Department of Chemistry, University of Rochester, Rochester, NY 14627, USA.
Materials Science Program, University of Rochester, Rochester, NY 14627, USA.
Soft Matter. 2022 Aug 17;18(32):5999-6008. doi: 10.1039/d2sm00713d.
Low molecular weight (LMW) supramolecular hydrogels have great potential as next-generation biomaterials for drug delivery, tissue engineering, and regenerative medicine. The design of LMW gelators is complicated by the lack of understanding regarding how the chemical structure of the gelator correlates to self-assembly potential and emergent hydrogel material properties. The fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-Phe) motif is a privileged scaffold that is prone to undergo self-assembly into self-supporting hydrogel networks. Cationic Fmoc-Phe-DAP derivatives modified with diaminopropane (DAP) at the C-terminus have been developed that self-assemble into hydrogel networks in aqueous solutions of sufficient ionic strength. We report herein the impact of side-chain halogenation on the self-assembly and hydrogelation properties of Fmoc-Phe-DAP derivatives. A systematic study of the self-assembly and hydrogelation of monohalogenated Fmoc-Phe-DAP derivatives with F, Cl, or Br atoms in the , , or positions of the phenyl side chain reveal significant differences in self-assembly and gelation potential, nanoscale assembly morphology, and hydrogel viscoelastic properties as a function of halogen identity and substitution position. These results demonstrate the profound impact that subtle changes to the chemical scaffold can have on the behavior of LMW supramolecular gelators and illustrate the ongoing difficulty of predicting the emergent self-assembly and hydrogelation behavior of LMW gelators that differ even modestly in chemical structure.
低分子量（LMW）超分子水凝胶作为下一代药物输送、组织工程和再生医学的生物材料具有巨大的潜力。由于缺乏对凝胶剂化学结构与自组装潜力和新兴水凝胶材料性能之间关系的理解，LMW 凝胶剂的设计变得复杂。芴甲氧羰基-苯丙氨酸（Fmoc-Phe）基序是一种特权支架，容易自组装成自支撑水凝胶网络。在具有足够离子强度的水溶液中，开发了在 C 末端用二氨基丙烷（DAP）修饰的带正电荷的 Fmoc-Phe-DAP 衍生物，这些衍生物可以自组装成水凝胶网络。本文报道了侧链卤化对 Fmoc-Phe-DAP 衍生物自组装和水凝胶化性质的影响。对在苯侧链的 、 或 位具有 F、Cl 或 Br 原子的单卤代 Fmoc-Phe-DAP 衍生物的自组装和水凝胶化进行了系统研究，结果表明，在卤原子的种类和取代位置的影响下，自组装和凝胶化潜力、纳米级组装形态以及水凝胶粘弹性性质存在显著差异。这些结果表明，对化学支架进行细微改变会对 LMW 超分子凝胶剂的行为产生深远影响，并说明了即使在化学结构上略有不同，预测 LMW 凝胶剂的自组装和水凝胶化行为仍然具有挑战性。
