Molecular Insights into Gelation of Di-Fmoc-l-Lysine in Organic Solvent–Water Mixtures

[Image: see text] Despite significant interest in molecular gels due to their intriguing structure formation through self-assembly and their stimuli-responsive behavior, our understanding of the gel formation mechanism of a low-molecular-weight gelator (LMWG) is incomplete. Here, we report a combined experimental and computational study on a LMWG, di-Fmoc-l-lysine, that has two aromatic moieties and multiple hydrogen bond donors and acceptors. Gelation in various organic solvent–water mixtures was obtained through the solvent-triggered technique. We show that an approach based on approximate cohesive energy density derived from density functional theory (DFT) calculations can capture the experimental solubility trend of LMWGs in different organic solvents. Furthermore, DFT calculations indicate parallel and helical structures to be the preferred structural motifs for gelator dimers. We believe that these motifs can potentially lead to fiber formation as observed with microscopy. Our work provides a relatively simple yet effective approach to quantify interactions between solvents and complex gelators that can help rationalize solubility and gelation behavior.