Rationalising Supramolecular Hydrogelation of Bis-Urea-Based Gelators through a Multiscale Approach

The current approach to designing low-molecular-weight gelators relies on a laborious trial-and-error process, mainly because of the lack of an accurate description of the noncovalent interactions crucial for supramolecular gelation. In this work, we report a multiscale bottom-up approach composed of several computational techniques to unravel the key interactions in a library of synthesized bis-urea-based gelators and rationalize their experimentally observed hydrogelation performance. In addition to density functional theory calculations and molecular dynamics, the noncovalent interaction index is applied as a tool to visualise and identify the different types of noncovalent interactions. Interestingly, as well as hydrogen bonds between urea moieties, hydrogen bonds between a urea moiety and a pyridine ring were shown to play a detrimental role in the early aggregation phase. These findings enabled us to explain the hydrogelation performance observed in a library of twelve bis-urea derivatives, which were synthesized with 58-95 % yields. From this library, three compounds were discovered to effectively gel water, with the most efficient hydrogelator only requiring a concentration of 0.2 w/v%.