Supramolecular Polymers: Inherently Dynamic Materials.

Inspired by the vast array of assemblies present in nature, supramolecular chemistry has attracted significant attention on account of its diverse supra-structures, which include micelles, vesicles, and fibers, in addition to its extensive applications in luminescent materials, sensors, bioimaging, and drug delivery over the past decades. Supramolecular polymers, which represent a combination of supramolecular chemistry and polymer science, are constructed by non-covalent interactions, such as host-guest interactions, hydrogen bonding, hydrophobic or hydrophilic interactions, metal-ligand interactions, π-π stacking, and electrostatic interactions. To date, numerous host-guest recognition systems have been reported, including crown ethers, cyclodextrins, calixarenes, cucurbituril, pillararenes, and other macrocyclic hosts. Among them, crown ethers, as the first generation of macrocyclic hosts, provide a promising and facile alternative route to supramolecular polymers. In addition, the incorporation of fluorophores into supramolecular polymers could endow them with multiple properties and functions, thereby presenting potential advantages in the context of smart materials. Thus, this review focuses on the fabrication strategies, interesting properties, and potential applications of fluorescent supramolecular polymers based on crown ethers. Typical examples are presented and discussed in terms of three different types of building blocks, namely covalently bonded low-molecular-weight compounds, polymers modified by hosts or guests, and supramolecular coordination complexes.

Owing to the mastery exhibited by Nature in integrating both covalent and noncovalent interactions in a highly efficient manner, the quest to construct polymeric systems that rival not only the precision and fidelity but also the structure of natural systems has remained a daunting challenge. Supramolecular chemists have long endeavored to control the interplay between covalent and noncovalent bond formation, so as to examine and fully comprehend how function is predicated on self-assembly. The ability to reliably control polymer self-assembly is essential to generate "smart" materials and has the potential to tailor polymer properties (i.e., viscosity, electronic properties) through fine-tuning the noncovalent interactions that comprise the polymer architecture. In this context, supramolecular polymers have a distinct advantage over fully covalent systems in that they are dynamically modular, since noncovalent recognition motifs can be engineered to either impart a desired functionality within the overall architecture or provide a designed bias for the self-assembly process. In this Account, we describe engineering principles being developed and pursued by our group that exploit the orthogonal nature of noncovalent interactions, such as hydrogen bonding, metal coordination, and Coulombic interactions, to direct the self-assembly of functionalized macromolecules, resulting in the formation of supramolecular polymers. To begin, we describe our efforts to fabricate a modular poly(norbornene)-based scaffold via ring-opening metathesis polymerization (ROMP), wherein pendant molecular recognition elements based upon nucleobase-mimicking elements (e.g., thymine, diaminotriazine) or SCS-Pd(II) pincer were integrated within covalent monofunctional or symmetrically functionalized polymers. The simple polymer backbones exhibited reliable self-assembly with complementary polymers or small molecules. Within these systems, we applied successful protecting group strategies and template polymerizations to enhance the control afforded by ROMP. Main-chain-functionalized alternating block polymers based upon SCS-Pd(II) pincer-pyridine motifs were achieved through the combined exploitation of bimetallic initiators and supramolecularly functionalized terminators. Our initial design principles led to the successful fabrication of both main-chain- and side-chain-functionalized poly(norbornenes) via ROMP. Utilizing all of these techniques in concert led to engineering orthogonality while achieving complexity through the installation of multiple supramolecular motifs within the side chain, main chain, or both in our polymer systems. The exploitation and modification of design principles based upon functional ROMP initiators and terminators has resulted in the first synthesis of main-chain heterotelechelic polymers that self-assemble into A/B/C supramolecular triblock polymers composed of orthogonal cyanuric acid-Hamilton wedge and SCS-Pd(II) pincer-pyridine motifs. Furthermore, supramolecular A/B/A triblock copolymers were realized through the amalgamation of functionalized monomers, ROMP initiators, and terminators. To date, this ROMP-fabricated system represents the only known method to afford polymer main chains and side chains studded with orthogonal motifs. We end by discussing the impetus to attain functional materials via orthogonal self-assembly. Collectively, our studies suggest that combining covalent and noncovalent bonds in a well-defined and precise manner is an essential design element to achieve complex architectures. The results discussed in this Account illustrate the finesse associated with engineering orthogonal interactions within supramolecular systems and are considered essential steps toward developing complex biomimetic materials with high precision and fidelity.

Polymers have long been known to us for their versatile utility in our daily lives. With many years of successful advancement in controlled polymer synthesis and supramolecular chemistry, currently an amalgamation of these two fields is becoming increasingly important for generating modern‐day emerging polymeric materials. Hydrogen bonding and other noncovalent interactions like π‐stacking, host‐guest interaction, electrostatic interaction, metal‐ligand coordination have been explored much to this context, unlike the recently emerged halogen bonding, which indeed shows advantageous features like superior hydrophobicity, directionality and polar solvent resistance compared to ubiquitous hydrogen bonding. Hence, rendering these properties of halogen bonding into polymeric domain for generating functional materials for application in advance nanotechnologies is highly desirable. In the recent years, substantial progress has been made in fulfilling this challenging goal. This is evident from the escalating number of scientific publications in this research area every year. In this minireview, we have summarized the most recent developments in the field of halogen bonded polymeric assemblies and supramolecular polymers and discussed them in the context of their emerging materials properties and functions. Emphasis is given on highlighting various design criteria adopted in crystal engineering, covalent and supramolecular polymers in the past five years for constructing diverse organic functional materials, viz. liquid crystals, photoresponsive and photochromic materials, biomaterials and gels, self‐healing materials and many others by virtue of this highly directional supramolecular tool. In conclusion, a brief perspective on the advantages, challenges and future prospects in this rapidly growing field of research is discussed.

Supramolecular polymers are widely utilized and applied in self-assembly or self-healing materials, which can be repaired when damaged. Normally, the healing process is classified into two types, including extrinsic and intrinsic self-healable materials. Therefore, the aim of this work is to review the intrinsic self-healing strategy based on supramolecular interaction or non-covalent interaction and molecular recognition to obtain the improvement of mechanical properties. In this review, we introduce the main background of non-covalent interaction, which consists of the metal–ligand coordination, hydrogen bonding, π–π interaction, electrostatic interaction, dipole–dipole interaction, and host–guest interactions, respectively. From the perspective of mechanical properties, these interactions act as transient crosslinking points to both prevent and repair the broken polymer chains. For material utilization in terms of self-healing products, this knowledge can be applied and developed to increase the lifetime of the products, causing rapid healing and reducing accidents and maintenance costs. Therefore, the self-healing materials using supramolecular polymers or non-covalent interaction provides a novel strategy to enhance the mechanical properties of materials causing the extended cycling lifetime of products before replacement with a new one.

The limited efficacy shown by drug delivery systems so far prompts the development of new molecular approaches for releasing drugs in a controlled and selective manner. Light is a privileged stimulus for delivery because it can be applied in sharp spatiotemporal patterns and is orthogonal to most biological processes. Supramolecular polymers form molecular nanostructures whose robustness, versatility, and responsivity to different stimuli have generated wide interest in materials chemistry. However, their application as drug delivery vehicles has received little attention. We built supramolecular polymers based on discotic amphiphiles that self-assemble in linear nanostructures in water. They can integrate diverse amphiphilic bioligands and release them upon illumination, acutely producing functional effects under physiological conditions. We devised two strategies for drug incorporation into the photoswitchable nanofibers. In the co-assembly strategy, discotic monomers with and without conjugated bioligands were co-assembled in helicoidal supramolecular fibers. In the drug embedding approach, we integrated a potent agonist of muscarinic receptors into the discotic polymer by noncovalent stacking interactions. This ligand can be released on demand with light ex situ and in situ, rapidly activating the target receptor and triggering intracellular responses. These novel discotic supramolecular polymers can be light-driven drug carriers for small, planar, and amphiphilic drugs.

R. Brady Williamson (1933–2007) Professor R. Brady Williamson passed away on 1 August 2007, after battling cancer for several years. He was born on 19 November 1933, studied at Harvard University, obtained his bachelor degree in physics, then a doctorate degree in applied physics in 1965. He was appointed to the faculty of MIT, and in 1968 he received a joint appointment to the Civil Engineering and Material Science departments at the University of California, Berkeley. His graduate work was on the morphology of ice crystals, and he performed significant research in Materials Science at MIT in metallurgy, polymers, and cementitious materials. When he came to UCB, his interests changed profoundly. UCB previously had two professors, Raymond E. Davis and G. Earl Troxell, who had focused on fire resistance research and built fire resistance testing facilities, primarily for use as a service to industry. Williamson took over the testing facility from Troxell and dramatically expanded the scope of fire research at UCB. Apart from his work in fire resistance (one of us, V. B., was his first PhD student and did his dissertation on that subject), Prof. Williamson will perhaps be most remembered for two other contributions: characterizing the fire hazards of plastics and helping establish fire safety engineering science education as a recognized branch of science. In doing so, as evidenced by his publications, the research he directed, and especially with his advising of students, he drew upon a diverse group of disciplines, including, architecture, systems analysis, materials science, wood and polymer science, and many other engineering fields. During this time Prof. Williamson also reached out to a diverse group outside the university, including regulators, public and private sector fire investigators, insurance industry personnel and attorneys, and the fire services. He regularly brought local fire service personnel to observe fire research in the Richmond Field Station laboratory to demonstrate how fire tests are conducted and to make the connection between fire testing and the performance of building assemblies in actual fires. His focus on relating fire-test performance to real-world events was even stronger when it involved his graduate students, who were each given a unique educational experience in relating fire tests to the behavior of real fires. In the early 1970s, the US National Science Foundation first established the RANN program—Research Applied to National Needs—to encourage the use of science and engineering research to address important problems that were national in scope. This was in sharp contrast to the previous focus at NSF, which had been solely on fundamental science. A specialty area for fire research was set up by RANN in response to dismal fire safety statistics in the U.S. A number of universities initiated NSF-funded research in the area, with the largest of these research groups being at UCB. The UCB research group was organized by Prof. Williamson and featured, at its peak, close to a dozen professors from various engineering disciplines and architecture, had numerous graduate students, and became a fertile ground for fostering new fire safety researchers. In the years since the mid-1970s, more scholars have obtained PhD degrees in fire-related subjects from UC Berkeley than from any other university. Although UCB never had a formal department for teaching fire safety science and engineering, its influence on this field has been enormous, and much of it was due to Prof. Williamson's leadership and vision. Prior to Prof. Williamson's research, there had not been a concerted recognition of the potential fire hazards of plastics—especially foam plastics—when used inappropriately. Williamson studied these hazards by developing a room-sized ‘corner test’, which allowed a highly graphical representation of fire safety—or lack thereof—to be demonstrated. Largely because of this research, the U.S. building codes banned the use of foams as a building insulation material, except where testing indicated that the material was indeed safe for the intended purpose. Williamson's focus on abuses of ‘standard’ test methods led to his discovery that some fire tests were potentially highly misleading and their use in evaluating safety could lead to serious fire hazards. The most extreme example was the ASTM D 1692 test, which provided florid ‘self-extinguishing’ and ‘slow burning’ designations for plastics which, in actual fact, burned fiercely in their end-use environment. The US Federal Trade Commission investigated this test and several other test methods and brought actions against 26 plastics manufacturers, American Society for Testing and Materials, and The Society of the Plastics Industry, Inc. in 1973. Prof. Williamson served as FTC's technical consultant in this matter and was pivotal in establishing a settlement with the plastics industry. The settlement, in addition to eliminating misleading test methods, also fostered fire safety science research because one of its terms was that the industry would fund what became known as the Products Research Committee. This ad hoc entity, which existed during the period 1974–1979, funded several dozen industry associates to do research at the National Bureau of Standards (now, NIST) and also funded several dozen research projects on plastics hazards at various research institutions and universities. When added to the existing NSF and NIST programs, the PRC work helped make the late-1970s the high-water mark of concerted fire safety science research in the U.S., a level that has not subsequently been exceeded. For this, we can thank Brady Williamson. Williamson became Professor Emeritus and a Professor in the Graduate school at Berkeley in 2001, and he remained an active and enthusiastic researcher and fire safety consultant until his death. He is survived by his wife Dr Nancy J. Brown Williamson, a well-known atmospheric sciences and combustion researcher, and five children. Brady will be fondly remembered by the numerous fire researchers who have interacted with him and found him a source of inspiration. Indeed, he was a rare professor whose most outstanding contribution was conveying to his students a boundless enthusiasm for fire safety engineering science and a deep conviction in the importance of this field as a true branch of science. ‘Outside the box’ is a perhaps over-used term, but Brady always encouraged his students and colleagues to work outside the box when solving problems and the results were invariably interesting, sometimes thrilling, and always worthy of serious consideration. Surprising though it may be to some of our younger colleagues, prior to the 1970s, when the activities described above took place, there was little appreciation of fire safety as a field worthy of consideration as a true scientific discipline. Fire protection engineering had already existed for many decades, but its focus was almost exclusively on the application of codes and standards, with little interest in research or scientific underpinnings. Prof. Williamson along with the late Prof. Howard Emmons were the two most prominent advocates for science in the fire safety profession, leading to today's situation, where fire safety science and fire protection engineering overlap significantly and fire protection engineering practitioners practice a discipline that has become greatly more science based.

Supramolecular polymeric assemblies of π-conjugated molecules possessing phenylisoxazoles

Supramolecular polymers are fascinating materials due to their strikingly self-healing capabilities empowered by reversible bonds. However, due to the lack of knowledge about the molecular structure evolution at the fractured interfaces, there is no existing theory to explain and predict the diverse healing times of different supramolecular materials observed in experiments. Here, we systematically study the self-adhesion of both unentangled and entangled supramolecular polymer networks through molecular simulations. We find that the recovery of macroscopic interfacial strength almost linearly depends on the microscopic molecular formations at fractured interfaces of supramolecular polymers, including reversible bonds and entanglements (entangled systems only). More importantly, we place the healing time into the context of intrinsic relaxation timescales of supramolecular polymer networks. It is found that the intrinsic sticky Rouse time features the self-adhesion process of all fractured supramolecular polymers, representing the full recovery of interfacial strength. At this critical timescale, two things happened to guarantee the full recovery of fractured systems: (i) polymer chains have diffused across the fractured interface with a displacement comparable to their sizes; (ii) the crossed stickers and polymer chains have updated their reversible bonds and entanglements (entangled systems only), respectively. The clear molecular description and suggested characteristic self-adhesion time will help the molecular design of supramolecular polymers.

Dynamers are defined as constitutional dynamic polymers, i.e. polymeric entities whose monomeric components are linked through reversible connections and have therefore the capacity to modify their constitution by exchange and reshuffling of their components. They may be either of supramolecular or molecular nature depending on whether the connections are non-covalent interactions or reversible covalent bonds. They are formed respectively either by polyassociation with interactional recognition or by polycondensation with functional recognition between the connecting subunits. Both types are illustrated by specific examples implementing hydrogen bonding on one hand and formation of imine-type bonds on the other. The dynamic properties confer to dynamers the ability to undergo adaptation and driven evolution under the effect of external chemical or physical triggers. Dynamers thus are constitutional dynamic materials resulting from the application of the principles of constitutional dynamic chemistry to polymer science.

Recent advances in DNA nanotechnology led to the development of biocompatible functional materials targeting different applications, including delivery, precise scaffolding, computation, etc. However, a standard toolbox of building blocks used by chemists is largely limited to canonical nucleobases. To further develop the functional potential of synthetic DNA systems, the use of sequence-specific DNA-polymer conjugates has emerged as an exciting alternative approach. Herein, we demonstrate the synthesis and self-assembly properties of monodisperse DNA-pyrene polyphosphate oligomers as essential units for DNA-grafted supramolecular polymers. Such systems become increasingly important for the creation of dynamic and stimuli-responsible materials. The unique self-recognition properties of oligonucleotides laid the foundation of modern DNA nanotechnology. Over the last two decades, man-made DNA assemblies led to the development of numerous biocompatible functional materials, including drug carriers, nanorobots, and scaffolding platforms. A standard toolbox of building blocks used by chemists in the field is largely limited to four units – A, G, C, T. To further develop the functional potential of synthetic DNA systems, the use of DNA-chromophore conjugates emerges as an exciting approach. Following our previous findings, we demonstrate herein the synthesis of the DNA-pyrene oligomers and the temperature-induced self-assembly of these conjugates into DNA-grafted supramolecular polymers. (see Figure 1). Such systems become increasingly important for the creation of dynamic and stimuli-responsible materials targeting various applications such as delivery and precise scaffolding.

Unlike conventional polymers, in which monomers are reacted to form strong covalent connections, supramolecular polymers are formed by linking together monomers via weaker, non-covalent interactions such as H-bonds, ion-dipole interactions and so on. One very well-studied class of supramolecular polymers are based on the ureidopyrimidones, UPy’s, which dimerize via 4 strong, linear H-bonds in non-competitive solvents. Monomers for supramolecular polymerization can be made by linking together 2 or more UPy units with short covalent chains. Under dimerization conditions, the UPy’s link up to form longer polymeric chains. One of the useful attributes of such polymers is their self-healing ability. Application of heat or mechanical stress will readily break the monomers apart at the H-bonds, but, upon cooling or relief of stress, the bonds reform. The goal of this research is to see if electron transfer can be used as an alternative, more selective stimulus to break apart the UPy chains. As a first step in this direction, the use of our previously studied electroactive UPy’s, 1a and 1b, are being investigated as redox-active chain terminators. For these studies the known UPy monomer, 2, was synthesized. Viscosity measurements of solutions of 2 in 0.1 M NBu4PF6/CH2Cl2 give a critical polymerization concentration of 20 mM. Based on this, 60 mM 2 was chosen as the working concentration for initial experiments giving a solution with a specific viscosity of 3.0 mPa∙s. Upon addition of 2 mM of the ferrocene containing UPy 1a, the viscosity dropped to 1.1 mPa∙s, indicating that 1a is an effective chain terminator, decreasing the lengths of the chains which results in a decrease in the viscosity of the solution The ferrocenes were then completely oxidized to the ferrocenium form in a two compartment electrochemical cell. This caused the viscosity of the solution to increase from 1.0 to 1.7 mPa∙s, suggesting decreased effectiveness of the ferrocenium form as a chain terminator. This is consistent with poorer binding of the ferrocenium form to the bis-UPy. Importantly, reduction back to the ferrocene led to a decrease in the viscosity back to close to where it was initially. In this presentation, the results of further studies on the ability of both 1a and 1b to act as redox-responsive chain terminators for UPy-based supramolecular polymers will be reported. Figure 1

Unlike conventional polymers, in which monomers are reacted to form strong covalent connections, supramolecular polymers are formed by linking monomers via weaker, non-covalent interactions such as H-bonds, ion-dipole interactions and so on. These imbue supramolecular polymers with unique properties since the linkages are readily broken, but also easily reformed as environmental conditions change. One particularly well-studied class of supramolecular polymers are based on the ureidopyrimidones, UPy’s, which dimerize via 4 strong, linear H-bonds in non-competitive solvents. Monomers for supramolecular polymerization can be made by linking together 2 or more UPy units with short covalent chains. Under dimerization conditions, the UPy’s link up to form longer polymeric chains. One of the useful attributes of such polymers is their self-healing ability. Application of heat or mechanical stress will readily break the monomers apart at the H-bonds, but, upon cooling or relief of stress, the bonds reform. The goal of this research is to see if electron transfer can be used as an alternative, more selective stimulus to break apart the UPy chains. As a first step in this direction, we have synthesized a known UPy monomer, 1, which is expected to polymerize at concentrations above ~20 mM in CH2Cl2. This can be verified by measuring the change in specific viscosity as a function of the concentration of 1. By adding simple UPy’s as chain terminators the degree of polymerization should decrease, with a corresponding decrease in the viscosity of solution. For this work, we plan to add our previously studied electroactive UPy’s, 2a and 2b. We have previously shown oxidation breaks apart the 2a and 2b dimers at mM concentrations in CH2Cl2. Thus, upon electrochemical oxidation, 2a or 2b will no longer be able to act as chain terminators and the linked UPy 1 should reform polymer chains. This can be detected by an increase in the viscosity of solution upon oxidation. Figure 1

Understanding the role of solvent in translating molecular anisotropy to supramolecular polymers is in the early stages. A solvent's influence on the strength of different noncovalent interactions can explain anisotropic growth in some cases, but its effect on cooperative processes, particularly in mixed solvents, remains obscure. We report the self-assembly of a series of chiral perylene bisimides in water-cosolvent mixtures, and the results highlight the fascinating influence of solvent-solute interactions on supramolecular anisotropy, both chiral and morphological. The initial assembly is agnostic to solvent composition, resulting in weakly chiral, spherical nanostructures. In an extremely narrow solvent composition range, the nanospheres transform into long, prominently chiral supramolecular polymers. Further, chirality can be fully reversed by changing the good (achiral) cosolvent. We elucidate how solvent modulates specific noncovalent interactions and governs the kinetics and thermodynamics of key processes, such as spontaneous phase segregation, secondary nucleation, and cooperative growth. In the context of supramolecular polymerization, our results encourage one to steer the focus away from the physical attributes of a solvent (polarity, phase diagram, etc.) and toward the complexities of solvent-solute interactions.

Supramolecular biomaterials can recapitulate the structural and functional facets of the native extracellular matrix and react to biochemical cues, leveraging the unique attributes of noncovalent interactions, including reversibility and tunability. However, the low mechanical properties of supramolecular biomaterials can restrict their utilization in specific applications. Combining the advantages of supramolecular polymers with covalent polymers can lead to the fabrication of tailor-made biomaterials with enhanced mechanical properties/degradability. Herein, we demonstrate a synergistic coassembled self-healing gel as a multifunctional supramolecular material. As the supramolecular polymer component, we chose folic acid (vitamin B9), an important biomolecule that forms a gel comprising one-dimensional (1D) supramolecular polymers. Integrating polyvinyl alcohol (PVA) into this supramolecular gel alters its ultrastructure and augments its mechanical properties. A drastic improvement of complex modulus (G*) (∼3674 times) was observed in the folic acid-PVA gel with 15% w/v PVA (33215 Pa) compared with the folic acid gel (9.04 Pa). The coassembled hydrogels possessed self-healing and injectable/thixotropic attributes and could be printed into specific three-dimensional (3D) shapes. Synergistically, the supramolecular polymers of folic acid also improve the toughness, durability, and ductility of the PVA films. A nanocomposite of the gels with silver nanoparticles exhibited excellent catalytic efficiency and antibacterial activity. The folic acid-PVA coassembled gels and films also possessed high cytocompatibility, substantiated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live-dead assays. Taken together, the antibacterial and cell-adhesive attributes suggest potential applications of these coassembled biomaterials for tissue engineering and wound healing.

Recent years have witnessed an increasing interest in hybrid molecular systems in which the programmability of DNA hybridization is used to introduce enhanced molecular control in synthetic systems. The first examples of DNA-functionalized supramolecular polymers have been reported only recently, but have already revealed structural and functional properties that are not easily obtained in either synthetic supramolecular polymers or DNA-only based systems. In this Topical Review, we provide an overview of the various forms of additional control offered by DNA hybridization for different types of supramolecular polymers and discuss how orthogonal supramolecular interactions in these hybrid systems can give rise to emergent structural and functional properties.