrylates. Polym. Chem. 2011, 2 (5), 1114– 1123, DOI: 10.1039/C0PY00417K[Crossref], [CAS], Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXltF2rtb0%253D&md5=fda4f91daffc36b87b549257b9f50a83Thermo-responsive cellulose-based architectures: tailoring LCST using poly(ethylene glycol) methacrylatesPorsch, Christian; Hansson, Susanne; Nordgren, Niklas; Malmstroem, EvaPolymer Chemistry (2011), 2 (5), 1114-1123CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)There is a growing interest in designing advanced macromol. architectures applicable for instance in drug delivery systems. Employing cellulose in these systems is particularly favorable due to attractive properties such as biocompatibility and low price. Addnl., thermo-responsive polymers of poly(ethylene glycol) methacrylates are promising in this field owing to their biocompatibility and non-toxicity. In the present study, amphiphilic thermo-responsive homo- and copolymers of oligo(ethylene glycol) Me ether methacrylate (OEGMA300) and di(ethylene glycol) Me ether methacrylate (DEGMA) were synthesized via ARGET ATRP. Both linear copolymers of DEGMA/OEGMA300 as well as comb architectures with copolymers of DEGMA/OEGMA300 grafted from hydroxypropyl cellulose were produced. The lower crit. soln. temp. of the linear copolymers was readily tailored by altering the monomer feed ratio. The grafting of the thermo-responsive polymers from hydroxypropyl cellulose resulted in a consistent decrease of the lower crit. soln. temp. compared to the linear analogs; however, interestingly the ability to tune the transition temp. remained. Moreover, the amphiphilic comb architectures formed polymeric micelles with low crit. micelle concns. Consequently, these advanced architectures combine the favorable properties of hydroxypropyl cellulose with the interesting thermo-responsive and stealth properties of poly(ethylene glycol) methacrylates, and may, therefore, find potential applications in biomedicine.
- 25Lutz, J.-F.; Hoth, A. Preparation of Ideal PEG Analogues with a Tunable Thermosensitivity by Controlled Radical Copolymerization of 2-(2-Methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) Methacrylate. Macromolecules 2006, 39 (2), 893– 896, DOI: 10.1021/ma0517042[ACS Full Text], [CAS], Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtlagu7jE&md5=d90758cc6a6f4a448a6fe3ee1e043fefPreparation of Ideal PEG Analogues with a Tunable Thermosensitivity by Controlled Radical Copolymerization of 2-(2-Methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) MethacrylateLutz, Jean-Francois; Hoth, AnnMacromolecules (2006), 39 (2), 893-896CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)A new class of water-sol. copolymers based on 2-(2-methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate P(MEO2MA-co-OEGMA) was investigated. ATRP at 60 °C in ethanol was found to be a very straightforward method for prepg. these copolymers in high yields. In the presence of the ATRP catalytic system CuCl/bipy, well-defined P(MEO2MA-co-OEGMA) samples with a controlled chain length and a narrow mol. wt. distribution could be prepd. Moreover, P(MEO2MA-co-OEGMA) copolymers were found to exhibit extremely interesting soln. properties in water. Indeed, the LCST of these copolymers could be accurately tuned by adjusting the fraction of OEGMA units in the copolymer chains. Thus, LCST can be predicted on demand by adjusting the initial compn. of the comonomer feed. For example, LCST of 37 or 39 °C could be precisely obtained by using either 8 or 10 % of OEGMA in the initial comonomer mixts. Moreover, the LCST of P(MEO2MA-co-OEGMA) samples was not found to be very dependent on polymer concn. Therefore, these new copolymers can be considered as ideal segments for constructing amphiphiles by CRP and moreover as very high potential candidates for application in biotechnol.
- 26Kokufuta, M. K.; Sato, S.; Kokufuta, E. LCST behavior of copolymers of N-isopropylacrylamide and N-isopropylmethacrylamide in water. Colloid Polym. Sci. 2012, 290 (16), 1671– 1681, DOI: 10.1007/s00396-012-2706-y[Crossref], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XovVahu7o%253D&md5=4d1048a706a5f3245d62a8adcb9333d9LCST behavior of copolymers of N-isopropylacrylamide and N-isopropylmethacrylamide in waterKokufuta, Mamoru K.; Sato, Saigo; Kokufuta, EtsuoColloid and Polymer Science (2012), 290 (16), 1671-1681CODEN: CPMSB6; ISSN:0303-402X. (Springer)The lower crit. soln. temp. (LCST) behavior of copolymers of N-isopropylacrylamide (NiPA) and N-isopropylmethacrylamide (NiPMA) in water was studied as a function of the copolymer compn., using a combination of turbidity measurements and differential scanning calorimetry (DSC). The copolymers were prepd. by free radical polymn. using N,N-dimethylformamide as a solvent and α,α'-azobis(isobutyronitrile) as an initiator. The copolymer compn. was detd. by elemental anal. It was found that the temp. (Tc) at which the copolymer undergoes a phase transition, i.e., LCST, increases linearly with increasing the mole fraction (fm) of NiPMA in the copolymer, within the Tc range from 32 °C (at fm = 0; NiPA homopolymer) to 42 °C (at fm = 1; NiPMA homopolymer). Also found from heating DSC thermograms were the linear dependencies of the enthalpy (ΔH) and entropy (ΔS) changes at Tc upon fm. However, the ΔH (5.5 kJ/unit-mol) at fm = 1 was slightly smaller than that (5.7 kJ/unit-mol) of poly(N-n-propylacrylamide) but considerably smaller than that (7.8 kJ/unit-mol) of poly(N-n-propylmethacrylamide). The same trend was obsd. in the fm dependence of ΔS. These results were discussed in terms of the structural effects of the NiPMA monomer unit on the heat-induced phase transition in water of poly(NiPA-co-NiPMA)s. It was suggested that a strong interaction of water with the amide group in the NiPMA would raise the transition temp., but a local dehydration which occurs around the iso-Pr side chain would not lead to large changes in the enthalpy and entropy at Tc.
- 27Kumbhakar, K.; Saha, B.; De, P.; Biswas, R. Cloud Point Driven Dynamics in Aqueous Solutions of Thermoresponsive Copolymers: Are They Akin to Criticality Driven Solution Dynamics?. J. Phys. Chem. B 2019, 123 (51), 11042– 11054, DOI: 10.1021/acs.jpcb.9b07840[ACS Full Text], [CAS], Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWhsrrN&md5=243abc0c504fe4d64cd02c58b15de186Cloud Point Driven Dynamics in Aqueous Solutions of Thermoresponsive Copolymers: Are They Akin to Criticality Driven Solution Dynamics?Kumbhakar, Kajal; Saha, Biswajit; De, Priyadarsi; Biswas, RanjitJournal of Physical Chemistry B (2019), 123 (51), 11042-11054CODEN: JPCBFK; ISSN:1520-5207. (American Chemical Society)Cloud point driven interaction and relaxation dynamics of aq. solns. of amphiphilic thermoresponsive copolymers were explored through picosecond resolved and steady state fluorescence measurements employing hydrophilic (coumarin 343, C343) and hydrophobic (coumarin 153, C153) solute probes of comparable sizes. These thermoresponsive random copolymers, with tunable cloud point temps. (Tcp's) between 298 and 323 K, were rationally designed first and then synthesized via reversible addn.-fragmentation chain transfer (RAFT) copolymn. of Me methacrylate (MMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). Subsequently, copolymers were characterized by NMR spectroscopy and size exclusion chromatog. (SEC). A balance between the hydrophilic (PEGMA) and the hydrophobic (MMA) content dictates the crit. aggregation concn. (CAC), with CAC ∼ 2-14 mg/L for these copolymers in aq. media. No abrupt changes in the steady state spectral features of both C153 and C343 in the aq. solns. of these polymers near but below the cloud point temps. were obsd. Interestingly, spectral properties of C153 in these solns. show the impact of hydrophobic/hydrophilic interaction balance but not by those of C343. More specifically, C153 reported a blue shift (relative to that in neat water) and heterogeneity in its local environment. This suggested different locations for the hydrophilic (C343) and the hydrophobic (C153) probes. In addn., the excited state fluorescence lifetime (〈τlife〉) of C153 increased with the increase of hydrophobic (MMA) content in these copolymers. However, C343 reported no such variations, although fluorescence anisotropy decays for both solutes were significantly slowed down in these aq. solns. compared to neat water. Anisotropy decays indicated bimodal time-dependent friction for these solutes in aq. solns. of these copolymers but monomodal in neat water. A linear dependence of the av. rotational relaxation rates (〈krot〉 = 〈τrot〉-1) of the type 〈krot〉 .varies. (|T - Tcp|/Tcp)γ with neg. values for the exponent γ was obsd. for both solutes. No slowing down of the solute rotation with temp. approaching the Tcp was detected; rather, rotation became faster upon increasing the soln. temp., suggesting domination of the local friction.
- 28Liu, H. Y.; Zhu, X. X. Lower critical solution temperatures of N-substituted acrylamide copolymers in aqueous solutions. Polymer 1999, 40 (25), 6985– 6990, DOI: 10.1016/S0032-3861(98)00858-1[Crossref], [CAS], Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXmt1GksLc%253D&md5=534efb7b99b0c1ea154a74776b6d68f8Lower critical solution temperatures of N-substituted acrylamide copolymers in aqueous solutionsLiu, H. Y.; Zhu, X. X.Polymer (1999), 40 (25), 6985-6990CODEN: POLMAG; ISSN:0032-3861. (Elsevier Science Ltd.)Copolymers were prepd. from N-substituted acrylamides by free radical polymn. in soln. We have selected a group of monomers with varying degree of hydrophilicity including acrylamide, N-ethylacrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-tert-butylacrylamide. The chem. compn. in the final copolymers was found to be very close to the original monomer compn. in the feed prior to polymn. In an effort to elucidate the effect of the chem. compn. on the phase sepns. of the aq. solns. of the copolymers, the lower crit. soln. temps. (LCST) of the copolymers in water were detd. by DSC and optical turbidimetry. In principal, the LCST of the copolymers can be adjusted within the freezing and b.ps. of the solns. The copolymers exhibit systematic changes in their LCSTs as a function of their comonomer compn., for which an empirical equation was established.
- 29Foster, J. C.; Akar, I.; Grocott, M. C.; Pearce, A. K.; Mathers, R. T.; O’Reilly, R. K. 100th Anniversary of Macromolecular Science Viewpoint: The Role of Hydrophobicity in Polymer Phenomena. ACS Macro Lett. 2020, 9 (11), 1700– 1707, DOI: 10.1021/acsmacrolett.0c00645[ACS Full Text], [CAS], Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1arsL3F&md5=3e5ffdafef555b0396584514dd2ae4ca100th Anniversary of Macromolecular Science Viewpoint: The Role of Hydrophobicity in Polymer PhenomenaFoster, Jeffrey C.; Akar, Irem; Grocott, Marcus C.; Pearce, Amanda K.; Mathers, Robert T.; OReilly, Rachel K.ACS Macro Letters (2020), 9 (11), 1700-1707CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)A review. The seemingly simple notion of the hydrophobic effect can be viewed from multiple angles involving theory, simulation, and expts. This viewpoint examines five attributes of predictive models to enhance synthetic efforts as well as exptl. methods to quantify hydrophobicity. In addn., we compare existing predictive models against exptl. data for polymer surface tension, lower crit. soln. temp., soln. self-assembly morphol., and degrdn. behavior. Key conclusions suggest that both the Hildebrand soly. parameters (HSPs) and surface area-normalized Log P (Log P SA-1) values provide unique and complementary insights into polymer phenomena. In particular, HSPs appear to better describe bulk polymer phenomena for thermoplastics such as surface tension, while Log P SA-1 values are well-suited for describing and predicting the behavior of polymers in soln.
- 30Padmanabhan, J.; Parthasarathi, R.; Subramanian, V.; Chattaraj, P. K. QSPR models for polychlorinated biphenyls: n-Octanol/water partition coefficient. Bioorg. Med. Chem. 2006, 14 (4), 1021– 1028, DOI: 10.1016/j.bmc.2005.09.017[Crossref], [PubMed], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhvFKkuw%253D%253D&md5=0af5f0ac844e65283297b57b3eaa3e4bQSPR models for polychlorinated biphenyls: n-Octanol/water partition coefficientPadmanabhan, J.; Parthasarathi, R.; Subramanian, V.; Chattaraj, P. K.Bioorganic & Medicinal Chemistry (2006), 14 (4), 1021-1028CODEN: BMECEP; ISSN:0968-0896. (Elsevier B.V.)The logarithmic n-octanol/water partition coeff. (log Kow) is an important property for pharmacol., toxicol. and medicinal chem. Quant. structure-property relationship (QSPR) model for the lipophilic behavior (log Kow) of the data set contg. 133 polychlorinated biphenyl (PCB) congeners is analyzed using the conceptual d. functional theory based global reactivity parameter such as electrophilicity index (ω) along with energy of LUMO (ELUMO) and no. of chlorine substituents (NCl) as descriptors. A reasonably good coeff. of detn. (r2 = 0.914) and the internal predictive ability (r2cv = 0.909) values are obtained indicating the significance of the considered descriptors in the property anal. of PCBs. Further, the developed method has widespread applicability from chem. reactivity to toxicity anal. and in studies related to various physicochem. properties in the series of dioxins and other polyarom. hydrocarbons.
- 31Bannan, C. C.; Calabró, G.; Kyu, D. Y.; Mobley, D. L. Calculating Partition Coefficients of Small Molecules in Octanol/Water and Cyclohexane/Water. J. Chem. Theory Comput. 2016, 12 (8), 4015– 4024, DOI: 10.1021/acs.jctc.6b00449[ACS Full Text], [CAS], Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtF2iurbO&md5=bae2268a466c95ff642596f771f271cbCalculating Partition Coefficients of Small Molecules in Octanol/Water and Cyclohexane/WaterBannan, Caitlin C.; Calabro, Gaetano; Kyu, Daisy Y.; Mobley, David L.Journal of Chemical Theory and Computation (2016), 12 (8), 4015-4024CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Partition coeffs. describe how a solute is distributed between two immiscible solvents. They are used in drug design as a measure of a solute's hydrophobicity and a proxy for its membrane permeability. We calc. partition coeffs. from transfer free energies using mol. dynamics simulations in explicit solvent. Setup is done by our new Solvation Toolkit which automates the process of creating input files for any combination of solutes and solvents for many popular mol. dynamics software packages. We calc. partition coeffs. between octanol/water and cyclohexane/water with the Generalized AMBER Force Field (GAFF) and the Dielec. Cor. GAFF (GAFF-DC). With similar methods in the past we found a root-mean-squared error (RMSE) of 6.3 kJ/mol in hydration free energies which would correspond to an error of around 1.6 log units in partition coeffs. if solvation free energies in both solvents were estd. with comparable accuracy. Here we find an overall RMSE of about 1.2 log units with both force fields. Results from GAFF and GAFF-DC seem to exhibit systematic biases in opposite directions for calcd. cyclohexane/water partition coeffs.
- 32Foster, J. C.; Varlas, S.; Couturaud, B.; Jones, J. R.; Keogh, R.; Mathers, R. T.; O’Reilly, R. K. Predicting Monomers for Use in Polymerization-Induced Self-Assembly. Angew. Chem. Int.l Ed. 2018, 57 (48), 15733– 15737, DOI: 10.1002/anie.201809614
- 33Varlas, S.; Foster, J. C.; Arkinstall, L. A.; Jones, J. R.; Keogh, R.; Mathers, R. T.; O’Reilly, R. K. Predicting Monomers for Use in Aqueous Ring-Opening Metathesis Polymerization-Induced Self-Assembly. ACS Macro Lett. 2019, 8 (4), 466– 472, DOI: 10.1021/acsmacrolett.9b00117[ACS Full Text], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmsVahurw%253D&md5=764942bb032063155839f4af8cd8fb1bPredicting Monomers for Use in Aqueous Ring-Opening Metathesis Polymerization-Induced Self-AssemblyVarlas, Spyridon; Foster, Jeffrey C.; Arkinstall, Lucy A.; Jones, Joseph R.; Keogh, Robert; Mathers, Robert T.; O'Reilly, Rachel K.ACS Macro Letters (2019), 8 (4), 466-472CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Aq. polymn.-induced self-assembly (PISA) is a well-established methodol. enabling in situ synthesis of polymeric nanoparticles of controllable morphol. Notably, PISA via ring-opening metathesis polymn. (ROMPISA) is an emerging technol. for block copolymer self-assembly, mainly due to its high versatility and robustness. However, a limited no. of monomers suitable for core-forming blocks in aq. ROMPISA have been reported to date. In this work, we identified seven monomers for use as either corona- or core-forming blocks during aq. ROMPISA by in silico calcn. of relative hydrophobicity for corresponding oligomeric models. The predicted monomers were validated exptl. by conducting ROMPISA using our previously reported two-step approach. In addn. to predictive data, our computational model was exploited to identify trends between polymer hydrophobicity and the morphol. of the self-assembled nano-objects they formed. We expect that this methodol. will greatly expand the scope of aq. ROMPISA, as monomers can be easily identified based on the structure-property relationships obsd. herein.
- 34Inam, M.; Cambridge, G.; Pitto-Barry, A.; Laker, Z. P. L.; Wilson, N. R.; Mathers, R. T.; Dove, A. P.; O’Reilly, R. K. 1D vs. 2D shape selectivity in the crystallization-driven self-assembly of polylactide block copolymers. Chem. Sci. 2017, 8 (6), 4223– 4230, DOI: 10.1039/C7SC00641A[Crossref], [PubMed], [CAS], Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtVeqtLo%253D&md5=7bf2d5494c613d5ceb273d98fba3feba1D vs. 2D shape selectivity in the crystallization-driven self-assembly of polylactide block copolymersInam, Maria; Cambridge, Graeme; Pitto-Barry, Anais; Laker, Zachary P. L.; Wilson, Neil R.; Mathers, Robert T.; Dove, Andrew P.; O'Reilly, Rachel K.Chemical Science (2017), 8 (6), 4223-4230CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)The 2D materials such as graphene, LAPONITE clays or molybdenum disulfide nanosheets are of extremely high interest to the materials community as a result of their high surface area and controllable surface properties. While several methods to access 2D inorg. materials are known, the investigation of 2D org. nanomaterials is less well developed on account of the lack of ready synthetic accessibility. Crystn.-driven self-assembly (CDSA) has become a powerful method to access a wide range of complex but precisely-defined nanostructures. The prepn. of 2D structures, however, particularly those aimed towards biomedical applications, is limited, with few offering biocompatible and biodegradable characteristics as well as control over self-assembly in two dimensions. Herein, in contrast to conventional self-assembly rules, we show that the soly. of polylactide (PLLA)-based amphiphiles in alcs. results in unprecedented shape selectivity based on unimer soly. We use log Poct anal. to drive solvent selection for the formation of large uniform 2D diamond-shaped platelets, up to several microns in size, using long, sol. coronal blocks. By contrast, less sol. PLLA-contg. block copolymers yield cylindrical micelles and mixed morphologies. The methods developed in this work provide a simple and consistently reproducible protocol for the prepn. of well-defined 2D org. nanomaterials, whose size and morphol. are expected to facilitate potential applications in drug delivery, tissue engineering and in nanocomposites.
- 35He, Y.; Eloi, J.-C.; Harniman, R. L.; Richardson, R. M.; Whittell, G. R.; Mathers, R. T.; Dove, A. P.; O’Reilly, R. K.; Manners, I. Uniform Biodegradable Fiber-Like Micelles and Block Comicelles via “Living” Crystallization-Driven Self-Assembly of Poly(l-lactide) Block Copolymers: The Importance of Reducing Unimer Self-Nucleation via Hydrogen Bond Disruption. J. Am. Chem. Soc. 2019, 141 (48), 19088– 19098, DOI: 10.1021/jacs.9b09885[ACS Full Text], [CAS], Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVGmtrfO&md5=997e3bc1e4ca01b6c97f0e22123e8532Uniform Biodegradable Fiber-Like Micelles and Block Comicelles via "Living" Crystallization-Driven Self-Assembly of Poly(L-lactide) Block Copolymers: The Importance of Reducing Unimer Self-Nucleation via Hydrogen Bond DisruptionHe, Yunxiang; Eloi, Jean-Charles; Harniman, Robert L.; Richardson, Robert M.; Whittell, George R.; Mathers, Robert T.; Dove, Andrew P.; O'Reilly, Rachel K.; Manners, IanJournal of the American Chemical Society (2019), 141 (48), 19088-19098CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Fiber-like micelles based on biodegradable and biocompatible polymers exhibit considerable promise for applications in nanomedicine, but until recently no convenient methods were available to prep. samples with uniform and controllable dimensions and spatial control of functionality. "Living" crystn.-driven self-assembly (CDSA) is a seeded growth method of growing importance for the prepn. of uniform 1D and 2D core-shell nanoparticles from a range of crystallizable polymeric amphiphiles. However, in the case of poly(L-lactide) (PLLA), arguably the most widely utilized biodegradable polymer as the crystallizable core-forming block, the controlled formation of uniform fiber-like structures over a substantial range of lengths by "living" CDSA has been a major challenge. Herein, we demonstrate that via simple modulation of the solvent conditions via the addn. of trifluoroethanol (TFE), DMSO, DMF and acetone, uniform fiber-like nanoparticles from PLLA diblock copolymers with controlled lengths up to 1μm can be prepd. The probable mechanism involves improved unimer solvation by a redn. of hydrogen bonding interactions among PLLA chains. We provide evidence that this minimizes undesirable unimer aggregation which otherwise favors self-nucleation that competes with epitaxial crystn. from seed termini. This approach has also allowed the formation of well-defined segmented block comicelles with PLLA cores via the sequential seeded-growth of PLLA block copolymers with different corona-forming blocks.
- 36Magenau, A. J. D.; Richards, J. A.; Pasquinelli, M. A.; Savin, D. A.; Mathers, R. T. Systematic Insights from Medicinal Chemistry To Discern the Nature of Polymer Hydrophobicity. Macromolecules 2015, 48 (19), 7230– 7236, DOI: 10.1021/acs.macromol.5b01758[ACS Full Text], [CAS], Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFGrtb%252FJ&md5=8241ccde882ceb1bb05c46fe4bad34c0Systematic Insights from Medicinal Chemistry To Discern the Nature of Polymer HydrophobicityMagenau, Andrew J. D.; Richards, Jeffrey A.; Pasquinelli, Melissa A.; Savin, Daniel A.; Mathers, Robert T.Macromolecules (Washington, DC, United States) (2015), 48 (19), 7230-7236CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Predicting polymer hydrophobicity based on monomer structure is an ill-posed problem. Generally, the hydrophobicity of a polymer or a series of polymers has been detd. through indirect methods (i.e., contact angle) after polymn. This sequence presents a problem for the systematic design and rapid evaluation of specialty polymers synthesized via controlled polymn. methods. Here, we propose an approach inspired by medicinal chem. to predict polymer hydrophobicity based on octanol-water partition coeffs. (LogPoct) detd. through simple computational approaches. We envisioned that LogPoct, analogous to what is used in drug design, could provide a rational methodol. to translate mol. structures of monomers and oligomers into quantifiable hydrophobicity values for polymers. A combination of crit. design criteria and the predictive power of LogPoct values, normalized by surface area (LogPoct/SA), accurately assess polymer hydrophobicity. Exptl. corroboration with a polarity-sensitive dye (i.e., Nile Red), advancing water contact angles measurements, and swelling ratio expts. verify the method represents a dramatic improvement. A direct and quant. correlation existed between spectral shifts of Nile Red and calcd. LogPoct/SA values, confirming a quantifiable metric for predicting polymer hydrophobicity. Computationally predicted values also resulted in a first approxn. of advancing contact angle measurements over a broad spectrum of common polymers providing a basis for estg. contact angles, a screening tool to enhanced monomer design a priori, and a criterion to understand polymer phys. properties. Furthermore, swelling ratio measurements elucidated boundary limits for swelling of relatively hydrophobic and hydrophilic polymers in water and hexanes, in addn. to alternative alc. deriv. solvents.
- 37Fischer, F.; Zufferey, D.; Tahoces, R. Lower critical solution temperature in superheated water: the highest in the poly(N, N-dialkylacrylamide) series. Polym. Int. 2011, 60 (8), 1259– 1262, DOI: 10.1002/pi.3071[Crossref], [CAS], Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXptlWksb4%253D&md5=1d99dfcf05810db5a5b9ee2b0e27e36bLower critical solution temperature in superheated water: the highest in the poly(N,N-dialkylacrylamide) seriesFischer, Fabian; Zufferey, Daniel; Tahoces, RaulPolymer International (2011), 60 (8), 1259-1262CODEN: PLYIEI; ISSN:0959-8103. (John Wiley & Sons Ltd.)Microcalorimetry and cloud point extrapolation indicate a lower crit. soln. temp. of 216 °C for poly(N,N-dimethylacrylamide) (PDMA). This is the highest phase-transition temp. in the poly(N,N-dialkylacrylamide) series. Cloud points were recorded from electrolyte solns. made of Na3PO4, CaCO3, (NH4)2SO4 and KOH. These measurements were realized below and beyond the b.p. of water. The hydrolytic properties of PDMA in superheated water (200 °C) were examd. and verified using 1H NMR anal. The knowledge of the phase-transition temp. of pure PDMA is of interest, as it is often a constituent of smart copolymers, to adjust the responsiveness to a desired temp. threshold. Copyright © 2011 Society of Chem. Industry.
- 38Lerch, A.; Käfer, F.; Prévost, S.; Agarwal, S.; Karg, M. Structural Insights into Polymethacrylamide-Based LCST Polymers in Solution: A Small-Angle Neutron Scattering Study. Macromolecules 2021, 54 (16), 7632– 7641, DOI: 10.1021/acs.macromol.1c00698[ACS Full Text], [CAS], Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhslSnt7%252FN&md5=31e1ce4c28a886673690cb29c2883a9fStructural Insights into Polymethacrylamide-Based LCST Polymers in Solution: A Small-Angle Neutron Scattering StudyLerch, Arne; Kaefer, Florian; Prevost, Sylvain; Agarwal, Seema; Karg, MatthiasMacromolecules (Washington, DC, United States) (2021), 54 (16), 7632-7641CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Copolymn. is a powerful method that offers access to new polymer materials with a tailored response to external stimuli like temp. and pH. Polymers with a lower crit. soln. temp. are well known to undergo a coil-to-globule transition when the temp. is raised above the transition temp. In particular, for copolymers, complex inter- and intrachain interactions may complicate this simple picture of a single-chain phase transition. In this work, we study the phase transition of poly((methylacrylamide)-stat-(N-cyclohexylacrylamide)) copolymers at different concns. in heavy water by using small-angle neutron scattering. Measurements are performed well below and above the resp. cloud points of polymers with two different mol. wts. We show that interchain interactions are already present below the cloud point even in the dil. regime. Above the cloud point, polymer-polymer interactions become more prominent and polydisperse aggregates form.
- 39Tsui, H.-W.; Wang, J.-H.; Hsu, Y.-H.; Chen, L.-J. Study of heat of micellization and phase separation for Pluronic aqueous solutions by using a high sensitivity differential scanning calorimetry. Colloid Polym. Sci. 2010, 288 (18), 1687– 1696, DOI: 10.1007/s00396-010-2308-5[Crossref], [CAS], Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXht1KnsrbI&md5=ec5e219cdaace3e1bfcab41814cb6e2eStudy of heat of micellization and phase separation for Pluronic aqueous solutions by using a high sensitivity differential scanning calorimetryTsui, Hung-Wei; Wang, Jing-Han; Hsu, Ya-Hui; Chen, Li-JenColloid and Polymer Science (2010), 288 (18), 1687-1696CODEN: CPMSB6; ISSN:0303-402X. (Springer)Heat of micellization and phase sepn. temp. (known as cloud point) for the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (abbreviated by PEO-PPO-PEO) triblock copolymers, the Pluronics F108, F98, F88, F68, F38, P65, and L62, in water are carefully detd. by using a high sensitivity differential scanning calorimeter. It is interesting to find out that there exists a max. heat of micellization for all these Pluronics. In this study, the heat of micellization of all of the Pluronics decreases as the temp. increases, as expected, at high temp. region (low Pluronic concn. region). However, the enthalpy change has a surprisingly pos. relationship with temp. at low temp. region (high Pluronic concn. region). The crit. micelle temp. consistently decreases as the Pluronic concn. increases. This unexpected behavior of the pos. heat capacity changes of Pluronic aq. solns. at higher concn. region is somewhat related to the variation of water accessible polar (PEO groups) and non-polar (PPO groups) surface areas in the micellization process. Esp., the removal of polar surface area from water may dominate the contribution to the pos. heat capacity change upon micellization. In addn., the cloud points of Pluronic solns. are also discussed. The enthalpy-entropy compensation phenomenon for the micellization of Pluronics is discussed, and the enthalpy-entropy compensation temp. is calcd.
- 40Dharmaratne, N. U.; Jouaneh, T. M. M.; Kiesewetter, M. K.; Mathers, R. T. Quantitative Measurements of Polymer Hydrophobicity Based on Functional Group Identity and Oligomer Length. Macromolecules 2018, 51 (21), 8461– 8468, DOI: 10.1021/acs.macromol.8b01747[ACS Full Text], [CAS], Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvFWrtr%252FO&md5=7473694ba112c04930cfeed026d9435aQuantitative Measurements of Polymer Hydrophobicity Based on Functional Group Identity and Oligomer LengthDharmaratne, Nayanthara U.; Jouaneh, Terra Marie M.; Kiesewetter, Matthew K.; Mathers, Robert T.Macromolecules (Washington, DC, United States) (2018), 51 (21), 8461-8468CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)A combined exptl. and computational investigation revealed a hydrophobicity trend for oxygen-contg. functional groups commonly encountered in monomers and polymers. Based on solvatochromatic dye expts., HPLC retention times, and theor. LogP values, the arrangement of the three oxygen atoms in carbonates results in more hydrophobicity than other permutations like anhydrides. Another trend emerged for functional groups with two oxygen atoms (acetals > esters). Overall, when comparing aliph. polymers with similarly sized monomers, hydrophobicity decreased as follows: carbonates > acetals > esters > anhydrides. These trends have important implications for degrdn., cond., and many other applications.
- 41Yildirim, E.; Dakshinamoorthy, D.; Peretic, M. J.; Pasquinelli, M. A.; Mathers, R. T. Synthetic Design of Polyester Electrolytes Guided by Hydrophobicity Calculations. Macromolecules 2016, 49 (20), 7868– 7876, DOI: 10.1021/acs.macromol.6b01452[ACS Full Text], [CAS], Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1SqsrbK&md5=460d1c464d255bf882d529dff329e44fSynthetic Design of Polyester Electrolytes Guided by Hydrophobicity CalculationsYildirim, Erol; Dakshinamoorthy, Deivasagayam; Peretic, Matthew J.; Pasquinelli, Melissa A.; Mathers, Robert T.Macromolecules (Washington, DC, United States) (2016), 49 (20), 7868-7876CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Partition coeffs. (LogP) help to quantify hydrophobicity, which can be used to guide the design of polymer electrolytes with targeted properties. Thus, this study combined synthetic expts. and mol. modeling to produce polyester electrolytes that solubilize lithium salts. These polyester electrolytes were derived from natural sources and polymd. with different ratios of polyols (diglycerol, glycerol, and diethylene glycol) and citric acid in the presence of lithium salts (LiTf and LiTFSI). The Fisher esterification produced homogeneous, cross-linked films with high optical transparency, whereas the lithium salts increased glass transition temps. The LogP values of monomers and the resulting polyesters were predict ed using cheminformatics tools and indicate changing diglycerol to glycerol or diethylene glycol alters the hydrophobicity. Comparison of different mol. modeling methods with predicted LogP values demonstrate that LogP values are a reliable means of tailoring phys. and chem. properties of these polymer electrolytes. Addnl., LogP values greatly benefit from being extremely less expensive from a computational standpoint as well as more convenient for calcg. precursory quant. information.
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Abstract
Figure 1
Figure 1. Our studies on how hydrophobicity influences thermoresponsive behavior of (A) brushy polymers and (B) nonbrushy polymers.
Figure 2
Figure 2. (A) Synthetic scheme for the preparation of P(DMA-co-RA) statistical copolymers. THFA is used as the comonomer in this example. (B) Molar composition (determined by 1H NMR spectroscopy), number-average MW (Mn), and dispersity (ĐM; determined by SEC) of P(DMA-co-THFA) copolymers. (C) 1H NMR spectra of P(DMA-co-THFA) copolymers in CDCl3 (300 MHz). (D) Normalized SEC molecular weight distributions for the P(DMA-co-THFA) series (eluent: CHCl3 + 0.5 v/v% NEt3, PMMA standards). (E) Percent transmittance as a function of temperature for the P(DMA-co-THFA) copolymers dissolved in H2O at 10 mg/mL as measured by UV–vis spectroscopy (λ = 550 nm, 0–90 °C, 1 °C min–1).
Figure 3
Figure 3. (A) Chemical structures of the repeating units for the P(DMA-co-nBuA), P(DMA-co-BA), P(DMA-co-THFA), and P(DMA-co-tBuA) copolymers, respectively. (B) Calculated Log Poct/SA values for P(DMA-co-RA) copolymer oligomers as a function of the mol % of the hydrophobic comonomer. (C) Plot of TCP as measured by UV–vis spectroscopy vs the mol % of hydrophobic comonomer. (D) Plot of TCP as measured by UV–vis spectroscopy vs the calculated Log Poct/SA values for P(DMA-co-RA) copolymer oligomers. The solid line represents a linear fit of these data. (E) Comparison between measured TCP values of P(DMA-co-RA) copolymers and those predicted from their Log Poct/SA. The solid line represents a linear fit of these data. The equation was generated using the linear fit of the data in the plot of Figure 3D.
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- 4Zhang, A.; Jung, K.; Li, A.; Liu, J.; Boyer, C. Recent advances in stimuli-responsive polymer systems for remotely controlled drug release. Prog. Polym. Sci. 2019, 99, 101164, DOI: 10.1016/j.progpolymsci.2019.101164[Crossref], [CAS], Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvFOkurvO&md5=b900ffcd67e430823eabd14a0093e313Recent advances in stimuli-responsive polymer systems for remotely controlled drug releaseZhang, Aitang; Jung, Kenward; Li, Aihua; Liu, Jingquan; Boyer, CyrilleProgress in Polymer Science (2019), 99 (), 101164CODEN: PRPSB8; ISSN:0079-6700. (Elsevier Ltd.)Promoted by recent advances in developing nanomaterials and drug delivery, stimuli-responsive polymer systems that can remotely trigger drug release in a spatiotemporal manner has attracted significant attention in biotechnol. Implementation of remote-controlled release requires functional polymers to be susceptible to specific phys. and/or chem. stimuli. In this minireview, we focus on the recent advances in the construction of stimuli-responsive polymer systems for remotely controlling drug release in response to an externally applied stimulus (light, microwave, magnetic field, elec. field and ultrasound). The design of the stimuli-responsive polymer systems and formulations to remotely control the release of drug mols. is also highlighted in this minireview. Furthermore, the potential in biomedical applications and the perspectives of future developments of these stimuli-responsive polymer systems are also briefly discussed.
- 5Zhang, X.; Han, L.; Liu, M.; Wang, K.; Tao, L.; Wan, Q.; Wei, Y. Recent progress and advances in redox-responsive polymers as controlled delivery nanoplatforms. Mater. Chem. Front. 2017, 1 (5), 807– 822, DOI: 10.1039/C6QM00135A[Crossref], [CAS], Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1elsL%252FK&md5=c1058f16e81fcbe65ee09bfda20c8229Recent progress and advances in redox-responsive polymers as controlled delivery nanoplatformsZhang, Xiaoyong; Han, Lu; Liu, Meiying; Wang, Ke; Tao, Lei; Wan, Qing; Wei, YenMaterials Chemistry Frontiers (2017), 1 (5), 807-822CODEN: MCFAC5; ISSN:2052-1537. (Royal Society of Chemistry)A review. Stimuli-responsive polymeric nanosystems that can respond to biol. stimuli such as pH, temp., glucose, enzymes or redox conditions have been extensively explored for different biomedical applications. Among these, redox conditions should be the most useful stimulus in biol. systems, which rely on the significantly different redox states in the circulation/extracellular fluids and intracellular compartments. By incorporation of redox-responsive linkages such as disulfide and diselenide into polymers, different redox-responsive polymeric nanosystems can be fabricated. In this article, a no. of redox-responsive polymeric therapeutic nanosystems and their design principles are included. Recent advances in these redox-responsive polymeric therapeutic nanosystems for controlled cytoplasmic delivery of a no. of bioactive mols. (e.g. drugs, biol. proteins, plasmid DNA, siRNA) are also highlighted. This will provide useful information for the design and biomedical applications of redox-responsive polymeric therapeutic nanosystems, which will attract great research interest from scientists in chem., materials, biol., medicine and interdisciplinary areas.
- 6Roy, D.; Brooks, W. L. A.; Sumerlin, B. S. New directions in thermoresponsive polymers. Chem. Soc. Rev. 2013, 42 (17), 7214– 7243, DOI: 10.1039/c3cs35499g[Crossref], [PubMed], [CAS], Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1WisbzF&md5=b8059145b96ed15e151c6da6bb348603New directions in thermoresponsive polymersRoy, Debashish; Brooks, William L. A.; Sumerlin, Brent S.Chemical Society Reviews (2013), 42 (17), 7214-7243CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Interest in thermoresponsive polymers has steadily grown over many decades, and a great deal of work has been dedicated to developing temp. sensitive macromols. that can be crafted into new smart materials. However, the overwhelming majority of previously reported temp.-responsive polymers are based on poly(N-isopropylacrylamide) (PNIPAM), despite the fact that a wide range of other thermoresponsive polymers have demonstrated similar promise for the prepn. of adaptive materials. Herein, we aim to highlight recent results that involve thermoresponsive systems that have not yet been as fully considered. Many of these (co)polymers represent clear opportunities for advancements in emerging biomedical and materials fields due to their increased biocompatibility and tuneable response. By highlighting recent examples of newly developed thermoresponsive polymer systems, we hope to promote the development of new generations of smart materials.
- 7Zhang, Q.; Hoogenboom, R. Polymers with upper critical solution temperature behavior in alcohol/water solvent mixtures. Prog. Polym. Sci. 2015, 48, 122– 142, DOI: 10.1016/j.progpolymsci.2015.02.003[Crossref], [CAS], Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXks1yks78%253D&md5=5db1fcf88f3936566abef042a6d8f9c7Polymers with upper critical solution temperature behavior in alcohol/water solvent mixturesZhang, Qilu; Hoogenboom, RichardProgress in Polymer Science (2015), 48 (), 122-142CODEN: PRPSB8; ISSN:0079-6700. (Elsevier Ltd.)A review. Thermoresponsive polymers are of great importance in numerous nanotechnol. and biomedical applications. Compared to polymers that undergo a lower crit. soln. temp. (LCST) phase transition in aq. soln., i.e., demixing occurs upon heating, polymers exhibiting the reversed upper crit. soln. temp. (UCST) behavior in aq. soln. have been much less documented as it is more challenging to achieve this behavior in aq. solns. Furthermore, the high sensitivity of UCST behavior to minor variation in polymer structure and soln. compn. hampered the development of applications based on these polymers [18]. However, polymers with UCST transition in alc./water solvent mixts. are more commonly reported and exhibit promising properties for the prepn. of 'smart' materials. This review will focus on the theory and development of such polymers with UCST behavior in alc./water solvent mixts. By highlighting the reported examples of UCST polymers in alc./water solvent mixts., we aim to demonstrate the versatility and potential that such UCST polymers possess as biomedical and 'smart' materials.
- 8Vanparijs, N.; Nuhn, L.; De Geest, B. G. Transiently thermoresponsive polymers and their applications in biomedicine. Chem. Soc. Rev. 2017, 46 (4), 1193– 1239, DOI: 10.1039/C6CS00748A[Crossref], [PubMed], [CAS], Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitFektbc%253D&md5=f0a3888358a833de232d6b2d7aa7ecc7Transiently thermoresponsive polymers and their applications in biomedicineVanparijs, Nane; Nuhn, Lutz; De Geest, Bruno G.Chemical Society Reviews (2017), 46 (4), 1193-1239CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)The focus of this review is on the class of transiently thermoresponsive polymers. These polymers are thermoresponsive, but gradually lose this property upon chem. transformation - often a hydrolysis reaction - in the polymer side chain or backbone. An overview of the different approaches used for the design of these polymers along with their physicochem. properties is given. Their amphiphilic properties and degradability into fully sol. compds. make this class of responsive polymers attractive for drug delivery and tissue engineering applications. Examples of these are also provided in this review.
- 9Doberenz, F.; Zeng, K.; Willems, C.; Zhang, K.; Groth, T. Thermoresponsive polymers and their biomedical application in tissue engineering - a review. J. Mater. Chem. B 2020, 8 (4), 607– 628, DOI: 10.1039/C9TB02052G[Crossref], [PubMed], [CAS], Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjvVWjtg%253D%253D&md5=a0ebe5ab84d7dd6e8d5c929584170d45Thermoresponsive polymers and their biomedical application in tissue engineering - a reviewDoberenz, Falko; Zeng, Kui; Willems, Christian; Zhang, Kai; Groth, ThomasJournal of Materials Chemistry B: Materials for Biology and Medicine (2020), 8 (4), 607-628CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)A review. Thermoresponsive polymers hold great potential in the biomedical field, since they enable the fabrication of cell sheets, in situ drug delivery and 3D-printing under physiol. conditions. In this review we provide an overview of several thermoresponsive polymers and their application, with focus on poly(N-isopropylacrylamide)-surfaces for cell sheet engineering. Basic knowledge of important processes like protein adsorption on surfaces and cell adhesion is provided. For different thermoresponsive polymers, namely PNIPAm, Pluronics, elastin-like polypeptides (ELP) and poly(N-vinylcaprolactam) (PNVCL), synthesis and basic chem. and phys. properties have been described and the mechanism of their thermoresponsive behavior highlighted. Fabrication methods of thermoresponsive surfaces have been discussed, focusing on PNIPAm, and describing several methods in detail. The latter part of this review is dedicated to the application of the thermoresponsive polymers and with regard to cell sheet engineering, the process of temp.-dependent cell sheet detachment is explained. We provide insight into several applications of PNIPAm surfaces in cell sheet engineering. For Pluronics, ELP and PNVCL we show their application in the field of drug delivery and tissue engineering. We conclude, that research of thermoresponsive polymers has made big progress in recent years, esp. for PNIPAm since the 1990s. However, manifold research possibilities, e.g. in surface fabrication and 3D-printing and further translational applications are conceivable in near future.
- 10Zhang, Q.; Weber, C.; Schubert, U. S.; Hoogenboom, R. Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditions. Mater. Horiz. 2017, 4 (2), 109– 116, DOI: 10.1039/C7MH00016B[Crossref], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1yjtb8%253D&md5=0b3b67a706a7ee1f549bbb03a734b0e0Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditionsZhang, Qilu; Weber, Christine; Schubert, Ulrich S.; Hoogenboom, RichardMaterials Horizons (2017), 4 (2), 109-116CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)Thermoresponsive polymers that undergo reversible phase transition by responding to an environmental temp. change, in particular polymers showing lower crit. soln. temp. (LCST), are frequently used as smart materials that have found increasing applications. Recently, there has been a rapid growth in interest on LCST polymers and many new research groups are entering the field from a wide range of application areas. While it is great to see more researchers working on LCST polymers, the downside of this rapid growth is that the fundamentals of the LCST phase transition behavior are not always clearly known and respected. Hence, this focus article provides a systematic discussion of the key aspects of the LCST behavior of polymers starting from fundamentals of LCST behavior to practical detn. of cloud point temp. (Tcp). Finally, we offer a basic set of recommended measuring conditions for detn. of Tcp (10 mg mL-1; 0.5°C min-1; 600 nm) to facilitate the comparison of the LCST behavior and Tcp values of polymers developed and studied in different labs. around the globe, which is nowadays nearly impossible since various techniques and parameters are being utilized for the measurements. It should be noted that these recommended conditions serve as a robust tool for turbidimetry, which is one out of the many characterization techniques one should utilize to fully understand LCST behavior of polymers.
- 11Ieong, N. S.; Hasan, M.; Phillips, D. J.; Saaka, Y.; O’Reilly, R. K.; Gibson, M. I. Polymers with molecular weight dependent LCSTs are essential for cooperative behaviour. Polym. Chem. 2012, 3 (3), 794– 799, DOI: 10.1039/c2py00604a[Crossref], [CAS], Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvFaltbY%253D&md5=141c23b5a069a98f4df6b8d74273a72cPolymers with molecular weight dependent LCSTs are essential for cooperative behaviorIeong, Nga Sze; Hasan, Muhammad; Phillips, Daniel J.; Saaka, Yussif; O'Reilly, Rachel K.; Gibson, Matthew I.Polymer Chemistry (2012), 3 (3), 794-799CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)The potential to fine-tune the transition temps. of polymers displaying lower-crit. soln. temps. (LCST) by a simple mixing strategy is investigated. Using a panel of four distinct polymer classes (poly[oligo(ethyleneglycol)methacrylate], poly(N-vinylpiperidone), poly(N-vinylcaprolactam) poly(N-isopropylacrylamide)) it was shown that only those with strong mol. wt. dependent LCSTs produced a single, cooperative, transition when blended together. Furthermore, the actual transition temp. was linked to the wt. av. not the no. av. mol. wt. The only polymer which did not show strong mol.-wt.-LCST correlation was poly(oligo(ethyleneglycol)methacrylate), which showed two independent transitions, one for each polymer.
- 12Liu, Z.; Guo, Y.; Inomata, K. LCST-type phase behavior of poly(2-chloroethyl vinyl ether-alt-maleic anhydride) in n-butyl acetate. Polym. J. 2011, 43 (8), 676– 682, DOI: 10.1038/pj.2011.41[Crossref], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpvV2itrc%253D&md5=accf8daccd588b9101ad3e7d5bdf5747LCST-type phase behavior of poly(2-chloroethyl vinyl ether-alt-maleic anhydride) in n-butyl acetateLiu, Zhenjie; Guo, Yongliang; Inomata, KatsuhiroPolymer Journal (Tokyo, Japan) (2011), 43 (8), 676-682CODEN: POLJB8; ISSN:0032-3896. (NPG Nature Asia-Pacific)Novel polymer solns. exhibiting lower crit. soln. temps. (LCSTs) have been studied. An alternating copolymer of 2-chloroethyl vinyl ether and maleic anhydride was synthesized through free-radical soln. polymn. This copolymer can exhibit LCST-type phase behavior in Bu acetate (BuAc) under relatively mild conditions at temps. sufficiently below its b.p. The effects of mol. wt., polymer concn. and addn. of cosolvent on the polymer soln.'s cloud point temp. (Tcp) were investigated. The Tcp value was nearly const. over a wide range of concns. and increased when the polymer concn. was reduced below a certain value. The exptl. LCST-type phase diagram can be reasonably described by Flory-Huggins theory. The addn. of non-solvents could reduce the Tcp of the polymer soln. in BuAc, whereas the addn. of good solvents could increase the Tcp. These LCST-type phase behaviors may be attributed to specific polar interactions between the polymer and the solvent.
- 13Keogh, R.; Blackman, L. D.; Foster, J. C.; Varlas, S.; O’Reilly, R. K. The Importance of Cooperativity in Polymer Blending: Toward Controlling the Thermoresponsive Behavior of Blended Block Copolymer Micelles. Macromol. Rapid Commun. 2020, 41 (6), 1900599, DOI: 10.1002/marc.201900599[Crossref], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFGjsL4%253D&md5=abeced61e31d53497d8dbe65c95f0fa2The Importance of Cooperativity in Polymer Blending: Toward Controlling the Thermoresponsive Behavior of Blended Block Copolymer MicellesKeogh, Robert; Blackman, Lewis D.; Foster, Jeffrey C.; Varlas, Spyridon; O'Reilly, Rachel K.Macromolecular Rapid Communications (2020), 41 (6), 1900599CODEN: MRCOE3; ISSN:1022-1336. (Wiley-VCH Verlag GmbH & Co. KGaA)Understanding, predicting, and controlling the self-assembly behavior of stimuli-responsive block copolymers remains a pertinent challenge. Copolymer blending protocol provides an accessible methodol. for obtaining a range of intermediate polymeric nanostructures simply by blending two or more block copolymers in desired molar ratio to target specific stimuli-responsiveness. Herein, thermoresponsive amphiphilic diblock copolymers are blended in various combinations that composed of statistical poly(Bu acrylate-co-N,N-dimethylacrylamide) core-forming blocks and four different thermoresponsive corona-forming blocks, namely poly(diethylene glycol monomethyl ether methacrylate) (p(DEGMA)), poly(N-isopropylacrylamide), poly(N,N-diethylacrylamide), and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (p(OEGMA)) are selected for evaluation. Using variable temp. turbidimetry, the thermoresponsive behavior of blended diblock copolymer self-assemblies is assessed and compared to thermoresponsive behavior of the constituent pure diblock copolymer micelles to det. whether comicellization is achieved or whether the two blended corona-forming thermoresponsive blocks exhibit cooperative behavior. Blended diblock copolymer micelles composed of p(DEGMA)/p(OEGMA) mixed coronae display cooperative behavior, highlighting the potential of copolymer blending for the prepn. of stimuli-responsive nanomaterials in applications such as oil recovery, drug delivery, biosensing, and catalysis.
- 14Miclotte, M. P. J.; Lawrenson, S. B.; Varlas, S.; Rashid, B.; Chapman, E.; O’Reilly, R. K. Tuning the Cloud-Point and Flocculation Temperature of Poly(2-(diethylamino)ethyl methacrylate)-Based Nanoparticles via a Postpolymerization Betainization Approach. ACS Polym. Au 2021, 1 (1), 47– 58, DOI: 10.1021/acspolymersau.1c00010[ACS Full Text], [CAS], Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsVyrsrrP&md5=a138208f5fd78b638defdf2d979d790fTuning the Cloud-Point and Flocculation Temperature of Poly(2-(diethylamino)ethyl methacrylate)-Based Nanoparticles via a Postpolymerization Betainization ApproachMiclotte, Matthieu P. J.; Lawrenson, Stefan B.; Varlas, Spyridon; Rashid, Bilal; Chapman, Emma; O'Reilly, Rachel K.ACS Polymers Au (2021), 1 (1), 47-58CODEN: APACCD; ISSN:2694-2453. (American Chemical Society)The ability to tune the behavior of temp.-responsive polymers and self-assembled nanostructures has attracted significant interest in recent years, particularly in regard to their use in biotechnol. applications. Herein, well-defined poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA)-based core-shell particles were prepd. by RAFT-mediated emulsion polymn., which displayed a lower-crit. soln. temp. (LCST) phase transition in aq. media. The tertiary amine groups of PDEAEMA units were then utilized as functional handles to modify the core-forming block chem. via a postpolymn. betainization approach for tuning both the cloud-point temp. (TCP) and flocculation temp. (TCFT) of these particles. In particular, four different sulfonate salts were explored aiming to investigate the effect of the carbon chain length and the presence of hydroxyl functionalities alongside the carbon spacer on the particle's thermoresponsiveness. In all cases, it was possible to regulate both TCP and TCFT of these nanoparticles upon varying the degree of betainization. Although TCP was found to be dependent on the type of betainization reagent utilized, it only significantly increased for particles betainized using sodium 3-chloro-2-hydroxy-1-propanesulfonate, while varying the aliph. chain length of the sulfobetaine only provided limited temp. variation. In comparison, the onset of flocculation for betainized particles varied over a much broader temp. range when varying the degree of betainization with no real correlation identified between TCFT and the sulfobetaine structure. Moreover, exptl. results were shown to partially correlate to computational oligomer hydrophobicity calcns. Overall, the innovative postpolymn. betainization approach utilizing various sulfonate salts reported herein provides a straightforward methodol. for modifying the thermoresponsive behavior of soft polymeric particles with potential applications in drug delivery, sensing, and oil/lubricant viscosity modification.
- 15Ramírez-Jiménez, A.; Montoya-Villegas, K. A.; Licea-Claverie, A.; Gónzalez-Ayón, M. A. Tunable Thermo-Responsive Copolymers from DEGMA and OEGMA Synthesized by RAFT Polymerization and the Effect of the Concentration and Saline Phosphate Buffer on Its Phase Transition. Polymer 2019, 11 (10), 1657, DOI: 10.3390/polym11101657
- 16Van Guyse, J. F. R.; Bera, D.; Hoogenboom, R. Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition. Polymer 2021, 13 (3), 374, DOI: 10.3390/polym13030374
- 17Eggenhuisen, T. M.; Becer, C. R.; Fijten, M. W. M.; Eckardt, R.; Hoogenboom, R.; Schubert, U. S. Libraries of Statistical Hydroxypropyl Acrylate Containing Copolymers with LCST Properties Prepared by NMP. Macromolecules. 2008, 41 (14), 5132– 5140, DOI: 10.1021/ma800469p[ACS Full Text], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXns1Cltbg%253D&md5=e5693c726708252bb4cfb43e3376d692Libraries of Statistical Hydroxypropyl Acrylate Containing Copolymers with LCST Properties Prepared by NMPEggenhuisen, Tamara M.; Becer, C. Remzi; Fijten, Martin W. M.; Eckardt, Rebecca; Hoogenboom, Richard; Schubert, Ulrich S.Macromolecules (Washington, DC, United States) (2008), 41 (14), 5132-5140CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)The nitroxide-mediated copolymn. of 2-hydroxypropyl acrylate (HPA) with N-acryloylmorpholine (Amor) or N,N-dimethylacrylamide (DMA) was studied using N-tert-butyl-N-(1'-diethylphosphono-2,2'-dimethylpropyl)-O-(2-carboxyl-prop-2-yl) (BlocBuilder) alkoxyamine initiator and addnl. free nitroxide (SG1). Different reaction conditions, such as the concn. of addnl. SG-1, were tested to optimize the homopolymns. using a Chemspeed ASW2000 automated parallel synthesizer. Best control for the homopolymns. (polydispersity indexes of 1.2-1.3) of all three monomers was achieved using 20% addnl. SG-1 (relative to the initiator) at a reaction temp. of 110 °C for 2 M solns. in N,N-dimethylformamide and a monomer/initiator ratio of 100/1. Libraries of P(Amor-stat-HPA) and P(DMA-stat-HPA) were synthesized with 0-100 mol % HPA with 10 mol % increments using the optimized conditions obtained for the homopolymns. The resulting polymers had narrow mol. wt. distributions, and their compns., detd. using 1H NMR spectroscopy and elemental anal., were close to the theor. compns. In addn., all copolymers of both libraries had single glass transition temps. (Tg), and the transition temps. decreased from the Tg of P(Amor) (147 °C) and P(DMA) (111 °C) to the Tg of P(HPA) (22 °C) with increasing HPA content. The cloud point of P(HPA) showed concn. dependence and a concn. dependent hysteresis. The cloud points of aq. solns. of the copolymer libraries could be tuned from 21.4 to 88.0 °C and to 82.9 °C for P(Amor-stat-HPA) and P(DMA-stat-HPA), resp., at a concn. of 1 wt. %. LCST behavior was obsd. for copolymers with >40 wt. % HPA in P(Amor-stat-HPA) and >55 wt. % HPA in the P(DMA-stat-HPA) library.
- 18Vogt, A. P.; Sumerlin, B. S. Tuning the Temperature Response of Branched Poly(N-isopropylacrylamide) Prepared by RAFT Polymerization. Macromolecules. 2008, 41 (20), 7368– 7373, DOI: 10.1021/ma801256k[ACS Full Text], [CAS], Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtFGjsLzJ&md5=d963455a09cb6258be16397a0043c390Tuning the Temperature Response of Branched Poly(N-isopropylacrylamide) Prepared by RAFT PolymerizationVogt, Andrew P.; Sumerlin, Brent S.Macromolecules (Washington, DC, United States) (2008), 41 (20), 7368-7373CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Reversible addn.-fragmentation chain transfer (RAFT) polymn. in the presence of a compd. capable of both reversible chain transfer through a thiocarbonylthio moiety and propagation via a vinyl group led to highly branched copolymers by a method analogous to self-condensing vinyl copolymn. An acryloyl trithiocarbonate prepd. by copper-catalyzed azide-alkyne cycloaddn. was copolymd. with N-isopropylacrylamide (NIPAM) in ratios selected to tune the distribution and length of branches in the resulting thermoresponsive polymers. The degree of branching increased with chain transfer agent (CTA) concn., as proven by NMR spectroscopy, size exclusion chromatog., and viscometry. Retention of the thiocarbonylthio compd. during the polymn. was evidenced by successful chain extension of a branched N-isopropylacrylamide (PNIPAM) macroCTA by RAFT polymn. of N,N-dimethylacrylamide. The branched polymers led to reduced lower crit. soln. temps. as compared to linear PNIPAM, an effect attributed primarily to an increased contribution of hydrophobic end groups. End group cleavage by radical-induced redn. resulted in an increased transition temp. more similar to that expected for linear PNIPAM.
- 19Smith, A. A. A.; Maikawa, C. L.; Lopez Hernandez, H.; Appel, E. A. Controlling properties of thermogels by tuning critical solution behaviour of ternary copolymers. Polym. Chem. 2021, 12 (13), 1918– 1923, DOI: 10.1039/D0PY01696A[Crossref], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXntlSjsb0%253D&md5=f85fc853b87c6d842ca10b34dc934d2bControlling properties of thermo-gels by tuning critical solution behavior of ternary copolymersSmith, Anton A. A.; Maikawa, Caitlin L.; Lopez Hernandez, Hector; Appel, Eric A.Polymer Chemistry (2021), 12 (13), 1918-1923CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)Thermoresponsive hydrogel materials show promise as biomaterials as their properties can be widely tuned to fit engineering requirements for an array of important applications. Here we show that the properties of thermo-gelling tri-block copolymers consisting of a central poly(ethylene glycol) block and pendant N-substituted polyacrylamides can be tuned by altering the random terpolymer compns. The heterogeneity of the pendant terpolymer blocks is reflected in the concn. dependence of their crit. soln. behavior. The lower crit. soln. temp. (LCST) of the pendant blocks can be finely tuned, enabling controlled modulation of thermo-gel properties. Altering terpolymer compn. to control LCST behavior, therefore, provides a facile approach to design thermo-gel properties.
- 20Luzon, M.; Boyer, C.; Peinado, C.; Corrales, T.; Whittaker, M.; Tao, L.; Davis, T. P. Water-soluble, thermoresponsive, hyperbranched copolymers based on PEG-methacrylates: Synthesis, characterization, and LCST behavior. J. Polym. Sci. A: Polym. Chem. 2010, 48 (13), 2783– 2792, DOI: 10.1002/pola.24027[Crossref], [CAS], Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXms1yhsbk%253D&md5=8754e2a808b5b0094971af9bf8913201Water-soluble, thermoresponsive, hyperbranched copolymers based on PEG-methacrylates: synthesis, characterization, and LCST behaviorLuzon, Mario; Boyer, Cyrille; Peinado, Carmen; Corrales, Teresa; Whittaker, Michael; Tao, Lei; Davis, Thomas P.Journal of Polymer Science, Part A: Polymer Chemistry (2010), 48 (13), 2783-2792CODEN: JPACEC; ISSN:0887-624X. (John Wiley & Sons, Inc.)A series of water-sol. thermoresponsive hyperbranched copoly(oligoethylene glycol)s were synthesized by copolymn. of di(ethylene glycol) methacrylate (DEG-MA) and oligo(ethylene glycol) methacrylate (OEG-MA, Mw = 475 g/mol), with ethylene glycol dimethacrylate (EGD-MA) used as the crosslinker, via reversible addn. fragmentation chain transfer polymn. Polymers were characterized by size exclusion chromatog. and NMR analyses. According to the monomer compn., i.e., the ratio of OEG-MA: DEG-MA: EGD-MA, the lower crit. soln. temp. (LCST) could be tuned from 25 °C to 90 °C. The thermoresponsive properties of these hyperbranched copolymers were studied carefully and compared with their linear analogs. It was found that mol. architecture influences thermoresponsive behavior, with a decrease of around 5-10 °C in the LCST of the hyperbranched polymers compared with the LCST of linear chains. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2783-2792, 2010.
- 21Akar, I.; Keogh, R.; Blackman, L. D.; Foster, J. C.; Mathers, R. T.; O’Reilly, R. K. Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical Copolymers. ACS Macro Lett. 2020, 9 (8), 1149– 1154, DOI: 10.1021/acsmacrolett.0c00461[ACS Full Text], [CAS], Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVChsrzP&md5=664a1eb64b5f92e900508e4e37b95a19Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical CopolymersAkar, Irem; Keogh, Robert; Blackman, Lewis D.; Foster, Jeffrey C.; Mathers, Robert T.; O'Reilly, Rachel K.ACS Macro Letters (2020), 9 (8), 1149-1154CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Thermoresponsive copolymers that exhibit a lower crit. soln. temp. (LCST) have been exploited to prep. stimuli-responsive materials for a broad range of applications. It is well understood that the LCST of such copolymers can be controlled by tuning mol. wt. or through copolymn. of two known thermoresponsive monomers. However, no general methodol. has been established to relate polymer properties to their temp. response in soln. Herein, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temp. (TCP). A series of statistical copolymers were synthesized based on hydrophilic oligoethylene glycol monomethyl ether methacrylate (OEGMA) and hydrophobic alkyl methacrylate monomers and their hydrophobicity was compared using surface area-normalized partition coeffs. (log Poct/SA). However, while some insight was gained by comparing TCP and hydrophobicity values, further statistical anal. on both exptl. and literature data showed that the molar percentage of comonomer (i.e., grafting d.) was the strongest influencer of TCP, regardless of the comonomer used. The lack of dependence of TCP on comonomer chem. implies that a broad range of functional, thermoresponsive materials can be prepd. based on OEGMA by simply tuning grafting d.
- 22Fournier, D.; Hoogenboom, R.; Thijs, H. M. L.; Paulus, R. M.; Schubert, U. S. Tunable pH- and Temperature-Sensitive Copolymer Libraries by Reversible Addition-Fragmentation Chain Transfer Copolymerizations of Methacrylates. Macromolecules 2007, 40 (4), 915– 920, DOI: 10.1021/ma062199r[ACS Full Text], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXlsl2gtg%253D%253D&md5=e750ef29e45f0b16be51ac313e30dbf2Tunable pH- and Temperature-Sensitive Copolymer Libraries by Reversible Addition-Fragmentation Chain Transfer Copolymerizations of MethacrylatesFournier, David; Hoogenboom, Richard; Thijs, Hanneke M. L.; Paulus, Renzo M.; Schubert, Ulrich S.Macromolecules (2007), 40 (4), 915-920CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Reversible addn.-fragmentation chain transfer (RAFT) polymns. were performed on a Chemspeed Accelerator SLT100 automated synthesizer to polymerize N,N-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) Me ether methacrylate (PEGMA) at 70 °C. Azobis(isobutyronitrile) (AIBN) was used as source of radicals and 2-cyano-2-Bu dithiobenzoate (CBDB) as RAFT agent. A complete screening in compn. of P(DMAEMA-stat-PEGMA) copolymers was elaborated from 0% of PEGMA to 100% of PEGMA. All polydispersity indexes of the obtained copolymers are comprised between 1.11 and 1.30. The reactivity ratios were detd. by the extended Kelen-Tuedoes method (rDMAEMA = 0.93 and rPEGMA = 0.66). The behavior of the pH- and temp.-sensitive copolymers was studied in aq. soln. by measuring the lower crit. soln. temp. (LCST) by UV/vis spectroscopy. The measurements were performed at three different pH values (4, 7, and 10). At pH 7 and pH 10 the LCST is increasing linearly with the wt. % PEGMA in the copolymer feed. On the contrary, at pH 4, the hydrophilicity of the P(DMAEMA-stat-PEGMA) copolymers is too high due to the protonation of the DMAEMA units. Thus, no LCST was detected for most of them. By varying the pH and the compn. of the P(DMAEMA-stat-PEGMA) copolymers, the LCST can be easily tuned between 34.7 and 82.0 °C.
- 23Bebis, K.; Jones, M. W.; Haddleton, D. M.; Gibson, M. I. Thermoresponsive behaviour of poly[(oligo(ethyleneglycol methacrylate)]s and their protein conjugates: importance of concentration and solvent system. Polym. Chem. 2011, 2 (4), 975– 982, DOI: 10.1039/c0py00408a[Crossref], [CAS], Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjvFWntr0%253D&md5=828ec2802f065d18f87c4021fe536c01Thermoresponsive behaviour of poly[(oligo(ethyleneglycol) methacrylate)]s and their protein conjugates: importance of concentration and solvent systemBebis, Konstantinos; Jones, Mathew W.; Haddleton, David M.; Gibson, Matthew I.Polymer Chemistry (2011), 2 (4), 975-982CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)Thermoresponsive poly[oligo(ethyleneglycol) methacrylate]s with a variety of different oligo(ethyleneglycol) graft lengths were synthesized by reversible-addn. fragmentation chain transfer (RAFT) polymn. The lower crit. soln. temp. (LCST) behavior of these polymers was evaluated as a function of polymer concn. and concn. of dissolved solutes, to understand their applicability for in vitro and in vivo expts. In the relevant dil. (<1 mg mL-1) concn. range, the obsd. LCSTs increased by approx. 6° compared to higher concns. This was confirmed by complimentary dynamic light scattering and differential scanning calorimetry measurements. The impact of biol. solns. on the LCST was detd. using bovine blood plasma, which resulted in obsd. LCSTs lower than what is found in traditional buffer or pure aq. solns. A well-defined polymer-protein conjugate was synthesized by the grafting from procedure, using single-electron transfer (SET) polymn. This model polymer-protein therapeutic also displayed similar concn. dependent behavior, highlighting the importance of testing novel smart materials and conjugates at both relevant concn. ranges and in appropriate solvent systems to use them in biotechnol. applications.
- 24Porsch, C.; Hansson, S.; Nordgren, N.; Malmström, E. Thermo-responsive cellulose-based architectures: tailoring LCST using poly(ethylene glycol) methacrylates. Polym. Chem. 2011, 2 (5), 1114– 1123, DOI: 10.1039/C0PY00417K[Crossref], [CAS], Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXltF2rtb0%253D&md5=fda4f91daffc36b87b549257b9f50a83Thermo-responsive cellulose-based architectures: tailoring LCST using poly(ethylene glycol) methacrylatesPorsch, Christian; Hansson, Susanne; Nordgren, Niklas; Malmstroem, EvaPolymer Chemistry (2011), 2 (5), 1114-1123CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)There is a growing interest in designing advanced macromol. architectures applicable for instance in drug delivery systems. Employing cellulose in these systems is particularly favorable due to attractive properties such as biocompatibility and low price. Addnl., thermo-responsive polymers of poly(ethylene glycol) methacrylates are promising in this field owing to their biocompatibility and non-toxicity. In the present study, amphiphilic thermo-responsive homo- and copolymers of oligo(ethylene glycol) Me ether methacrylate (OEGMA300) and di(ethylene glycol) Me ether methacrylate (DEGMA) were synthesized via ARGET ATRP. Both linear copolymers of DEGMA/OEGMA300 as well as comb architectures with copolymers of DEGMA/OEGMA300 grafted from hydroxypropyl cellulose were produced. The lower crit. soln. temp. of the linear copolymers was readily tailored by altering the monomer feed ratio. The grafting of the thermo-responsive polymers from hydroxypropyl cellulose resulted in a consistent decrease of the lower crit. soln. temp. compared to the linear analogs; however, interestingly the ability to tune the transition temp. remained. Moreover, the amphiphilic comb architectures formed polymeric micelles with low crit. micelle concns. Consequently, these advanced architectures combine the favorable properties of hydroxypropyl cellulose with the interesting thermo-responsive and stealth properties of poly(ethylene glycol) methacrylates, and may, therefore, find potential applications in biomedicine.
- 25Lutz, J.-F.; Hoth, A. Preparation of Ideal PEG Analogues with a Tunable Thermosensitivity by Controlled Radical Copolymerization of 2-(2-Methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) Methacrylate. Macromolecules 2006, 39 (2), 893– 896, DOI: 10.1021/ma0517042[ACS Full Text], [CAS], Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtlagu7jE&md5=d90758cc6a6f4a448a6fe3ee1e043fefPreparation of Ideal PEG Analogues with a Tunable Thermosensitivity by Controlled Radical Copolymerization of 2-(2-Methoxyethoxy)ethyl Methacrylate and Oligo(ethylene glycol) MethacrylateLutz, Jean-Francois; Hoth, AnnMacromolecules (2006), 39 (2), 893-896CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)A new class of water-sol. copolymers based on 2-(2-methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate P(MEO2MA-co-OEGMA) was investigated. ATRP at 60 °C in ethanol was found to be a very straightforward method for prepg. these copolymers in high yields. In the presence of the ATRP catalytic system CuCl/bipy, well-defined P(MEO2MA-co-OEGMA) samples with a controlled chain length and a narrow mol. wt. distribution could be prepd. Moreover, P(MEO2MA-co-OEGMA) copolymers were found to exhibit extremely interesting soln. properties in water. Indeed, the LCST of these copolymers could be accurately tuned by adjusting the fraction of OEGMA units in the copolymer chains. Thus, LCST can be predicted on demand by adjusting the initial compn. of the comonomer feed. For example, LCST of 37 or 39 °C could be precisely obtained by using either 8 or 10 % of OEGMA in the initial comonomer mixts. Moreover, the LCST of P(MEO2MA-co-OEGMA) samples was not found to be very dependent on polymer concn. Therefore, these new copolymers can be considered as ideal segments for constructing amphiphiles by CRP and moreover as very high potential candidates for application in biotechnol.
- 26Kokufuta, M. K.; Sato, S.; Kokufuta, E. LCST behavior of copolymers of N-isopropylacrylamide and N-isopropylmethacrylamide in water. Colloid Polym. Sci. 2012, 290 (16), 1671– 1681, DOI: 10.1007/s00396-012-2706-y[Crossref], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XovVahu7o%253D&md5=4d1048a706a5f3245d62a8adcb9333d9LCST behavior of copolymers of N-isopropylacrylamide and N-isopropylmethacrylamide in waterKokufuta, Mamoru K.; Sato, Saigo; Kokufuta, EtsuoColloid and Polymer Science (2012), 290 (16), 1671-1681CODEN: CPMSB6; ISSN:0303-402X. (Springer)The lower crit. soln. temp. (LCST) behavior of copolymers of N-isopropylacrylamide (NiPA) and N-isopropylmethacrylamide (NiPMA) in water was studied as a function of the copolymer compn., using a combination of turbidity measurements and differential scanning calorimetry (DSC). The copolymers were prepd. by free radical polymn. using N,N-dimethylformamide as a solvent and α,α'-azobis(isobutyronitrile) as an initiator. The copolymer compn. was detd. by elemental anal. It was found that the temp. (Tc) at which the copolymer undergoes a phase transition, i.e., LCST, increases linearly with increasing the mole fraction (fm) of NiPMA in the copolymer, within the Tc range from 32 °C (at fm = 0; NiPA homopolymer) to 42 °C (at fm = 1; NiPMA homopolymer). Also found from heating DSC thermograms were the linear dependencies of the enthalpy (ΔH) and entropy (ΔS) changes at Tc upon fm. However, the ΔH (5.5 kJ/unit-mol) at fm = 1 was slightly smaller than that (5.7 kJ/unit-mol) of poly(N-n-propylacrylamide) but considerably smaller than that (7.8 kJ/unit-mol) of poly(N-n-propylmethacrylamide). The same trend was obsd. in the fm dependence of ΔS. These results were discussed in terms of the structural effects of the NiPMA monomer unit on the heat-induced phase transition in water of poly(NiPA-co-NiPMA)s. It was suggested that a strong interaction of water with the amide group in the NiPMA would raise the transition temp., but a local dehydration which occurs around the iso-Pr side chain would not lead to large changes in the enthalpy and entropy at Tc.
- 27Kumbhakar, K.; Saha, B.; De, P.; Biswas, R. Cloud Point Driven Dynamics in Aqueous Solutions of Thermoresponsive Copolymers: Are They Akin to Criticality Driven Solution Dynamics?. J. Phys. Chem. B 2019, 123 (51), 11042– 11054, DOI: 10.1021/acs.jpcb.9b07840[ACS Full Text], [CAS], Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWhsrrN&md5=243abc0c504fe4d64cd02c58b15de186Cloud Point Driven Dynamics in Aqueous Solutions of Thermoresponsive Copolymers: Are They Akin to Criticality Driven Solution Dynamics?Kumbhakar, Kajal; Saha, Biswajit; De, Priyadarsi; Biswas, RanjitJournal of Physical Chemistry B (2019), 123 (51), 11042-11054CODEN: JPCBFK; ISSN:1520-5207. (American Chemical Society)Cloud point driven interaction and relaxation dynamics of aq. solns. of amphiphilic thermoresponsive copolymers were explored through picosecond resolved and steady state fluorescence measurements employing hydrophilic (coumarin 343, C343) and hydrophobic (coumarin 153, C153) solute probes of comparable sizes. These thermoresponsive random copolymers, with tunable cloud point temps. (Tcp's) between 298 and 323 K, were rationally designed first and then synthesized via reversible addn.-fragmentation chain transfer (RAFT) copolymn. of Me methacrylate (MMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). Subsequently, copolymers were characterized by NMR spectroscopy and size exclusion chromatog. (SEC). A balance between the hydrophilic (PEGMA) and the hydrophobic (MMA) content dictates the crit. aggregation concn. (CAC), with CAC ∼ 2-14 mg/L for these copolymers in aq. media. No abrupt changes in the steady state spectral features of both C153 and C343 in the aq. solns. of these polymers near but below the cloud point temps. were obsd. Interestingly, spectral properties of C153 in these solns. show the impact of hydrophobic/hydrophilic interaction balance but not by those of C343. More specifically, C153 reported a blue shift (relative to that in neat water) and heterogeneity in its local environment. This suggested different locations for the hydrophilic (C343) and the hydrophobic (C153) probes. In addn., the excited state fluorescence lifetime (〈τlife〉) of C153 increased with the increase of hydrophobic (MMA) content in these copolymers. However, C343 reported no such variations, although fluorescence anisotropy decays for both solutes were significantly slowed down in these aq. solns. compared to neat water. Anisotropy decays indicated bimodal time-dependent friction for these solutes in aq. solns. of these copolymers but monomodal in neat water. A linear dependence of the av. rotational relaxation rates (〈krot〉 = 〈τrot〉-1) of the type 〈krot〉 .varies. (|T - Tcp|/Tcp)γ with neg. values for the exponent γ was obsd. for both solutes. No slowing down of the solute rotation with temp. approaching the Tcp was detected; rather, rotation became faster upon increasing the soln. temp., suggesting domination of the local friction.
- 28Liu, H. Y.; Zhu, X. X. Lower critical solution temperatures of N-substituted acrylamide copolymers in aqueous solutions. Polymer 1999, 40 (25), 6985– 6990, DOI: 10.1016/S0032-3861(98)00858-1[Crossref], [CAS], Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXmt1GksLc%253D&md5=534efb7b99b0c1ea154a74776b6d68f8Lower critical solution temperatures of N-substituted acrylamide copolymers in aqueous solutionsLiu, H. Y.; Zhu, X. X.Polymer (1999), 40 (25), 6985-6990CODEN: POLMAG; ISSN:0032-3861. (Elsevier Science Ltd.)Copolymers were prepd. from N-substituted acrylamides by free radical polymn. in soln. We have selected a group of monomers with varying degree of hydrophilicity including acrylamide, N-ethylacrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-tert-butylacrylamide. The chem. compn. in the final copolymers was found to be very close to the original monomer compn. in the feed prior to polymn. In an effort to elucidate the effect of the chem. compn. on the phase sepns. of the aq. solns. of the copolymers, the lower crit. soln. temps. (LCST) of the copolymers in water were detd. by DSC and optical turbidimetry. In principal, the LCST of the copolymers can be adjusted within the freezing and b.ps. of the solns. The copolymers exhibit systematic changes in their LCSTs as a function of their comonomer compn., for which an empirical equation was established.
- 29Foster, J. C.; Akar, I.; Grocott, M. C.; Pearce, A. K.; Mathers, R. T.; O’Reilly, R. K. 100th Anniversary of Macromolecular Science Viewpoint: The Role of Hydrophobicity in Polymer Phenomena. ACS Macro Lett. 2020, 9 (11), 1700– 1707, DOI: 10.1021/acsmacrolett.0c00645[ACS Full Text], [CAS], Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1arsL3F&md5=3e5ffdafef555b0396584514dd2ae4ca100th Anniversary of Macromolecular Science Viewpoint: The Role of Hydrophobicity in Polymer PhenomenaFoster, Jeffrey C.; Akar, Irem; Grocott, Marcus C.; Pearce, Amanda K.; Mathers, Robert T.; OReilly, Rachel K.ACS Macro Letters (2020), 9 (11), 1700-1707CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)A review. The seemingly simple notion of the hydrophobic effect can be viewed from multiple angles involving theory, simulation, and expts. This viewpoint examines five attributes of predictive models to enhance synthetic efforts as well as exptl. methods to quantify hydrophobicity. In addn., we compare existing predictive models against exptl. data for polymer surface tension, lower crit. soln. temp., soln. self-assembly morphol., and degrdn. behavior. Key conclusions suggest that both the Hildebrand soly. parameters (HSPs) and surface area-normalized Log P (Log P SA-1) values provide unique and complementary insights into polymer phenomena. In particular, HSPs appear to better describe bulk polymer phenomena for thermoplastics such as surface tension, while Log P SA-1 values are well-suited for describing and predicting the behavior of polymers in soln.
- 30Padmanabhan, J.; Parthasarathi, R.; Subramanian, V.; Chattaraj, P. K. QSPR models for polychlorinated biphenyls: n-Octanol/water partition coefficient. Bioorg. Med. Chem. 2006, 14 (4), 1021– 1028, DOI: 10.1016/j.bmc.2005.09.017[Crossref], [PubMed], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhvFKkuw%253D%253D&md5=0af5f0ac844e65283297b57b3eaa3e4bQSPR models for polychlorinated biphenyls: n-Octanol/water partition coefficientPadmanabhan, J.; Parthasarathi, R.; Subramanian, V.; Chattaraj, P. K.Bioorganic & Medicinal Chemistry (2006), 14 (4), 1021-1028CODEN: BMECEP; ISSN:0968-0896. (Elsevier B.V.)The logarithmic n-octanol/water partition coeff. (log Kow) is an important property for pharmacol., toxicol. and medicinal chem. Quant. structure-property relationship (QSPR) model for the lipophilic behavior (log Kow) of the data set contg. 133 polychlorinated biphenyl (PCB) congeners is analyzed using the conceptual d. functional theory based global reactivity parameter such as electrophilicity index (ω) along with energy of LUMO (ELUMO) and no. of chlorine substituents (NCl) as descriptors. A reasonably good coeff. of detn. (r2 = 0.914) and the internal predictive ability (r2cv = 0.909) values are obtained indicating the significance of the considered descriptors in the property anal. of PCBs. Further, the developed method has widespread applicability from chem. reactivity to toxicity anal. and in studies related to various physicochem. properties in the series of dioxins and other polyarom. hydrocarbons.
- 31Bannan, C. C.; Calabró, G.; Kyu, D. Y.; Mobley, D. L. Calculating Partition Coefficients of Small Molecules in Octanol/Water and Cyclohexane/Water. J. Chem. Theory Comput. 2016, 12 (8), 4015– 4024, DOI: 10.1021/acs.jctc.6b00449[ACS Full Text], [CAS], Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtF2iurbO&md5=bae2268a466c95ff642596f771f271cbCalculating Partition Coefficients of Small Molecules in Octanol/Water and Cyclohexane/WaterBannan, Caitlin C.; Calabro, Gaetano; Kyu, Daisy Y.; Mobley, David L.Journal of Chemical Theory and Computation (2016), 12 (8), 4015-4024CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Partition coeffs. describe how a solute is distributed between two immiscible solvents. They are used in drug design as a measure of a solute's hydrophobicity and a proxy for its membrane permeability. We calc. partition coeffs. from transfer free energies using mol. dynamics simulations in explicit solvent. Setup is done by our new Solvation Toolkit which automates the process of creating input files for any combination of solutes and solvents for many popular mol. dynamics software packages. We calc. partition coeffs. between octanol/water and cyclohexane/water with the Generalized AMBER Force Field (GAFF) and the Dielec. Cor. GAFF (GAFF-DC). With similar methods in the past we found a root-mean-squared error (RMSE) of 6.3 kJ/mol in hydration free energies which would correspond to an error of around 1.6 log units in partition coeffs. if solvation free energies in both solvents were estd. with comparable accuracy. Here we find an overall RMSE of about 1.2 log units with both force fields. Results from GAFF and GAFF-DC seem to exhibit systematic biases in opposite directions for calcd. cyclohexane/water partition coeffs.
- 32Foster, J. C.; Varlas, S.; Couturaud, B.; Jones, J. R.; Keogh, R.; Mathers, R. T.; O’Reilly, R. K. Predicting Monomers for Use in Polymerization-Induced Self-Assembly. Angew. Chem. Int.l Ed. 2018, 57 (48), 15733– 15737, DOI: 10.1002/anie.201809614
- 33Varlas, S.; Foster, J. C.; Arkinstall, L. A.; Jones, J. R.; Keogh, R.; Mathers, R. T.; O’Reilly, R. K. Predicting Monomers for Use in Aqueous Ring-Opening Metathesis Polymerization-Induced Self-Assembly. ACS Macro Lett. 2019, 8 (4), 466– 472, DOI: 10.1021/acsmacrolett.9b00117[ACS Full Text], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmsVahurw%253D&md5=764942bb032063155839f4af8cd8fb1bPredicting Monomers for Use in Aqueous Ring-Opening Metathesis Polymerization-Induced Self-AssemblyVarlas, Spyridon; Foster, Jeffrey C.; Arkinstall, Lucy A.; Jones, Joseph R.; Keogh, Robert; Mathers, Robert T.; O'Reilly, Rachel K.ACS Macro Letters (2019), 8 (4), 466-472CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Aq. polymn.-induced self-assembly (PISA) is a well-established methodol. enabling in situ synthesis of polymeric nanoparticles of controllable morphol. Notably, PISA via ring-opening metathesis polymn. (ROMPISA) is an emerging technol. for block copolymer self-assembly, mainly due to its high versatility and robustness. However, a limited no. of monomers suitable for core-forming blocks in aq. ROMPISA have been reported to date. In this work, we identified seven monomers for use as either corona- or core-forming blocks during aq. ROMPISA by in silico calcn. of relative hydrophobicity for corresponding oligomeric models. The predicted monomers were validated exptl. by conducting ROMPISA using our previously reported two-step approach. In addn. to predictive data, our computational model was exploited to identify trends between polymer hydrophobicity and the morphol. of the self-assembled nano-objects they formed. We expect that this methodol. will greatly expand the scope of aq. ROMPISA, as monomers can be easily identified based on the structure-property relationships obsd. herein.
- 34Inam, M.; Cambridge, G.; Pitto-Barry, A.; Laker, Z. P. L.; Wilson, N. R.; Mathers, R. T.; Dove, A. P.; O’Reilly, R. K. 1D vs. 2D shape selectivity in the crystallization-driven self-assembly of polylactide block copolymers. Chem. Sci. 2017, 8 (6), 4223– 4230, DOI: 10.1039/C7SC00641A[Crossref], [PubMed], [CAS], Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtVeqtLo%253D&md5=7bf2d5494c613d5ceb273d98fba3feba1D vs. 2D shape selectivity in the crystallization-driven self-assembly of polylactide block copolymersInam, Maria; Cambridge, Graeme; Pitto-Barry, Anais; Laker, Zachary P. L.; Wilson, Neil R.; Mathers, Robert T.; Dove, Andrew P.; O'Reilly, Rachel K.Chemical Science (2017), 8 (6), 4223-4230CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)The 2D materials such as graphene, LAPONITE clays or molybdenum disulfide nanosheets are of extremely high interest to the materials community as a result of their high surface area and controllable surface properties. While several methods to access 2D inorg. materials are known, the investigation of 2D org. nanomaterials is less well developed on account of the lack of ready synthetic accessibility. Crystn.-driven self-assembly (CDSA) has become a powerful method to access a wide range of complex but precisely-defined nanostructures. The prepn. of 2D structures, however, particularly those aimed towards biomedical applications, is limited, with few offering biocompatible and biodegradable characteristics as well as control over self-assembly in two dimensions. Herein, in contrast to conventional self-assembly rules, we show that the soly. of polylactide (PLLA)-based amphiphiles in alcs. results in unprecedented shape selectivity based on unimer soly. We use log Poct anal. to drive solvent selection for the formation of large uniform 2D diamond-shaped platelets, up to several microns in size, using long, sol. coronal blocks. By contrast, less sol. PLLA-contg. block copolymers yield cylindrical micelles and mixed morphologies. The methods developed in this work provide a simple and consistently reproducible protocol for the prepn. of well-defined 2D org. nanomaterials, whose size and morphol. are expected to facilitate potential applications in drug delivery, tissue engineering and in nanocomposites.
- 35He, Y.; Eloi, J.-C.; Harniman, R. L.; Richardson, R. M.; Whittell, G. R.; Mathers, R. T.; Dove, A. P.; O’Reilly, R. K.; Manners, I. Uniform Biodegradable Fiber-Like Micelles and Block Comicelles via “Living” Crystallization-Driven Self-Assembly of Poly(l-lactide) Block Copolymers: The Importance of Reducing Unimer Self-Nucleation via Hydrogen Bond Disruption. J. Am. Chem. Soc. 2019, 141 (48), 19088– 19098, DOI: 10.1021/jacs.9b09885[ACS Full Text], [CAS], Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVGmtrfO&md5=997e3bc1e4ca01b6c97f0e22123e8532Uniform Biodegradable Fiber-Like Micelles and Block Comicelles via "Living" Crystallization-Driven Self-Assembly of Poly(L-lactide) Block Copolymers: The Importance of Reducing Unimer Self-Nucleation via Hydrogen Bond DisruptionHe, Yunxiang; Eloi, Jean-Charles; Harniman, Robert L.; Richardson, Robert M.; Whittell, George R.; Mathers, Robert T.; Dove, Andrew P.; O'Reilly, Rachel K.; Manners, IanJournal of the American Chemical Society (2019), 141 (48), 19088-19098CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Fiber-like micelles based on biodegradable and biocompatible polymers exhibit considerable promise for applications in nanomedicine, but until recently no convenient methods were available to prep. samples with uniform and controllable dimensions and spatial control of functionality. "Living" crystn.-driven self-assembly (CDSA) is a seeded growth method of growing importance for the prepn. of uniform 1D and 2D core-shell nanoparticles from a range of crystallizable polymeric amphiphiles. However, in the case of poly(L-lactide) (PLLA), arguably the most widely utilized biodegradable polymer as the crystallizable core-forming block, the controlled formation of uniform fiber-like structures over a substantial range of lengths by "living" CDSA has been a major challenge. Herein, we demonstrate that via simple modulation of the solvent conditions via the addn. of trifluoroethanol (TFE), DMSO, DMF and acetone, uniform fiber-like nanoparticles from PLLA diblock copolymers with controlled lengths up to 1μm can be prepd. The probable mechanism involves improved unimer solvation by a redn. of hydrogen bonding interactions among PLLA chains. We provide evidence that this minimizes undesirable unimer aggregation which otherwise favors self-nucleation that competes with epitaxial crystn. from seed termini. This approach has also allowed the formation of well-defined segmented block comicelles with PLLA cores via the sequential seeded-growth of PLLA block copolymers with different corona-forming blocks.
- 36Magenau, A. J. D.; Richards, J. A.; Pasquinelli, M. A.; Savin, D. A.; Mathers, R. T. Systematic Insights from Medicinal Chemistry To Discern the Nature of Polymer Hydrophobicity. Macromolecules 2015, 48 (19), 7230– 7236, DOI: 10.1021/acs.macromol.5b01758[ACS Full Text], [CAS], Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFGrtb%252FJ&md5=8241ccde882ceb1bb05c46fe4bad34c0Systematic Insights from Medicinal Chemistry To Discern the Nature of Polymer HydrophobicityMagenau, Andrew J. D.; Richards, Jeffrey A.; Pasquinelli, Melissa A.; Savin, Daniel A.; Mathers, Robert T.Macromolecules (Washington, DC, United States) (2015), 48 (19), 7230-7236CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Predicting polymer hydrophobicity based on monomer structure is an ill-posed problem. Generally, the hydrophobicity of a polymer or a series of polymers has been detd. through indirect methods (i.e., contact angle) after polymn. This sequence presents a problem for the systematic design and rapid evaluation of specialty polymers synthesized via controlled polymn. methods. Here, we propose an approach inspired by medicinal chem. to predict polymer hydrophobicity based on octanol-water partition coeffs. (LogPoct) detd. through simple computational approaches. We envisioned that LogPoct, analogous to what is used in drug design, could provide a rational methodol. to translate mol. structures of monomers and oligomers into quantifiable hydrophobicity values for polymers. A combination of crit. design criteria and the predictive power of LogPoct values, normalized by surface area (LogPoct/SA), accurately assess polymer hydrophobicity. Exptl. corroboration with a polarity-sensitive dye (i.e., Nile Red), advancing water contact angles measurements, and swelling ratio expts. verify the method represents a dramatic improvement. A direct and quant. correlation existed between spectral shifts of Nile Red and calcd. LogPoct/SA values, confirming a quantifiable metric for predicting polymer hydrophobicity. Computationally predicted values also resulted in a first approxn. of advancing contact angle measurements over a broad spectrum of common polymers providing a basis for estg. contact angles, a screening tool to enhanced monomer design a priori, and a criterion to understand polymer phys. properties. Furthermore, swelling ratio measurements elucidated boundary limits for swelling of relatively hydrophobic and hydrophilic polymers in water and hexanes, in addn. to alternative alc. deriv. solvents.
- 37Fischer, F.; Zufferey, D.; Tahoces, R. Lower critical solution temperature in superheated water: the highest in the poly(N, N-dialkylacrylamide) series. Polym. Int. 2011, 60 (8), 1259– 1262, DOI: 10.1002/pi.3071[Crossref], [CAS], Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXptlWksb4%253D&md5=1d99dfcf05810db5a5b9ee2b0e27e36bLower critical solution temperature in superheated water: the highest in the poly(N,N-dialkylacrylamide) seriesFischer, Fabian; Zufferey, Daniel; Tahoces, RaulPolymer International (2011), 60 (8), 1259-1262CODEN: PLYIEI; ISSN:0959-8103. (John Wiley & Sons Ltd.)Microcalorimetry and cloud point extrapolation indicate a lower crit. soln. temp. of 216 °C for poly(N,N-dimethylacrylamide) (PDMA). This is the highest phase-transition temp. in the poly(N,N-dialkylacrylamide) series. Cloud points were recorded from electrolyte solns. made of Na3PO4, CaCO3, (NH4)2SO4 and KOH. These measurements were realized below and beyond the b.p. of water. The hydrolytic properties of PDMA in superheated water (200 °C) were examd. and verified using 1H NMR anal. The knowledge of the phase-transition temp. of pure PDMA is of interest, as it is often a constituent of smart copolymers, to adjust the responsiveness to a desired temp. threshold. Copyright © 2011 Society of Chem. Industry.
- 38Lerch, A.; Käfer, F.; Prévost, S.; Agarwal, S.; Karg, M. Structural Insights into Polymethacrylamide-Based LCST Polymers in Solution: A Small-Angle Neutron Scattering Study. Macromolecules 2021, 54 (16), 7632– 7641, DOI: 10.1021/acs.macromol.1c00698[ACS Full Text], [CAS], Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhslSnt7%252FN&md5=31e1ce4c28a886673690cb29c2883a9fStructural Insights into Polymethacrylamide-Based LCST Polymers in Solution: A Small-Angle Neutron Scattering StudyLerch, Arne; Kaefer, Florian; Prevost, Sylvain; Agarwal, Seema; Karg, MatthiasMacromolecules (Washington, DC, United States) (2021), 54 (16), 7632-7641CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Copolymn. is a powerful method that offers access to new polymer materials with a tailored response to external stimuli like temp. and pH. Polymers with a lower crit. soln. temp. are well known to undergo a coil-to-globule transition when the temp. is raised above the transition temp. In particular, for copolymers, complex inter- and intrachain interactions may complicate this simple picture of a single-chain phase transition. In this work, we study the phase transition of poly((methylacrylamide)-stat-(N-cyclohexylacrylamide)) copolymers at different concns. in heavy water by using small-angle neutron scattering. Measurements are performed well below and above the resp. cloud points of polymers with two different mol. wts. We show that interchain interactions are already present below the cloud point even in the dil. regime. Above the cloud point, polymer-polymer interactions become more prominent and polydisperse aggregates form.
- 39Tsui, H.-W.; Wang, J.-H.; Hsu, Y.-H.; Chen, L.-J. Study of heat of micellization and phase separation for Pluronic aqueous solutions by using a high sensitivity differential scanning calorimetry. Colloid Polym. Sci. 2010, 288 (18), 1687– 1696, DOI: 10.1007/s00396-010-2308-5[Crossref], [CAS], Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXht1KnsrbI&md5=ec5e219cdaace3e1bfcab41814cb6e2eStudy of heat of micellization and phase separation for Pluronic aqueous solutions by using a high sensitivity differential scanning calorimetryTsui, Hung-Wei; Wang, Jing-Han; Hsu, Ya-Hui; Chen, Li-JenColloid and Polymer Science (2010), 288 (18), 1687-1696CODEN: CPMSB6; ISSN:0303-402X. (Springer)Heat of micellization and phase sepn. temp. (known as cloud point) for the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (abbreviated by PEO-PPO-PEO) triblock copolymers, the Pluronics F108, F98, F88, F68, F38, P65, and L62, in water are carefully detd. by using a high sensitivity differential scanning calorimeter. It is interesting to find out that there exists a max. heat of micellization for all these Pluronics. In this study, the heat of micellization of all of the Pluronics decreases as the temp. increases, as expected, at high temp. region (low Pluronic concn. region). However, the enthalpy change has a surprisingly pos. relationship with temp. at low temp. region (high Pluronic concn. region). The crit. micelle temp. consistently decreases as the Pluronic concn. increases. This unexpected behavior of the pos. heat capacity changes of Pluronic aq. solns. at higher concn. region is somewhat related to the variation of water accessible polar (PEO groups) and non-polar (PPO groups) surface areas in the micellization process. Esp., the removal of polar surface area from water may dominate the contribution to the pos. heat capacity change upon micellization. In addn., the cloud points of Pluronic solns. are also discussed. The enthalpy-entropy compensation phenomenon for the micellization of Pluronics is discussed, and the enthalpy-entropy compensation temp. is calcd.
- 40Dharmaratne, N. U.; Jouaneh, T. M. M.; Kiesewetter, M. K.; Mathers, R. T. Quantitative Measurements of Polymer Hydrophobicity Based on Functional Group Identity and Oligomer Length. Macromolecules 2018, 51 (21), 8461– 8468, DOI: 10.1021/acs.macromol.8b01747[ACS Full Text], [CAS], Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvFWrtr%252FO&md5=7473694ba112c04930cfeed026d9435aQuantitative Measurements of Polymer Hydrophobicity Based on Functional Group Identity and Oligomer LengthDharmaratne, Nayanthara U.; Jouaneh, Terra Marie M.; Kiesewetter, Matthew K.; Mathers, Robert T.Macromolecules (Washington, DC, United States) (2018), 51 (21), 8461-8468CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)A combined exptl. and computational investigation revealed a hydrophobicity trend for oxygen-contg. functional groups commonly encountered in monomers and polymers. Based on solvatochromatic dye expts., HPLC retention times, and theor. LogP values, the arrangement of the three oxygen atoms in carbonates results in more hydrophobicity than other permutations like anhydrides. Another trend emerged for functional groups with two oxygen atoms (acetals > esters). Overall, when comparing aliph. polymers with similarly sized monomers, hydrophobicity decreased as follows: carbonates > acetals > esters > anhydrides. These trends have important implications for degrdn., cond., and many other applications.
- 41Yildirim, E.; Dakshinamoorthy, D.; Peretic, M. J.; Pasquinelli, M. A.; Mathers, R. T. Synthetic Design of Polyester Electrolytes Guided by Hydrophobicity Calculations. Macromolecules 2016, 49 (20), 7868– 7876, DOI: 10.1021/acs.macromol.6b01452[ACS Full Text], [CAS], Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1SqsrbK&md5=460d1c464d255bf882d529dff329e44fSynthetic Design of Polyester Electrolytes Guided by Hydrophobicity CalculationsYildirim, Erol; Dakshinamoorthy, Deivasagayam; Peretic, Matthew J.; Pasquinelli, Melissa A.; Mathers, Robert T.Macromolecules (Washington, DC, United States) (2016), 49 (20), 7868-7876CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Partition coeffs. (LogP) help to quantify hydrophobicity, which can be used to guide the design of polymer electrolytes with targeted properties. Thus, this study combined synthetic expts. and mol. modeling to produce polyester electrolytes that solubilize lithium salts. These polyester electrolytes were derived from natural sources and polymd. with different ratios of polyols (diglycerol, glycerol, and diethylene glycol) and citric acid in the presence of lithium salts (LiTf and LiTFSI). The Fisher esterification produced homogeneous, cross-linked films with high optical transparency, whereas the lithium salts increased glass transition temps. The LogP values of monomers and the resulting polyesters were predict ed using cheminformatics tools and indicate changing diglycerol to glycerol or diethylene glycol alters the hydrophobicity. Comparison of different mol. modeling methods with predicted LogP values demonstrate that LogP values are a reliable means of tailoring phys. and chem. properties of these polymer electrolytes. Addnl., LogP values greatly benefit from being extremely less expensive from a computational standpoint as well as more convenient for calcg. precursory quant. information.
- 42Chandler, D. Interfaces and the driving force of hydrophobic assembly. Nature 2005, 437 (7059), 640– 647, DOI: 10.1038/nature04162[Crossref], [PubMed], [CAS], Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtVCjsLzM&md5=58e58a6f3dfaf11a9a158308bdcacbaeInterfaces and the driving force of hydrophobic assemblyChandler, DavidNature (London, United Kingdom) (2005), 437 (7059), 640-647CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)A review. The hydrophobic effect - the tendency for oil and water to segregate - is important in diverse phenomena, from the cleaning of laundry, to the creation of micro-emulsions to make new materials, to the assembly of proteins into functional complexes. This effect is multifaceted depending on whether hydrophobic mols. are individually hydrated or driven to assemble into larger structures. Despite the basic principles underlying the hydrophobic effect being qual. well understood, only recently have theor. developments begun to explain and quantify many features of this ubiquitous phenomenon.
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