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An Azobenzene-Based Single-Component Supramolecular Polymer Responsive to Multiple Stimuli in WaterClick to copy article linkArticle link copied!
- Edgar FuentesEdgar FuentesInstitute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, SpainMore by Edgar Fuentes
- Marieke GerthMarieke GerthLaboratory of Self-Organizing Soft Matter, Department of Chemical Engineering and Chemistry & Institute of Complex Molecular Systems (ICMS), Eindhoven University of Technology (TUE), Eindhoven 5612 AZ, The NetherlandsLaboratory of Physical Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology (TUE), Eindhoven 5612 AZ, The NetherlandsMore by Marieke Gerth
- José Augusto BerrocalJosé Augusto BerrocalAdolphe Merkle Institute, Polymer Chemistry and Materials, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, SwitzerlandMore by José Augusto Berrocal
- Carlo MateraCarlo MateraInstitute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, SpainNetwork Biomedical Research Centre in Biomaterials, Bioengineering and Nanomedicine (CIBER-BBN), Madrid 28029, SpainMore by Carlo Matera
- Pau GorostizaPau GorostizaInstitute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, SpainNetwork Biomedical Research Centre in Biomaterials, Bioengineering and Nanomedicine (CIBER-BBN), Madrid 28029, SpainCatalan Institution for Research and Advanced Studies (ICREA), Barcelona 08011, SpainMore by Pau Gorostiza
- Ilja K. VoetsIlja K. VoetsLaboratory of Physical Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology (TUE), Eindhoven 5612 AZ, The NetherlandsMore by Ilja K. Voets
- Silvia Pujals*Silvia Pujals*[email protected]Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, SpainDepartment of Electronics and Biomedical Engineering, Faculty of Physics, Universitat de Barcelona, Barcelona 08011, SpainMore by Silvia Pujals
- Lorenzo Albertazzi*Lorenzo Albertazzi*[email protected]/[email protected]Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, SpainDepartment of Biomedical Engineering, Institute of Complex Molecular Systems (ICMS), Eindhoven University of Technology (TUE), Eindhoven 5612 AZ, The NetherlandsMore by Lorenzo Albertazzi
Abstract
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One of the most appealing features of supramolecular assemblies is their ability to respond to external stimuli due to their noncovalent nature. This provides the opportunity to gain control over their size, morphology, and chemical properties and is key toward some of their applications. However, the design of supramolecular systems able to respond to multiple stimuli in a controlled fashion is still challenging. Here we report the synthesis and characterization of a novel discotic molecule, which self-assembles in water into a single-component supramolecular polymer that responds to multiple independent stimuli. The building block of such an assembly is a C3-symmetric monomer, consisting of a benzene-1,3,5-tricarboxamide core conjugated to a series of natural and non-natural functional amino acids. This design allows the use of rapid and efficient solid-phase synthesis methods and the modular implementation of different functionalities. The discotic monomer incorporates a hydrophobic azobenzene moiety, an octaethylene glycol chain, and a C-terminal lysine. Each of these blocks was chosen for two reasons: to drive the self-assembly in water by a combination of H-bonding and hydrophobicity and to impart specific responsiveness. With a combination of microscopy and spectroscopy techniques, we demonstrate self-assembly in water and responsiveness to temperature, light, pH, and ionic strength. This work shows the potential to integrate independent mechanisms for controlling self-assembly in a single-component supramolecular polymer by the rational monomer design and paves the way toward the use of multiresponsive systems in water.
Copyright © 2020 American Chemical Society
1. Introduction
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Supramolecular polymers are promising self-assembled structures for a variety of applications. In particular, water-soluble assemblies (1) show great potential for medical applications such as drug delivery systems, (2−6) contrast agents, (7) or hydrogels for tissue engineering. (8−11)
Inspired by naturally existing supramolecular polymers, e.g., actin filaments, chemists attempt to create synthetic materials with life-like properties. In this framework, the design of dynamic structures capable of mimicking the polymerization–depolymerization equilibrium of biological polymers allows the preparation of functional adaptive materials that change properties in response to a specific stimulus. This responsiveness is interesting at a fundamental level, but is also appealing for a variety of applications. For example, the possibility to disassemble supramolecular drug carriers in a controlled fashion allows for spatiotemporal control over the release of drugs. (12) Many efforts have been carried out to explore new responsive materials and new strategies to impart responsivity into the monomer design. The groups of Besenius, Schmuck, and Stupp designed systems using pH as a trigger to change stability and promote disassembly. (13−16) Yagai and co-workers explored the use of light, temperature, and ultrasound as triggers to control foldability of supramolecular polymers. (17−19) Lee reported supramolecular nanotubules that undergo a contraction in response to temperature. (20) Voets reported salt-triggered changes in dimensions and cooperativity of the self-assembly. (21) Moreover, in light of biological applications, the possibility to obtain response to protein binding and enzyme activity has also been studied. (22−27)
Multiresponsivity, i.e., the ability to independently respond to different cues, in aqueous media proved to be more challenging to implement. Using multiple stimuli appears as a promising strategy to achieve fine control over supramolecular polymers’ properties. Moreover, it opens the way to logic-gate assemblies able to generate a response only when two stimuli are simultaneously present, increasing selectivity. (28−30) This is particularly interesting in the case of biological applications where the complex cellular environment provides multiple cues to the administered synthetic material.
Few pioneering examples of multiresponsivity have recently been reported. Besenius and co-workers designed a system responsive to pH and reactive oxygen species, which together with temperature was able to tune the gelating properties of the material. (31) Bhosale and co-workers reported supramolecular ribbons with both pH- and temperature-dependent helicity. (32) Thayumanavan and co-workers showed the possibility to incorporate different responsive moieties into polymeric amphiphiles through a postpolymerization step, enabling response to light, protein, and redox environment. (33) Li and co-workers designed a molecule that self-assembled into fibers, responsive to different ions and temperature. (34) However, these interesting properties come at the price of complex design, by incorporating either multiple components or synthetically challenging building blocks. Using multiple response mechanisms in the same monomer appears as a promising strategy to achieve fine control over supramolecular polymers.
Here we present the straightforward synthesis of a single-component supramolecular polymer, self-assembled in water, which is capable of independently responding to four stimuli, namely, light, pH, ionic strength, and temperature. This system is designed to offer control over self-assembly through distinct mechanisms, modifying the assembly state in terms of both length and configuration. By a combination of techniques including transmission electron microscopy (TEM), circular dichroism (CD), high-performance liquid chromatography (HPLC), and static light scattering (SLS), we demonstrate that the assembly/disassembly of supramolecular polymers in water is pursued through controlled stimulations.
Our results pave the way toward simpler and highly controllable supramolecular polymers, contributing to the fundamental development of self-assembly in water as well as to their biomedical applications.
2. Results and Discussion
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2.1. Molecular Design and Synthesis
The discotic amphiphile was designed to self-assemble and to exhibit responsiveness to light, pH, salt concentration, and temperature. The design was based on a C3-symmetrical core, bearing three identical wedges. These wedges were designed to be modular, combining natural and non-natural amino acids chosen to induce self-assembly in water by a combination of hydrophobic effect and H-bonding as well as to imprint specific responsiveness. Notably, the choice of amino acid building blocks allows for a modular approach by using solid-phase synthesis. The synthetic route toward and structure of monomer 1 are shown in Figure 1a and b.
Figure 1
Figure 1. (a) Synthesis of monomer 1: (i) Coupling of Fmoc-Lys(Boc)-OH to 2-chlorotrityl chloride resin (represented by the gray circle), DCM, DIEA, 1 h. (ii) Fmoc removal, 20% piperidine in DMF. (iii) Coupling of Fmoc-octa(ethylene glycol)-OH, DCM–DMF (1:1), PyBOP, DIEA, 15 h. (iv) Fmoc removal, 20% piperidine in DMF. (v) Coupling of Fmoc-Azo, DCM–DMF (1:1), PyBOP, DIEA, 15 h. (vi) Fmoc removal, 20% piperidine in DMF. (vii) Cleavage, TFA 95% v/v in H2O. (viii) Core coupling, BT-Cl, CHCl3, DIEA PyBOP, 15 h. (ix) Boc removal, TFA 95% H2O. (b) Molecular structure of monomer 1. (c) Molecular structure of monomer 2. (d) Schematic representation of monomer 1 and its self-assembly into supramolecular fibers. The moieties responsible for responsiveness are highlighted in different colors: orange, light responsive moiety; blue, temperature responsive moiety; green, pH and ionic strength responsive moiety.
To promote self-assembly, benzene-1,3,5-tricarboxamide (BTA) was chosen as a core to drive aggregation due to the well-known H-bonding behavior. (35) The BTA core is functionalized with three amphiphilic wedges composed of amino acid modules that promote assembly in water and induce responsivity as well (Figure 1d). A non-natural azobenzene amino acid (l-phenylalanine-4′-azobenzene, Figure 1b highlighted in orange) was placed as the innermost block of the wedge to enhance self-assembly by increasing hydrophobicity and by shielding the intermolecular H-bonds of the BTA core from water. At the same time, the azobenzene moiety imparts light responsivity through the well-known E–Z isomerization. Azobenzenes are a well-established class of molecular photoswitches in the fields of smart materials and photocontrol of biological systems because of some favorable characteristics, such as design flexibility, ease of synthesis, large changes in geometry upon isomerization, high quantum yields, and low photobleaching rates. (36,37) We hypothesized that the E form favors assembly due to its planar hydrophobic nature, while the nonplanar and more polar Z form will destabilize monomer stacking and increase monomer solubility. (38) The second module of the wedge is an octa(ethylene glycol) amino acid (Figure 1 b, highlighted in blue), which grants flexibility and solubility in water, while it confers thermal responsivity due to its temperature-dependent hydrophilicity. (39−42) Finally, a C-terminal lysine (Figure 1b, highlighted in green) was added to enhance water solubility owing to the charged groups and induce the ampholytic character of this particular amino acid, which can result in dual pH and ionic strength response.
The described monomer was designed to be synthesized through standard solid-phase peptide synthesis (SPPS), offering a modular and straightforward synthesis. All building blocks are commercially available or are synthesized as fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids, allowing to iteratively repeat the same synthetic steps (Figure 1a). Following an Fmoc strategy, the wedge is grown sequentially on the resin from C-terminus to N-terminus using the proper Fmoc-protected building blocks. Both octa(ethylene glycol) and azobenzene couplings were not standard and were optimized (see SI). After its completion (steps i to vi, Figure 1a), the wedge was cleaved from the resin keeping the tert-butyloxycarbonyl (Boc) protecting group (step vii) and subsequently purified through H2O–DCM extraction (Figures S2, S3).
The final step, consisting of the convergent coupling to form the BTA, was performed in solution. The wedge was reacted with a benzene tricarbonyl chloride, thereby forming the Boc-protected monomer 1 (step viii). Boc deprotection was performed, and the final product was purified through reversed-phase HPLC (step ix). The purity and molecular weight of the desired product were confirmed using reversed-phase HPLC-MS, MALDI, and 1H NMR (Figure S6). Detailed synthetic procedures and material characterizations are provided in the SI.
This synthetic strategy allows the facile and precise control over the structure by using SPPS. The use of properly protected natural and non-natural amino acids reduces the number of necessary purifications in comparison with in-solution synthesis. Moreover, the sequence, the chemical nature, and the number of amino acids can be changed without modifying the synthetic procedure. This is a great advantage in light of structure optimization as well as for the generation of libraries of compounds.
2.2. Self-Assembly and Spectroscopic Behavior
To investigate the self-assembly behavior, monomer 1 was first dissolved in DMSO at a concentration of 2.5–10 mM, in which it is molecularly dissolved, eliminating any possible pre-existing aggregates. Next, the concentrated stock solution was diluted with Milli-Q water to obtain a 25–100 μM monomer, triggering the self-assembly. Unless stated otherwise, a temperature cycle (70 °C for 1 h + 24 h at rt) was applied to obtain a reproducible equilibrium.
TEM showed the absence of aggregates in DMSO (Figure 2a), confirming, together with the resolved 1H NMR, the molecularly dissolved state in this solvent. In water, monomer 1 assembled into μm-long and flexible fibers as shown in Figure 2b. A quantitative analysis of the TEM images reveals a diameter of 6.48 ± 1.15 nm, in good agreement with other reported water-soluble BTAs. (43)
Figure 2
Figure 2. TEM image of 100 μM monomer 1 (a) in DMSO and (b) in water (scale bar: 500 nm). E–Z photoisomerization of monomer 1 at 25 μM in (c) DMSO and (d) water, with UV (λ = 365 nm) irradiations of 30 s. HPLC chromatogram of monomer 1 in (e) DMSO and (f) water at 280 nm (measured isosbestic point).
Initially, two discotic amphiphiles were synthesized following the same design, differing only in the azobenzene amino acid. In monomer 1 (Figure 1b), which contains a l-phenylalanine-4′-azobenzene, the azobenzene is placed as a side chain of the wedge. In monomer 2 (Figure 1c), which comprises a [3-(3-aminomethyl)phenylazo]phenylacetic acid, the azobenzene is placed as backbone of the wedge. Since the azobenzene moiety is in close proximity to the core in both cases, very different behaviors can be expected for monomer 1 (Figure 1b) and 2 (Figure 1c). Remarkably, despite the similar structures of both monomers, monomer 2 did not self-assemble under any of the tested conditions of concentration, temperature, and light irradiation. We hypothesize that the orientation and proximity to the core of the azobenzene moiety of monomer 2 prevent effective stacking. All the work reported in the following sections will therefore focus exclusively on monomer 1.
In order to characterize the monomer isomerization state and switching ability inside the assemblies, we performed UV–vis spectroscopy and HPLC of monomer 1 prepared in in both DMSO and water (Figure 2). Azobenzene has a characteristic absorbance spectrum that allows studying the relative population of the two isomers, namely, for the E isomer λmax = 330 nm and for Z λmax = 430 nm. The UV–vis spectra were recorded in DMSO (nonstacked monomer) and milli-Q (mainly stacked monomer) at different UV irradiation (λ = 365 nm) times (Figure 2c and d). Initially, one absorbance peak was visible at λ = 330 nm, corresponding to the E-configured azobenzene, the most stable isomer at standard conditions. Upon UV irradiation, the E-azobenzene peak decreases while the Z-azobenzene peak at 440 nm appears, resulting in two isosbestic points, at 280 and 387 nm, indicating that the isomerization took place. Moreover, we were able to compare the kinetics of photoisomerization by plotting the ratio between the peaks at 430 and 330 nm in time, which as a first approximation we define as the “E/Z ratio”. This shows a maximum conversion in less than 5 min and concludes that the azobenzene moiety can efficiently isomerize as a free molecule in solution (DMSO) and in the assembled state (water) (Figure S9). Interestingly, the Z configuration is stable when kept in the dark at 25 °C at least for 24 h (Figure S10), confirming the measured isomer distribution is not affected by the thermal back-isomerization. This is an important feature to consider when using photochromic ligands, especially for functional biological assays. (44,45) Finally, monomers in the Z configuration can isomerize back to E-azobenzene by irradiating with blue light (455 nm). It was possible to reproduce 10 isomerization cycles, showing no signs of fatigue in both DMSO and water (Figure S11).
Altogether, these observations highlight a number of crucial features of our system. First, the azobenzenes can isomerize both in the molecularly dissolved state and inside the fibers. This is far from trivial, as the steric hindrance and interactions inside the assembly can prevent isomerization. (46−48) Second, the very slow thermal recovery allows the photocontrol of the system in time. Lastly, the system is fully reversible and can undergo multiple photoisomerization cycles.
Interestingly, even though spectroscopically we differentiate two states (E and Z), the monomer can actually be found in four different configurations. Considering that each monomer has three independent azobenzene moieties, which can be either E or Z, the monomer can be found as EEE, EEZ, EZZ, and ZZZ. Indeed, the analysis of samples of 1 in both DMSO and water by HPLC-UV-MS (Figure 2e,f) displayed four peaks, in agreement with previous reports. (43) HPLC also allowed the analysis of the relative distribution in population of the isomers, which is valuable information since the isomers’ distribution can have an impact on the self-assembly. (49) As shown in Figure 2e,f, monomers start mostly with azobenzenes in the E configuration (EEE), while a significant population of EEZ is present in the nonirradiated state. UV irradiation will change the distribution of these populations, which can be recovered through irradiation with blue light (455 nm). With these premises we proceed in studying the responsive behavior of these fibers.
2.3. Light Responsive Self-Assembly
As discussed, we hypothesized that the E–Z isomerization of an azobenzene placed close to the BTA would disrupt the self-assembly, due to the decreased propensity of the bent Z-azobenzenes to stack and the higher solubility in water. (38,50) Thus, UV irradiation would result in dissolution of the fibers, and visible irradiation would promote fiber reassociation.
To confirm this hypothesis, a combination of HPLC, TEM, and CD was used. In Figure 3a–i we report a comparison among samples before/after irradiation with UV light and after irradiation with blue light, making use of the three different techniques. The pristine sample contains a large fraction of EEE monomer (about 60%), as indicated by HPLC (Figure 3a), which results in the assembly of long fibers as observed by TEM (Figure 3b). Due to the chirality of the azobenzene-containing amino acid, a helical stack with a preferred helicity is formed, which can be followed by CD. (51)Figure 3c shows the CD spectrum of the fibers, revealing a band at 260–380 nm, centered at 330 nm, corresponding to the stacking of the azobenzene moieties.
Figure 3
Figure 3. HPLC-UV at 280 nm of the sample at 25 μM (a) before UV, (b) after UV irradiation (365 nm, 8 s 100% at 1000 mA of the LED intensity), and (c) after blue light (455 nm, 10 s, 100% at 1000 mA of the LED intensity). TEM of the sample at 25 μM (d) before UV, (e) after UV, and (f) after blue light irradiation (scale bar: 500 nm). CD of the sample at 25 μM (g) before UV, (h) after 365 nm irradiation for 8 s, and (i) after 455 nm irradiation for 10 s. (j) HPLC-UV analysis of isomer distribution at different UV irradiation times. (k) CD at 304 nm at different E isomer % (the line was added to guide the eye).
After UV irradiation several dramatic changes can be observed. First, significant isomerization takes place as shown by HPLC. Before UV treatment the photostationary state is primarily (>90%) composed of EEE and EEZ monomers, while Z-rich monomers are the majority species (EZZ 42% and ZZZ 42%) after UV irradiation. This photoisomerization is accompanied by the disappearance of the CD peak at 330 nm (Figure 3f), indicating loss of helical order, and most strikingly by the complete disappearance of long fibrillar aggregates in the TEM characterization (Figure 3e). These observations showed that the E–Z isomerization of the azobenzene moieties results in the disassembly of the supramolecular polymers. Notably, after irradiation with blue light, recovery of the initial supramolecular polymers was obtained: HPLC shows that the population of isomers is reverted (Figure 3g), the CD signal is restablished (Figure 3i, and TEM again shows the presence of fibers of the same length and morphology (Figure 3h). Therefore, the material designed here is photoresponsive, the response is reversible, and a correlation between monomer configuration and assembly state is established.
To demonstrate that this switch is not abrupt but is gradual and therefore controllable, we performed a kinetic study to evaluate the isomer distribution and the assembly state at different irradiation times by HPLC and CD. In Figure 3j a plot of the distribution of isomers after stepwise UV irradiation is presented. Initially, the system contains predominantly monomers in EEE configuration, while very gradually Z-forms are enriched. This shows the potential to precisely control relative abundance of the isomers by irradiation time. Interestingly, the CD signal, and therefore the amount of monomers in a helical fiber, is proportional to the amount of E form of monomers (Figure 3k). This tendency points out that the crucial feature for the self-assembly of the monomers is the amount of E isomers. This indicates that there is a constructive interaction between azobenzenes in E inside the assembly, favoring the stacking of EEE, over EEZ or EZZ.
These results demonstrate a strong relationship between self-assembly and concentration of the EEE isomer, as well as fine-tuning the self-assembly by UV irradiation. By this means, specific degrees of assembly are accessible by controlling the concentration of the EEE monomer (Figures 3k, S12).
In brief, we demonstrated by a combination of HPLC, TEM, and CD that self-assembly in our system can be finely modulated by irradiation with UV and blue light to tune the isomer population distribution.
2.4. Temperature Responsiveness
Due to the weak nature of the noncovalent bonding, supramolecular polymers generally display temperature-dependent behavior, typically disassembling at high temperatures, a property that is often used to study the self-assembly mechanism. (52) However, it has also been extensively reported that polyethylene glycol-containing supramolecular structures exhibit a different temperature response in water, showing a transition to an enhanced aggregation state at higher temperatures due to entropic effects. (31,53−56) Aiming to elucidate the temperature responsiveness of our system, we studied the assembly state at different temperatures by TEM, CD, and SLS.
First, a temperature cycle (25–75–25 °C) was performed on the sample, and TEM images were taken at the three different temperature points. Before heating, TEM showed few fibers per field with a length in the range of 300 nm (Figure 4a). When increasing the temperature to 75 °C, an increase in both number and length of the fibers can be clearly observed (Figure 4b). After cooling and subsequent equilibration for 24 h, the number of fibers decreased again, resembling the situation before heating (Figure 4c) and strongly suggesting a reversible character of the response. In all cases, the sample preserved the fiber-like shape and diameter, although an increase in number, length, and degree of entanglements can be observed at the higher temperature.
Figure 4
Figure 4. TEM of monomer 1 at 20 μM at (a) 20 °C, (b) 75 °C, and (c) 20 °C after cooling from 75 °C. (d) SLS temperature cycle on the sample at 100 μM at 60 °C/h measuring in steps of 5 °C (the line was added to guide the eye). (e) CD heating ramp experiment on the sample at 25 μM at 60 °C/h, measuring in steps of 5 °C.
To corroborate this, a temperature cycling experiment was performed with SLS (Figure 4d). We observed a very low scattering intensity (close to the limit of detection) at low temperatures. However, a linear increase was obtained ramping up from 25 °C to 30 °C to 70 °C. This trend is also reversible, matching with TEM results, but shows a hysteresis because of the long time required to reach equilibrium (S13). In order to confirm that the increase in scattering intensity is due to an increase in aggregation and not due to an increase in the refractive index at higher temperatures, we made use of the UV response of the system. We proceeded to warm the sample at 40 °C and equilibrate, obtaining the increase in scattering, and then we irradiated the sample with UV light. The experiment resulted in a decrease of the scattering signal to detection limits (S13), for which the only explanation can be a loss in aggregation. Thus, the UV irradiation can trigger the disassembly even when the polymerization is enhanced.
To further investigate the mechanism of this phenomenon, a temperature cycling experiment was performed also with CD, showing two transitions: first, a signal inversion for the stacked azobenzene from 5 to 40 °C and, second, a decrease in signal intensity above 50 °C (Figures 4e, S14). The spectrum showed a positive Cotton effect between 260 and 380 nm (corresponding to the azobenzene absorbance) below rt, which changed to a negative Cotton effect at 20–25 °C. On the contrary the CD signal corresponding to the BTA cores (λmax = 220 nm, only a peak shoulder can be observed, S15) did not seem altered even though the cutoff wavelength of DMSO prevented a detailed analysis. Therefore, a full helix inversion seems unlikely, while a change in the packing and helicity of the azobenzenes along the fibers seems responsible for the observed transition. The signal kept increasing until 50 °C and then started decreasing in a reversible manner (S14). This inflection could imply a “classical” loss in aggregation due to temperature-induced depolymerization.
Interestingly, this unusual temperature-enhanced polymerization is the consequence of the synergistic response of the azobenzene moiety and the octa(ethylene glycol) chain together. First, temperature modifies the distribution of E and Z isomers of the azobenzene moiety, favoring the more thermodynamically stable EEE isomer at high temperatures (S14) and thus increasing aggregation. However, this increase in the concentration (+20%) on its own cannot explain the increased SLS signal (+2000%) or the signal inversion observed in CD spectroscopy. Second, octa(ethylene glycol) hydrophobicity is increased upon heating because of loss of solvating water molecules, (40,42) thereby increasing the driving forces for self-assembly driving forces. We hypothesize that the monomer rearrangement inside the fibers is related to the desolvation of octa(ethylene glycol), because it leads to an increased hydrophobicity and a reduced steric hindrance between octa(ethylene glycol) chains. Analogous results have been reported before in similar scenarios. (20)
Together, these two effects are amplified. The temperature increases at the same time as the hydrophobicity of each monomer and the distribution of azobenzene moieties in the E configuration. Therefore, there are more monomers able to stack than at rt and their hydrophobicity is higher. The sum brings the systems to the highest aggregation state at 40–50 °C.
Summarizing, we have a supramolecular system with a reversible response to temperature, enhancing monomer aggregation above room temperature and changing the internal conformation of the lateral chain packing. Furthermore, even when the polymerization is enhanced, the assemblies remain responsive to light. Considering that the kinetics of the photoisomerization is much faster than the kinetics of the thermal back-isomerization, the light response dominates over the temperature response.
2.5. pH and Ionic Strength Responsiveness
Previous work highlighted that the stability of a supramolecular polymer can be affected by the repulsion between charged monomers. (57) An elegant strategy to design responsive systems using this phenomenon consists of introducing specific groups, whose protonation, and consequently charge, depends on pH. (13)
Inspired by this work and aiming for an ampholytic behavior in a single component, we included a C-terminal lysine in our design, exposing a carboxylic acid and a primary amine at the periphery of the monomer. Considering the pKa’s of both amino (10.79) and carboxylic groups (2.20), we can delimit three pH ranges in which the net charge of the discotic monomer undergoes significant variations. Approximately, between pH 3.9 and pH 9.6 monomers are zwitterionic, comprising three carboxylate groups and three ammonium groups, with a net charge of 0 (Figure S16). When approaching pH 2.2, the carboxylate groups become protonated, resulting in a net positive charge, which would destabilize the aggregates and promote disassembly. A similar process would happen when approaching pH 12, when the ammonium moieties are deprotonated, resulting in a net negative charge. Therefore, the system can evolve from a zwitterionic monomer, where the assembly would be favored through potential ionic bridges between stacked discs, to electrostatic repulsion-induced disassembly.
In order to demonstrate that this ampholytic behavior has an impact on self-assembly, we performed a series of experiments including TEM, CD, and SLS. We prepared samples at three different pH values and compared the self-assembly of zwitterionic monomers (+3/–3 at pH 7.2 ± 0.8) with positively charged monomers (+3 at pH 2.2 ± 0.2) and negatively charged monomers (−3 at pH 12.0 ± 0.2). These pH values were chosen according to the expected maximum of population of each charged species (Figure S16).
TEM revealed the formation of fibers at neutral pH, while very few were observed at low pH and none at high pH (Figure 5a). This indicates that the repulsion at high and low pH values is sufficient to destabilize the aggregates, resulting in monomers or small aggregates. In order to reinforce this result and explore the combination of the temperature and pH responses, a temperature ramping experiment with CD and SLS was performed at the different pH values. Very low signal was obtained for nonzwitterionic samples using CD, showing also a very weak temperature response (Figure 5b). This can be attributed to the few monomers still zwitterionic and, hence, able to aggregate. SLS showed a low count rate that did not increase upon heating (Figure 5c), indicating no (significant) aggregation, confirming the TEM and CD results. In addition, we irradiated the samples with UV light at the different pH’s to demonstrate the compatibility of the two responsiveness (S17), showing higher degrees of disassembly. These indications altogether support the pH responsiveness of our fibers and the existence of three pH windows in which the system’s net charge changes, producing a dramatic change in aggregation. Furthermore, it demonstrated that the temperature effect on the self-assembly at extreme pH’s, where the increased hydrophobicity due to desolvation of the octaethylene glycol chain competes against the electrostatic repulsion, is too subtle to make a change. Thus, in this scenario the pH response dominates over the temperature response.
Figure 5
Figure 5. TEM image of monomer 1 at 100 μM (a) at pH 2.0 ± 0.2, 7.0 ± 0.2, and 11.6 ± 0.2 (scale bar: 250 nm). CD heating experiment at 25 μM (b) at pH 2.2 ± 0.2, 7.2 ± 0.8, and 12.0 ± 0.2 (60 °C/h, measuring in steps of 5 °C). SLS heating experiment at 100 μM (c) at pH 2.0 ± 0.2, 7.0 ± 0.2, and 11.6 ± 0.2 (60 °C/h measuring in steps of 5 °C) (the line was added to guide the eye). CD at 5 °C with and without NaCl 150 mM (d) at pH 2.2 ± 0.2, 7.2 ± 0.8, and 12.0 ± 0.2.
Previous reports have also shown that ionic strength can modulate monomer repulsion through shielding of charges. (56) Here, we tested if our fibers respond to changes in ionic strength in the three pH windows. In particular, we added NaCl at a physiological concentration (150 mM) with the purpose of shielding the charges. In Figure 5d we compare CD spectra from samples at pH 2.2, 7.2, and 12.0, with and without salt. In all cases, we observe an increase in CD signal, associated with an increased aggregation. Under the acidic and basic conditions, the influence is more pronounced, because the sample changes from a disassembled to an assembled state. Interestingly, we did this experiment at two different temperatures, 5 and 20 °C, observing a reduced signal at 20 °C due to the proximity to the signal inversion temperature (Figure S18). These results demonstrate that the repulsion can be modified by the ionic strength, confirming the mechanism of the responsiveness to pH and its reversibility, and indicate the temperature response remains.
3. Conclusions
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In conclusion, we demonstrated the possibility to condense different response mechanisms in single-component supramolecular polymers through a rational monomer design. Following a modular synthesis, we incorporate moieties in the monomer design that, simultaneously, drive the self-assembly and introduce responsiveness to different stimuli (Figure 6). Our system responds in a controlled and reversible fashion to light, temperature, pH, and ionic strength, modulating the assembly–disassembly equilibrium. By these means, we describe a system with multiple equilibria (Figure 6) in which each state is accessible through different pathways, applying the stimuli either orthogonally or in combination, thereby facilitating a sophisticated degree of control.
Figure 6
Figure 6. Schematic representation of the system. Above, molecular responsiveness to light and pH. Below, supramolecular responsiveness to light, pH, ionic strength, and temperature.
Our results pave the way toward effective and highly controllable supramolecular materials in which the responsiveness is fully imprinted in a single monomer. This is especially interesting for biological applications, such as drug delivery or tissue engineering, where controlling the material performance in a complex environment is challenging.
Supporting Information
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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.0c02067.
Experimental procedure for the synthesis of 1 and 2 as well as analytical, spectral, and self-assembly characterization data (PDF)
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- Lorenzo Albertazzi - Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, Spain; Department of Biomedical Engineering, Institute of Complex Molecular Systems (ICMS), Eindhoven University of Technology (TUE), Eindhoven 5612 AZ, The Netherlands;
http://orcid.org/0000-0002-6837-0812;
- José Augusto Berrocal - Adolphe Merkle Institute, Polymer Chemistry and Materials, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland;http://orcid.org/0000-0003-3435-8310
- Carlo Matera - Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, Spain; Network Biomedical Research Centre in Biomaterials, Bioengineering and Nanomedicine (CIBER-BBN), Madrid 28029, Spain;http://orcid.org/0000-0001-6939-3859
- Pau Gorostiza - Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona 08036, Spain; Network Biomedical Research Centre in Biomaterials, Bioengineering and Nanomedicine (CIBER-BBN), Madrid 28029, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona 08011, Spain;http://orcid.org/0000-0002-7268-5577
- Ilja K. Voets - Laboratory of Physical Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology (TUE), Eindhoven 5612 AZ, The Netherlands;http://orcid.org/0000-0003-3543-4821
Acknowledgments
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This work was financially supported by the EURONANOMED (NANOVAX: PCIN-2016-025), MINECO-FPI (BES-2017-080188), TARGESTORM (SAF2016-75241-R), and the Generalitat de Catalunya (2017 SGR 01536) to E.F., S.P., and L.A. The AGAUR/Generalitat de Catalunya (CERCA Programme 2017-SGR-1442); FEDER funds; Human Brain Project (SGA3 Grant Agreement 945539); MINECO (Deepred); “la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR19/52160010); and the CECH project that is co-financed by the European Union Regional Development Fund within the framework of the ERDF Operational Program of Catalonia 2014-2020 with a grant of 50% of total eligible cost. L.A. and I.K.V. acknowledge The Netherlands Organisation for Scientific Research (NWO VIDI Grants 723.014.006 and 192.028) for financial support.
References
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This article references 57 other publications.
- 1Krieg, E.; Bastings, M. M. C.; Besenius, P.; Rybtchinski, B. Supramolecular Polymers in Aqueous Media. Chem. Rev. 2016, 116 (4), 2414– 2477, DOI: 10.1021/acs.chemrev.5b00369Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtVCls7Y%253D&md5=f925f8858d9766bad8c978db3870c589Supramolecular Polymers in Aqueous MediaKrieg, Elisha; Bastings, Maartje M. C.; Besenius, Pol; Rybtchinski, BorisChemical Reviews (Washington, DC, United States) (2016), 116 (4), 2414-2477CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)This review discusses one-dimensional supramol. polymers that form in aq. media. First, naturally occurring supramol. polymers are described, in particular, amyloid fibrils, actin filaments, and microtubules. Their structural, thermodn., kinetic, and nanomech. properties are highlighted, as well as their importance for the advancement of biol. inspired supramol. polymer materials. Second, five classes of synthetic supramol. polymers are described: systems based on (1) hydrogen-bond motifs, (2) large π-conjugated surfaces, (3) host-guest interactions, (4) peptides, and (5) DNA. We focus on recent studies that address key challenges in the field, providing mechanistic understanding, rational polymer design, important functionality, robustness, or unusual thermodn. and kinetic properties.
- 2Albertazzi, L.; Martinez-Veracoechea, F. J.; Leenders, C. M. A.; Voets, I. K.; Frenkel, D.; Meijer, E. W. Spatiotemporal Control and Superselectivity in Supramolecular Polymers Using Multivalency. Proc. Natl. Acad. Sci. U. S. A. 2013, 110 (30), 12203– 12208, DOI: 10.1073/pnas.1303109110Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1emu7rN&md5=d33082502f124a26cd4394b791549fb6Spatiotemporal control and superselectivity in supramolecular polymers using multivalencyAlbertazzi, Lorenzo; Martinez-Veracoechea, Francisco J.; Leenders, Christianus M. A.; Voets, Ilja K.; Frenkel, Daan; Meijer, E. W.Proceedings of the National Academy of Sciences of the United States of America (2013), 110 (30), 12203-12208,S12203/1-S12203/10CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Multivalency has an important but poorly understood role in mol. self-organization. We present the noncovalent synthesis of a multicomponent supramol. polymer in which chem. distinct monomers spontaneously coassemble into a dynamic, functional structure. We show that a multivalent recruiter is able to bind selectively to one subset of monomers (receptors) and trigger their clustering along the self-assembled polymer, behavior that mimics raft formation in cell membranes. This phenomenon is reversible and affords spatiotemporal control over the monomer distribution inside the supramol. polymer by superselective binding of single-strand DNA to pos. charged receptors. Our findings reveal the pivotal role of multivalency in enabling structural order and nonlinear recognition in water-sol. supramol. polymers, and it offers a design principle for functional, structurally defined supramol. architectures.
- 3Matson, J. B.; Stupp, S. I. Drug Release from Hydrazone-Containing Peptide Amphiphiles. Chem. Commun. 2011, 47 (28), 7962– 7964, DOI: 10.1039/c1cc12570bGoogle Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXotl2jt74%253D&md5=f3e478701d293418b7e856857f3b36a2Drug release from hydrazone-containing peptide amphiphilesMatson, John B.; Stupp, Samuel I.Chemical Communications (Cambridge, United Kingdom) (2011), 47 (28), 7962-7964CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addn. of the novel compd. tri-Boc-hydrazido adipic acid to a lysine ε-amine allowed for precise placement of a hydrazide in a peptide sequence.
- 4Bakker, M. H.; Lee, C. C.; Meijer, E. W.; Dankers, P. Y. W.; Albertazzi, L. Multicomponent Supramolecular Polymers as a Modular Platform for Intracellular Delivery. ACS Nano 2016, 10 (2), 1845– 1852, DOI: 10.1021/acsnano.5b05383Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlyntL4%253D&md5=bf0c9f6ab3034d400c014d21c7557e04Multicomponent Supramolecular Polymers as a Modular Platform for Intracellular DeliveryBakker, Maarten H.; Lee, Cameron C.; Meijer, E. W.; Dankers, Patricia Y. W.; Albertazzi, LorenzoACS Nano (2016), 10 (2), 1845-1852CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Supramol. polymers are an emerging family of nanosized structures with potential use in materials chem. and medicine. Surprisingly, application of supramol. polymers in the field of drug delivery has received only limited attention. Here, we explore the potential of PEGylated 1,3,5-benzenetricarboxamide (BTA) supramol. polymers for intracellular delivery. Exploiting the unique modular approach of supramol. chem., we can coassemble neutral and cationic BTAs and control the overall properties of the polymer by simple monomer mixing. Moreover, this platform offers a versatile approach toward functionalization. The core can be efficiently loaded with a hydrophobic guest mol., while the exterior can be electrostatically complexed with siRNA. It is demonstrated that both compds. can be delivered in living cells, and that they can be combined to enable a dual delivery strategy. These results show the advantages of employing a modular system and pave the way for application of supramol. polymers in intracellular delivery.
- 5Su, H.; Zhang, W.; Wang, H.; Wang, F.; Cui, H. Paclitaxel-Promoted Supramolecular Polymerization of Peptide Conjugates. J. Am. Chem. Soc. 2019, 141 (30), 11997– 12004, DOI: 10.1021/jacs.9b04730Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXht1als77F&md5=8b1c5f9b7f1363b2a1cd26b020e9ed1dPaclitaxel-Promoted Supramolecular Polymerization of Peptide ConjugatesSu, Hao; Zhang, Weijie; Wang, Han; Wang, Feihu; Cui, HonggangJournal of the American Chemical Society (2019), 141 (30), 11997-12004CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Spontaneous assocn. above a threshold concn. is a hallmark of supramol. polymn., in which monomeric units self-assemble into polymeric aggregates through noncovalent interactions. This self-initiated supramol. process differs from the conventional covalent chain-growth polymn. in that the latter often involves the use of a different chem. entity as an initiator to trigger/control the polymn. process. We report here the use of a small mol. hydrophobe, paclitaxel (PTX), as an effective promoter to induce the supramol. polymn. of a peptide-paclitaxel conjugate, Spheropax (Spax). We found that Spax monomers alone in water self-assemble into spherical micelles of approx. 6.5 nm in diam. but, in the presence of free PTX, undergo a supramol. polymn. process to form filamentous assemblies of several micrometers in length. Increasing the ratio of promoter to monomer (PTX/Spax) induces Spax's directional polymn. and expedites its kinetic process. We believe these findings provide important insight into the initiator-controlled supramol. polymn. process.
- 6Su, H.; Wang, F.; Wang, Y.; Cheetham, A. G.; Cui, H. Macrocyclization of a Class of Camptothecin Analogues into Tubular Supramolecular Polymers. J. Am. Chem. Soc. 2019, 141 (43), 17107– 17111, DOI: 10.1021/jacs.9b09848Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvFOktrjM&md5=7dedbe0c3556fddb61e07377bb50059aMacrocyclization of a Class of Camptothecin Analogues into Tubular Supramolecular PolymersSu, Hao; Wang, Feihu; Wang, Yuzhu; Cheetham, Andrew G.; Cui, HonggangJournal of the American Chemical Society (2019), 141 (43), 17107-17111CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Nanostructured supramol. polymers (SPs) are filamentous assemblies possessing a high degree of internal order and have important uses in regenerative medicine, drug delivery, and soft matter electronics. Despite recent advances in functional SPs, a challenging topic is the development of robust assembly protocols enabling the incorporation of various functional units without altering its supramol. architecture. We report here the robust tubular assembly of camptothecin (CPT) analogs into functional SPs. Covalent linkage of two CPT moieties to various short hydrophilic segments (e.g., nonionic, cationic, anionic, and zwitterionic) leads to a class of CPT analogs that self-assemble in water into tubular SPs. Systemic administration of nonionic SPs effectively suppresses tumor growth. Furthermore, these tubular SPs act as universal dispersing agents in water for low-mol.-wt. hydrophobes.
- 7Besenius, P.; Heynens, J. L.; Straathof, R.; Niuwenhuizen, M. M.; Bomans, P.; Terreno, E.; Aime, S.; Strijkers, G.; Nicolay, K.; Meijer, E. W. Paramagnetic self-assembled nanoparticles as supramolecular MRI contrast agents. Contrast Media Mol. Imaging 2012, 7 (3), 356– 361, DOI: 10.1002/cmmi.498Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmtFGhtrg%253D&md5=e2209a32b2f0821ddf91e23444573ceeParamagnetic self-assembled nanoparticles as supramolecular MRI contrast agentsBesenius, Pol; Heynens, Joeri L. M.; Straathof, Roel; Nieuwenhuizen, Marko M. L.; Bomans, Paul H. H.; Terreno, Enzo; Aime, Silvio; Strijkers, Gustav J.; Nicolay, Klaas; Meijer, E. W.Contrast Media & Molecular Imaging (2012), 7 (3), 356-361CODEN: CMMICO; ISSN:1555-4309. (Wiley-Blackwell)Nanometer-sized materials offer a wide range of applications in biomedical technologies, particularly imaging and diagnostics. Current scaffolds in the nanometer range predominantly make use of inorg. particles, org. polymers or natural peptide-based macromols. In contrast we hereby report a supramol. approach for the prepn. of self-assembled dendritic-like nanoparticles for applications as MRI contrast agents. This strategy combines the benefits from low mol. wt. imaging agents with the ones of high mol. wt. Their in vitro properties are confirmed by in vivo measurements: post injection of well-defined and meta-stable nanoparticles allows for high-resoln. blood-pool imaging, even at very low Gd(III) doses. These dynamic and modular imaging agents are an important addn. to the young field of supramol. medicine using well-defined nanometer-sized assemblies. Copyright © 2012 John Wiley & Sons, Ltd.
- 8Orbach, R.; Adler-Abramovich, L.; Zigerson, S.; Mironi-Harpaz, I.; Seliktar, D.; Gazit, E. Self-Assembled Fmoc-Peptides as a Platform for the Formation of Nanostructures and Hydrogels. Biomacromolecules 2009, 10 (9), 2646– 2651, DOI: 10.1021/bm900584mGoogle Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVeqsrbO&md5=2140af9a384230ef35879157d4816151Self-Assembled Fmoc-Peptides as a Platform for the Formation of Nanostructures and HydrogelsOrbach, Ron; Adler-Abramovich, Lihi; Zigerson, Sivan; Mironi-Harpaz, Iris; Seliktar, Dror; Gazit, EhudBiomacromolecules (2009), 10 (9), 2646-2651CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Hydrogels are of great interest as a class of materials for tissue engineering, axonal regeneration, and controlled drug delivery, as they offer 3D interwoven scaffolds to support the growth of cells. Herein, we extend the family of the arom. Fmoc-dipeptides with a library of new Fmoc-peptides, which include natural and synthetic amino acids with an arom. nature. We describe the self-assembly of these Fmoc-peptides into various structures and characterize their distinctive mol. and phys. properties. Moreover, we describe the fabrication of the bioactive RGD sequence into a hydrogel. This unique material offers new opportunities for developing cell-adhesive biomedical hydrogel scaffolds, as well as for establishing strategies to modify surfaces with bioactive materials.
- 9Mata, A.; Geng, Y.; Henrikson, K. J.; Aparicio, C.; Stock, S. R.; Stacher, R. L.; Stupp, S. I. Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix. Biomaterials 2010, 31 (23), 6004– 6012, DOI: 10.1016/j.biomaterials.2010.04.013Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnslamt7g%253D&md5=31b506ca096d15e5545c810d5ddf4424Bone regeneration mediated by biomimetic mineralization of a nanofiber matrixMata, Alvaro; Geng, Yanbiao; Henrikson, Karl J.; Aparicio, Conrado; Stock, Stuart R.; Satcher, Robert L.; Stupp, Samuel I.Biomaterials (2010), 31 (23), 6004-6012CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Rapid bone regeneration within a three-dimensional defect without the use of bone grafts, exogenous growth factors, or cells remains a major challenge. We report here on the use of self-assembling peptide nanostructured gels to promote bone regeneration that have the capacity to mineralize in biomimetic fashion. The main mol. design was the use of phosphoserine residues in the sequence of a peptide amphiphile known to nucleate hydroxyapatite crystals on the surfaces of nanofibers. We tested the system in a rat femoral crit.-size defect by placing pre-assembled nanofiber gels in a 5 mm gap and analyzed bone formation with micro-computed tomog. and histol. We found within 4 wk significantly higher bone formation relative to controls lacking phosphorylated residues and comparable bone formation to that obsd. in animals treated with a clin. used allogenic bone matrix.
- 10Choe, S.; Bond, C. W.; Harrington, D. A.; Stupp, S. I.; McVary, K. T.; Podlasek, C. A. Peptide Amphiphile Nanofiber Hydrogel Delivery of Sonic Hedgehog Protein to the Cavernous Nerve to Promote Regeneration and Prevent Erectile Dysfunction. Nanomedicine 2017, 13 (1), 95– 101, DOI: 10.1016/j.nano.2016.08.032Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFWit7%252FJ&md5=1d859345de737d0bde59e16f1d4b2178Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunctionChoe, Shawn; Bond, Christopher W.; Harrington, Daniel A.; Stupp, Samuel I.; McVary, Kevin T.; Podlasek, Carol A.Nanomedicine (New York, NY, United States) (2017), 13 (1), 95-101CODEN: NANOBF; ISSN:1549-9634. (Elsevier)Erectile dysfunction (ED) has high impact on quality of life in prostatectomy, diabetic and aging patients. An underlying mechanism is cavernous nerve (CN) injury, which causes ED in up to 80% of prostatectomy patients. We examine how sonic hedgehog (SHH) treatment with innovative peptide amphiphile nanofiber hydrogels (PA), promotes CN regeneration after injury. SHH and its receptors patched (PTCH1) and smoothened (SMO) are localized in PG neurons and glia. SMO undergoes anterograde transport to signal to downstream targets. With crush injury, PG neurons degenerate and undergo apoptosis. SHH protein decreases, SMO localization changes to the neuronal cell surface, and anterograde transport stops. With SHH treatment SHH is taken up at the injury site and undergoes retrograde transport to PG neurons, allowing SMO transport to occur, and neurons remain intact. SHH treatment prevents neuronal degeneration, maintains neuronal, glial and downstream target signaling, and is significant as a regenerative therapy.
- 11Saunders, L.; Ma, P. X. Self-Healing Supramolecular Hydrogels for Tissue Engineering Applications. Macromol. Biosci. 2019, 19, 1800313, DOI: 10.1002/mabi.201800313Google ScholarThere is no corresponding record for this reference.
- 12Blum, A. P.; Kammeyer, J. K.; Rush, A. M.; Callmann, C. E.; Hahn, M. E.; Gianneschi, N. C. Stimuli-Responsive Nanomaterials for Biomedical Applications. J. Am. Chem. Soc. 2015, 137 (6), 2140– 2154, DOI: 10.1021/ja510147nGoogle Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVegurbN&md5=0d7f6aa46b2a4567a04ac2ecdb2d1addStimuli-Responsive Nanomaterials for Biomedical ApplicationsBlum, Angela P.; Kammeyer, Jacquelin K.; Rush, Anthony M.; Callmann, Cassandra E.; Hahn, Michael E.; Gianneschi, Nathan C.Journal of the American Chemical Society (2015), 137 (6), 2140-2154CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A review. Nature employs a variety of tactics to precisely time and execute the processes and mechanics of life, relying on sequential sense and response cascades to transduce signaling events over multiple length and time scales. Many of these tactics, such as the activation of a zymogen, involve the direct manipulation of a material by a stimulus. Similarly, effective therapeutics and diagnostics require the selective and efficient homing of material to specific tissues and biomol. targets with appropriate temporal resoln. These systems must also avoid undesirable or toxic side effects and evade unwanted removal by endogenous clearing mechanisms. Nanoscale delivery vehicles have been developed to package materials with the hope of delivering them to select locations with rates of accumulation and clearance governed by an interplay between the carrier and its cargo. Many modern approaches to drug delivery have taken inspiration from natural activatable materials like zymogens, membrane proteins, and metabolites, whereby stimuli initiate transformations that are required for cargo release, prodrug activation, or selective transport. This Perspective describes key advances in the field of stimuli-responsive nanomaterials while highlighting some of the many challenges faced and opportunities for development. Major hurdles include the increasing need for powerful new tools and strategies for characterizing the dynamics, morphol., and behavior of advanced delivery systems in situ and the perennial problem of identifying truly specific and useful phys. or mol. biomarkers that allow a material to autonomously distinguish diseased from normal tissue.
- 13Frisch, H.; Unsleber, J. P.; Lüdeker, D.; Peterlechner, M.; Brunklaus, G.; Waller, M.; Besenius, P. pH-Switchable Ampholytic Supramolecular Copolymers. Angew. Chem., Int. Ed. 2013, 52 (38), 10097– 10101, DOI: 10.1002/anie.201303810Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1CrsL7O&md5=2d8a4b433da658958c6e77cdef367d3dpH-switchable ampholytic supramolecular copolymersFrisch, Hendrik; Unsleber, Jan Patrick; Luedeker, David; Peterlechner, Martin; Brunklaus, Gunther; Waller, Mark; Besenius, PolAngewandte Chemie, International Edition (2013), 52 (38), 10097-10101CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)We have synthesized β-sheet-encoded anionic and cationic supramol. co-monomers. These dendritic peptide amphiphiles, when self-assembled from a 1:1 monomer feed ratio, form supramol. copolymers through a combination of Coulomb attractive forces and hydrogen-bonding interactions. The obtained ampholytic supramol. materials have been designed for on-off polymn. in response to pH triggers. Decreasing or increasing g the pH value outside of this pH window results in polymn. being switched off and disassembly occurs through the loss of the salt bridges of the peptide side arms. The use of a supramol. engineering approach enables the pH window to be increased by enhancing the affinity of the supramol. co-monomers.
- 14Gröger, G.; Meyer-Zaika, W.; Böttcher, C.; Gröhn, F.; Ruthard, C.; Schmuck, C. Switchable Supramolecular Polymers from the Self-Assembly of a Small Monomer with Two Orthogonal Binding Interactions. J. Am. Chem. Soc. 2011, 133 (23), 8961– 8971, DOI: 10.1021/ja200941aGoogle Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3Mjht1Cksw%253D%253D&md5=a6a3171f6ce694c564a6075089a138f6Switchable supramolecular polymers from the self-assembly of a small monomer with two orthogonal binding interactionsGroger Gerd; Meyer-Zaika Wolfgang; Bottcher Christoph; Grohn Franziska; Ruthard Christian; Schmuck CarstenJournal of the American Chemical Society (2011), 133 (23), 8961-71 ISSN:.The low molecular weight heteroditopic monomer 1 forms supramolecular polymers in polar solution as shown, for example, by infrared laser-based dynamic light scattering (DLS), small-angle neutron scattering (SANS), electron microscopy (TEM, cryo-TEM), and viscosity measurements. Self-assembly of 1 is based on two orthogonal binding interactions, the formation of a Fe(II)-terpyridine 1:2 metal-ligand complex and the dimerization of a self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterion. Both binding interactions have a sufficient stability in polar (DMSO) and even aqueous solutions to ensure formation of linear polymers of considerable length (up to 100 nm). The supramolecular polymerization follows a ring-chain mechanism causing a significant increase in the viscosity of the solutions at millimolar concentrations and above. The linear polymers then further aggregate in solution into larger globular aggregates with a densely packed core and a loose shell. Both binding interactions can be furthermore switched on and off either by adding a competing ligand to remove the metal ion and subsequent readdition of Fe(II) or by reversible protonation and deprotonation of the zwitterion upon addition of acid or base. The self-assembly of 1 can therefore be switched back and forth between four different states, the monomer, a metal-complexed dimer or an ion paired dimer, and finally the polymer.
- 15Moyer, T. J.; Finbloom, J. A.; Chen, F.; Toft, D. J.; Cryns, V. L.; Stupp, S. I. pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies. J. Am. Chem. Soc. 2014, 136 (42), 14746– 14752, DOI: 10.1021/ja5042429Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsleksrvI&md5=80691b308deb24ebbedcaf631f9498e2pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional AssembliesMoyer, Tyson J.; Finbloom, Joel A.; Chen, Feng; Toft, Daniel J.; Cryns, Vincent L.; Stupp, Samuel I.Journal of the American Chemical Society (2014), 136 (42), 14746-14752CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Supramol. self-assembly offers promising new ways to control nanostructure morphol. and respond to external stimuli. A pH-sensitive self-assembled system was developed to both control nanostructure shape and respond to the acidic microenvironment of tumors using self-assembling peptide amphiphiles (PAs). By incorporating an oligo-histidine H6 sequence, we developed two PAs that self-assembled into distinct morphologies on the nanoscale, either as nanofibers or spherical micelles, based on the incorporation of the aliph. tail on the N-terminus or near the C-terminus, resp. Both cylinder and sphere-forming PAs demonstrated reversible disassembly between pH 6.0 and 6.5 upon protonation of the histidine residues in acidic solns. These PAs were then characterized and assessed for their potential to encapsulate hydrophobic chemotherapies. The H6-based nanofiber assemblies encapsulated camptothecin (CPT) with up to 60% efficiency, a 7-fold increase in CPT encapsulation relative to spherical micelles. Addnl., pH-sensitive nanofibers showed improved tumor accumulation over both spherical micelles and nanofibers that did not change morphologies in acidic environments. We have demonstrated that the morphol. transitions upon changes in pH of supramol. nanostructures affect drug encapsulation and tumor accumulation. Our findings also suggest that these supramol. events can be tuned by mol. design to improve the pharmacol. properties of nanomedicines.
- 16Ahlers, P.; Frisch, H.; Holm, R.; Spitzer, D.; Barz, M.; Besenius, P. Tuning the pH-Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH. Macromol. Biosci. 2017, 17 (10), 1700111, DOI: 10.1002/mabi.201700111Google ScholarThere is no corresponding record for this reference.
- 17Adhikari, B.; Yamada, Y.; Yamauchi, M.; Wakita, K.; Lin, X.; Aratsu, K.; Ohba, T.; Karatsu, T.; Hollamby, M. J.; Shimizu, N.; Takagi, H.; Haruki, R.; Adachi, S.; Yagai, S. Light-induced unfolding and refolding of supramolecular polymer nanofibers. Nat. Commun. 2017, 8, 15254, DOI: 10.1038/ncomms15254Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1crlslartw%253D%253D&md5=0c1b5b3d808c0243e540d47555d7dcedLight-induced unfolding and refolding of supramolecular polymer nanofibresAdhikari Bimalendu; Yamada Yuki; Yamauchi Mitsuaki; Wakita Kengo; Lin Xu; Aratsu Keisuke; Karatsu Takashi; Yagai Shiki; Adhikari Bimalendu; Ohba Tomonori; Hollamby Martin J; Shimizu Nobutaka; Takagi Hideaki; Haruki Rie; Adachi Shin-IchiNature communications (2017), 8 (), 15254 ISSN:.Unlike classical covalent polymers, one-dimensionally (1D) elongated supramolecular polymers (SPs) can be encoded with high degrees of internal order by the cooperative aggregation of molecular subunits, which endows these SPs with extraordinary properties and functions. However, this internal order has not yet been exploited to generate and dynamically control well-defined higher-order (secondary) conformations of the SP backbone, which may induce functionality that is comparable to protein folding/unfolding. Herein, we report light-induced conformational changes of SPs based on the 1D exotic stacking of hydrogen-bonded azobenzene hexamers. The stacking causes a unique internal order that leads to spontaneous curvature, which allows accessing conformations that range from randomly folded to helically folded coils. The reversible photoisomerization of the azobenzene moiety destroys or recovers the curvature of the main chain, which demonstrates external control over the SP conformation that may ultimately lead to biological functions.
- 18Yagai, S.; Yamauchi, M.; Kobayashi, A.; Karatsu, T.; Kitamura, A.; Ohba, T.; Kikkawa, Y. Control over Hierarchy Levels in the Self-Assembly of Stackable Nanotoroids. J. Am. Chem. Soc. 2012, 134 (44), 18205– 18208, DOI: 10.1021/ja308519bGoogle Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFChs77I&md5=3bfcf614ea7a5ae80a05c02c74348f2eControl over Hierarchy Levels in the Self-Assembly of Stackable NanotoroidsYagai, Shiki; Yamauchi, Mitsuaki; Kobayashi, Ai; Karatsu, Takashi; Kitamura, Akihide; Ohba, Tomonori; Kikkawa, YoshihiroJournal of the American Chemical Society (2012), 134 (44), 18205-18208CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report a precise control over the hierarchy levels in the outstanding self-organization process shown by chiral azobenzene dimer I. This compd. forms uniform toroidal nanostructures that can hierarchically organize into chiral nanotubes under the control by temp., concn., or light. The nanotubes further organized into supercoiled fibrils, which finally intertwined to form double helixes with one-handed helical sense.
- 19Prabhu, D. D.; Aratsu, K.; Kitamoto, Y.; Ouchi, H.; Ohba, T.; Hollamby, M. J.; Shimizu, N.; Takagi, H.; Haruki, R.; Adachi, S.; Yagai, S. Self-folding of supramolecular polymers into bioinspired topology. Sci. Adv. 2018, 4 (9), 8466, DOI: 10.1126/sciadv.aat8466Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1Wmsr3O&md5=5f507c647b7d523bc021aaff5c20fbd2Self-folding of supramolecular polymers into bioinspired topologyPrabhu, Deepak D.; Aratsu, Keisuke; Kitamoto, Yuichi; Ouchi, Hayato; Ohba, Tomonori; Hollamby, Martin J.; Shimizu, Nobutaka; Takagi, Heaki; Haruki, Rie; Adachi, Shin-ichi; Yagai, ShikiScience Advances (2018), 4 (9), eaat8466/1-eaat8466/9CODEN: SACDAF; ISSN:2375-2548. (American Association for the Advancement of Science)Folding one-dimensional polymer chains into well-defined topologies represents an important organization process for proteins, but replicating this process for supramol. polymers remains a challenging task. We report supramol. polymers that can fold into protein-like topologies. Our approach is based on curvature-forming supramol. rosettes, which affords kinetic control over the extent of helical folding in the resulting supramol. fibers by changing the cooling rate for polymn. When using a slow cooling rate, we obtained misfolded fibers contg. a minor amt. of helical domains that folded on a time scale of days into unique topologies reminiscent of the protein tertiary structures. Thermodn. anal. of fibers with varying degrees of folding revealed that the folding is accompanied by a large enthalpic gain. The self-folding proceeds via ordering of misfolded domains in the main chain using helical domains as templates, as fully misfolded fibers prepd. by a fast cooling rate do not self-fold.
- 20Huang, Z.; Lee, E.; Kim, H.-J.; Lee, M. Aqueous Nanofibers with Switchable Chirality Formed of Self-Assembled Dumbbell-Shaped Rod Amphiphiles. Chem. Commun. 2009, 44, 6819– 6821, DOI: 10.1039/b913286dGoogle ScholarThere is no corresponding record for this reference.
- 21Feijter, I.; Besenius, P.; Albertazzi, L.; Meijer, E. W.; Palmans, A. R. A.; Voets, I. K. Mechanistic control over morphology: self-assembly of a discotic amphiphile in water. Soft Matter 2013, 9 (42), 10025– 10030, DOI: 10.1039/C3SM52104DGoogle ScholarThere is no corresponding record for this reference.
- 22Alemán García, M. Á.; Magdalena Estirado, E.; Milroy, L.-G.; Brunsveld, L. Dual-Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic Supramolecular Wires. Angew. Chem., Int. Ed. 2018, 57 (18), 4976– 4980, DOI: 10.1002/anie.201800148Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXlslShsrk%253D&md5=ee85add14428be38381d914191baace7Dual-Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic Supramolecular WiresAleman Garcia, Miguel Angel; Estirado, Eva Magdalena; Milroy, Lech-Gustav; Brunsveld, LucAngewandte Chemie, International Edition (2018), 57 (18), 4976-4980CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The combination of oligonucleotides and synthetic supramol. systems allows for novel and long-needed modes of regulation of the self-assembly of both mol. elements. Discotic mols. were conjugated with short oligonucleotides and their assembly into responsive supramol. wires studied. The self-assembly of the discotic mols. provides addnl. stability for DNA-duplex formation owing to a cooperative effect. The appended oligonucleotides allow for positional control of the discotic elements within the supramol. wire. The programmed assembly of these hybrid architectures can be modulated through the DNA, for example, by changing the no. of base pairs or salt concn., and through the discotic platform by the addn. of discotic elements without oligonucleotide handles. These hybrid supramol.-DNA structures allow for advanced levels of control over 1D dynamic platforms with responsive regulatory elements at the interface with biol. systems.
- 23Kumar, M.; Brocorens, P.; Tonnelé, C.; Beljonne, D.; Surin, M.; George, S. J. A Dynamic Supramolecular Polymer with Stimuli-Responsive Handedness for in Situ Probing of Enzymatic ATP Hydrolysis. Nat. Commun. 2014, 5, 5793, DOI: 10.1038/ncomms6793Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjvFWqtrk%253D&md5=cdca02a3dd1c51bda752aa461361e762A dynamic supramolecular polymer with stimuli-responsive handedness for in situ probing of enzymatic ATP hydrolysisKumar, Mohit; Brocorens, Patrick; Tonnele, Claire; Beljonne, David; Surin, Mathieu; George, Subi J.Nature Communications (2014), 5 (), 5793CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Design of artificial systems, which can respond to fluctuations in concn. of adenosine phosphates (APs), can be useful in understanding various biol. processes. Helical assemblies of chromophores, which dynamically respond to such changes, can provide real-time chiroptical readout of various chem. transformations. Towards this concept, here we present a supramol. helix of achiral chromophores, which shows chiral APs responsive tunable handedness along with dynamically switchable helicity. This system, composing of naphthalenediimides with phosphate recognition unit, shows opposite handedness on binding with ATP compared with ADP or AMP, which is comprehensively analyzed with mol. dynamic simulations. Such differential signalling along with stimuli-dependent fast stereomutations have been capitalized to probe the reaction kinetics of enzymic ATP hydrolysis. Detailed chiroptical analyses provide mechanistic insights into the enzymic hydrolysis and various intermediate steps. Thus, a unique dynamic helical assembly to monitor the real-time reaction processes via its stimuli-responsive chiroptical signalling is conceptualized.
- 24Mishra, A.; Korlepara, D. B.; Balasubramanian, S.; George, S. J. Bioinspired, ATP-driven co-operative supramolecular polymerization and its pathway dependence. Chem. Commun. 2020, 56, 1505– 1508, DOI: 10.1039/C9CC08790GGoogle Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVeqt7zI&md5=76ff5a3066f873654bff12dcee47b8e2Bioinspired, ATP-driven co-operative supramolecular polymerization and its pathway dependenceMishra, Ananya; Korlepara, Divya B.; Balasubramanian, Sundaram; George, Subi J.Chemical Communications (Cambridge, United Kingdom) (2020), 56 (10), 1505-1508CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A bio-inspired, ATP-driven nucleation growth assembly is demonstrated using an amphiphilic naphthalene diimide (NDI) deriv. appended with guanidinium receptors to promote specific salt-bridge type interaction with nucleotide phosphates. Detailed spectroscopic and microscopic probing revealed a pathway-dependent co-operative self-assembly to yield two-dimensional and scrolled nano-tubular bilayer assemblies under kinetic and thermodn. conditions, resp.
- 25Albertazzi, L.; van der Veeken, N.; Baker, M. B.; Palmans, A. R. A.; Meijer, E. W. Supramolecular Copolymers with Stimuli-Responsive Sequence Control. Chem. Commun. 2015, 51 (90), 16166– 16168, DOI: 10.1039/C5CC06951CGoogle Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsV2nu7zK&md5=d27a83c7347d275a9b211bd4cd9b66f1Supramolecular copolymers with stimuli-responsive sequence controlAlbertazzi, Lorenzo; van der Veeken, Nick; Baker, Matthew B.; Palmans, Anja R. A.; Meijer, E. W.Chemical Communications (Cambridge, United Kingdom) (2015), 51 (90), 16166-16168CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The authors report a novel responsive supramol. copolymer able to change its monomer sequence as a result of mol. stimuli. Nucleic acids and RNase were used as mol. inputs, controlling the clustering of specific monomers along the polymer backbone. This opens new ways towards the mol. control of synthetic supramol. networks.
- 26Molla, M. R.; Prasad, P.; Thayumanavan, S. Protein-Induced Supramolecular Disassembly of Amphiphilic Polypeptide Nanoassemblies. J. Am. Chem. Soc. 2015, 137 (23), 7286– 7289, DOI: 10.1021/jacs.5b04285Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXptFWqtb8%253D&md5=3f99c9e43c3b037b15ded5c1001f8603Protein-Induced Supramolecular Disassembly of Amphiphilic Polypeptide NanoassembliesMolla, Mijanur Rahaman; Prasad, Priyaa; Thayumanavan, S.Journal of the American Chemical Society (2015), 137 (23), 7286-7289CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Mimicking noncovalent interaction based processes in nature has been an important goal of supramol. chem. Here, the authors report on amphiphilic polypeptides that self-assemble to form nanoscale supramol. assemblies and are programmed to disassemble in response to a specific protein. Benzenesulfonamide and carbonic anhydrase have been chosen as the ligand and protein, resp., to demonstrate this possibility. Since the amphiphilic nanoassembly sequesters hydrophobic guest mols., the protein-specific disassembly event provides a protein-sensitive mol. release as well. The authors envision that the binding induced disassembly and guest release might open up new opportunities for the next generation of supramol. assemblies for protein-specific delivery and diagnostics.
- 27van Dun, S.; Ottmann, C.; Milroy, L.; Brunsveld, L. Supramolecular Chemistry Targeting Proteins. J. Am. Chem. Soc. 2017, 139 (40), 13960– 13968, DOI: 10.1021/jacs.7b01979Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFeit7vL&md5=56422173d029b081e10d773705b8a478Supramolecular Chemistry Targeting Proteinsvan Dun, Sam; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, LucJournal of the American Chemical Society (2017), 139 (40), 13960-13968CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A review. The specific recognition of protein surface elements is a fundamental challenge in the life sciences. New developments in this field will form the basis of advanced therapeutic approaches and lead to applications such as sensors, affinity tags, immobilization techniques, and protein-based materials. Synthetic supramol. mols. and materials are creating new opportunities for protein recognition that are orthogonal to classical small mol. and protein-based approaches. As outlined here, their unique mol. features enable the recognition of amino acids, peptides, and even whole protein surfaces, which can be applied to the modulation and assembly of proteins. The authors believe that structural insights into these processes are of great value for the further development of this field and have therefore focused this Perspective on contributions that provide such structural data.
- 28Guo, J.; Zhuang, J.; Wang, F.; Raghupathi, K. R.; Thayumanavan, S. Protein AND Enzyme Gated Supramolecular Disassembly. J. Am. Chem. Soc. 2014, 136 (6), 2220– 2223, DOI: 10.1021/ja4108676Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslKhtw%253D%253D&md5=80c1264a4b6933e4040321f47478d119Protein AND Enzyme Gated Supramolecular DisassemblyGuo, Jing; Zhuang, Jiaming; Wang, Feng; Raghupathi, Krishna R.; Thayumanavan, S.Journal of the American Chemical Society (2014), 136 (6), 2220-2223CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An amphiphilic nanoassembly was designed to respond to the concurrent presence of a protein and an enzyme. We present herein a system, where in the presence of these two stimuli supramol. disassembly and mol. release occur. This mol. release arises in the form a fluorescence response that has been shown to be specific. We also show that this system can be modified to respond only if light stimulus is also present in addn. to the protein and the enzyme. Demonstration of such supramol. disassembly principles could have broad implications in a variety of biol. applications.
- 29Erbas-Cakmak, S.; Kolemen, S.; Sedgwick, A. C.; Gunnlaugsson, T.; James, T. D.; Yoon, J.; Akkaya, E. U. Molecular logic gates: the past, present and future. Chem. Soc. Rev. 2018, 47, 2228, DOI: 10.1039/C7CS00491EGoogle Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXjs1Sgs7c%253D&md5=24baae5c80c872d2f4470a63751a3482Molecular logic gates: the past, present and futureErbas-Cakmak, Sundus; Kolemen, Safacan; Sedgwick, Adam C.; Gunnlaugsson, Thorfinnur; James, Tony D.; Yoon, Juyoung; Akkaya, Engin U.Chemical Society Reviews (2018), 47 (7), 2228-2248CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)The field of mol. logic gates originated 25 years ago, when A. P. de Silva published a seminal article in Nature. Stimulated by this ground breaking research, scientists were inspired to join the race to simulate the workings of the fundamental components of integrated circuits using mols. The rules of this game of mimicry were flexible, and have evolved and morphed over the years. This tutorial review takes a look back on and provides an overview of the birth and growth of the field of mol. logics. Spinning-off from chemosensor research, mol. logic gates quickly proved themselves to be more than intellectual exercises and are now poised for many potential practical applications. The ultimate goal of this vein of research became clearer only recently - to "boldly go where no silicon-based logic gate has gone before" and seek out a new deeper understanding of life inside tissues and cells.
- 30Gao, J.; Wu, P.; Fernandez, A.; Zhuang, J.; Thayumanavan, S. Cellular AND Gates: Synergistic Recognition to Boost Selective Uptake of Polymeric Nanoassemblies. Angew. Chem., Int. Ed. 2020, 59, 1– 6, DOI: 10.1002/anie.202002748Google ScholarThere is no corresponding record for this reference.
- 31Spitzer, D.; Rodrigues, L. L.; Straßburger, D.; Mezger, M.; Besenius, P. Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated Supramolecular Polymerization. Angew. Chem., Int. Ed. 2017, 56 (48), 15461– 15465, DOI: 10.1002/anie.201708857Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslKnsLrO&md5=89b28c4580d076d46294ad9d2386be19Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated Supramolecular PolymerizationSpitzer, Daniel; Rodrigues, Leona Lucas; Strassburger, David; Mezger, Markus; Besenius, PolAngewandte Chemie, International Edition (2017), 56 (48), 15461-15465CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A multistimuli-responsive transient supramol. polymn. of β-sheet-encoded dendritic peptide monomers in water is presented. The amphiphiles, which contain glutamic acid and methionine, undergo a glucose oxidase catalyzed, glucose-fueled transient hydrogelation in response to an interplay of pH and oxidn. stimuli, promoted by the prodn. of reactive oxygen species (ROS). Adjusting the enzyme and glucose concn. allows tuning of the assembly and the disassembly rates of the supramol. polymers, which dictate the stiffness and transient stability of the hydrogels. The incorporation of triethylene glycol chains introduces thermoresponsive properties to the materials. We further show that repair enzymes are able to reverse the oxidative damage in the methionine-based thioether side chains. Since ROS play an important role in signal transduction cascades, our strategy offers great potential for applications of these dynamic biomaterials in redox microenvironments.
- 32Goskulwad, S.; La, D. D.; Kobaisi, M. A.; Bhosale, S. V.; Bansal, V.; Vinu, A.; Ariga, K.; Bhosale, S. V. Dynamic multistimuli-responsive reversible chiral transformation in supramolecular helices. Sci. Rep. 2018, 8 (1), 1– 11, DOI: 10.1038/s41598-018-29152-9Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXovVKl&md5=5378b63023442f2f272fc2fe4704e855Dynamic multistimuli-responsive reversible chiral transformation in supramolecular helicesGoskulwad, Santosh; La, Duong Duc; Al Kobaisi, Mohammad; Bhosale, Sidhanath V.; Bansal, Vipul; Vinu, Ajayan; Ariga, Katsuhiko; Bhosale, Sheshanath V.Scientific Reports (2018), 8 (1), 1-11CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)The design of new chiral chromophores that allow tunable assembly of higher order helical structures by using natural stimuli offers promising avenue in understanding various biol. processes. In particular, access to dynamic multistimuli-responsive systems can provide real-time monitoring of chiral transformation in chem. and biol. systems. We report on the synthesis of naphthalenediimide appended L-glutamate (NDI-L-Glu) that self-assembles into chiral supramol. structures under physiol. conditions. Specifically, NDI-L-Glu shows a mixt. of left- and right-handed helixes under physiol. conditions, and any deviation from the ambient biochem. environment has a remarkable influence on the chirality of these structures. For instance, acidic environments shift the helicity to left-handedness while the alk. conditions reversed the helical structures to right-handedness, thereby mimicking the mol. virulence mechanism of tobacco mosaic virus (TMV). The chirality of these supramol. assemblies can also be controllably tuned by using temp. as an external stimulus, allowing reversible flip of helicity.
- 33Liu, X.; Hu, D.; Jiang, Z.; Zhuang, J.; Xu, Y.; Guo, X.; Thayumanavan, S. Multi-Stimuli-Responsive Amphiphilic Assemblies through Simple Postpolymerization Modifications. Macromolecules 2016, 49 (17), 6186– 6192, DOI: 10.1021/acs.macromol.6b01397Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlarurbL&md5=b9b63811e43c99a189702991d2540197Multi-Stimuli-Responsive Amphiphilic Assemblies through Simple Postpolymerization ModificationsLiu, Xiaochi; Hu, Ding; Jiang, Ziwen; Zhuang, Jiaming; Xu, Yisheng; Guo, Xuhong; Thayumanavan, S.Macromolecules (Washington, DC, United States) (2016), 49 (17), 6186-6192CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)A strategy to construct different stimuli-responsive polymers from postpolymn. modifications of a single polymer scaffold via thiol-disulfide exchange has been developed. Here, we report on a random copolymer that enables the design and syntheses of a series of dual or multi-stimuli-responsive nanoassemblies using a simple postpolymn. modification step. The reactive functional group involves a side chain monopyridyl disulfide unit, which rapidly and quant. reacts with various thiols under mild conditions. Independent and concurrent incorporation of phys., chem., or biol. responsive properties have been demonstrated. We envision that this strategy may open up opportunities to simplify the synthesis of multifunctional polymers with broad implications in a variety of biol. applications.
- 34Chen, J.; Zhang, S.; Sun, F.; Li, N.; Cui, K.; He, J.; Niu, D.; Li, Y. Multi-stimuli responsive supramolecular polymers and their electrospun nanofibers. Polym. Chem. 2016, 7 (17), 2947– 2954, DOI: 10.1039/C6PY00445HGoogle Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xlt1Gmtbg%253D&md5=eb4e88bf7a98fd252ce83da0a837b59eMulti-stimuli responsive supramolecular polymers and their electrospun nanofibersChen, Jianzhuang; Zhang, Shuangshuang; Sun, Fugen; Li, Nan; Cui, Kun; He, Jianping; Niu, Dechao; Li, YongshengPolymer Chemistry (2016), 7 (17), 2947-2954CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)A novel type of multi-stimuli responsive supramol. polymer (MRSP) has been successfully constructed based on the self-assembly of heteroditopic macromonomers in a mixed solvent (CDCl3 : CD3CN = 2 : 1, vol./vol.), which contain benzo-21-crown-7 (B21C7) host units and secondary ammonium salt guest moieties at each end of a poly(ε-caprolactone) (PCL) chain. Owing to the reversible host-guest complexation between B21C7 and the secondary ammonium salt, the resulting MRSPs exhibit multi-stimuli responsiveness to cations, pH, anions and temp. More interestingly, nanofibers were facilely obtained via the soln. electrospinning of a MRSP, which presented enhanced degrdn. behaviors in the presence of K+, Cl-, Et3N, or heating, indicating a multiple stimuli-responsive nature.
- 35Cantekin, S.; Nakano, Y.; Everts, J. C.; van der Schoot, P.; Meijer, E. W.; Palmans, A. R. A. A Stereoselectively Deuterated Supramolecular Motif to Probe the Role of Solvent during Self-Assembly Processes. Chem. Commun. 2012, 48 (32), 3803– 3805, DOI: 10.1039/c2cc17284dGoogle Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XksVajtrs%253D&md5=aa66a69320b85c1cae431d63530148f8A stereoselectively deuterated supramolecular motif to probe the role of solvent during self-assembly processesCantekin, Seda; Nakano, Yoko; Everts, Jeffrey C.; van der Schoot, Paul; Meijer, E. W.; Palmans, Anja R. A.Chemical Communications (Cambridge, United Kingdom) (2012), 48 (32), 3803-3805CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Small changes in the alkane solvent structure in combination with temp. effects lead to four different conformations of stereoselectively deuterated benzene-1,3,5-tricarboxamides in the aggregated state, affecting the expression of the supramol. chirality and highlighting the role of the solvent structure in self-assembly processes.
- 36Pianowski, Z. L. Recent Implementations of Molecular Photoswitches into Smart Materials and Biological Systems. Chem. - Eur. J. 2019, 25 (20), 5128– 5144, DOI: 10.1002/chem.201805814Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXivFyisbk%253D&md5=cfcdedf7debbd69ae2510fdd40d8344fRecent implementations of molecular photoswitches into smart materials and biological systemsPianowski, Zbigniew L.Chemistry - A European Journal (2019), 25 (20), 5128-5144CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Light is a nearly ideal stimulus for mol. systems. It delivers information encoded in the form of wavelengths and their intensities with high precision in space and time. Light is a mild trigger that does not permanently contaminate targeted samples. Its energy can be reversibly transformed into mol. motion, polarity, or flexibility changes. This leads to sophisticated functions at the supramol. and macroscopic levels, from light-triggered nanomaterials to photocontrol over biol. systems. New methods and mol. adapters of light are reported almost daily. Recently reported applications of photoresponsive systems, particularly azobenzenes, spiropyrans, diarylethenes, and indigoids, for smart materials and photocontrol of biol. setups are described herein with the aim to demonstrate that the 21st century has become the Age of Enlightenment-"Le siecle des Lumieres"-in mol. sciences.
- 37Szymański, W.; Beierle, J. M.; Kistemaker, H. A. V.; Velema, W. A.; Feringa, B. L. Reversible Photocontrol of Biological Systems by the Incorporation of Molecular Photoswitches. Chem. Rev. 2013, 113 (8), 6114– 6178, DOI: 10.1021/cr300179fGoogle Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXms1Wjtbc%253D&md5=5e3785c5753c2f108e2c5ab1872e93c9Reversible Photocontrol of Biological Systems by the Incorporation of Molecular PhotoswitchesSzymanski, Wiktor; Beierle, John M.; Kistemaker, Hans A. V.; Velema, Willem A.; Feringa, Ben L.Chemical Reviews (Washington, DC, United States) (2013), 113 (8), 6114-6178CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Photoswitches have been developed to control the conformation and activity of biomols. in a reversible manner. This review aims at providing a comprehensive and crit. literature review on reversible photocontrol of biomols.'structure and function with mol. photoswitches.
- 38Ishikawa, M.; Ohzono, T.; Yamaguchi, T.; Norikane, Y. Photo-Enhanced Aqueous Solubilization of an Azo-Compound. Sci. Rep. 2017, 7 (1), 1– 6, DOI: 10.1038/s41598-017-06947-wGoogle Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXltFejsw%253D%253D&md5=69e68704cce6d4aab16384efd15e59e0MicroRNA-449a deficiency promotes colon carcinogenesisNiki, Masanori; Nakajima, Kohei; Ishikawa, Daichi; Nishida, Jun; Ishifune, Chieko; Tsukumo, Shin-ichi; Shimada, Mitsuo; Nagahiro, Shinji; Mitamura, Yoshinori; Yasutomo, KojiScientific Reports (2017), 7 (1), 1-10CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our anal. found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the nos. and sizes of colon tumors. These effects were assocd. with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histol. scores and was pos. correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Addnl., activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.
- 39Vancoillie, G.; Frank, D.; Hoogenboom, R. Thermoresponsive Poly(oligo Ethylene Glycol Acrylates). Prog. Polym. Sci. 2014, 39 (6), 1074– 1095, DOI: 10.1016/j.progpolymsci.2014.02.005Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksFyqsL4%253D&md5=87a0ed1321a810862cbfefa56af74bb9Thermoresponsive poly(oligo ethylene glycol acrylates)Vancoillie, Gertjan; Frank, Daniel; Hoogenboom, RichardProgress in Polymer Science (2014), 39 (6), 1074-1095CODEN: PRPSB8; ISSN:0079-6700. (Elsevier Ltd.)A review. Thermoresponsive polymers have been the subject of numerous publications and research topics in the last few decades mostly driven by their easily controllable temp. stimulus and high potential for in vitro and in vivo applications. P(NIPAAm) is the most studied amongst these polymers, but recently other types of polymers are increasingly being investigated for their thermoresponsive behavior. In particular, polymers bearing a short oligo ethylene glycol (OEG) side chain have been shown to combine the biocompatibility of polyethylene glycol (PEG) with a versatile and controllable LCST behavior. These polymers can be synthesized via controlled radical polymn. techniques from various monomers consisting of an OEG chain and a polymerizable group like a (meth)acrylate, styrene or acrylamide. OEG acrylates offer significant advantages over, e.g., OEG methacrylates as the lower hydrophilicity of the backbone facilitates thermoresponsive behavior with smaller, more defined side chains. Furthermore, PEG acrylates can be polymd. using all major controlled radical polymn. techniques, unlike OEG methacrylates. This review will focus on OEG acrylate based (co)polymers and will provide a comprehensive overview of their reported thermoresponsive properties. The combination and comparison of this data will not only highlight the potential of these monomers, but will also serve as a starting point for future studies.
- 40Lüsse, S.; Arnold, K. The Interaction of Poly(ethylene Glycol) with Water Studied by 1H and 2H NMR Relaxation Time Measurements. Macromolecules 1996, 29 (12), 4251– 4257, DOI: 10.1021/ma9508616Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XivFShsLc%253D&md5=5f19d0ed5034e64d390d2cc48f8a970cThe Interaction of Poly(ethylene glycol) with Water Studied by 1H and 2H NMR Relaxation Time MeasurementsLuesse, S.; Arnold, K.Macromolecules (1996), 29 (12), 4251-4257CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)NMR relaxation time investigations of water protons (1H) and deuterons (2H) in aq. poly(ethylene glycol) (PEG) solns. are presented for the water content range of 3-90 wt.-%. The no. of bound water mols. per PEG repeat unit is estd. to be 1 from the water relaxation times by a model of fast exchange of water mols. between a bound and an unbound water fraction. For water contents <1 water mol. per PEG monomer, large restrictions in polymer mobility occur which also influence water NMR relaxation. For these low water contents, small ranges of oriented PEG chains are present in the solns. resulting in observable quadrupole splittings in the 2H NMR spectra.
- 41Chandler, D. Interfaces and the Driving Force of Hydrophobic Assembly. Nature 2005, 437 (7059), 640– 647, DOI: 10.1038/nature04162Google Scholar41https://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.
- 42Smith, G. D.; Bedrov, D. Roles of Enthalpy, Entropy, and Hydrogen Bonding in the Lower Critical Solution Temperature Behavior of Poly(ethylene oxide)/Water Solutions. J. Phys. Chem. B 2003, 107 (14), 3095– 3097, DOI: 10.1021/jp0270046Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXhvF2lur8%253D&md5=9001be86b94c5b711bfad4d652ff2c6fRoles of Enthalpy, Entropy, and Hydrogen Bonding in the Lower Critical Solution Temperature Behavior of Poly(ethylene oxide)/Water SolutionsSmith, Grant D.; Bedrov, DmitryJournal of Physical Chemistry B (2003), 107 (14), 3095-3097CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)Anal. of the temp. and compn. dependence of the excess thermodn. properties for oligomers of poly(ethylene oxide) (PEO) in aq. soln. obtained from mol. dynamics simulations reveals that the lower crit. soln. temp. (LCST) behavior of PEO/water solns. is enthalpy-driven. At lower temps., the formation of ether-water hydrogen bonds results in a very favorable ΔG EX consistent with the consoly. of PEO and water. Increasing temp. leads to a dramatic redn. in favorable ether-water interactions due to break-up of ether-water hydrogen bonding, while relatively persistent water-water hydrogen bonding maintains the energetic penalty assocd. with disrupted water-water interactions upon insertion of the ether. The entropy gain assocd. with the break-up of ether-water hydrogen bonds and redn. in the structure of hydrating water with increasing temp. is insufficient to offset the unfavorable enthalpic effects assocd. with the break-up of the ether-water hydrogen bonds.
- 43Besenius, P.; Goedegebure, Y.; Driesse, M.; Koay, M.; Bomans, P.; Palmans, A. R. A.; Dankers, P. Y. W.; Meijer, E. W. Peptide functionalised discotic amphiphiles and their self-assembly into supramolecular nanofibres. Soft Matter 2011, 7 (18), 7980– 7983, DOI: 10.1039/c1sm05896gGoogle Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFahsbvN&md5=8cb1621ba056e989f6bda87293876425Peptide functionalised discotic amphiphiles and their self-assembly into supramolecular nanofibresBesenius, P.; Goedegebure, Y.; Driesse, M.; Koay, M.; Bomans, P. H. H.; Palmans, A. R. A.; Dankers, P. Y. W.; Meijer, E. W.Soft Matter (2011), 7 (18), 7980-7983CODEN: SMOABF; ISSN:1744-683X. (Royal Society of Chemistry)The multicomponent co-assembly of discotic amphiphiles provides a modular and versatile approach to prep. RGDS- and PHSRN-peptide functionalized supramol. nanofibers, bearing pendant paramagnetic Gd(III)-chelates.
- 44Volgraf, M.; Gorostiza, P.; Szobota, S.; Helix, M. R.; Isacoff, E. Y.; Trauner, D. Reversibly Caged Glutamate: A Photochromic Agonist of Ionotropic Glutamate Receptors. J. Am. Chem. Soc. 2007, 129, 260– 261, DOI: 10.1021/ja067269oGoogle Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xhtleiu7bI&md5=67923334e30c8bc5c3135b6d89124339Reversibly Caged Glutamate: A Photochromic Agonist of Ionotropic Glutamate ReceptorsVolgraf, Matthew; Gorostiza, Pau; Szobota, Stephanie; Helix, Max R.; Isacoff, Ehud Y.; Trauner, DirkJournal of the American Chemical Society (2007), 129 (2), 260-261CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The design, synthesis, and biol. evaluation of a photochromic glutamate analog I is described. I functions as a reversibly caged neurotransmitter and can be used to influence neural activity with light.
- 45Riefolo, F.; Matera, C.; Garrido-Charles, A.; Gomila, A. M. J.; Sortino, R.; Agnetta, L.; Claro, E.; Masgrau, R.; Holzgrabe, U.; Batlle, M.; Decker, M.; Guasch, E.; Gorostiza, P. Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist. J. Am. Chem. Soc. 2019, 141, 7628– 7636, DOI: 10.1021/jacs.9b03505Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnvFCgt7o%253D&md5=bd8db9ec8fcc66d2fec94d8cdafa31f2Optical Control of Cardiac Function with a Photoswitchable Muscarinic AgonistRiefolo, Fabio; Matera, Carlo; Garrido-Charles, Aida; Gomila, Alexandre M. J.; Sortino, Rosalba; Agnetta, Luca; Claro, Enrique; Masgrau, Roser; Holzgrabe, Ulrike; Batlle, Montserrat; Decker, Michael; Guasch, Eduard; Gorostiza, PauJournal of the American Chemical Society (2019), 141 (18), 7628-7636CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Light-triggered reversible modulation of physiol. functions offers the promise of enabling on-demand spatiotemporally controlled therapeutic interventions. Optogenetics has been successfully implemented in the heart, but significant barriers to its use in the clinic remain, such as the need for genetic transfection. Herein, we present a method to modulate cardiac function with light through a photoswitchable compd. and without genetic manipulation. The mol., named PAI, was designed by introduction of a photoswitch into the mol. structure of an M2 mAChR agonist. In vitro assays revealed that PAI enables light-dependent activation of M2 mAChRs. To validate the method, we show that PAI photoisomers display different cardiac effects in a mammalian animal model, and demonstrate reversible, real-time photocontrol of cardiac function in translucent wildtype tadpoles. PAI can also effectively activate M2 receptors using two-photon excitation with near-IR light, which overcomes the scattering and low penetration of short-wavelength illumination, and offers new opportunities for intravital imaging and control of cardiac function.
- 46Bandara, H. M. D.; Burdette, S. C. Photoisomerization in Different Classes of Azobenzene. Chem. Soc. Rev. 2012, 41 (5), 1809– 1825, DOI: 10.1039/C1CS15179GGoogle Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XitFyjsLg%253D&md5=33ad953f692613475d922490922bc2b2Photoisomerization in different classes of azobenzeneBandara, H. M. Dhammika; Burdette, Shawn C.Chemical Society Reviews (2012), 41 (5), 1809-1825CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Azobenzene undergoes trans cis isomerization when irradiated with light tuned to an appropriate wavelength. The reverse cis trans isomerization can be driven by light or occurs thermally in the dark. Azobenzene's photochromatic properties make it an ideal component of numerous mol. devices and functional materials. Despite the abundance of application-driven research, azobenzene photochem. and the isomerization mechanism remain topics of study. Addnl. substituents on the azobenzene ring system change the spectroscopic properties and isomerization mechanism. This crit. review details the studies completed to date on the 3 main classes of azobenzene derivs. Understanding the differences in photochem., which originate from substitution, is imperative in exploiting azobenzene in the desired applications.
- 47Titov, E.; Granucci, G.; Götze, J. P.; Persico, M.; Saalfrank, P. Dynamics of Azobenzene Dimer Photoisomerization: Electronic and Steric Effects. J. Phys. Chem. Lett. 2016, 7 (18), 3591– 3596, DOI: 10.1021/acs.jpclett.6b01401Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlOqu7rP&md5=acdc1bc0bd1dff46f544dbd93b00e7abDynamics of Azobenzene Dimer Photoisomerization: Electronic and Steric EffectsTitov, Evgenii; Granucci, Giovanni; Goetze, Jan Philipp; Persico, Maurizio; Saalfrank, PeterJournal of Physical Chemistry Letters (2016), 7 (18), 3591-3596CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)While azobenzenes readily photoswitch in soln., their photoisomerization in densely packed self-assembled monolayers (SAMs) can be suppressed. Reasons for this can be steric hindrance and/or electronic quenching, e.g., by exciton coupling. The authors address these possibilities by means of nonadiabatic mol. dynamics with trajectory surface hopping calcns., investigating the trans → cis isomerization of azobenzene after excitation into the ππ* absorption band. The authors consider a free monomer, an isolated dimer and a dimer embedded in a SAM-like environment of addnl. azobenzene mols., imitating in this way the gradual transition from an unconstrained over an electronically coupled to an electronically coupled and sterically hindered, mol. switch. Simulations reveal that in comparison to the single mol. the quantum yield of the trans → cis photoisomerization is similar for the isolated dimer, but greatly reduced in the sterically constrained situation. Other implications of dimerization and steric constraints are also discussed.
- 48Cocchi, C.; Draxl, C. Understanding the Effects of Packing and Chemical Terminations on the Optical Excitations of Azobenzene-Functionalized Self-Assembled Monolayers. J. Phys.: Condens. Matter 2017, 29 (39), 394005, DOI: 10.1088/1361-648X/aa7ca7Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVyjsLY%253D&md5=dc98c9f992354e441bb262791a29e8b3Understanding the effects of packing and chemical terminations on the optical excitations of azobenzene-functionalized self-assembled monolayersCocchi, Caterina; Draxl, ClaudiaJournal of Physics: Condensed Matter (2017), 29 (39), 394005/1-394005/12CODEN: JCOMEL; ISSN:0953-8984. (IOP Publishing Ltd.)In a 1st-principles study based on many-body perturbation theory, the authors analyze the optical excitations of azobenzene-functionalized self-assembled monolayers (SAMs) with increasing packing d. and different terminations, considering for comparison the corresponding gas-phase mols. and dimers. Intermol. coupling increases with the d. of the chromophores independently of the functional groups. The intense π → π* resonance that triggers photo-isomerization is present in the spectra of isolated dimers and dild. SAMs, but it is almost completely washed out in tightly packed architectures. Intermol. coupling is partially inhibited by mixing differently functionalized azobenzene derivs., in particular when large groups are involved. In this way, the excitation band inducing the photo-isomerization process is partially preserved and the effects of dense packing partly counterbalanced. Results suggest that a tailored design of azobenzene-functionalized SAMs which optimizes the interplay between the packing d. of the chromophores and their termination can lead to significant improvements in the photo-switching efficiency of these systems.
- 49Galanti, A.; Diez-Cabanes, V.; Santoro, J.; Valasek, M.; Minoia, A.; Mayor, M.; Cornil, J.; Samorì, P. Electronic Decoupling in C3-Symmetrical Light-Responsive Tris(Azobenzene) Scaffolds: Self-Assembly and Multiphotochromism. J. Am. Chem. Soc. 2018, 140 (47), 16062– 16070, DOI: 10.1021/jacs.8b06324Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVKltb7P&md5=8762de2eeca6f98f3d8ab4a16e122e07Electronic Decoupling in C3-Symmetrical Light-Responsive Tris(Azobenzene) Scaffolds: Self-Assembly and MultiphotochromismGalanti, Agostino; Diez-Cabanes, Valentin; Santoro, Jasmin; Valasek, Michal; Minoia, Andrea; Mayor, Marcel; Cornil, Jerome; Samori, PaoloJournal of the American Chemical Society (2018), 140 (47), 16062-16070CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report the synthesis of a novel C3-sym. multiphotochromic mol. bearing three azobenzene units at positions 1, 3, 5 of the central Ph ring. The unique geometrical design of such a rigid scaffold enables the electronic decoupling of the azobenzene moieties to guarantee their simultaneous isomerization. Photoswitching of all azobenzenes in soln. was demonstrated by means of UV-vis absorption spectroscopy and high performance liq. chromatog. (HPLC) anal. Scanning tunneling microscopy investigations at the solid-liq. interface, corroborated by mol. modeling, made it possible to unravel the dynamic self-assembly of such systems into ordered supramol. architectures, by visualizing and identifying the patterns resulting from three different isomers, thereby demonstrating that the multiphotochromism is retained when the mols. are confined in two dimensions.
- 50Tong, X.; Wang, G.; Soldera, A.; Zhao, Y. How Can Azobenzene Block Copolymer Vesicles Be Dissociated and Reformed by Light?. J. Phys. Chem. B 2005, 109 (43), 20281– 20287, DOI: 10.1021/jp0524274Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtVymu7nJ&md5=bf60aa2d269fe72b44469a73c5bded45How Can Azobenzene Block Copolymer Vesicles Be Dissociated and Reformed by Light?Tong, Xia; Wang, Guang; Soldera, Armand; Zhao, YueJournal of Physical Chemistry B (2005), 109 (43), 20281-20287CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)The underlying mechanism of UV light-induced dissocn. and visible light-induced reformation of vesicles formed by an azobenzene diblock copolymer was investigated. These processes were studied in situ by monitoring changes in optical transmittance of the vesicular soln. while being exposed to UV or visible light irradn. The results indicate that the UV-induced dissocn. of the vesicles results from their thermodn. instability due to a shift of the hydrophilic/hydrophobic balance arising from the trans-cis isomerization, while their reaggregation takes place upon visible light irradn. that shifts the hydrophilic/hydrophobic balance in the opposite direction after the reverse cis-trans isomerization. The study suggests a specific design principle for obtaining UV light-dissociable and visible light-recoverable vesicles based on azobenzene block copolymers. On one hand, the structure of azobenzene moiety used in the hydrophobic block should have a small (near zero) dipole moment in the trans form and a significantly higher dipole moment in the cis form, which ensures a significant increase in polarity of the hydrophobic block under UV light irradn. On the other hand, the hydrophilic block should be weakly hydrophilic. The conjunction of the two conditions can make the light-induced shift of the hydrophilic/hydrophobic balance important enough to lead to the reversible change in vesicular aggregation.
- 51Liu, M.; Zhang, L.; Wang, T. Supramolecular Chirality in Self-Assembled Systems. Chem. Rev. 2015, 115 (15), 7304– 7397, DOI: 10.1021/cr500671pGoogle Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2ltr%252FO&md5=f6de0aeac890026c6815651d60f8e832Supramolecular Chirality in Self-Assembled SystemsLiu, Minghua; Zhang, Li; Wang, TianyuChemical Reviews (Washington, DC, United States) (2015), 115 (15), 7304-7397CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)Chiral self-assembly from the mol. to the supramol. level were discussed.
- 52Casellas, N. M.; Pujals, S.; Bochicchio, D.; Pavan, G. M.; Torres, T.; Albertazzi, L.; García-Iglesias, M. From isodesmic to highly cooperative: reverting the supramolecular polymerization mechanism in water by fine monomer design. Chem. Commun. 2018, 54 (33), 4112– 4115, DOI: 10.1039/C8CC01259HGoogle Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmt1ajt7g%253D&md5=e5fb36d6c82719a4a3a248d3d0f353daFrom isodesmic to highly cooperative: reverting the supramolecular polymerization mechanism in water by fine monomer designCasellas, Nicolas M.; Pujals, Silvia; Bochicchio, Davide; Pavan, Giovanni M.; Torres, Tomas; Albertazzi, Lorenzo; Garcia-Iglesias, MiguelChemical Communications (Cambridge, United Kingdom) (2018), 54 (33), 4112-4115CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Two structurally-similar discotic mols. able to self-assemble in water, forming supramol. fibers, are reported. While both self-assembled polymers are indistinguishable from a morphol. point-of-view, a dramatic change in their polymn. mechanism is obsd. (i.e., one self-assemble via an isodesmic mechanism, while the other shows one of the highest cooperativity values).
- 53Hamley, I. W.; Cheng, G.; Castelletto, V. A. Thermoresponsive Hydrogel Based on Telechelic PEG End-Capped with Hydrophobic Dipeptides. Macromol. Biosci. 2011, 11 (8), 1068– 1078, DOI: 10.1002/mabi.201100022Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpslyisbg%253D&md5=44302424e8e04b4a806ea39e80fdd807A Thermoresponsive Hydrogel Based on Telechelic PEG End-Capped with Hydrophobic DipeptidesHamley, Ian W.; Cheng, Ge; Castelletto, ValeriaMacromolecular Bioscience (2011), 11 (8), 1068-1078CODEN: MBAIBU; ISSN:1616-5187. (Wiley-VCH Verlag GmbH & Co. KGaA)The self-assembly in aq. soln. of PEG (1 500 Da) telechelically end-capped with hydrophobic dipeptides has been investigated using spectroscopic, microscopic, scattering, and rheol. methods. A self-assembled β-sheet fibril-based hydrogel has been identified (contg. dityrosine end groups), which exhibits a gel-sol transition near body temp. This thermo-responsive PEG-based biofunctional hydrogel is expected to have diverse potential uses in delivery or diagnostics for biomedical applications.
- 54Fuller, J. M.; Raghupathi, K. R.; Ramireddy, R. R.; Subrahmanyam, A. V.; Yesilyurt, V.; Thayumanavan, S. Temperature-Sensitive Transitions below LCST in Amphiphilic Dendritic Assemblies: Host–Guest Implications. J. Am. Chem. Soc. 2013, 135 (24), 8947– 8954, DOI: 10.1021/ja402019cGoogle Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnvFyisb0%253D&md5=6f69aeacedd93ef2b488bfde1b01b80eTemperature-Sensitive Transitions below LCST in Amphiphilic Dendritic Assemblies: Host-Guest ImplicationsFuller, Jack M.; Raghupathi, Krishna R.; Ramireddy, Rajasekhar R.; Subrahmanyam, Ayyagari V.; Yesilyurt, Volkan; Thayumanavan, S.Journal of the American Chemical Society (2013), 135 (24), 8947-8954CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Oligo(ethylene glycol)-decorated supramol. assemblies have been of great interest due to their charge-neutral character and thus their propensity to avoid nonspecific interactions. These systems are known to exhibit a macroscopic temp.-sensitive transition, where the assembly phase-separates from the aq. phase at higher temps. While this so-called lower crit. soln. temp. (LCST) behavior has been well-studied, there have been no studies on the fate of these supramol. assemblies below this transition temp. The work here brings to light the presence of a second, sub-LCST transition, obsd. well below the LCST of oligo(ethylene glycol) (OEG)-based dendrons, where the host-guest properties of the assembly are significantly altered. This sub-LCST transition is accompanied by changes in the guest encapsulation stability and dynamics of host exchange.
- 55Engel, S.; Spitzer, D.; Rodrigues, L. L.; Fritz, E.; Straßburger, D.; Schönhoff, M.; Ravoo, B. J.; Besenius, P. Kinetic control in the temperature-dependent sequential growth of surface-confined supramolecular copolymers. Faraday Discuss. 2017, 204 (0), 53– 67, DOI: 10.1039/C7FD00100BGoogle Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlvFyksLs%253D&md5=c1f671698a1d48c9c7b14ae64cf05ad0Kinetic control in the temperature-dependent sequential growth of surface-confined supramolecular copolymersEngel, Sabrina; Spitzer, Daniel; Rodrigues, Leona Lucas; Fritz, Eva-Corinna; Strassburger, David; Schoenhoff, Monika; Ravoo, Bart Jan; Besenius, PolFaraday Discussions (2017), 204 (Complex Molecular Surfaces and Interfaces), 53-67CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)We report the sequential growth of supramol. copolymers on gold surfaces, using oppositely charged dendritic peptide amphiphiles. By including water-solubilizing thermoresponsive chains in the monomer design, we obsd. non-linear effects in the temp.-dependent sequential growth. The step-wise copolymn. process is characterized using temp. dependent SPR and QCM-D measurements. At higher temps., dehydration of peripheral oligoethylene glycol chains supports copolymer growth due to more favorable comonomer interactions. Both monomers incorporate methionine amino acids but remarkably, desorption of the copolymers via competing sulfur gold interactions with the initial monomer layer is not obsd. The surface-confined supramol. copolymers remain kinetically trapped on the metal surface at near neutral pH and form viscoelastic films with a tuneable thickness.
- 56Frisch, H.; Fritz, E.; Stricker, F.; Schmüser, L.; Spitzer, D.; Weidner, T.; Ravoo, B. J.; Besenius, P. Kinetically Controlled Sequential Growth of Surface-Grafted Chiral Supramolecular Copolymers. Angew. Chem., Int. Ed. 2016, 55 (25), 7242– 7246, DOI: 10.1002/anie.201601048Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xks1elurk%253D&md5=f6ebcbf0350c43c379503a5b721e6471Kinetically Controlled Sequential Growth of Surface-Grafted Chiral Supramolecular CopolymersFrisch, Hendrik; Fritz, Eva-Corinna; Stricker, Friedrich; Schmueser, Lars; Spitzer, Daniel; Weidner, Tobias; Ravoo, Bart Jan; Besenius, PolAngewandte Chemie, International Edition (2016), 55 (25), 7242-7246CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The authors report a facile strategy to grow supramol. copolymers on Au surfaces by successively exposing a surface-anchored monomer to solns. of oppositely charged peptide comonomers. Charge regulation on the active chain end of the polymer sufficiently slows down the kinetics of the self-assembly process to produce kinetically trapped copolymers at near-neutral pH. The authors thereby achieve architectural control at three levels: the β-sheet sequences direct the polymn. away from the surface, the height of the supramol. copolymer brushes is well-controlled by the stepwise nature of the alternating copolymer growth, and 2D spatial resoln. is realized by using micropatterned initiating monomers. The programmable nature of the resulting architectures renders this concept attractive for the development of customized biomaterials or chiral interfaces for optoelectronics and sensor applications.
- 57Besenius, P.; Portale, G.; Bomans, P.; Janssen, H. M.; Palmans, A. R. A.; Meijer, E. W. Controlling the Growth and Shape of Chiral Supramolecular Polymers in Water. Proc. Natl. Acad. Sci. U. S. A. 2010, 107 (42), 17888– 17893, DOI: 10.1073/pnas.1009592107Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlCqsbnJ&md5=f8b455492ff130f0af2ab16dbb205d1eControlling the growth and shape of chiral supramolecular polymers in waterBesenius, Pol; Portale, Giuseppe; Bomans, Paul H. H.; Janssen, Henk M.; Palmans, Anja R. A.; Meijer, E. W.Proceedings of the National Academy of Sciences of the United States of America (2010), 107 (42), 17888-17893, S17888/1-S17888/19CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)A challenging target in the noncovalent synthesis of nanostructured functional materials is the formation of uniform features that exhibit well-defined properties, e.g., precise control over the aggregate shape, size, and stability. In particular, for aq.-based 1-dimensional supramol. polymers, this is a daunting task. Here the authors disclose a strategy based on self-assembling discotic amphiphiles (I; Q = Gd/Y DOTA/DTPA chelates) that leads to the control over stack length and shape of ordered, chiral columnar aggregates. By balancing out attractive noncovalent forces within the hydrophobic core of the polymg. building blocks with electrostatic repulsive interactions on the hydrophilic rim the authors managed to switch from elongated, rod-like assemblies to small and discrete objects. Intriguingly this rod-to-sphere transition is expressed in a loss of cooperativity in the temp.-dependent self-assembly mechanism. The aggregates were characterized using CD, UV and 1H-NMR spectroscopy, small angle x-ray scattering, and cryoTEM. In analogy to many systems found in biol., mechanistic details of the self-assembly pathways emphasize the importance of cooperativity as a key feature that dictates the phys. properties of the produced supramol. polymers.
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Abstract
Figure 1
Figure 1. (a) Synthesis of monomer 1: (i) Coupling of Fmoc-Lys(Boc)-OH to 2-chlorotrityl chloride resin (represented by the gray circle), DCM, DIEA, 1 h. (ii) Fmoc removal, 20% piperidine in DMF. (iii) Coupling of Fmoc-octa(ethylene glycol)-OH, DCM–DMF (1:1), PyBOP, DIEA, 15 h. (iv) Fmoc removal, 20% piperidine in DMF. (v) Coupling of Fmoc-Azo, DCM–DMF (1:1), PyBOP, DIEA, 15 h. (vi) Fmoc removal, 20% piperidine in DMF. (vii) Cleavage, TFA 95% v/v in H2O. (viii) Core coupling, BT-Cl, CHCl3, DIEA PyBOP, 15 h. (ix) Boc removal, TFA 95% H2O. (b) Molecular structure of monomer 1. (c) Molecular structure of monomer 2. (d) Schematic representation of monomer 1 and its self-assembly into supramolecular fibers. The moieties responsible for responsiveness are highlighted in different colors: orange, light responsive moiety; blue, temperature responsive moiety; green, pH and ionic strength responsive moiety.
Figure 2
Figure 2. TEM image of 100 μM monomer 1 (a) in DMSO and (b) in water (scale bar: 500 nm). E–Z photoisomerization of monomer 1 at 25 μM in (c) DMSO and (d) water, with UV (λ = 365 nm) irradiations of 30 s. HPLC chromatogram of monomer 1 in (e) DMSO and (f) water at 280 nm (measured isosbestic point).
Figure 3
Figure 3. HPLC-UV at 280 nm of the sample at 25 μM (a) before UV, (b) after UV irradiation (365 nm, 8 s 100% at 1000 mA of the LED intensity), and (c) after blue light (455 nm, 10 s, 100% at 1000 mA of the LED intensity). TEM of the sample at 25 μM (d) before UV, (e) after UV, and (f) after blue light irradiation (scale bar: 500 nm). CD of the sample at 25 μM (g) before UV, (h) after 365 nm irradiation for 8 s, and (i) after 455 nm irradiation for 10 s. (j) HPLC-UV analysis of isomer distribution at different UV irradiation times. (k) CD at 304 nm at different E isomer % (the line was added to guide the eye).
Figure 4
Figure 4. TEM of monomer 1 at 20 μM at (a) 20 °C, (b) 75 °C, and (c) 20 °C after cooling from 75 °C. (d) SLS temperature cycle on the sample at 100 μM at 60 °C/h measuring in steps of 5 °C (the line was added to guide the eye). (e) CD heating ramp experiment on the sample at 25 μM at 60 °C/h, measuring in steps of 5 °C.
Figure 5
Figure 5. TEM image of monomer 1 at 100 μM (a) at pH 2.0 ± 0.2, 7.0 ± 0.2, and 11.6 ± 0.2 (scale bar: 250 nm). CD heating experiment at 25 μM (b) at pH 2.2 ± 0.2, 7.2 ± 0.8, and 12.0 ± 0.2 (60 °C/h, measuring in steps of 5 °C). SLS heating experiment at 100 μM (c) at pH 2.0 ± 0.2, 7.0 ± 0.2, and 11.6 ± 0.2 (60 °C/h measuring in steps of 5 °C) (the line was added to guide the eye). CD at 5 °C with and without NaCl 150 mM (d) at pH 2.2 ± 0.2, 7.2 ± 0.8, and 12.0 ± 0.2.
Figure 6
Figure 6. Schematic representation of the system. Above, molecular responsiveness to light and pH. Below, supramolecular responsiveness to light, pH, ionic strength, and temperature.
References
This article references 57 other publications.
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- 3Matson, J. B.; Stupp, S. I. Drug Release from Hydrazone-Containing Peptide Amphiphiles. Chem. Commun. 2011, 47 (28), 7962– 7964, DOI: 10.1039/c1cc12570b3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXotl2jt74%253D&md5=f3e478701d293418b7e856857f3b36a2Drug release from hydrazone-containing peptide amphiphilesMatson, John B.; Stupp, Samuel I.Chemical Communications (Cambridge, United Kingdom) (2011), 47 (28), 7962-7964CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addn. of the novel compd. tri-Boc-hydrazido adipic acid to a lysine ε-amine allowed for precise placement of a hydrazide in a peptide sequence.
- 4Bakker, M. H.; Lee, C. C.; Meijer, E. W.; Dankers, P. Y. W.; Albertazzi, L. Multicomponent Supramolecular Polymers as a Modular Platform for Intracellular Delivery. ACS Nano 2016, 10 (2), 1845– 1852, DOI: 10.1021/acsnano.5b053834https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlyntL4%253D&md5=bf0c9f6ab3034d400c014d21c7557e04Multicomponent Supramolecular Polymers as a Modular Platform for Intracellular DeliveryBakker, Maarten H.; Lee, Cameron C.; Meijer, E. W.; Dankers, Patricia Y. W.; Albertazzi, LorenzoACS Nano (2016), 10 (2), 1845-1852CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Supramol. polymers are an emerging family of nanosized structures with potential use in materials chem. and medicine. Surprisingly, application of supramol. polymers in the field of drug delivery has received only limited attention. Here, we explore the potential of PEGylated 1,3,5-benzenetricarboxamide (BTA) supramol. polymers for intracellular delivery. Exploiting the unique modular approach of supramol. chem., we can coassemble neutral and cationic BTAs and control the overall properties of the polymer by simple monomer mixing. Moreover, this platform offers a versatile approach toward functionalization. The core can be efficiently loaded with a hydrophobic guest mol., while the exterior can be electrostatically complexed with siRNA. It is demonstrated that both compds. can be delivered in living cells, and that they can be combined to enable a dual delivery strategy. These results show the advantages of employing a modular system and pave the way for application of supramol. polymers in intracellular delivery.
- 5Su, H.; Zhang, W.; Wang, H.; Wang, F.; Cui, H. Paclitaxel-Promoted Supramolecular Polymerization of Peptide Conjugates. J. Am. Chem. Soc. 2019, 141 (30), 11997– 12004, DOI: 10.1021/jacs.9b047305https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXht1als77F&md5=8b1c5f9b7f1363b2a1cd26b020e9ed1dPaclitaxel-Promoted Supramolecular Polymerization of Peptide ConjugatesSu, Hao; Zhang, Weijie; Wang, Han; Wang, Feihu; Cui, HonggangJournal of the American Chemical Society (2019), 141 (30), 11997-12004CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Spontaneous assocn. above a threshold concn. is a hallmark of supramol. polymn., in which monomeric units self-assemble into polymeric aggregates through noncovalent interactions. This self-initiated supramol. process differs from the conventional covalent chain-growth polymn. in that the latter often involves the use of a different chem. entity as an initiator to trigger/control the polymn. process. We report here the use of a small mol. hydrophobe, paclitaxel (PTX), as an effective promoter to induce the supramol. polymn. of a peptide-paclitaxel conjugate, Spheropax (Spax). We found that Spax monomers alone in water self-assemble into spherical micelles of approx. 6.5 nm in diam. but, in the presence of free PTX, undergo a supramol. polymn. process to form filamentous assemblies of several micrometers in length. Increasing the ratio of promoter to monomer (PTX/Spax) induces Spax's directional polymn. and expedites its kinetic process. We believe these findings provide important insight into the initiator-controlled supramol. polymn. process.
- 6Su, H.; Wang, F.; Wang, Y.; Cheetham, A. G.; Cui, H. Macrocyclization of a Class of Camptothecin Analogues into Tubular Supramolecular Polymers. J. Am. Chem. Soc. 2019, 141 (43), 17107– 17111, DOI: 10.1021/jacs.9b098486https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvFOktrjM&md5=7dedbe0c3556fddb61e07377bb50059aMacrocyclization of a Class of Camptothecin Analogues into Tubular Supramolecular PolymersSu, Hao; Wang, Feihu; Wang, Yuzhu; Cheetham, Andrew G.; Cui, HonggangJournal of the American Chemical Society (2019), 141 (43), 17107-17111CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Nanostructured supramol. polymers (SPs) are filamentous assemblies possessing a high degree of internal order and have important uses in regenerative medicine, drug delivery, and soft matter electronics. Despite recent advances in functional SPs, a challenging topic is the development of robust assembly protocols enabling the incorporation of various functional units without altering its supramol. architecture. We report here the robust tubular assembly of camptothecin (CPT) analogs into functional SPs. Covalent linkage of two CPT moieties to various short hydrophilic segments (e.g., nonionic, cationic, anionic, and zwitterionic) leads to a class of CPT analogs that self-assemble in water into tubular SPs. Systemic administration of nonionic SPs effectively suppresses tumor growth. Furthermore, these tubular SPs act as universal dispersing agents in water for low-mol.-wt. hydrophobes.
- 7Besenius, P.; Heynens, J. L.; Straathof, R.; Niuwenhuizen, M. M.; Bomans, P.; Terreno, E.; Aime, S.; Strijkers, G.; Nicolay, K.; Meijer, E. W. Paramagnetic self-assembled nanoparticles as supramolecular MRI contrast agents. Contrast Media Mol. Imaging 2012, 7 (3), 356– 361, DOI: 10.1002/cmmi.4987https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmtFGhtrg%253D&md5=e2209a32b2f0821ddf91e23444573ceeParamagnetic self-assembled nanoparticles as supramolecular MRI contrast agentsBesenius, Pol; Heynens, Joeri L. M.; Straathof, Roel; Nieuwenhuizen, Marko M. L.; Bomans, Paul H. H.; Terreno, Enzo; Aime, Silvio; Strijkers, Gustav J.; Nicolay, Klaas; Meijer, E. W.Contrast Media & Molecular Imaging (2012), 7 (3), 356-361CODEN: CMMICO; ISSN:1555-4309. (Wiley-Blackwell)Nanometer-sized materials offer a wide range of applications in biomedical technologies, particularly imaging and diagnostics. Current scaffolds in the nanometer range predominantly make use of inorg. particles, org. polymers or natural peptide-based macromols. In contrast we hereby report a supramol. approach for the prepn. of self-assembled dendritic-like nanoparticles for applications as MRI contrast agents. This strategy combines the benefits from low mol. wt. imaging agents with the ones of high mol. wt. Their in vitro properties are confirmed by in vivo measurements: post injection of well-defined and meta-stable nanoparticles allows for high-resoln. blood-pool imaging, even at very low Gd(III) doses. These dynamic and modular imaging agents are an important addn. to the young field of supramol. medicine using well-defined nanometer-sized assemblies. Copyright © 2012 John Wiley & Sons, Ltd.
- 8Orbach, R.; Adler-Abramovich, L.; Zigerson, S.; Mironi-Harpaz, I.; Seliktar, D.; Gazit, E. Self-Assembled Fmoc-Peptides as a Platform for the Formation of Nanostructures and Hydrogels. Biomacromolecules 2009, 10 (9), 2646– 2651, DOI: 10.1021/bm900584m8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVeqsrbO&md5=2140af9a384230ef35879157d4816151Self-Assembled Fmoc-Peptides as a Platform for the Formation of Nanostructures and HydrogelsOrbach, Ron; Adler-Abramovich, Lihi; Zigerson, Sivan; Mironi-Harpaz, Iris; Seliktar, Dror; Gazit, EhudBiomacromolecules (2009), 10 (9), 2646-2651CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Hydrogels are of great interest as a class of materials for tissue engineering, axonal regeneration, and controlled drug delivery, as they offer 3D interwoven scaffolds to support the growth of cells. Herein, we extend the family of the arom. Fmoc-dipeptides with a library of new Fmoc-peptides, which include natural and synthetic amino acids with an arom. nature. We describe the self-assembly of these Fmoc-peptides into various structures and characterize their distinctive mol. and phys. properties. Moreover, we describe the fabrication of the bioactive RGD sequence into a hydrogel. This unique material offers new opportunities for developing cell-adhesive biomedical hydrogel scaffolds, as well as for establishing strategies to modify surfaces with bioactive materials.
- 9Mata, A.; Geng, Y.; Henrikson, K. J.; Aparicio, C.; Stock, S. R.; Stacher, R. L.; Stupp, S. I. Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix. Biomaterials 2010, 31 (23), 6004– 6012, DOI: 10.1016/j.biomaterials.2010.04.0139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnslamt7g%253D&md5=31b506ca096d15e5545c810d5ddf4424Bone regeneration mediated by biomimetic mineralization of a nanofiber matrixMata, Alvaro; Geng, Yanbiao; Henrikson, Karl J.; Aparicio, Conrado; Stock, Stuart R.; Satcher, Robert L.; Stupp, Samuel I.Biomaterials (2010), 31 (23), 6004-6012CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Rapid bone regeneration within a three-dimensional defect without the use of bone grafts, exogenous growth factors, or cells remains a major challenge. We report here on the use of self-assembling peptide nanostructured gels to promote bone regeneration that have the capacity to mineralize in biomimetic fashion. The main mol. design was the use of phosphoserine residues in the sequence of a peptide amphiphile known to nucleate hydroxyapatite crystals on the surfaces of nanofibers. We tested the system in a rat femoral crit.-size defect by placing pre-assembled nanofiber gels in a 5 mm gap and analyzed bone formation with micro-computed tomog. and histol. We found within 4 wk significantly higher bone formation relative to controls lacking phosphorylated residues and comparable bone formation to that obsd. in animals treated with a clin. used allogenic bone matrix.
- 10Choe, S.; Bond, C. W.; Harrington, D. A.; Stupp, S. I.; McVary, K. T.; Podlasek, C. A. Peptide Amphiphile Nanofiber Hydrogel Delivery of Sonic Hedgehog Protein to the Cavernous Nerve to Promote Regeneration and Prevent Erectile Dysfunction. Nanomedicine 2017, 13 (1), 95– 101, DOI: 10.1016/j.nano.2016.08.03210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFWit7%252FJ&md5=1d859345de737d0bde59e16f1d4b2178Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunctionChoe, Shawn; Bond, Christopher W.; Harrington, Daniel A.; Stupp, Samuel I.; McVary, Kevin T.; Podlasek, Carol A.Nanomedicine (New York, NY, United States) (2017), 13 (1), 95-101CODEN: NANOBF; ISSN:1549-9634. (Elsevier)Erectile dysfunction (ED) has high impact on quality of life in prostatectomy, diabetic and aging patients. An underlying mechanism is cavernous nerve (CN) injury, which causes ED in up to 80% of prostatectomy patients. We examine how sonic hedgehog (SHH) treatment with innovative peptide amphiphile nanofiber hydrogels (PA), promotes CN regeneration after injury. SHH and its receptors patched (PTCH1) and smoothened (SMO) are localized in PG neurons and glia. SMO undergoes anterograde transport to signal to downstream targets. With crush injury, PG neurons degenerate and undergo apoptosis. SHH protein decreases, SMO localization changes to the neuronal cell surface, and anterograde transport stops. With SHH treatment SHH is taken up at the injury site and undergoes retrograde transport to PG neurons, allowing SMO transport to occur, and neurons remain intact. SHH treatment prevents neuronal degeneration, maintains neuronal, glial and downstream target signaling, and is significant as a regenerative therapy.
- 11Saunders, L.; Ma, P. X. Self-Healing Supramolecular Hydrogels for Tissue Engineering Applications. Macromol. Biosci. 2019, 19, 1800313, DOI: 10.1002/mabi.201800313There is no corresponding record for this reference.
- 12Blum, A. P.; Kammeyer, J. K.; Rush, A. M.; Callmann, C. E.; Hahn, M. E.; Gianneschi, N. C. Stimuli-Responsive Nanomaterials for Biomedical Applications. J. Am. Chem. Soc. 2015, 137 (6), 2140– 2154, DOI: 10.1021/ja510147n12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVegurbN&md5=0d7f6aa46b2a4567a04ac2ecdb2d1addStimuli-Responsive Nanomaterials for Biomedical ApplicationsBlum, Angela P.; Kammeyer, Jacquelin K.; Rush, Anthony M.; Callmann, Cassandra E.; Hahn, Michael E.; Gianneschi, Nathan C.Journal of the American Chemical Society (2015), 137 (6), 2140-2154CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A review. Nature employs a variety of tactics to precisely time and execute the processes and mechanics of life, relying on sequential sense and response cascades to transduce signaling events over multiple length and time scales. Many of these tactics, such as the activation of a zymogen, involve the direct manipulation of a material by a stimulus. Similarly, effective therapeutics and diagnostics require the selective and efficient homing of material to specific tissues and biomol. targets with appropriate temporal resoln. These systems must also avoid undesirable or toxic side effects and evade unwanted removal by endogenous clearing mechanisms. Nanoscale delivery vehicles have been developed to package materials with the hope of delivering them to select locations with rates of accumulation and clearance governed by an interplay between the carrier and its cargo. Many modern approaches to drug delivery have taken inspiration from natural activatable materials like zymogens, membrane proteins, and metabolites, whereby stimuli initiate transformations that are required for cargo release, prodrug activation, or selective transport. This Perspective describes key advances in the field of stimuli-responsive nanomaterials while highlighting some of the many challenges faced and opportunities for development. Major hurdles include the increasing need for powerful new tools and strategies for characterizing the dynamics, morphol., and behavior of advanced delivery systems in situ and the perennial problem of identifying truly specific and useful phys. or mol. biomarkers that allow a material to autonomously distinguish diseased from normal tissue.
- 13Frisch, H.; Unsleber, J. P.; Lüdeker, D.; Peterlechner, M.; Brunklaus, G.; Waller, M.; Besenius, P. pH-Switchable Ampholytic Supramolecular Copolymers. Angew. Chem., Int. Ed. 2013, 52 (38), 10097– 10101, DOI: 10.1002/anie.20130381013https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1CrsL7O&md5=2d8a4b433da658958c6e77cdef367d3dpH-switchable ampholytic supramolecular copolymersFrisch, Hendrik; Unsleber, Jan Patrick; Luedeker, David; Peterlechner, Martin; Brunklaus, Gunther; Waller, Mark; Besenius, PolAngewandte Chemie, International Edition (2013), 52 (38), 10097-10101CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)We have synthesized β-sheet-encoded anionic and cationic supramol. co-monomers. These dendritic peptide amphiphiles, when self-assembled from a 1:1 monomer feed ratio, form supramol. copolymers through a combination of Coulomb attractive forces and hydrogen-bonding interactions. The obtained ampholytic supramol. materials have been designed for on-off polymn. in response to pH triggers. Decreasing or increasing g the pH value outside of this pH window results in polymn. being switched off and disassembly occurs through the loss of the salt bridges of the peptide side arms. The use of a supramol. engineering approach enables the pH window to be increased by enhancing the affinity of the supramol. co-monomers.
- 14Gröger, G.; Meyer-Zaika, W.; Böttcher, C.; Gröhn, F.; Ruthard, C.; Schmuck, C. Switchable Supramolecular Polymers from the Self-Assembly of a Small Monomer with Two Orthogonal Binding Interactions. J. Am. Chem. Soc. 2011, 133 (23), 8961– 8971, DOI: 10.1021/ja200941a14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3Mjht1Cksw%253D%253D&md5=a6a3171f6ce694c564a6075089a138f6Switchable supramolecular polymers from the self-assembly of a small monomer with two orthogonal binding interactionsGroger Gerd; Meyer-Zaika Wolfgang; Bottcher Christoph; Grohn Franziska; Ruthard Christian; Schmuck CarstenJournal of the American Chemical Society (2011), 133 (23), 8961-71 ISSN:.The low molecular weight heteroditopic monomer 1 forms supramolecular polymers in polar solution as shown, for example, by infrared laser-based dynamic light scattering (DLS), small-angle neutron scattering (SANS), electron microscopy (TEM, cryo-TEM), and viscosity measurements. Self-assembly of 1 is based on two orthogonal binding interactions, the formation of a Fe(II)-terpyridine 1:2 metal-ligand complex and the dimerization of a self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterion. Both binding interactions have a sufficient stability in polar (DMSO) and even aqueous solutions to ensure formation of linear polymers of considerable length (up to 100 nm). The supramolecular polymerization follows a ring-chain mechanism causing a significant increase in the viscosity of the solutions at millimolar concentrations and above. The linear polymers then further aggregate in solution into larger globular aggregates with a densely packed core and a loose shell. Both binding interactions can be furthermore switched on and off either by adding a competing ligand to remove the metal ion and subsequent readdition of Fe(II) or by reversible protonation and deprotonation of the zwitterion upon addition of acid or base. The self-assembly of 1 can therefore be switched back and forth between four different states, the monomer, a metal-complexed dimer or an ion paired dimer, and finally the polymer.
- 15Moyer, T. J.; Finbloom, J. A.; Chen, F.; Toft, D. J.; Cryns, V. L.; Stupp, S. I. pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies. J. Am. Chem. Soc. 2014, 136 (42), 14746– 14752, DOI: 10.1021/ja504242915https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsleksrvI&md5=80691b308deb24ebbedcaf631f9498e2pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional AssembliesMoyer, Tyson J.; Finbloom, Joel A.; Chen, Feng; Toft, Daniel J.; Cryns, Vincent L.; Stupp, Samuel I.Journal of the American Chemical Society (2014), 136 (42), 14746-14752CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Supramol. self-assembly offers promising new ways to control nanostructure morphol. and respond to external stimuli. A pH-sensitive self-assembled system was developed to both control nanostructure shape and respond to the acidic microenvironment of tumors using self-assembling peptide amphiphiles (PAs). By incorporating an oligo-histidine H6 sequence, we developed two PAs that self-assembled into distinct morphologies on the nanoscale, either as nanofibers or spherical micelles, based on the incorporation of the aliph. tail on the N-terminus or near the C-terminus, resp. Both cylinder and sphere-forming PAs demonstrated reversible disassembly between pH 6.0 and 6.5 upon protonation of the histidine residues in acidic solns. These PAs were then characterized and assessed for their potential to encapsulate hydrophobic chemotherapies. The H6-based nanofiber assemblies encapsulated camptothecin (CPT) with up to 60% efficiency, a 7-fold increase in CPT encapsulation relative to spherical micelles. Addnl., pH-sensitive nanofibers showed improved tumor accumulation over both spherical micelles and nanofibers that did not change morphologies in acidic environments. We have demonstrated that the morphol. transitions upon changes in pH of supramol. nanostructures affect drug encapsulation and tumor accumulation. Our findings also suggest that these supramol. events can be tuned by mol. design to improve the pharmacol. properties of nanomedicines.
- 16Ahlers, P.; Frisch, H.; Holm, R.; Spitzer, D.; Barz, M.; Besenius, P. Tuning the pH-Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH. Macromol. Biosci. 2017, 17 (10), 1700111, DOI: 10.1002/mabi.201700111There is no corresponding record for this reference.
- 17Adhikari, B.; Yamada, Y.; Yamauchi, M.; Wakita, K.; Lin, X.; Aratsu, K.; Ohba, T.; Karatsu, T.; Hollamby, M. J.; Shimizu, N.; Takagi, H.; Haruki, R.; Adachi, S.; Yagai, S. Light-induced unfolding and refolding of supramolecular polymer nanofibers. Nat. Commun. 2017, 8, 15254, DOI: 10.1038/ncomms1525417https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1crlslartw%253D%253D&md5=0c1b5b3d808c0243e540d47555d7dcedLight-induced unfolding and refolding of supramolecular polymer nanofibresAdhikari Bimalendu; Yamada Yuki; Yamauchi Mitsuaki; Wakita Kengo; Lin Xu; Aratsu Keisuke; Karatsu Takashi; Yagai Shiki; Adhikari Bimalendu; Ohba Tomonori; Hollamby Martin J; Shimizu Nobutaka; Takagi Hideaki; Haruki Rie; Adachi Shin-IchiNature communications (2017), 8 (), 15254 ISSN:.Unlike classical covalent polymers, one-dimensionally (1D) elongated supramolecular polymers (SPs) can be encoded with high degrees of internal order by the cooperative aggregation of molecular subunits, which endows these SPs with extraordinary properties and functions. However, this internal order has not yet been exploited to generate and dynamically control well-defined higher-order (secondary) conformations of the SP backbone, which may induce functionality that is comparable to protein folding/unfolding. Herein, we report light-induced conformational changes of SPs based on the 1D exotic stacking of hydrogen-bonded azobenzene hexamers. The stacking causes a unique internal order that leads to spontaneous curvature, which allows accessing conformations that range from randomly folded to helically folded coils. The reversible photoisomerization of the azobenzene moiety destroys or recovers the curvature of the main chain, which demonstrates external control over the SP conformation that may ultimately lead to biological functions.
- 18Yagai, S.; Yamauchi, M.; Kobayashi, A.; Karatsu, T.; Kitamura, A.; Ohba, T.; Kikkawa, Y. Control over Hierarchy Levels in the Self-Assembly of Stackable Nanotoroids. J. Am. Chem. Soc. 2012, 134 (44), 18205– 18208, DOI: 10.1021/ja308519b18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFChs77I&md5=3bfcf614ea7a5ae80a05c02c74348f2eControl over Hierarchy Levels in the Self-Assembly of Stackable NanotoroidsYagai, Shiki; Yamauchi, Mitsuaki; Kobayashi, Ai; Karatsu, Takashi; Kitamura, Akihide; Ohba, Tomonori; Kikkawa, YoshihiroJournal of the American Chemical Society (2012), 134 (44), 18205-18208CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report a precise control over the hierarchy levels in the outstanding self-organization process shown by chiral azobenzene dimer I. This compd. forms uniform toroidal nanostructures that can hierarchically organize into chiral nanotubes under the control by temp., concn., or light. The nanotubes further organized into supercoiled fibrils, which finally intertwined to form double helixes with one-handed helical sense.
- 19Prabhu, D. D.; Aratsu, K.; Kitamoto, Y.; Ouchi, H.; Ohba, T.; Hollamby, M. J.; Shimizu, N.; Takagi, H.; Haruki, R.; Adachi, S.; Yagai, S. Self-folding of supramolecular polymers into bioinspired topology. Sci. Adv. 2018, 4 (9), 8466, DOI: 10.1126/sciadv.aat846619https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1Wmsr3O&md5=5f507c647b7d523bc021aaff5c20fbd2Self-folding of supramolecular polymers into bioinspired topologyPrabhu, Deepak D.; Aratsu, Keisuke; Kitamoto, Yuichi; Ouchi, Hayato; Ohba, Tomonori; Hollamby, Martin J.; Shimizu, Nobutaka; Takagi, Heaki; Haruki, Rie; Adachi, Shin-ichi; Yagai, ShikiScience Advances (2018), 4 (9), eaat8466/1-eaat8466/9CODEN: SACDAF; ISSN:2375-2548. (American Association for the Advancement of Science)Folding one-dimensional polymer chains into well-defined topologies represents an important organization process for proteins, but replicating this process for supramol. polymers remains a challenging task. We report supramol. polymers that can fold into protein-like topologies. Our approach is based on curvature-forming supramol. rosettes, which affords kinetic control over the extent of helical folding in the resulting supramol. fibers by changing the cooling rate for polymn. When using a slow cooling rate, we obtained misfolded fibers contg. a minor amt. of helical domains that folded on a time scale of days into unique topologies reminiscent of the protein tertiary structures. Thermodn. anal. of fibers with varying degrees of folding revealed that the folding is accompanied by a large enthalpic gain. The self-folding proceeds via ordering of misfolded domains in the main chain using helical domains as templates, as fully misfolded fibers prepd. by a fast cooling rate do not self-fold.
- 20Huang, Z.; Lee, E.; Kim, H.-J.; Lee, M. Aqueous Nanofibers with Switchable Chirality Formed of Self-Assembled Dumbbell-Shaped Rod Amphiphiles. Chem. Commun. 2009, 44, 6819– 6821, DOI: 10.1039/b913286dThere is no corresponding record for this reference.
- 21Feijter, I.; Besenius, P.; Albertazzi, L.; Meijer, E. W.; Palmans, A. R. A.; Voets, I. K. Mechanistic control over morphology: self-assembly of a discotic amphiphile in water. Soft Matter 2013, 9 (42), 10025– 10030, DOI: 10.1039/C3SM52104DThere is no corresponding record for this reference.
- 22Alemán García, M. Á.; Magdalena Estirado, E.; Milroy, L.-G.; Brunsveld, L. Dual-Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic Supramolecular Wires. Angew. Chem., Int. Ed. 2018, 57 (18), 4976– 4980, DOI: 10.1002/anie.20180014822https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXlslShsrk%253D&md5=ee85add14428be38381d914191baace7Dual-Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic Supramolecular WiresAleman Garcia, Miguel Angel; Estirado, Eva Magdalena; Milroy, Lech-Gustav; Brunsveld, LucAngewandte Chemie, International Edition (2018), 57 (18), 4976-4980CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The combination of oligonucleotides and synthetic supramol. systems allows for novel and long-needed modes of regulation of the self-assembly of both mol. elements. Discotic mols. were conjugated with short oligonucleotides and their assembly into responsive supramol. wires studied. The self-assembly of the discotic mols. provides addnl. stability for DNA-duplex formation owing to a cooperative effect. The appended oligonucleotides allow for positional control of the discotic elements within the supramol. wire. The programmed assembly of these hybrid architectures can be modulated through the DNA, for example, by changing the no. of base pairs or salt concn., and through the discotic platform by the addn. of discotic elements without oligonucleotide handles. These hybrid supramol.-DNA structures allow for advanced levels of control over 1D dynamic platforms with responsive regulatory elements at the interface with biol. systems.
- 23Kumar, M.; Brocorens, P.; Tonnelé, C.; Beljonne, D.; Surin, M.; George, S. J. A Dynamic Supramolecular Polymer with Stimuli-Responsive Handedness for in Situ Probing of Enzymatic ATP Hydrolysis. Nat. Commun. 2014, 5, 5793, DOI: 10.1038/ncomms679323https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjvFWqtrk%253D&md5=cdca02a3dd1c51bda752aa461361e762A dynamic supramolecular polymer with stimuli-responsive handedness for in situ probing of enzymatic ATP hydrolysisKumar, Mohit; Brocorens, Patrick; Tonnele, Claire; Beljonne, David; Surin, Mathieu; George, Subi J.Nature Communications (2014), 5 (), 5793CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Design of artificial systems, which can respond to fluctuations in concn. of adenosine phosphates (APs), can be useful in understanding various biol. processes. Helical assemblies of chromophores, which dynamically respond to such changes, can provide real-time chiroptical readout of various chem. transformations. Towards this concept, here we present a supramol. helix of achiral chromophores, which shows chiral APs responsive tunable handedness along with dynamically switchable helicity. This system, composing of naphthalenediimides with phosphate recognition unit, shows opposite handedness on binding with ATP compared with ADP or AMP, which is comprehensively analyzed with mol. dynamic simulations. Such differential signalling along with stimuli-dependent fast stereomutations have been capitalized to probe the reaction kinetics of enzymic ATP hydrolysis. Detailed chiroptical analyses provide mechanistic insights into the enzymic hydrolysis and various intermediate steps. Thus, a unique dynamic helical assembly to monitor the real-time reaction processes via its stimuli-responsive chiroptical signalling is conceptualized.
- 24Mishra, A.; Korlepara, D. B.; Balasubramanian, S.; George, S. J. Bioinspired, ATP-driven co-operative supramolecular polymerization and its pathway dependence. Chem. Commun. 2020, 56, 1505– 1508, DOI: 10.1039/C9CC08790G24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVeqt7zI&md5=76ff5a3066f873654bff12dcee47b8e2Bioinspired, ATP-driven co-operative supramolecular polymerization and its pathway dependenceMishra, Ananya; Korlepara, Divya B.; Balasubramanian, Sundaram; George, Subi J.Chemical Communications (Cambridge, United Kingdom) (2020), 56 (10), 1505-1508CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A bio-inspired, ATP-driven nucleation growth assembly is demonstrated using an amphiphilic naphthalene diimide (NDI) deriv. appended with guanidinium receptors to promote specific salt-bridge type interaction with nucleotide phosphates. Detailed spectroscopic and microscopic probing revealed a pathway-dependent co-operative self-assembly to yield two-dimensional and scrolled nano-tubular bilayer assemblies under kinetic and thermodn. conditions, resp.
- 25Albertazzi, L.; van der Veeken, N.; Baker, M. B.; Palmans, A. R. A.; Meijer, E. W. Supramolecular Copolymers with Stimuli-Responsive Sequence Control. Chem. Commun. 2015, 51 (90), 16166– 16168, DOI: 10.1039/C5CC06951C25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsV2nu7zK&md5=d27a83c7347d275a9b211bd4cd9b66f1Supramolecular copolymers with stimuli-responsive sequence controlAlbertazzi, Lorenzo; van der Veeken, Nick; Baker, Matthew B.; Palmans, Anja R. A.; Meijer, E. W.Chemical Communications (Cambridge, United Kingdom) (2015), 51 (90), 16166-16168CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The authors report a novel responsive supramol. copolymer able to change its monomer sequence as a result of mol. stimuli. Nucleic acids and RNase were used as mol. inputs, controlling the clustering of specific monomers along the polymer backbone. This opens new ways towards the mol. control of synthetic supramol. networks.
- 26Molla, M. R.; Prasad, P.; Thayumanavan, S. Protein-Induced Supramolecular Disassembly of Amphiphilic Polypeptide Nanoassemblies. J. Am. Chem. Soc. 2015, 137 (23), 7286– 7289, DOI: 10.1021/jacs.5b0428526https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXptFWqtb8%253D&md5=3f99c9e43c3b037b15ded5c1001f8603Protein-Induced Supramolecular Disassembly of Amphiphilic Polypeptide NanoassembliesMolla, Mijanur Rahaman; Prasad, Priyaa; Thayumanavan, S.Journal of the American Chemical Society (2015), 137 (23), 7286-7289CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Mimicking noncovalent interaction based processes in nature has been an important goal of supramol. chem. Here, the authors report on amphiphilic polypeptides that self-assemble to form nanoscale supramol. assemblies and are programmed to disassemble in response to a specific protein. Benzenesulfonamide and carbonic anhydrase have been chosen as the ligand and protein, resp., to demonstrate this possibility. Since the amphiphilic nanoassembly sequesters hydrophobic guest mols., the protein-specific disassembly event provides a protein-sensitive mol. release as well. The authors envision that the binding induced disassembly and guest release might open up new opportunities for the next generation of supramol. assemblies for protein-specific delivery and diagnostics.
- 27van Dun, S.; Ottmann, C.; Milroy, L.; Brunsveld, L. Supramolecular Chemistry Targeting Proteins. J. Am. Chem. Soc. 2017, 139 (40), 13960– 13968, DOI: 10.1021/jacs.7b0197927https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFeit7vL&md5=56422173d029b081e10d773705b8a478Supramolecular Chemistry Targeting Proteinsvan Dun, Sam; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, LucJournal of the American Chemical Society (2017), 139 (40), 13960-13968CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A review. The specific recognition of protein surface elements is a fundamental challenge in the life sciences. New developments in this field will form the basis of advanced therapeutic approaches and lead to applications such as sensors, affinity tags, immobilization techniques, and protein-based materials. Synthetic supramol. mols. and materials are creating new opportunities for protein recognition that are orthogonal to classical small mol. and protein-based approaches. As outlined here, their unique mol. features enable the recognition of amino acids, peptides, and even whole protein surfaces, which can be applied to the modulation and assembly of proteins. The authors believe that structural insights into these processes are of great value for the further development of this field and have therefore focused this Perspective on contributions that provide such structural data.
- 28Guo, J.; Zhuang, J.; Wang, F.; Raghupathi, K. R.; Thayumanavan, S. Protein AND Enzyme Gated Supramolecular Disassembly. J. Am. Chem. Soc. 2014, 136 (6), 2220– 2223, DOI: 10.1021/ja410867628https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslKhtw%253D%253D&md5=80c1264a4b6933e4040321f47478d119Protein AND Enzyme Gated Supramolecular DisassemblyGuo, Jing; Zhuang, Jiaming; Wang, Feng; Raghupathi, Krishna R.; Thayumanavan, S.Journal of the American Chemical Society (2014), 136 (6), 2220-2223CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An amphiphilic nanoassembly was designed to respond to the concurrent presence of a protein and an enzyme. We present herein a system, where in the presence of these two stimuli supramol. disassembly and mol. release occur. This mol. release arises in the form a fluorescence response that has been shown to be specific. We also show that this system can be modified to respond only if light stimulus is also present in addn. to the protein and the enzyme. Demonstration of such supramol. disassembly principles could have broad implications in a variety of biol. applications.
- 29Erbas-Cakmak, S.; Kolemen, S.; Sedgwick, A. C.; Gunnlaugsson, T.; James, T. D.; Yoon, J.; Akkaya, E. U. Molecular logic gates: the past, present and future. Chem. Soc. Rev. 2018, 47, 2228, DOI: 10.1039/C7CS00491E29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXjs1Sgs7c%253D&md5=24baae5c80c872d2f4470a63751a3482Molecular logic gates: the past, present and futureErbas-Cakmak, Sundus; Kolemen, Safacan; Sedgwick, Adam C.; Gunnlaugsson, Thorfinnur; James, Tony D.; Yoon, Juyoung; Akkaya, Engin U.Chemical Society Reviews (2018), 47 (7), 2228-2248CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)The field of mol. logic gates originated 25 years ago, when A. P. de Silva published a seminal article in Nature. Stimulated by this ground breaking research, scientists were inspired to join the race to simulate the workings of the fundamental components of integrated circuits using mols. The rules of this game of mimicry were flexible, and have evolved and morphed over the years. This tutorial review takes a look back on and provides an overview of the birth and growth of the field of mol. logics. Spinning-off from chemosensor research, mol. logic gates quickly proved themselves to be more than intellectual exercises and are now poised for many potential practical applications. The ultimate goal of this vein of research became clearer only recently - to "boldly go where no silicon-based logic gate has gone before" and seek out a new deeper understanding of life inside tissues and cells.
- 30Gao, J.; Wu, P.; Fernandez, A.; Zhuang, J.; Thayumanavan, S. Cellular AND Gates: Synergistic Recognition to Boost Selective Uptake of Polymeric Nanoassemblies. Angew. Chem., Int. Ed. 2020, 59, 1– 6, DOI: 10.1002/anie.202002748There is no corresponding record for this reference.
- 31Spitzer, D.; Rodrigues, L. L.; Straßburger, D.; Mezger, M.; Besenius, P. Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated Supramolecular Polymerization. Angew. Chem., Int. Ed. 2017, 56 (48), 15461– 15465, DOI: 10.1002/anie.20170885731https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslKnsLrO&md5=89b28c4580d076d46294ad9d2386be19Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated Supramolecular PolymerizationSpitzer, Daniel; Rodrigues, Leona Lucas; Strassburger, David; Mezger, Markus; Besenius, PolAngewandte Chemie, International Edition (2017), 56 (48), 15461-15465CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A multistimuli-responsive transient supramol. polymn. of β-sheet-encoded dendritic peptide monomers in water is presented. The amphiphiles, which contain glutamic acid and methionine, undergo a glucose oxidase catalyzed, glucose-fueled transient hydrogelation in response to an interplay of pH and oxidn. stimuli, promoted by the prodn. of reactive oxygen species (ROS). Adjusting the enzyme and glucose concn. allows tuning of the assembly and the disassembly rates of the supramol. polymers, which dictate the stiffness and transient stability of the hydrogels. The incorporation of triethylene glycol chains introduces thermoresponsive properties to the materials. We further show that repair enzymes are able to reverse the oxidative damage in the methionine-based thioether side chains. Since ROS play an important role in signal transduction cascades, our strategy offers great potential for applications of these dynamic biomaterials in redox microenvironments.
- 32Goskulwad, S.; La, D. D.; Kobaisi, M. A.; Bhosale, S. V.; Bansal, V.; Vinu, A.; Ariga, K.; Bhosale, S. V. Dynamic multistimuli-responsive reversible chiral transformation in supramolecular helices. Sci. Rep. 2018, 8 (1), 1– 11, DOI: 10.1038/s41598-018-29152-932https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXovVKl&md5=5378b63023442f2f272fc2fe4704e855Dynamic multistimuli-responsive reversible chiral transformation in supramolecular helicesGoskulwad, Santosh; La, Duong Duc; Al Kobaisi, Mohammad; Bhosale, Sidhanath V.; Bansal, Vipul; Vinu, Ajayan; Ariga, Katsuhiko; Bhosale, Sheshanath V.Scientific Reports (2018), 8 (1), 1-11CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)The design of new chiral chromophores that allow tunable assembly of higher order helical structures by using natural stimuli offers promising avenue in understanding various biol. processes. In particular, access to dynamic multistimuli-responsive systems can provide real-time monitoring of chiral transformation in chem. and biol. systems. We report on the synthesis of naphthalenediimide appended L-glutamate (NDI-L-Glu) that self-assembles into chiral supramol. structures under physiol. conditions. Specifically, NDI-L-Glu shows a mixt. of left- and right-handed helixes under physiol. conditions, and any deviation from the ambient biochem. environment has a remarkable influence on the chirality of these structures. For instance, acidic environments shift the helicity to left-handedness while the alk. conditions reversed the helical structures to right-handedness, thereby mimicking the mol. virulence mechanism of tobacco mosaic virus (TMV). The chirality of these supramol. assemblies can also be controllably tuned by using temp. as an external stimulus, allowing reversible flip of helicity.
- 33Liu, X.; Hu, D.; Jiang, Z.; Zhuang, J.; Xu, Y.; Guo, X.; Thayumanavan, S. Multi-Stimuli-Responsive Amphiphilic Assemblies through Simple Postpolymerization Modifications. Macromolecules 2016, 49 (17), 6186– 6192, DOI: 10.1021/acs.macromol.6b0139733https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlarurbL&md5=b9b63811e43c99a189702991d2540197Multi-Stimuli-Responsive Amphiphilic Assemblies through Simple Postpolymerization ModificationsLiu, Xiaochi; Hu, Ding; Jiang, Ziwen; Zhuang, Jiaming; Xu, Yisheng; Guo, Xuhong; Thayumanavan, S.Macromolecules (Washington, DC, United States) (2016), 49 (17), 6186-6192CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)A strategy to construct different stimuli-responsive polymers from postpolymn. modifications of a single polymer scaffold via thiol-disulfide exchange has been developed. Here, we report on a random copolymer that enables the design and syntheses of a series of dual or multi-stimuli-responsive nanoassemblies using a simple postpolymn. modification step. The reactive functional group involves a side chain monopyridyl disulfide unit, which rapidly and quant. reacts with various thiols under mild conditions. Independent and concurrent incorporation of phys., chem., or biol. responsive properties have been demonstrated. We envision that this strategy may open up opportunities to simplify the synthesis of multifunctional polymers with broad implications in a variety of biol. applications.
- 34Chen, J.; Zhang, S.; Sun, F.; Li, N.; Cui, K.; He, J.; Niu, D.; Li, Y. Multi-stimuli responsive supramolecular polymers and their electrospun nanofibers. Polym. Chem. 2016, 7 (17), 2947– 2954, DOI: 10.1039/C6PY00445H34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xlt1Gmtbg%253D&md5=eb4e88bf7a98fd252ce83da0a837b59eMulti-stimuli responsive supramolecular polymers and their electrospun nanofibersChen, Jianzhuang; Zhang, Shuangshuang; Sun, Fugen; Li, Nan; Cui, Kun; He, Jianping; Niu, Dechao; Li, YongshengPolymer Chemistry (2016), 7 (17), 2947-2954CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)A novel type of multi-stimuli responsive supramol. polymer (MRSP) has been successfully constructed based on the self-assembly of heteroditopic macromonomers in a mixed solvent (CDCl3 : CD3CN = 2 : 1, vol./vol.), which contain benzo-21-crown-7 (B21C7) host units and secondary ammonium salt guest moieties at each end of a poly(ε-caprolactone) (PCL) chain. Owing to the reversible host-guest complexation between B21C7 and the secondary ammonium salt, the resulting MRSPs exhibit multi-stimuli responsiveness to cations, pH, anions and temp. More interestingly, nanofibers were facilely obtained via the soln. electrospinning of a MRSP, which presented enhanced degrdn. behaviors in the presence of K+, Cl-, Et3N, or heating, indicating a multiple stimuli-responsive nature.
- 35Cantekin, S.; Nakano, Y.; Everts, J. C.; van der Schoot, P.; Meijer, E. W.; Palmans, A. R. A. A Stereoselectively Deuterated Supramolecular Motif to Probe the Role of Solvent during Self-Assembly Processes. Chem. Commun. 2012, 48 (32), 3803– 3805, DOI: 10.1039/c2cc17284d35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XksVajtrs%253D&md5=aa66a69320b85c1cae431d63530148f8A stereoselectively deuterated supramolecular motif to probe the role of solvent during self-assembly processesCantekin, Seda; Nakano, Yoko; Everts, Jeffrey C.; van der Schoot, Paul; Meijer, E. W.; Palmans, Anja R. A.Chemical Communications (Cambridge, United Kingdom) (2012), 48 (32), 3803-3805CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Small changes in the alkane solvent structure in combination with temp. effects lead to four different conformations of stereoselectively deuterated benzene-1,3,5-tricarboxamides in the aggregated state, affecting the expression of the supramol. chirality and highlighting the role of the solvent structure in self-assembly processes.
- 36Pianowski, Z. L. Recent Implementations of Molecular Photoswitches into Smart Materials and Biological Systems. Chem. - Eur. J. 2019, 25 (20), 5128– 5144, DOI: 10.1002/chem.20180581436https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXivFyisbk%253D&md5=cfcdedf7debbd69ae2510fdd40d8344fRecent implementations of molecular photoswitches into smart materials and biological systemsPianowski, Zbigniew L.Chemistry - A European Journal (2019), 25 (20), 5128-5144CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Light is a nearly ideal stimulus for mol. systems. It delivers information encoded in the form of wavelengths and their intensities with high precision in space and time. Light is a mild trigger that does not permanently contaminate targeted samples. Its energy can be reversibly transformed into mol. motion, polarity, or flexibility changes. This leads to sophisticated functions at the supramol. and macroscopic levels, from light-triggered nanomaterials to photocontrol over biol. systems. New methods and mol. adapters of light are reported almost daily. Recently reported applications of photoresponsive systems, particularly azobenzenes, spiropyrans, diarylethenes, and indigoids, for smart materials and photocontrol of biol. setups are described herein with the aim to demonstrate that the 21st century has become the Age of Enlightenment-"Le siecle des Lumieres"-in mol. sciences.
- 37Szymański, W.; Beierle, J. M.; Kistemaker, H. A. V.; Velema, W. A.; Feringa, B. L. Reversible Photocontrol of Biological Systems by the Incorporation of Molecular Photoswitches. Chem. Rev. 2013, 113 (8), 6114– 6178, DOI: 10.1021/cr300179f37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXms1Wjtbc%253D&md5=5e3785c5753c2f108e2c5ab1872e93c9Reversible Photocontrol of Biological Systems by the Incorporation of Molecular PhotoswitchesSzymanski, Wiktor; Beierle, John M.; Kistemaker, Hans A. V.; Velema, Willem A.; Feringa, Ben L.Chemical Reviews (Washington, DC, United States) (2013), 113 (8), 6114-6178CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Photoswitches have been developed to control the conformation and activity of biomols. in a reversible manner. This review aims at providing a comprehensive and crit. literature review on reversible photocontrol of biomols.'structure and function with mol. photoswitches.
- 38Ishikawa, M.; Ohzono, T.; Yamaguchi, T.; Norikane, Y. Photo-Enhanced Aqueous Solubilization of an Azo-Compound. Sci. Rep. 2017, 7 (1), 1– 6, DOI: 10.1038/s41598-017-06947-w38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXltFejsw%253D%253D&md5=69e68704cce6d4aab16384efd15e59e0MicroRNA-449a deficiency promotes colon carcinogenesisNiki, Masanori; Nakajima, Kohei; Ishikawa, Daichi; Nishida, Jun; Ishifune, Chieko; Tsukumo, Shin-ichi; Shimada, Mitsuo; Nagahiro, Shinji; Mitamura, Yoshinori; Yasutomo, KojiScientific Reports (2017), 7 (1), 1-10CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our anal. found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the nos. and sizes of colon tumors. These effects were assocd. with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histol. scores and was pos. correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Addnl., activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.
- 39Vancoillie, G.; Frank, D.; Hoogenboom, R. Thermoresponsive Poly(oligo Ethylene Glycol Acrylates). Prog. Polym. Sci. 2014, 39 (6), 1074– 1095, DOI: 10.1016/j.progpolymsci.2014.02.00539https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksFyqsL4%253D&md5=87a0ed1321a810862cbfefa56af74bb9Thermoresponsive poly(oligo ethylene glycol acrylates)Vancoillie, Gertjan; Frank, Daniel; Hoogenboom, RichardProgress in Polymer Science (2014), 39 (6), 1074-1095CODEN: PRPSB8; ISSN:0079-6700. (Elsevier Ltd.)A review. Thermoresponsive polymers have been the subject of numerous publications and research topics in the last few decades mostly driven by their easily controllable temp. stimulus and high potential for in vitro and in vivo applications. P(NIPAAm) is the most studied amongst these polymers, but recently other types of polymers are increasingly being investigated for their thermoresponsive behavior. In particular, polymers bearing a short oligo ethylene glycol (OEG) side chain have been shown to combine the biocompatibility of polyethylene glycol (PEG) with a versatile and controllable LCST behavior. These polymers can be synthesized via controlled radical polymn. techniques from various monomers consisting of an OEG chain and a polymerizable group like a (meth)acrylate, styrene or acrylamide. OEG acrylates offer significant advantages over, e.g., OEG methacrylates as the lower hydrophilicity of the backbone facilitates thermoresponsive behavior with smaller, more defined side chains. Furthermore, PEG acrylates can be polymd. using all major controlled radical polymn. techniques, unlike OEG methacrylates. This review will focus on OEG acrylate based (co)polymers and will provide a comprehensive overview of their reported thermoresponsive properties. The combination and comparison of this data will not only highlight the potential of these monomers, but will also serve as a starting point for future studies.
- 40Lüsse, S.; Arnold, K. The Interaction of Poly(ethylene Glycol) with Water Studied by 1H and 2H NMR Relaxation Time Measurements. Macromolecules 1996, 29 (12), 4251– 4257, DOI: 10.1021/ma950861640https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XivFShsLc%253D&md5=5f19d0ed5034e64d390d2cc48f8a970cThe Interaction of Poly(ethylene glycol) with Water Studied by 1H and 2H NMR Relaxation Time MeasurementsLuesse, S.; Arnold, K.Macromolecules (1996), 29 (12), 4251-4257CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)NMR relaxation time investigations of water protons (1H) and deuterons (2H) in aq. poly(ethylene glycol) (PEG) solns. are presented for the water content range of 3-90 wt.-%. The no. of bound water mols. per PEG repeat unit is estd. to be 1 from the water relaxation times by a model of fast exchange of water mols. between a bound and an unbound water fraction. For water contents <1 water mol. per PEG monomer, large restrictions in polymer mobility occur which also influence water NMR relaxation. For these low water contents, small ranges of oriented PEG chains are present in the solns. resulting in observable quadrupole splittings in the 2H NMR spectra.
- 41Chandler, D. Interfaces and the Driving Force of Hydrophobic Assembly. Nature 2005, 437 (7059), 640– 647, DOI: 10.1038/nature0416241https://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.
- 42Smith, G. D.; Bedrov, D. Roles of Enthalpy, Entropy, and Hydrogen Bonding in the Lower Critical Solution Temperature Behavior of Poly(ethylene oxide)/Water Solutions. J. Phys. Chem. B 2003, 107 (14), 3095– 3097, DOI: 10.1021/jp027004642https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXhvF2lur8%253D&md5=9001be86b94c5b711bfad4d652ff2c6fRoles of Enthalpy, Entropy, and Hydrogen Bonding in the Lower Critical Solution Temperature Behavior of Poly(ethylene oxide)/Water SolutionsSmith, Grant D.; Bedrov, DmitryJournal of Physical Chemistry B (2003), 107 (14), 3095-3097CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)Anal. of the temp. and compn. dependence of the excess thermodn. properties for oligomers of poly(ethylene oxide) (PEO) in aq. soln. obtained from mol. dynamics simulations reveals that the lower crit. soln. temp. (LCST) behavior of PEO/water solns. is enthalpy-driven. At lower temps., the formation of ether-water hydrogen bonds results in a very favorable ΔG EX consistent with the consoly. of PEO and water. Increasing temp. leads to a dramatic redn. in favorable ether-water interactions due to break-up of ether-water hydrogen bonding, while relatively persistent water-water hydrogen bonding maintains the energetic penalty assocd. with disrupted water-water interactions upon insertion of the ether. The entropy gain assocd. with the break-up of ether-water hydrogen bonds and redn. in the structure of hydrating water with increasing temp. is insufficient to offset the unfavorable enthalpic effects assocd. with the break-up of the ether-water hydrogen bonds.
- 43Besenius, P.; Goedegebure, Y.; Driesse, M.; Koay, M.; Bomans, P.; Palmans, A. R. A.; Dankers, P. Y. W.; Meijer, E. W. Peptide functionalised discotic amphiphiles and their self-assembly into supramolecular nanofibres. Soft Matter 2011, 7 (18), 7980– 7983, DOI: 10.1039/c1sm05896g43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFahsbvN&md5=8cb1621ba056e989f6bda87293876425Peptide functionalised discotic amphiphiles and their self-assembly into supramolecular nanofibresBesenius, P.; Goedegebure, Y.; Driesse, M.; Koay, M.; Bomans, P. H. H.; Palmans, A. R. A.; Dankers, P. Y. W.; Meijer, E. W.Soft Matter (2011), 7 (18), 7980-7983CODEN: SMOABF; ISSN:1744-683X. (Royal Society of Chemistry)The multicomponent co-assembly of discotic amphiphiles provides a modular and versatile approach to prep. RGDS- and PHSRN-peptide functionalized supramol. nanofibers, bearing pendant paramagnetic Gd(III)-chelates.
- 44Volgraf, M.; Gorostiza, P.; Szobota, S.; Helix, M. R.; Isacoff, E. Y.; Trauner, D. Reversibly Caged Glutamate: A Photochromic Agonist of Ionotropic Glutamate Receptors. J. Am. Chem. Soc. 2007, 129, 260– 261, DOI: 10.1021/ja067269o44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xhtleiu7bI&md5=67923334e30c8bc5c3135b6d89124339Reversibly Caged Glutamate: A Photochromic Agonist of Ionotropic Glutamate ReceptorsVolgraf, Matthew; Gorostiza, Pau; Szobota, Stephanie; Helix, Max R.; Isacoff, Ehud Y.; Trauner, DirkJournal of the American Chemical Society (2007), 129 (2), 260-261CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The design, synthesis, and biol. evaluation of a photochromic glutamate analog I is described. I functions as a reversibly caged neurotransmitter and can be used to influence neural activity with light.
- 45Riefolo, F.; Matera, C.; Garrido-Charles, A.; Gomila, A. M. J.; Sortino, R.; Agnetta, L.; Claro, E.; Masgrau, R.; Holzgrabe, U.; Batlle, M.; Decker, M.; Guasch, E.; Gorostiza, P. Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist. J. Am. Chem. Soc. 2019, 141, 7628– 7636, DOI: 10.1021/jacs.9b0350545https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnvFCgt7o%253D&md5=bd8db9ec8fcc66d2fec94d8cdafa31f2Optical Control of Cardiac Function with a Photoswitchable Muscarinic AgonistRiefolo, Fabio; Matera, Carlo; Garrido-Charles, Aida; Gomila, Alexandre M. J.; Sortino, Rosalba; Agnetta, Luca; Claro, Enrique; Masgrau, Roser; Holzgrabe, Ulrike; Batlle, Montserrat; Decker, Michael; Guasch, Eduard; Gorostiza, PauJournal of the American Chemical Society (2019), 141 (18), 7628-7636CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Light-triggered reversible modulation of physiol. functions offers the promise of enabling on-demand spatiotemporally controlled therapeutic interventions. Optogenetics has been successfully implemented in the heart, but significant barriers to its use in the clinic remain, such as the need for genetic transfection. Herein, we present a method to modulate cardiac function with light through a photoswitchable compd. and without genetic manipulation. The mol., named PAI, was designed by introduction of a photoswitch into the mol. structure of an M2 mAChR agonist. In vitro assays revealed that PAI enables light-dependent activation of M2 mAChRs. To validate the method, we show that PAI photoisomers display different cardiac effects in a mammalian animal model, and demonstrate reversible, real-time photocontrol of cardiac function in translucent wildtype tadpoles. PAI can also effectively activate M2 receptors using two-photon excitation with near-IR light, which overcomes the scattering and low penetration of short-wavelength illumination, and offers new opportunities for intravital imaging and control of cardiac function.
- 46Bandara, H. M. D.; Burdette, S. C. Photoisomerization in Different Classes of Azobenzene. Chem. Soc. Rev. 2012, 41 (5), 1809– 1825, DOI: 10.1039/C1CS15179G46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XitFyjsLg%253D&md5=33ad953f692613475d922490922bc2b2Photoisomerization in different classes of azobenzeneBandara, H. M. Dhammika; Burdette, Shawn C.Chemical Society Reviews (2012), 41 (5), 1809-1825CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Azobenzene undergoes trans cis isomerization when irradiated with light tuned to an appropriate wavelength. The reverse cis trans isomerization can be driven by light or occurs thermally in the dark. Azobenzene's photochromatic properties make it an ideal component of numerous mol. devices and functional materials. Despite the abundance of application-driven research, azobenzene photochem. and the isomerization mechanism remain topics of study. Addnl. substituents on the azobenzene ring system change the spectroscopic properties and isomerization mechanism. This crit. review details the studies completed to date on the 3 main classes of azobenzene derivs. Understanding the differences in photochem., which originate from substitution, is imperative in exploiting azobenzene in the desired applications.
- 47Titov, E.; Granucci, G.; Götze, J. P.; Persico, M.; Saalfrank, P. Dynamics of Azobenzene Dimer Photoisomerization: Electronic and Steric Effects. J. Phys. Chem. Lett. 2016, 7 (18), 3591– 3596, DOI: 10.1021/acs.jpclett.6b0140147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlOqu7rP&md5=acdc1bc0bd1dff46f544dbd93b00e7abDynamics of Azobenzene Dimer Photoisomerization: Electronic and Steric EffectsTitov, Evgenii; Granucci, Giovanni; Goetze, Jan Philipp; Persico, Maurizio; Saalfrank, PeterJournal of Physical Chemistry Letters (2016), 7 (18), 3591-3596CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)While azobenzenes readily photoswitch in soln., their photoisomerization in densely packed self-assembled monolayers (SAMs) can be suppressed. Reasons for this can be steric hindrance and/or electronic quenching, e.g., by exciton coupling. The authors address these possibilities by means of nonadiabatic mol. dynamics with trajectory surface hopping calcns., investigating the trans → cis isomerization of azobenzene after excitation into the ππ* absorption band. The authors consider a free monomer, an isolated dimer and a dimer embedded in a SAM-like environment of addnl. azobenzene mols., imitating in this way the gradual transition from an unconstrained over an electronically coupled to an electronically coupled and sterically hindered, mol. switch. Simulations reveal that in comparison to the single mol. the quantum yield of the trans → cis photoisomerization is similar for the isolated dimer, but greatly reduced in the sterically constrained situation. Other implications of dimerization and steric constraints are also discussed.
- 48Cocchi, C.; Draxl, C. Understanding the Effects of Packing and Chemical Terminations on the Optical Excitations of Azobenzene-Functionalized Self-Assembled Monolayers. J. Phys.: Condens. Matter 2017, 29 (39), 394005, DOI: 10.1088/1361-648X/aa7ca748https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVyjsLY%253D&md5=dc98c9f992354e441bb262791a29e8b3Understanding the effects of packing and chemical terminations on the optical excitations of azobenzene-functionalized self-assembled monolayersCocchi, Caterina; Draxl, ClaudiaJournal of Physics: Condensed Matter (2017), 29 (39), 394005/1-394005/12CODEN: JCOMEL; ISSN:0953-8984. (IOP Publishing Ltd.)In a 1st-principles study based on many-body perturbation theory, the authors analyze the optical excitations of azobenzene-functionalized self-assembled monolayers (SAMs) with increasing packing d. and different terminations, considering for comparison the corresponding gas-phase mols. and dimers. Intermol. coupling increases with the d. of the chromophores independently of the functional groups. The intense π → π* resonance that triggers photo-isomerization is present in the spectra of isolated dimers and dild. SAMs, but it is almost completely washed out in tightly packed architectures. Intermol. coupling is partially inhibited by mixing differently functionalized azobenzene derivs., in particular when large groups are involved. In this way, the excitation band inducing the photo-isomerization process is partially preserved and the effects of dense packing partly counterbalanced. Results suggest that a tailored design of azobenzene-functionalized SAMs which optimizes the interplay between the packing d. of the chromophores and their termination can lead to significant improvements in the photo-switching efficiency of these systems.
- 49Galanti, A.; Diez-Cabanes, V.; Santoro, J.; Valasek, M.; Minoia, A.; Mayor, M.; Cornil, J.; Samorì, P. Electronic Decoupling in C3-Symmetrical Light-Responsive Tris(Azobenzene) Scaffolds: Self-Assembly and Multiphotochromism. J. Am. Chem. Soc. 2018, 140 (47), 16062– 16070, DOI: 10.1021/jacs.8b0632449https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVKltb7P&md5=8762de2eeca6f98f3d8ab4a16e122e07Electronic Decoupling in C3-Symmetrical Light-Responsive Tris(Azobenzene) Scaffolds: Self-Assembly and MultiphotochromismGalanti, Agostino; Diez-Cabanes, Valentin; Santoro, Jasmin; Valasek, Michal; Minoia, Andrea; Mayor, Marcel; Cornil, Jerome; Samori, PaoloJournal of the American Chemical Society (2018), 140 (47), 16062-16070CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report the synthesis of a novel C3-sym. multiphotochromic mol. bearing three azobenzene units at positions 1, 3, 5 of the central Ph ring. The unique geometrical design of such a rigid scaffold enables the electronic decoupling of the azobenzene moieties to guarantee their simultaneous isomerization. Photoswitching of all azobenzenes in soln. was demonstrated by means of UV-vis absorption spectroscopy and high performance liq. chromatog. (HPLC) anal. Scanning tunneling microscopy investigations at the solid-liq. interface, corroborated by mol. modeling, made it possible to unravel the dynamic self-assembly of such systems into ordered supramol. architectures, by visualizing and identifying the patterns resulting from three different isomers, thereby demonstrating that the multiphotochromism is retained when the mols. are confined in two dimensions.
- 50Tong, X.; Wang, G.; Soldera, A.; Zhao, Y. How Can Azobenzene Block Copolymer Vesicles Be Dissociated and Reformed by Light?. J. Phys. Chem. B 2005, 109 (43), 20281– 20287, DOI: 10.1021/jp052427450https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtVymu7nJ&md5=bf60aa2d269fe72b44469a73c5bded45How Can Azobenzene Block Copolymer Vesicles Be Dissociated and Reformed by Light?Tong, Xia; Wang, Guang; Soldera, Armand; Zhao, YueJournal of Physical Chemistry B (2005), 109 (43), 20281-20287CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)The underlying mechanism of UV light-induced dissocn. and visible light-induced reformation of vesicles formed by an azobenzene diblock copolymer was investigated. These processes were studied in situ by monitoring changes in optical transmittance of the vesicular soln. while being exposed to UV or visible light irradn. The results indicate that the UV-induced dissocn. of the vesicles results from their thermodn. instability due to a shift of the hydrophilic/hydrophobic balance arising from the trans-cis isomerization, while their reaggregation takes place upon visible light irradn. that shifts the hydrophilic/hydrophobic balance in the opposite direction after the reverse cis-trans isomerization. The study suggests a specific design principle for obtaining UV light-dissociable and visible light-recoverable vesicles based on azobenzene block copolymers. On one hand, the structure of azobenzene moiety used in the hydrophobic block should have a small (near zero) dipole moment in the trans form and a significantly higher dipole moment in the cis form, which ensures a significant increase in polarity of the hydrophobic block under UV light irradn. On the other hand, the hydrophilic block should be weakly hydrophilic. The conjunction of the two conditions can make the light-induced shift of the hydrophilic/hydrophobic balance important enough to lead to the reversible change in vesicular aggregation.
- 51Liu, M.; Zhang, L.; Wang, T. Supramolecular Chirality in Self-Assembled Systems. Chem. Rev. 2015, 115 (15), 7304– 7397, DOI: 10.1021/cr500671p51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2ltr%252FO&md5=f6de0aeac890026c6815651d60f8e832Supramolecular Chirality in Self-Assembled SystemsLiu, Minghua; Zhang, Li; Wang, TianyuChemical Reviews (Washington, DC, United States) (2015), 115 (15), 7304-7397CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)Chiral self-assembly from the mol. to the supramol. level were discussed.
- 52Casellas, N. M.; Pujals, S.; Bochicchio, D.; Pavan, G. M.; Torres, T.; Albertazzi, L.; García-Iglesias, M. From isodesmic to highly cooperative: reverting the supramolecular polymerization mechanism in water by fine monomer design. Chem. Commun. 2018, 54 (33), 4112– 4115, DOI: 10.1039/C8CC01259H52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmt1ajt7g%253D&md5=e5fb36d6c82719a4a3a248d3d0f353daFrom isodesmic to highly cooperative: reverting the supramolecular polymerization mechanism in water by fine monomer designCasellas, Nicolas M.; Pujals, Silvia; Bochicchio, Davide; Pavan, Giovanni M.; Torres, Tomas; Albertazzi, Lorenzo; Garcia-Iglesias, MiguelChemical Communications (Cambridge, United Kingdom) (2018), 54 (33), 4112-4115CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Two structurally-similar discotic mols. able to self-assemble in water, forming supramol. fibers, are reported. While both self-assembled polymers are indistinguishable from a morphol. point-of-view, a dramatic change in their polymn. mechanism is obsd. (i.e., one self-assemble via an isodesmic mechanism, while the other shows one of the highest cooperativity values).
- 53Hamley, I. W.; Cheng, G.; Castelletto, V. A. Thermoresponsive Hydrogel Based on Telechelic PEG End-Capped with Hydrophobic Dipeptides. Macromol. Biosci. 2011, 11 (8), 1068– 1078, DOI: 10.1002/mabi.20110002253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpslyisbg%253D&md5=44302424e8e04b4a806ea39e80fdd807A Thermoresponsive Hydrogel Based on Telechelic PEG End-Capped with Hydrophobic DipeptidesHamley, Ian W.; Cheng, Ge; Castelletto, ValeriaMacromolecular Bioscience (2011), 11 (8), 1068-1078CODEN: MBAIBU; ISSN:1616-5187. (Wiley-VCH Verlag GmbH & Co. KGaA)The self-assembly in aq. soln. of PEG (1 500 Da) telechelically end-capped with hydrophobic dipeptides has been investigated using spectroscopic, microscopic, scattering, and rheol. methods. A self-assembled β-sheet fibril-based hydrogel has been identified (contg. dityrosine end groups), which exhibits a gel-sol transition near body temp. This thermo-responsive PEG-based biofunctional hydrogel is expected to have diverse potential uses in delivery or diagnostics for biomedical applications.
- 54Fuller, J. M.; Raghupathi, K. R.; Ramireddy, R. R.; Subrahmanyam, A. V.; Yesilyurt, V.; Thayumanavan, S. Temperature-Sensitive Transitions below LCST in Amphiphilic Dendritic Assemblies: Host–Guest Implications. J. Am. Chem. Soc. 2013, 135 (24), 8947– 8954, DOI: 10.1021/ja402019c54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnvFyisb0%253D&md5=6f69aeacedd93ef2b488bfde1b01b80eTemperature-Sensitive Transitions below LCST in Amphiphilic Dendritic Assemblies: Host-Guest ImplicationsFuller, Jack M.; Raghupathi, Krishna R.; Ramireddy, Rajasekhar R.; Subrahmanyam, Ayyagari V.; Yesilyurt, Volkan; Thayumanavan, S.Journal of the American Chemical Society (2013), 135 (24), 8947-8954CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Oligo(ethylene glycol)-decorated supramol. assemblies have been of great interest due to their charge-neutral character and thus their propensity to avoid nonspecific interactions. These systems are known to exhibit a macroscopic temp.-sensitive transition, where the assembly phase-separates from the aq. phase at higher temps. While this so-called lower crit. soln. temp. (LCST) behavior has been well-studied, there have been no studies on the fate of these supramol. assemblies below this transition temp. The work here brings to light the presence of a second, sub-LCST transition, obsd. well below the LCST of oligo(ethylene glycol) (OEG)-based dendrons, where the host-guest properties of the assembly are significantly altered. This sub-LCST transition is accompanied by changes in the guest encapsulation stability and dynamics of host exchange.
- 55Engel, S.; Spitzer, D.; Rodrigues, L. L.; Fritz, E.; Straßburger, D.; Schönhoff, M.; Ravoo, B. J.; Besenius, P. Kinetic control in the temperature-dependent sequential growth of surface-confined supramolecular copolymers. Faraday Discuss. 2017, 204 (0), 53– 67, DOI: 10.1039/C7FD00100B55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlvFyksLs%253D&md5=c1f671698a1d48c9c7b14ae64cf05ad0Kinetic control in the temperature-dependent sequential growth of surface-confined supramolecular copolymersEngel, Sabrina; Spitzer, Daniel; Rodrigues, Leona Lucas; Fritz, Eva-Corinna; Strassburger, David; Schoenhoff, Monika; Ravoo, Bart Jan; Besenius, PolFaraday Discussions (2017), 204 (Complex Molecular Surfaces and Interfaces), 53-67CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)We report the sequential growth of supramol. copolymers on gold surfaces, using oppositely charged dendritic peptide amphiphiles. By including water-solubilizing thermoresponsive chains in the monomer design, we obsd. non-linear effects in the temp.-dependent sequential growth. The step-wise copolymn. process is characterized using temp. dependent SPR and QCM-D measurements. At higher temps., dehydration of peripheral oligoethylene glycol chains supports copolymer growth due to more favorable comonomer interactions. Both monomers incorporate methionine amino acids but remarkably, desorption of the copolymers via competing sulfur gold interactions with the initial monomer layer is not obsd. The surface-confined supramol. copolymers remain kinetically trapped on the metal surface at near neutral pH and form viscoelastic films with a tuneable thickness.
- 56Frisch, H.; Fritz, E.; Stricker, F.; Schmüser, L.; Spitzer, D.; Weidner, T.; Ravoo, B. J.; Besenius, P. Kinetically Controlled Sequential Growth of Surface-Grafted Chiral Supramolecular Copolymers. Angew. Chem., Int. Ed. 2016, 55 (25), 7242– 7246, DOI: 10.1002/anie.20160104856https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xks1elurk%253D&md5=f6ebcbf0350c43c379503a5b721e6471Kinetically Controlled Sequential Growth of Surface-Grafted Chiral Supramolecular CopolymersFrisch, Hendrik; Fritz, Eva-Corinna; Stricker, Friedrich; Schmueser, Lars; Spitzer, Daniel; Weidner, Tobias; Ravoo, Bart Jan; Besenius, PolAngewandte Chemie, International Edition (2016), 55 (25), 7242-7246CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The authors report a facile strategy to grow supramol. copolymers on Au surfaces by successively exposing a surface-anchored monomer to solns. of oppositely charged peptide comonomers. Charge regulation on the active chain end of the polymer sufficiently slows down the kinetics of the self-assembly process to produce kinetically trapped copolymers at near-neutral pH. The authors thereby achieve architectural control at three levels: the β-sheet sequences direct the polymn. away from the surface, the height of the supramol. copolymer brushes is well-controlled by the stepwise nature of the alternating copolymer growth, and 2D spatial resoln. is realized by using micropatterned initiating monomers. The programmable nature of the resulting architectures renders this concept attractive for the development of customized biomaterials or chiral interfaces for optoelectronics and sensor applications.
- 57Besenius, P.; Portale, G.; Bomans, P.; Janssen, H. M.; Palmans, A. R. A.; Meijer, E. W. Controlling the Growth and Shape of Chiral Supramolecular Polymers in Water. Proc. Natl. Acad. Sci. U. S. A. 2010, 107 (42), 17888– 17893, DOI: 10.1073/pnas.100959210757https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlCqsbnJ&md5=f8b455492ff130f0af2ab16dbb205d1eControlling the growth and shape of chiral supramolecular polymers in waterBesenius, Pol; Portale, Giuseppe; Bomans, Paul H. H.; Janssen, Henk M.; Palmans, Anja R. A.; Meijer, E. W.Proceedings of the National Academy of Sciences of the United States of America (2010), 107 (42), 17888-17893, S17888/1-S17888/19CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)A challenging target in the noncovalent synthesis of nanostructured functional materials is the formation of uniform features that exhibit well-defined properties, e.g., precise control over the aggregate shape, size, and stability. In particular, for aq.-based 1-dimensional supramol. polymers, this is a daunting task. Here the authors disclose a strategy based on self-assembling discotic amphiphiles (I; Q = Gd/Y DOTA/DTPA chelates) that leads to the control over stack length and shape of ordered, chiral columnar aggregates. By balancing out attractive noncovalent forces within the hydrophobic core of the polymg. building blocks with electrostatic repulsive interactions on the hydrophilic rim the authors managed to switch from elongated, rod-like assemblies to small and discrete objects. Intriguingly this rod-to-sphere transition is expressed in a loss of cooperativity in the temp.-dependent self-assembly mechanism. The aggregates were characterized using CD, UV and 1H-NMR spectroscopy, small angle x-ray scattering, and cryoTEM. In analogy to many systems found in biol., mechanistic details of the self-assembly pathways emphasize the importance of cooperativity as a key feature that dictates the phys. properties of the produced supramol. polymers.
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Supporting Information
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Experimental procedure for the synthesis of 1 and 2 as well as analytical, spectral, and self-assembly characterization data (PDF)
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