Supramolecular polymeric hydrogels

Review: 264 refs.

The supramolecular cross-linking of polymer chains in water has led to the development of novel hydrogel materials with dynamic behaviour and properties and a wide variety of potential applications. We present here a thorough overview of the formation of transient polymeric networks, with particular emphasis on those systems based on host-guest interactions. Aqueous supramolecular chemistry at this point of its research has allowed unlocking a toolbox for the design and fine-tuning of the properties of the hydrogels.

The bottom–up synthesis of highly complex functional materials from simple modular blocks is an intriguing area of research. Driven by the chemistry of supramolecular assembly, modules which self-assemble into intricate structures have been described. These hierarchically assembled systems extend beyond the individual molecule and rely on non-covalent interactions in a directed self-assembly process. The intrinsic properties of the materials can be modified by exploiting the dynamic and specific uni-directional interactions among the building. This also allows the building of novel supramolecular structures such as hydrogels, micelles and vesicles. These aqueous supramolecular networks belong to a novel category of soft biomaterials exhibiting attractive properties such as stimuli-responsiveness and self-healing properties derived from their dynamic behavior. These are important for a wide variety of emerging applications. In this review, the latest literature describing the formation of dynamic polymeric networks through host–guest complex formation will be summarised. These approaches carried out in the aqueous medium have unlocked a versatile toolbox for the design and fine-tuning of supramolecular self-assembled materials.

Specific noncovalent interactions that are indicative of attractive, directional intermolecular forces have always been of key interest to medicinal chemists in their search for the "glue" that holds drugs and their targets together. With the rapid increase in the number of solved biomolecular structures as well as the performance enhancement of computer hardware and software in recent years, it is now possible to give more comprehensive insight into the geometrical characteristics and energetic landscape of certain sophisticated noncovalent interactions present at the binding interface of protein receptors and small ligands based on accumulated knowledge gaining from the combination of two quite disparate but complementary approaches: crystallographic data analysis and quantum-mechanical ab initio calculation. In this perspective, we survey massive body of published works relating to structural characterization and theoretical investigation of three kinds of strong, specific, direct, enthalpy-driven intermolecular forces, including hydrogen bond, halogen bond and salt bridge, involved in the formation of protein-ligand complex architecture in order to characterize their biological functions in conferring affinity and specificity for ligand recognition by host protein. In particular, the biomedical implications of raised knowledge are discussed with respect to potential applications in rational drug design.

Reinforcing DNA Supramolecular Hydrogel with Polymeric Multiple-Unit Linker

SUMOylation – a protein post-translational modification (PTM) related to ubiquitylation – involves the reversible covalent attachment of the small ubiquitin-like modifier (SUMO) to proteins. During the conjugation and deconjugation cycle, SUMO is recognised and positioned by various enzymes through specific non-covalent interactions. This review discusses the core interactions with the SAE2 subunit of the SUMOspecific heterodimeric E1 enzyme SAE1:SAE2, the SUMO E2 enzyme UBC9 and the SUMO-specific proteases of the SENP family and USPL1. We describe the evolutionary origins of these interactions and their structural basis; moreover, as SUMO:enzyme interactions are generally similar in their overall outline to those between ubiquitin and its specific enzymes, we highlight these similarities, as well as the differences. All of the mentioned interactions use a similar surface on SUMO, which is distinct from the groove that binds SUMO-interacting motifs (SIMs), meaning that while the enzyme interactions are mutually exclusive, each is compatible with simultaneous SIM binding. This review is accompanied by another in the same issue that focuses on interactions with SUMO E3 ligases and downstream effectors of SUMOylation, together providing comprehensive coverage of the non-covalent interactions formed by SUMO proteins.

In this thesis, original applications of the Density Overlap Region Indicator (DORI), a density dependent bonding descriptor capable of simultaneously capturing covalent and noncovalent interactions, are discussed. The use of scalar fields, such as DORI, were generally restricted to visualizing bonding situations in static gas phase molecules. Here, DORI is pushed out of its comfort zone and used to probe systems prone to electronic and geometric fluctuations, or those constrained by their condensed phase environments. The applications to challenging chemical systems highlighted within demonstrate the capabilities of DORI as a formidable tool that can be beneficial in many facets of chemistry. Molecules in the excited state are difficult to analyze using popular bonding descriptors, primarily because the required information (orbitals) are not given by standard computational methodologies. DORI, which relies exclusively on the electron density and its derivatives, overcomes previous limitations and permits the characterization of excitation processes (charge transfer, excimer, Rydberg, ...) through visual and numerical signatures. Using DORI, the evolution of covalent and non-covalent excited state interactions where used to rationalize photoemission in BODIPY-derivatives. Certain BODIPY substituents formnon-covalent intramolecular interactions in the excited state, which are crucial for stabilizing the Sx - S0 intersection and prompting nonradiative decay. This application demonstrates that DORI is ideally suited for characterizing excited state phenomena. Dynamical fluctuations represent another domain beyond the standard usage of bonding descriptors. Highly fluxionalmolecules, such as molecular machines or proteins, have complex multi-dimensional conformational spaces that are generally explored using a handful of geometrical collective variables (bond lengths, angles, etc.), or dimensionality reduction algorithms. DORIâ s covalent and non-covalent patterns are exploited as alternative sets of descriptors, which are simpler than geometrical parameters because electronic and geometrical fluctuations can be captured by a single-dimensional variable. DORI is also synergistically used alongside dimensionality reduction algorithms to reveal enhanced descriptions of the conformational spaces of a molecular rotor and a photoswitch. Thus, cost effective bonding descriptors are well adapted and beneficial in analyzing electronic and geometrical fluctuations requiring extended mapping of conformational spaces. Finally, DORI allows for simultaneous visualization of covalent and non-covalent interactions, and is thus particularly suited to investigate their interplay, notably present in dense environments of high-pressure crystals and in protein-ligand cavities. Using actual experimental electron densities of an organic crystal, DORI exposes pressure-induced disruptions of intramolecular delocalization and identifies the directional non-covalent interactions that cause these perturbations. Similarly, the scalar field pinpoints the specific non-covalent proteinligand interactions which modify the covalent regions of the ligand and facilitate the reactive process. Overall, the examples presented in this thesis demonstrate the versatility of DORI in translating complex chemical behavior into intuitive representations, greatly extending the range of applications that benefit from visual bonding descriptors.

Growth factor activity is localized within the natural extracellular matrix (ECM) by specific non-covalent interactions with core ECM biomolecules, such as proteins and proteoglycans. Recently, these interactions have inspired us and others to develop synthetic biomaterials that can non-covalently regulate growth factor activity for tissue engineering applications. For example, biomaterials covalently or non-covalently modified with heparin glycosaminoglycans can augment growth factor release strategies. In addition, recent studies demonstrate that biomaterials modified with heparin-binding peptides can sequester cell-secreted heparin proteoglycans and, in turn, sequester growth factors and regulate stem cell behavior. Another set of studies show that modular versions of growth factor molecules can be designed to interact with specific components of natural and synthetic ECMs, including collagen and hydroxyapatite. In addition, layer-by-layer assemblies of GAGs and other natural polyelectrolytes retain growth factors at a cell-material interface via specific non-covalent interactions. This review will detail the various bioinspired strategies being used to non-covalently localize growth factor activity within biomaterials, and will highlight in vivo examples of the efficacy of these materials to promote tissue regeneration.

Detection of specific noncovalent interaction of peptide with DNA by MALDI-TOF

We propose a self-consistent molecular theory of conformational properties of flexible polymers in solution. It is applied to the collapse of a hydrophobic polymer chain in water, and can be readily generalized to any polymer-solvent system (e.g., copolymers with high complexity). We stress the potential of this method for a variety of problems, such as protein folding.

This paper is devoted to a mathematical model of a chaotic dynamics of a polymer chain in water. The model consists of a parabolic equation that is derived according to the self-consistent field approach. This model is employed for the numerical simulation of a biological sensor that detects the presence of a specific protein in the fluid. The sensor is absolutely simple and seems to be new. Besides that, the suggested equation is interesting from the mathematical point of view. It includes a non-local operator of integration not only over the past time interval as in the problems with memory but also over the future time interval. It is unusual for parabolic problems.

Despite the interaction between polyphenols and polysaccharides in food products, their specific non-covalent interactions and effects on macrophage functions are not well understood. Therefore, the interaction and mechanism of purified lotus root polysaccharide (PLRP) with polyphenols, and the regulatory mechanisms of the PLRP-polyphenol complex on the macrophage functionals were studied. By combining ferulic acid (FA) and chlorogenic acid (CHA) with PLRP, the complexes PLRP-FA, PLRP-CHA and the physical mixtures PLRP&FA and PLRP&CHA were prepared, where their mass ratios of polyphenols to PLRP were 143.97 and 601.67 mg g-1. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Ultraviolet (UV), and Transmission electron microscopy (TEM) analyses confirmed that PLRP and polyphenols may engage in non-covalent interactions via hydrogen bonds and hydrophobic interactions. We confirmed that non-covalent interactions led to high molecular weight, dense complexes. Both PLRP and its polyphenol complexes stimulated NO production by macrophages to varying degrees without exacerbating lipopolysaccharide-induced inflammatory responses. PLRP and PLRP-polyphenol complexes repaired cells with impaired antioxidant capacity, depending on doses. Those results indicated that after the combination of lotus root polysaccharide and polyphenol, the molecular weight and conformation changed significantly, which influenced the biological activity. RNA-seq analysis suggested that the regulatory mechanism of PLRP-polyphenol complex in macrophages may mainly involve oxidative phosphorylation, FoxO, TNF, IL-17, MAPK, NF-kappa B, and other signaling pathways. This study investigated the effects of polyphenol binding on the physicochemical characteristics and functional activities of polysaccharides, which provided references for the development of polysaccharide functional products and the control of nutritional quality.

The supramolecular self-assembly of polymer chains by specific, directional, and dynamic non-covalent interactions, including hydrogen bonds, host-guest interactions, and amphiphilic associations, has led to the development of novel polymeric supramolecular materials (PSMs). PSMs in the form of micelles, fibers, and hydrogels, which exhibit unique chemical, physical, and biological properties, have been fabricated and shown to have great potential in biomedical applications. This review focuses on recent advances in the construction, as well as biomedical applications, of PSMs, such as in drug delivery matrices, tissue engineering scaffolds, and biosensors. Keywords: Biosensor, drug delivery, supramolecular, tissue engineering.

It is our great pleasure as Guest Editors of the journal ‘Current Organic Chemistry’ to present you with a ‘hot topic issue’ on supramolecular chemistry, 'chemistry beyond the molecule'. Supramolecular chemistry examines the weaker interactions that hold groups of molecules together, no bonds that hold atoms together in a molecule [1]. The weaker interactions provide control, which allows the development of functional molecular and supramoleclar devices, defined as structurally organized and functionally integrated systems built from suitably designed molecular components performing a given action and endowed with the structural features required for assembly into an organized supramolecular architecture [1, 2]. The purpose of this special issue is to underscore the concepts and techniques of modern supramolecular chemistry, demonstrating how these paradigms evolve into nanometric size systems, nanotechnology, and materials science. The supramolecular self-assembly of polymer chains by specific, directional, and dynamic non-covalent interactions, including H-bond interaction, host-guest interaction, and amphiphilic association, has led to the development of novel polymeric supramolecular materials (PSMs). The first review of this issue is written by Drs. Liao, Zhang and their colleagues, who summarized the main strategies for the construction of PSMs and their applications in biomedical fields, such as drug delivery, tissues engineering, and biosensors. As they mentioned, it is still a challenge to finely control the process of selfassembly to produce PSMs with well-controlled properties. In the following article, Dr. Liang and his colleagues summarized recent advances in nanopore DNA sequencing, DNA Sequencing by Recognition, evolution of recognition molecules applied in Sequencing by Recognition, and discussed the opportunities and challenges in this rapidly growing field. Proposed interactions between recognition molecules and DNA bases in the nanopore should be investigated in detail by supramolecular chemist to help understand Sequencing by Recognition technique. In the third article of this issue, Dr. Fang and his colleagues highlighted the recent advances in the development of electronic sensors, in which the active conducting/semiconducting materials are incorporated with specific supramolecular receptors. Depending on the nature of the active conducting layer, these devices can be categorized into carbon materials-based sensors and organic semiconductor-based sensors. As they noted, recent groundbreaking developments of conductive Covalent Organic Frameworks (COFs)/ Metal Organic Frameworks (MOFs), supramolecular host-incorporated MOFs, and surface grown COFs have paved the way to the next generation electronic sensing materials. In the forth article of this issue, Dr. Wang and his colleagues summarized the recent research progress in the field of Organic Molecular Cages (OMCs) from synthesis, functionalization, and applications aspects. Since the gained specific surface areas are now comparable to those of MOFs and COFs, OMCs will definitely play a distinct role in the future of porous materials. In the fifth review, Dr. Zhang and his colleagues outlined the common design strategies and synthetic approaches used for the preparation of Ionic MOFs (I-MOFs), which are a unique type of MOFs that are composed of charged (positive or negative) frameworks containing mobile or loosely bound extra-framework counter ions. Enhanced gas adsorption and small molecules uptake due to the ionic feature of I-MOFs was discussed in detail. Recently reported potential applications for IMOFs in catalysis, optics, and photonics were also addressed. In the sixth article, Dr. Gassensmith and his colleagues discussed the chemistry within confined spaces. It was noted that the field is moving more toward solid-state and naturally porous systems in the short-term future; in particular, catalysis and reactivity within porous solids will likely dominate the landscape. Self-healing or self-repairing materials are a kind of ‘smart material’ that are able to repair their damage caused by mechanical force, and represent the forefront developments of 21st century in materials chemistry and engineering. In the seventh review, Dr. Liu and his colleagues described a few excellent examples of self-healing supramolecular polymers based on host–guest interactions, and discussed their advantages and versatility. In the last article of this issue, Drs. Yuan, and Liang reviewed the recent advances in the development and application of amphiphilic photomicroreactors with “soft” cavities in terms of supramolecular chemistry. In the limited space of the article, attention was focused primarily upon the microreactors bearing “soft” cavities including micelles, vesicles, polymers and dendrimers. Contrary to the “hard” cavities that usually show specific selectivity to the guests, “soft” cavities have a large applicability towards the substrates, since the size, shape and other properties of the “soft” cavities can be easily altered by such conditions as temperature, solvent, light or by the guest molecules themselves. We would like to sincerely thank all authors for their excellent work, and thank all reviewers for their scrutiny of manuscripts published in this special issue. It was a great opportunity for us to cooperate with researchers involved in this special issue. We hope that readers will enjoy this issue, obtain useful information, and be inspired with new ideas for future research on molecular recognition and supramolecular devices.

Noncovalent interactions provide a flexible method of engineering various chemical entities with tailored properties. Specific noncovalent interactions between functionalized small molecules, macromolecules or both of them bearing complementary binding sites can be used to engineer supramolecular complexes that display unique structure and properties of polymers, which can be defined as supramolecularly engineered polymers. Due to their dynamic tunable structures and interesting physical/chemical properties, supramolecularly engineered polymers have recently received more and more attention from both academia and industry. In this feature article, we summarize the recent progress in the self-assembly of supramolecularly engineered polymers as well as their biomedical applications. In view of different molecular building units, the supramolecularly engineered polymers can be classified into the following three major types: supramolecularly engineered polymers built by small molecules, supramolecularly engineered polymers built by small molecules and macromolecules, and supramolecularly engineered polymers built by macromolecules, which possess distinct morphologies, definite architectures and specific functions. Owing to the reversible nature of the noncovalent interactions, the supramolecularly engineered polymers have exhibited unique features or advantages in molecular self-assembly, for example, facile preparation and functionalization, controllable morphologies and structures, dynamic self-assembly processes, adjustable performance, and so on. Furthermore, the self-assembled supramolecular structures hold great potential as promising candidates in various biomedical fields, including bioimaging, drug delivery, gene transfection, protein delivery, regenerative medicine and tissue engineering. Such developments in the self-assembly of supramolecularly engineered polymers and their biomedical applications greatly promote the interdiscipline research among supramolecular chemistry, polymer materials, biomedicine, nano-science and technology.