Ferrocenoyl Phenylalanine: A New Strategy Toward Supramolecular Hydrogels with Multistimuli Responsive Properties

In this paper we present a new paradigm for designing hydrogelators that exhibit sharp phase transitions in response to a series of disparate stimuli, including oxidation–reduction reactions (redox), guest–host interactions, and pH changes. We have serendipitously discovered that ferrocenoyl phenylalanine (Fc-F) monomers aggregate in water via a rapid self-assembly mechanism to form stable, multistimuli hydrogels. In comparison to other known mono- and multiresponsive gelators, Fc-F is unique because of its small size, economy of gel-forming components, and exceptionally simple molecular structure. Density functional theory (DFT) ab initio calculations suggest gel formation initially involves an antiparallel, noncovalent dimerization step wherein the ferrocenoyl moiety of one axe-like monomer conjoins with the phenyl group of the second monomer via a π–π stacking interaction to form brick-like dimers. This stacking creates a cavity in which the carboxylic acid groups of each monomer mutually interact via hydrogen bond formation, which affords additional stability to the dimer. On the basis of structural analysis via optical and electrical measurements and additional DFT calculations, we propose a possible stepwise hierachical assembly mechanism for fibril formation. Insights into the self-assembly pathway of Fc-F should prove useful for understanding gelation processes of more complex systems. We expect that Fc-F will serve as a helpful archetypical template for others to use when designing new, stimuli specific hydrogelation agents.

本研究提出了一种全新的水凝胶因子（hydrogelators）设计范式，可制备对一系列不同刺激响应并呈现尖锐相变的水凝胶，刺激类型涵盖氧化还原反应（redox）、主客体相互作用以及pH变化。我们偶然发现二茂铁酰基苯丙氨酸（ferrocenoyl phenylalanine, Fc-F）单体可通过快速自组装机制在水中聚集，形成稳定的多响应水凝胶。相较于其他已知的单响应与多响应胶凝剂，Fc-F具有尺寸小巧、凝胶形成组分简洁经济、分子结构异常简单的独特优势。密度泛函理论（Density Functional Theory, DFT）从头算结果表明，凝胶形成的初始阶段涉及反平行非共价二聚步骤：一个斧状单体的二茂铁酰基官能团通过π-π堆积相互作用，与第二个单体的苯基结合，形成砖状二聚体。该堆积作用形成一个空腔，两个单体的羧酸基团可在空腔内通过氢键形成相互作用，为二聚体提供额外的稳定性。基于光学、电学表征的结构分析以及额外的DFT计算结果，我们提出了一种可行的纤维形成分步层级组装机制。阐明Fc-F的自组装路径，将为理解更复杂体系的凝胶化过程提供重要参考。我们预期Fc-F可作为一款实用的原型模板，为其他研究者设计新型刺激特异性水凝胶胶凝剂提供借鉴。