Integrating Macromolecules with Molecular Switches

Long before their development by synthetic chemists, molecular machines have been operating in nature, where they perform functions critical to life. Examples of natural molecular machines include adenosine triphosphate (ATP) synthase, which enables endergonic ATP synthesis by coupling to proton concentration gradients, and linear motors, such as kinesins and myosins, whose movement along the surfaces is driven by ATP hydrolysis. Inspired by the elegance with which these and other molecular machines operate in nature, chemists have been involved in synthesizing artificial molecular machines—entities designed to perform desired tasks (such as controlling directional motion and synthesizing other molecules) in the presence of an energy source. The successful development of artificial molecular machines requires integrating switchable elements within larger objects. In that respect, polymers have attracted considerable attention: they can be prepared inexpensively and have a wide range of useful mechanical properties (depending on the structural formulae), and they can be recycled. This Special Issue highlights the diverse ways by which molecular switches can be incorporated into macromolecular architectures, as well as the emerging properties and applications of the resulting materials. Most attention over the past decade has been devoted to molecular switches operated by light, which is reflected in the contents of this Special Issue. Barrett and co-workers discuss the current status of polymers functionalized with the archetypal molecular photoswitch, azobenzene (https://doi.org/10.1002/marc.201700253). These authors review systems that can perform bending motion as well as more complex movements (such as oscillations or helical deformations) and highlight the importance of harvesting sunlight for these operations. At the same time, they point out that the light-to-mechanical energy conversion can result from not only molecular isomerization events, but can also occur because of photothermal effects. A novel example of one such “molecular robotic machine” is reported by Priimagi, Zeng, and co-workers, who incorporated a red-shifted azobenzene into a liquid crystal elastomer (https://doi.org/10.1002/marc.201700224). The authors describe how the movement's directionality of their caterpillar-shaped “robot” can be controlled by the topology of the underlying surface. In a related contribution, Yu, Wei et al. focus on some key engineering aspects of photoactuating polymers, namely, their easy fabrication and the use of low-cost polymer matrices (https://doi.org/10.1002/marc.201700237). By dispersing crosslinked azobenzene polymers within a flexible polyurethane matrix, they were able to effectively transfer light-responsiveness to the otherwise photoinert matrix. The photoinduced bending could be reversed by combining thermal treatment and mesogen realignment, conferring to the films the ability to deform reversibly. The potential of analytical methods—in particular, vibrational (infrared and Raman) spectroscopy—for probing photoswitching in azo-polymers, is highlighted by Pellerin, Vapaavuori, and Bazuin (https://doi.org/10.1002/marc.201700430), who contend that the development of such analytical tools is essential for a better mechanistic understanding of key processes, such as translation of molecular-scale photochemical events into macroscopic motion. Light-triggered changes, such as unfolding/folding of macromolecules, mass-transport, and photoinduced chirality in azo-materials can now be studied in great detail with the help of these techniques, owing to their ability to finely probe the molecular environment, orientation, and chiral order. An important direction in the optical manipulation of molecular systems lies in the development of strategies allowing one to overcome the use of UV irradiation and instead, to operate the systems using visible or near-infrared light. This has several important advantages, including decreased invasiveness towards the other components of the system, biocompatibility, selectivity, increased penetration depth, and the ability to harvest sunlight. In their Review, Wu and Weis discuss key achievements in this direction using macromolecules incorporating azobenzene derivatives (https://doi.org/10.1002/marc.201700220). The conceptual approaches used to avoid UV light can be classified into (1) red-shifting the absorption of the molecular switches (i.e., direct photoexcitation) and (2) leveraging energy/electron transfer (indirect photoexcitation), for example, by using upconverting nanoparticles or triplet-triplet annihilation systems. Following in this direction, Bléger and co-workers reported on visible-light-activated hydrogels, whose elasticity can be reversibly tuned upon exposure to green and blue light (https://doi.org/10.1002/marc.201700527). Hydrogels have found multiple applications in biomedicine and are a suitable platform for introducing molecular switches into soft materials. Modulating the elasticity of such materials “on demand” is relevant for influencing complex biological processes, such as the differentiation of stem cells. The molecular structure of the hydrogels is based on ortho-fluoroazobenzene-containing PEGylated networks, which were prepared by bioorthogonal chemistry. In addition to being fully addressable in the visible region, ortho-fluorinated azobenzenes can exhibit remarkable bistability (i.e., high thermal stability of both the E and Z isomers). This property was utilized by Katsonis and co-workers to design photochromic chiral dopants leading to long-lived helical states in nematic liquid crystals, which can be rapidly and reversibly interconverted into one another using two wavelengths of visible light (https://doi.org/10.1002/marc.201700387). Interestingly, the Z → E relaxation times were longer when the F-azobenzenes were doped in the liquid crystal than when dissolved in solution, which could be attributed to a decreased molecular degree of freedom. Nevertheless, care should be taken to avoid fully suppressing the isomerization of molecular switches when interfacing them with higher-order structures and materials. Photoactive crosslinkers are convenient tools to remotely connect larger objects via supramolecular interactions or dynamic covalent bonds, giving rise to diverse novel applications. Building on their previous studies on cyclodextrin vesicles, Ravoo et al. assembled ternary complexes comprising the vesicles, DNA, and azo-switches appended with positively charged groups (https://doi.org/10.1002/marc.201700256). The complexes were held together by means of multivalent electrostatic interactions between DNA and the vesicle-bound positively charged dyes. Upon E → Z photoisomerization, the dyes lose their ability to bind to cyclodextrin vesicles, and the complexes disassemble. The researchers contend that this strategy holds promise for applications in the controlled capture and release of DNA. It is covalent crosslinking, however, that is better suited for fabricating robust macroscopic materials. Hecht and co-workers employed diarylethene (DAE)-based crosslinkers for connecting polymer chains to generate dynamic covalent polymer networks (https://doi.org/10.1002/marc.201700376). Crosslinking was achieved by a Diels-Alder reaction between dienophile units appended to polymer chains and dienes contained within the open form of DAEs. The photoinduced ring closure of DAEs efficiently inhibits the Diels-Alder reaction and hence removes the thermal healing ability of the polymer networks. Therefore, the healability of the material could be activated reversibly (and locally) using light. Importantly, the decrosslinking barrier could be lowered—and the healing temperatures decreased—by optimizing the polymer's composition and the DAE crosslinker's design. Although usually not regarded as macromolecules, metal-organic frameworks (MOFs) represent an interesting class of supramolecular polymers that feature nanometer-sized, regularly arranged nanopores. The excellent sorption properties often associated with these nanopores give rise to many important applications in, for example, gas storage, separations, and catalysis. Installing molecular switches inside these nanopores is an attractive route towards controlling the properties of MOFs using external stimuli. In their Feature Article, Wang, Sue, and co-workers introduce the emerging field of MOFs equipped with molecular switches (https://doi.org/10.1002/marc.201700388). They describe two approaches developed to fabricate such switchable MOFs: one based on assembling MOFs from organic building blocks incorporating molecular switches, and the other relying on post-synthetic modifications of MOFs with switchable molecules. These methods have been used to prepare pH-, light-, and redox-responsive MOFs, whose diverse applications in sensing, CO2 adsorption, gas separation, drug delivery, and photodynamic therapy are discussed. In a related contribution, Heinke et al. focused on photoresponsive MOFs functionalized with azobenzene groups (https://doi.org/10.1002/marc.201700239). This Review highlights an important issue that needs to be considered when designing switchable polymers, namely, the conformational freedom that many molecular switches need to have in order to switch efficiently. Azobenzenes have attracted the most attention as far as the integration of molecular switches with macromolecules is concerned: they are chemically robust, exhibit low fatigue, can be readily functionalized, and have tunable light absorption properties. However, other light-responsive molecular switches offer other advantages: spiropyrans, for example, can be switched using several distinct types of external stimuli, including light, metal ions, and acid/base signals. This unique feature enabled the development of thermoresponsive polymers, whose phase transitions can be induced by light (rather than temperature). Building on these previous studies, Schenning, den Toonder, and co-workers demonstrated a creative application of spiropyran-functionalized hydrogels as light-responsive passive micromixers (https://doi.org/10.1002/marc.201700086). They decorated the walls of microfluidic devices with tiny pillars composed of this material, which acted as mixers for the liquids passing through the channel. Upon exposure to blue light, however, the hydrophobic closed-ring isomer of spiropyran was generated and the micropillars collapsed, resulting in laminar flow with no mixing. Interestingly, the degree of mixing could be controlled by tuning the light intensity. In a related study, Sumaru et al. considered a more fundamental problem, namely, how the light-induced collapse is affected by the presence of macrocyclic hosts. Working with α-, β-, and γ-cyclodextrin, they found that the closed-ring isomer of spiropyran could be readily encircled by the mid-sized β ring, thus preventing the dehydration and collapse of the thermoresponsive polymer (https://doi.org/10.1002/marc.201700234). It is interesting to consider the possibility of combining these two studies, with solutions of the different cyclodextrins flowing through channels decorated with spiropyran-functionalized thermoresponsive polymer micropillars. Beyond light-controlled switches, Wang, Jiang, and co-workers developed a supramolecular polymer, which could be reversibly disassembled and reassembled using a base and an acid, respectively (https://doi.org/10.1002/marc.201700218). The key component of the polymer was a newly synthesized unsymmetrical cryptand featuring cavities having two different sizes: one exhibiting strong affinity towards the viologens, the other, binding dibenzylammonium ions. In the presence of a mixture of a bis-ammonium and a bis-viologen crosslinker, the cryptand induced the formation of a one-dimensional supramolecular polymer. Interestingly, the simultaneous complexation of the ammonium and the viologen groups took place despite both of them bearing a positive charge and hence repelling each other. Treating the polymer with a base caused the deprotonation of the ammonium groups, which disassembled the polymer. The polymer could be re-formed upon subsequent addition of an acid. An intriguing question is whether the binding of the other guest (i.e., the redox-active viologen) could also be cancelled—in this case, using a reducing agent—which would render the system responsive to two kinds of orthogonal stimuli. The development of such dual-responsive systems has, in fact, attracted increasing attention: Huang, Wu, and co-workers devised a crosslinked polymer gel that could be toggled between a tough and a soft state upon modulating pH or temperature (https://doi.org/10.1002/marc.201700361). The mechanical properties of the gel were determined by the state of the mechanically interlocked, catenane-based crosslinks, which could be either rigid (stabilized by multiple hydrogen bonds) or flexible (no H-bonds present; catenane rings freely rotating with respect to each other), depending on pH and temperature. Another thermo-/pH-responsive system was proposed by Liu, Hu, et al., who synthesized double-hydrophilic block copolymers terminated with a β-cyclodextrin moiety (https://doi.org/10.1002/marc.201700225). The two blocks of the polymers could be rendered hydrophobic upon heating or increasing pH, respectively. In either case, free polymer chains spontaneously assembled into micelles containing the hydrophobic block in the center. Finally, a state-of-the-art, triple-responsive system was proposed by Theato and co-workers, who designed a triblock copolymer featuring i) a permanently hydrophilic block, ii) a block incorporating moieties sensitive to two kinds of chemical signals (O2 and CO2), and iii) a UV-responsive, azobenzene-based block (https://doi.org/10.1002/marc.201700313). When placed in water, the triblock copolymer self-assembled into vesicles, which gradually swelled when subjected to these three stimuli. Importantly, this swelling was accompanied by increasing permeability through the vesicle walls, with potential applications in controlled release systems. The “breathing” behavior of the vesicles was demonstrated by alternately adding and removing the gaseous stimuli. We would like to thank all of the contributing authors of this Special Issue and the editorial staff members for their assistance. We hope that this collection of Communications, Feature Articles, and Reviews will inspire others to think about and contribute to research on synthetic macromolecular machines, whose functional potential is great, yet remains to be fully exploited.