Effectiveness of cell adhesive additives in different supramolecular polymers

Supramolecular motifs in elastomeric biomaterials facilitate the modular incorporation of additives with corresponding motifs. The influence of the elastomeric supramolecular base polymer on the presentation of additives has been sparsely examined, limiting the knowledge of transferability of effective functionalization between polymers. Here it was investigated if the polymer backbone and the additive influence biomaterial modification in two different types of hydrogen bonding supramolecular systems, that is, based on ureido-pyrimidinone or bis-urea units. Two different cell-adhesive additives, that is, catechol or cyclic RGD, were incorporated into different elastomeric polymers, that is, polycaprolactone, priplast or polycarbonate. The additive effectiveness was evaluated with three different cell types. AFM measurements showed modest alterations on nano-scale assembly in ureido-pyrimidinone materials modified with additives. On the contrary, additive addition was highly intrusive in bis-urea materials. Detailed cell adhesive studies revealed additive effectiveness varied between base polymers and the supramolecular platform, with bis-urea materials more potently affecting cell behavior. This research highlights that additive transposition might not always be as evident. Therefore, additive effectiveness requires re-evaluation in supramolecular biomaterials when altering the polymer backbone to suit the biomaterial application.     

Elucidating dynamic behavior of synthetic supramolecular polymers in water by hydrogen/deuterium exchange mass spectrometry

A comprehensive understanding of the structure, self-assembly mechanism, and dynamics of one-dimensional supramolecular polymers in water is essential for their application as biomaterials. Although a plethora of techniques are available to study the first two properties, there is a paucity in possibilities to study dynamic exchange of monomers between supramolecular polymers in solution. We recently introduced hydrogen/deuterium exchange mass spectrometry (HDX-MS) to characterize the dynamic nature of synthetic supramolecular polymers with only a minimal perturbation of the chemical structure. To further expand the application of this powerful technique some essential experimental aspects have been reaffirmed and the technique has been applied to a diverse library of assemblies. HDX-MS is widely applicable if there are exchangeable hydrogen atoms protected from direct contact with the solvent and if the monomer concentration is sufficiently high to ensure the presence of supramolecular polymers during dilution. In addition, we demonstrate that the kinetic behavior as probed by HDX-MS is influenced by the internal order within the supramolecular polymers and by the self-assembly mechanism.     

Tunable Multiple Morphological Transformation of Supramolecular Hyperbranched Polymers Based on an A2B6-type POSS Monomer

The growing demands of supramolecular hyperbranched polymers integrating noncovalent interaction and unique topological structure merits had received considerable interest in the fabrication of novel materials for advanced applications.Herein,we prepared A2B6-type POSS-containing supramolecular hyperbranched polymers with multiple morphologies including lamellar-like,branched,hollow,core-shell and porous spherical structures through regulating self-assembling monomer concentrations and solvent polarities.The incorporation of appropriate emulative guest molecules would further trigger morphological transformations (such as vesicles and spherical micelles) by synergistic effects of unique POSS aggregation ability,supramolecular complexations and hydrophilic-hydrophobic interactions.Thus,this facile and universal strategy may enable a modular nanofabrication of supramolecular hyperbranched polymers with diversiform topological structure and sophisticated multifunctionality for their potential applications.     

Modular synthesis of supramolecular ureidopyrimidinone-peptide conjugates using an oxime ligation strategy

A convenient method to prepare supramolecular bioconjugates in a facile and scalable manner is by a modular approach, whereby self-assembling units and peptides are coupled using oxime chemistry. We here report syntheses of bioactive ureidopyrimidinone-based peptide conjugates, and their resultant self-assembly into fibrous structures.     

氢键型超分子聚合物的合成、结构与应用

氢键型超分子聚合物是重复单元经氢键相互作用连接在一起的阵列,可生成液晶态,多样化的几何形状和高有序的凝聚态结构。氢键的温度敏感性和可逆性导致氢键型超分子聚合物具有和传统共价键结合的聚合物不同的性能。氢键型超分子聚合物是一类动态的智能型功能高分子材料,可在光化学、光电转换、非线性光学、弹性体、水凝胶和生物医用工程等领域广泛应用。本文从氢键型超分子聚合物化学(合成与机理)、物理(结构与性能)和工程(加工与应用)三个方面介绍氢键型超分子聚合物的进展。     

Supramolecular polymers as dynamic multicomponent cellular uptake carriers

Supramolecular synthesis represents a flexible approach to the generation of dynamic multicomponent materials with tunable properties. Here, cellular uptake systems based on dynamic supramolecular copolymers have been developed using a combination of differently functionalized discotic molecules. Discotics featuring peripheral amine functionalities that endow the supramolecular polymer with cellular uptake capabilities were readily synthesized. This enabled the uptake of otherwise cell-impermeable discotics via cotransport as a function of supramolecular coassembly. Dynamic multicomponent and multifunctional supramolecular polymers represent a novel and unique platform for modular cellular uptake systems.     

Mechanically Robust Electrospun Hydrogel Scaffolds Crosslinked via Supramolecular Interactions

One of the major challenges in the processing of hydrogels based on poly(ethylene glycol) (PEG) is to create mechanically robust electrospun hydrogel scaffolds without chemical crosslinking postprocessing. In this study, this is achieved by the introduction of physical crosslinks in the form of supramolecular hydrogen bonding ureido‐pyrimidinone (UPy) moieties, resulting in chain‐extended UPy‐PEG polymers (CE‐UPy‐PEG) that can be electrospun from organic solvent. The resultant fibrous meshes are swollen in contact with water and form mechanically stable, elastic hydrogels, while the fibrous morphology remains intact. Mixing up to 30 wt% gelatin with these CE‐UPy‐PEG polymers introduce bioactivity into these scaffolds, without affecting the mechanical properties. Manipulating the electrospinning parameters results in meshes with either small or large fiber diameters, i.e., 0.63 ± 0.36 and 2.14 ± 0.63 µm, respectively. In that order, these meshes provide support for renal epithelial monolayer formation or a niche for the culture of cardiac progenitor cells.     

Physical organic chemistry of supramolecular polymers

Unlike the case of traditional covalent polymers, the entanglements that determine properties of supramolecular polymers are defined by very specific, intermolecular interactions. Recent work using modular molecular platforms to probe the mechanisms underlying mechanical response of supramolecular polymers is reviewed. The contributions of supramolecular kinetics, thermodynamics, and conformational flexibility to supramolecular polymer properties in solutions of discrete polymers, in networks, and at interfaces, are described. Molecule-to-material relationships are established through methods reminiscent of classic physical organic chemistry.     

Diverse Role of Solvents in Controlling Supramolecular Chirality

Supramolecular self-assembly stands for the spontaneous aggregation of small organic compounds or polymers into ordered structures at any scale. When being induced by inherent molecular chiral centers or ambient asymmetric factors, asymmetric spatial arrangement between building units shall occur, which is defined as supramolecular chirality. Except for molecular design, utilizing external stimulus factors to tune supramolecular chirality is a promising approach. In this Concept article, we particularly discuss the important role of solvents in manipulating the chirality of self-assembled systems. The impact of solvents on the chirality is generally based on three properties of solvents, i.e., chirality, polarity, and active coassembly with building blocks. Molecular self-assembly in chiral solvents could undergo the chirality transfer, exhibiting a chiral induction effect. Solvent polarity often determines intermolecular orientation. As a consequence, those building blocks with both polar and apolar segments might change their chirality depending on the solvent polarity. We elaborate the active participation of solvent molecules into ordered structures together with building blocks, where solvents and building blocks exhibit a coassembly manner. By specific treatments such as heating and cooling, solvents could be released or re-entrapped, allowing a smart control over supramolecular chirality. The solvent effect in manipulating two-dimensional chiral self-assemblies is then discussed. The perspective and future development in this research field are presented at last.     

The Assembly of Supramolecular Boxes and Coordination Polymers Based on Bis‐Zinc‐Salphen Building Blocks

We report the assembly of supramolecular boxes and coordination polymers based on a rigid bis‐zinc(II)‐salphen complex and various ditopic nitrogen ligands. The use of the bis‐zinc(II)‐salphen building block in combination with small ditopic nitrogen ligands gave organic coordination polymers both in solution as well as in the solid state. Molecular modeling shows that supramolecular boxes with small internal cavities can be formed. However, the inability to accommodate solvent molecules (such as toluene) in these cavities explains why coordination polymers are prevailing over well‐defined boxes, as it would lead to an energetically unfavorable vacuum. In contrast, for relatively longer ditopic nitrogen ligands, we observed the selective formation of supramolecular box assemblies in all cases studied. The approach can be easily extended to chiral analogues by using chiral ditopic nitrogen ligands.     

Deep Eutectic Supramolecular Polymers: Bulk Supramolecular Materials

Application of new strategies for supramolecular self‐assembly can significantly impact the properties and/or functions of supramolecular polymers. To realize a facial strategy for the development of solvent‐free supramolecular polymers in bulk, “deep eutectic solvents” were employed. Cyclodextrins and natural acids were used to prepare deep eutectic supramolecular polymers ( DESP s). Deep eutectic solvents have special characteristics that endow DESP s with unique macroscopic properties and excellent processability. DESP s exhibit supramolecular adhesion and temperature‐dependent behavior originating from the combined effects of deep eutectic solvents and supramolecular polymerization. Because DESP s are solvent‐free and display interesting macroscopic properties, they have potential as new adaptive materials.     

Modular Columnar Supramolecular Polymers as Scaffolds for Biomedical Applications

Self‐assembly of discotic molecules into supramolecular polymers offers a flexible approach for the generation of multicomponent one‐dimensional columnar architectures with tuneable biomedical properties. Decoration with ligands induces specific binding of the self‐assembled scaffold to biological targets. The modular design allows the easy co‐assembly of different discotics for the generation of probes for targeted imaging and cellular targeting with adjustable ligand density and composition.     

Recent Progress in Azobenzene-Based Supramolecular Materials and Applications

Azobenzene-containing small molecules and polymers are functional photoswitchable molecules to form supramolecular nanomaterials for various applications. Recently, supramolecular nanomaterials have received enormous attention in material science because of their simple bottom-up synthesis approach, understandable mechanisms and structural features, and batch-to-batch reproducibility. Azobenzene is a light-responsive functional moiety in the molecular design of small molecules and polymers and is used to switch the photophysical properties of supramolecular nanomaterials. Herein, we review the latest literature on supramolecular nano- and micro-materials formed from azobenzene-containing small molecules and polymers through the combinatorial effect of weak molecular interactions. Different classes including complex coacervates, host-guest systems, co-assembled, and self-assembled supramolecular materials, where azobenzene is an essential moiety in small molecules, and photophysical properties are discussed. Afterward, azobenzene-containing polymers-based supramolecular photoresponsive materials formed through the host-guest approach, polymerization-induced self-assembly, and post-polymerization assembly techniques are highlighted. In addition to this, the applications of photoswitchable supramolecular materials in pH sensing, and CO₂ capture are presented. In the end, the conclusion and future perspective of azobenzene-based supramolecular materials for molecular assembly design, and applications are given.     

Influence of thermodynamic conditions of polymerization on supramolecular and molecular structure of the polymers

The problems of the formation of the supramolecular and molecular structure of polymers are considered. Based on kinetic investigations of trioxane polymerization, the thermodynamic approach to the problem of regulating the supramolecular and molecular structure of polymers during synthesis is formulated. A method for producing polymers with the given supramolecular structure is suggested. It is noted that the application of this method allows one to regulate the structure during the synthesis of three-dimensional cross-linked polymer systems as single-component, filled, reinforced, and other composite materials.     

Synthesis and single-molecule studies of a well-defined biomimetic modular multidomain polymer using a peptidomimetic beta-sheet module

In the pursuit of advanced biomaterials with combined strength, toughness, and elasticity, a new class of well-defined modular polymers has been synthesized, and their nanomechanical properties have been studied using atomic force microscopy. These polymers are based on a peptidomimetic beta-sheet-based double-closed loop (DCL) module, which was designed to overcome the limitation of the modular polymers we reported previously (J. Am. Chem. Soc. 2004, 126, 2059). Single-molecule force-extension experiments revealed the sequential unfolding of these modules as the polymer is stretched, resulting in more regular sawtooth-patterned curves similar to those seen in titin and other biopolymers. The single-molecule data agreed well with computer modeling, which suggested that hydrogen bonding and pi-stacking are both involved in the formation of small DCL clusters along the polymer chain.     

Mechanistic Study of the Solvent-Dependent Formation of Extended and Stacked Supramolecular Polymers Composed of Bis(imidazolylporphyrinatozinc) Molecules

Bis(imidazolylporphyrinatozinc) molecules linked through a 1,3-butadiynylene moiety respond to the solvents they are dissolved in to afford exclusively extended (E) or stacked (S) supramolecular polymers. This system is expected to be a solvation/desolvation indicator. However, the principles underlying the solvent-dependent formation of the two types of polymers and the mechanism of the transformation between them are unclear. The formation of the polymers is considered to depend on the two types of complementary coordination bonds that can be formed and the π–π interactions between the porphyrins. In this study, the contributions and solvent dependence of both the coordination bonds and the π–π interactions have been investigated. The results clearly indicate that the coordination bonds are weakly or little solvent-dependent, and that the π–π interactions function effectively only in the inner porphyrins of the S-polymer and are strongly solvent-dependent. Thermodynamic analysis revealed that the formation of the E- or S-polymer in solution is determined by the total energies and the type of solvent used. The transformation of the E- to S-polymer was investigated by gel permeation chromatography. The kinetics of the transformation were also determined. The role of the terminal imidazolylporphyrinatozinc moieties was also investigated: The results indicate that the transformation from the E- to S-polymer occurs by an exchange mechanism between the polymers, induced by attack of terminal free imidazolyl groups on a polymer to zinc porphyrins on other polymers.     

Non-covalent side-chain polymers: design principles, functionalization strategies, and perspectives

Side-chain functionalized polymers have a profound impact on complex materials synthesis with a variety of applications ranging from liquid crystalline and electro-optical materials to drug delivery systems. In the last decade, the use of self-assembly towards the synthesis of side-chain functionalized polymers has been investigated extensively as a result of its modular character and ease of synthesis. This tutorial review describes recent advances in the literature and establishes basic design principles and synthetic approaches towards the fabrication of supramolecular materials that are based on side-chain functionalized polymers.     

A supramolecular approach to the preparation of charge-tunable dendritic polycations for efficient gene delivery

A facile supramolecular approach for the preparation of charge-tunable dendritic polycations, by a combination of the multi-functionality of dendritic polymers with the dynamic-tunable ability of supramolecular polymers, has been developed. It provides a new strategy for designing and developing efficient gene vectors via noncovalent interactions.     

Mixing Biomimetic Heterodimers of Nucleopeptides to Generate Biocompatible and Biostable Supramolecular Hydrogels

As a new class of biomaterials, most supramolecular hydrogels formed by small peptides require the attachment of long alkyl chains, multiple aromatic groups, or strong electrostatic interactions. Based on the fact that the most abundant protein assemblies in nature are dimeric, we select short peptide sequences from the interface of a heterodimer of proteins with known crystal structure to conjugate with nucleobases to form nucleopeptides. Being driven mainly by hydrogen bonds, the nucleopeptides self‐assemble to form nanofibers, which results in supramolecular hydrogels upon simple mixing of two distinct nucleopeptides in water. Moreover, besides being biocompatible to mammalian cells, the heterodimer of the nucleopeptides exhibit excellent proteolytic resistance against proteinase K. This work illustrates a new and rational approach to create soft biomaterials by a supramolecular hydrogelation triggered by mixing heterodimeric nucleopeptides.     

Aqueous chromatography system using temperature-responsive polymer-modified stationary phases

Extensive research has been carried out on functional polymers which are currently playing important roles in various fields such as medicine and engineering. Such functional polymers which respond to various kinds of stimuli are termed 'intelligent materials'. Poly(N-isopropylacrylamide) (PNIPAAm), a temperature-responsive polymer, was utilized as a chromatography column matrix modifier for a novel chromatographic approach in which only aqueous media are used as a mobile phase. The ability of the developed temperature-responsive chromatography system to separate solutes without using an organic solvent is advantageous from the point of view of maintaining the structure and activity of bioactive compounds. Recently, we designed and synthesized a new pH- and temperature-responsive copolymer as a representative of such environment-responsive polymers and grafted it onto aminopropyl silica beads. The products were evaluated as HPLC packing materials for separation systems based on a new concept, according to which the properties of the stationary phase surface are altered by external stimuli such as pH and temperature. This chromatography system utilizing the PNIPAAm copolymer is very useful for the separation of bioactive substances, such as proteins and peptides, because separation in the aqueous mobile phase is controlled solely by changing the temperature. This analytical system reduces organic waste because no organic solvent is used to separate the solutes and can therefore be classified as environmentally friendly. Future medical and pharmaceutical applications are expected.