Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

Abstract

ConspectusConstitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers.In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular biodynamers are commonly produced in aqueous media under mild or even physiological conditions to suit their biorelated applications.In contrast to static biopolymers emphasizing structural stability and unity by using irreversible covalent bonds, molecular biodynamers are seeking relative structural adaptability and diversity through the formation of reversible covalent bonds. Based on these considerations, molecular biodynamers are capable of reorganizing their monomers, generating, identifying, and amplifying the fittest structures in response to environmental factors. Hence, molecular biodynamers have received considerable research attention over the past decades. Accordingly, the construction of molecular biodynamers through equilibrium polymerization of nucleobase-, carbohydrate- or amino-acid-based monomers can lead to the fabrication of dynamic analogues of nucleic acids (DyNAs), polysaccharides (glycodynamers), or proteins (dynamic proteoids), respectively. In this Account, we summarize recent advances in developing different types of...

Dynamic Proteoids Generated From Dipeptide‐Based Monomers

“…We have reported that polycondensation of dialdehyde 1 with amino acid hydrazides is driven by hydrophobic interactions derived from the tricyclic core, while the hexaglyme chains endow the resulting biodynamers with water-solubility and stabilize them in aqueous media. [9] Dipeptide hydrazides 2-4 (Scheme 1a) are designed as an enhancement of one beneficial factor, such as two aromatic rings (2), two negative charges (3), and two hydroxyl groups (4). While dipeptide hydrazides 5-7 are a combination of two beneficial factors, including an aromatic ring with a positive charge (5), an aromatic ring with a hydroxyl group (6), and a positive charge with a hydroxyl group (7).…”

“…The implementation of dynamic covalent chemistry (DCC) in biopolymer science leads to the generation of molecular biodynamers, including DyNAs, glycodynamers, and dynamic proteoids, which are covalent dynamic analogues of nucleic acids, polysaccharides, or proteins, respectively. Due to the inherent nature of reversible covalent bonds and bioactive constituents, molecular biodynamers feature both dynamic character (i.e., changeable, tunable, controllable, self‐healing, and stimuli‐responsive capacities) and biorelevant properties (i.e., biocompatibility, biodegradability, biofunctionality).…”

“…Due to the inherent nature of reversible covalent bonds and bioactive constituents, molecular biodynamers feature both dynamic character (i.e., changeable, tunable, controllable, self‐healing, and stimuli‐responsive capacities) and biorelevant properties (i.e., biocompatibility, biodegradability, biofunctionality). As a consequence, they can be employed as adaptive biofunctional biomaterials . Chemists have generated various types of molecular dynamers through the reversible polymerization of nucleobase‐, carbohydrate‐, amino‐acid‐, or dipeptide‐derived monomers in aqueous media under mild or even physiological conditions to suit their bio‐related applications .…”

“…As a consequence, they can be employed as adaptive biofunctional biomaterials. [4] Chemists have generated various types of molecular dynamers through the reversible poly merization of nucleobase-, carbohydrate-, amino-acid-, or dipeptide-derived monomers in aqueous media under mild or even physiological conditions to suit their biorelated applications. [10][11][12][13] In particular, we reported the design and synthesis of a range of dynamic proteoids based on the polycondensation of different types of amino acid hydrazides with a nonbiological dialdehyde 1 (Scheme 1a), through formation of two types of reversible CN bonds, including both imine and acylhydrazone bonds.…”

Dynamic covalent bond from first principles: Diarylbibenzofuranone structural, electronic, and oxidation studies

“…[31,32] Recently, studies furthering on these and other issues are on shape memory polymers that restore contact of damaged surfaces, [33,34] multiple networks combining two or more types of dynamic bonds, [35][36][37][38][39] functional self-healing composites, [40] and also the overlap of these concepts to biomaterials, giving rise to biodynamers: dynamic analogs of DNA, protein, and carbohydrates. [41] Imato et al [42][43][44][45][46][47] achieved a unique set of conditions. Using as cross-linker diarylbibenzofuranone (DABBF), the dimer of arylbenzofuranone (ABF, analog to widely used commercial product HP-136), the polymer gel synthesized was able to undergo self-healing under mild conditions at room temperature, due to the dynamic covalent bond in its structure.…”