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.

本文提出了一种全新的水凝胶因子（hydrogelator）设计范式，此类因子可响应多种迥异的刺激信号并发生尖锐相变，刺激类型涵盖氧化还原（redox）反应、主客体相互作用及pH变化。我们偶然发现，二茂铁酰基苯丙氨酸（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。相较于其他已报道的单响应及多响应凝胶因子，Fc-F的独特优势在于尺寸小巧、凝胶组分经济且分子结构极为简洁。密度泛函理论（DFT）从头算结果显示，凝胶形成的初始步骤为反平行非共价二聚化：一个轴状单体的二茂铁酰基片段通过π-π堆积相互作用，与另一单体的苯环结合，形成砖状二聚体。该堆积作用形成空腔，两个单体的羧酸基团在此通过氢键形成相互作用，进一步提升二聚体的稳定性。基于光学与电学表征的结构分析及补充DFT计算结果，我们提出了原纤维形成的分步分级组装机制。对Fc-F自组装路径的深入解析，将有助于理解更为复杂体系的凝胶化过程。我们预期，Fc-F可作为一款实用的典型模板，为后续设计新型响应特异性水凝胶剂提供参考。