A Comprehensive Study on Self-Assembly and Gelation of C₁₃-Dipeptides-From Design Strategies to Functionalities

Computational and experimental methods were applied to investigate the self-assembly and gelation of C₁₃-dipeptides. A modified aggregation propensity (AP_S) was introduced to correlate the effects of side chains of amino acids on the tendency to aggregate. From the experimental results, the ranges of 0.156 < AP_S < 0.250 seemed to be a proper region for the C₁₃-dipeptides to form hydrogels, while other molecules with higher or lower AP_S were insoluble or dissociated. As observed from molecular dynamics simulations, the C₁₃-dipeptides first formed small aggregates through hydrophobic interactions and then rearranged through electrostatic attractions and hydrogen bonds for self-assembly. The C₁₃-dipeptides tended to be antiparallel packed, as shown by hydrogen bonding analyses. Experimental observations and analyses on the structures of C₁₃-dipeptide hydrogels matched the computational conclusions very well. From the five selected gelators, i.e., C₁₃-GW, C₁₃-VY, and C₁₃-WT, strong π-π stacking was observed. For C₁₃-WS, strong hydrogen bonding was found, and in C₁₃-WY, both strong π-π interactions and hydrogen bonds were found. It takes around 90 min or longer for C₁₃-dipeptides to form hydrogels, and those formed by C₁₃-WY and C₁₃-WS had weak water holding capacities, which might be due to strong intermolecular hydrogen bonding. From rheological studies, the C₁₃-dipeptides formed strong chemical gels that were stabilized by strong interactions between the molecular aggregates. These gelators exhibit the potentials to be environmentally friendly substitutes for the common functionalized peptide gelators.