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 APS were insoluble or dissociated. As observed from molecular dynamics simulations, the C₁₃-dipeptides firstly form small aggregates through hydrophobic interactions and then rearranged through electrostatic attractions and hydrogen bonds for self-assembly. The C₁₃-dipeptides tended to be anti-parallel 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 5 selected gelators, i.e. C₁₃-GW, C₁₃-VY and C₁₃-WT, strong - stacking was observed. For C₁₃-WS strong hydrogen bonding was found, and in C₁₃-WY both of strong pi-pi interactions and hydrogen bonds were found. It takes around 90 minutes 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.