pH as a Design Tool for Low-Molecular-Weight Hydrogelators: Triggers, Structural Control, and Orthogonal Assembly

pH值作为低分子量水凝胶剂的设计工具:触发因素、结构控制和正交组装

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Abstract

Low-molecular-weight gelators (LMWGs) have attracted growing attention as versatile alternatives to conventional polymeric thickeners and gelators, owing to their ability to form three-dimensional fibrillar networks through non-covalent self-assembly and to undergo reversible sol-gel transitions in response to external stimuli. Among the various stimuli that can be exploited, pH represents a particularly attractive trigger given its direct relevance to biological and physiological environments. This review focuses on three categories of pH-responsive LMWGs that have shown notable progress over the past decade yet remain relatively underexplored in the literature. First, N-oxide-type hydrogelators are discussed, with emphasis on amide amine oxide-based surfactants and pyridine-N-oxide frameworks. The pH-dependent protonation of the N-oxide moiety modulates intermolecular hydrogen bonding, thereby governing self-assembly and gel formation. The structural versatility of these gelators enables rational tuning of aggregate morphology and confers clear pH and temperature responsiveness. Second, recent advances in phenylboronic acid-based LMWGs are highlighted. Although boronic acid derivatives have long been studied as dynamic crosslinking units in polymeric hydrogels, 3-isobutoxyphenylboronic acid was recently identified as the first example of phenylboronic acid functioning as an LMWG, in which gelation is driven primarily by hydrogen bonding and pH responsiveness is exploited for stimuli-triggered gel disruption rather than gel formation. Third, pH-responsive orthogonal self-assembly systems are reviewed. Representative examples include multicomponent hybrid hydrogels combining pH-activated LMWGs with polymer gelators for controlled drug release, pH-triggered self-sorting of two LMWGs without any polymeric component, and bio-based orthogonal hydrogels composed of a glucolipid LMWG and cellulose nanocrystals. For each system, both advantages and remaining limitations are critically assessed. Collectively, this review aims to provide a timely overview of emerging trends in pH-responsive LMWG research and to offer perspectives on the rational design of next-generation stimuli-responsive soft materials.

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