Structure-Solvent Interplay in Amphiphilic Organogelators: An RSM Study based on Hansen Solubility Parameters

Low-molecular-weight organogelators (LMWGs) are still difficult to rationally design because of the intricate interactions between solvent characteristics and molecule structure that control gelation. In this work, we examine the gelation behavior of amphiphilic gelators based on carbohydrates that include both hydrophilic (derived from sugar) and hydrophobic (alkyl chain and aromatic moiety) components. By combining experimental data from a thioglycoside-based gelator with a structurally similar benzylideneprotected sugar system documented in the literature, a comparison framework was created. Both individual and interaction effects of various parameters were measured using Response Surface Methodology (RSM). According to the findings, gelation takes place within a certain Hansen parameter window that is characterized by low polarity (δP ≈ 0-6 MPa 1/2), moderate dispersion interactions (δD ≈ 15-20 MPa 1/2), and restricted hydrogen bonding capability (δH ≈ 0-6 MPa 1/2), whereas high polarity accounts for gelation inhibition. Through ANOVA analysis, we could observe that the quadratic term of chain length is highly significant (p < 0.001), demonstrating a non-linear dependency of gelation on molecular hydrophobicity, while linear solvent parameters (δD, δP, and δH) are not statistically significant (p > 0.05). Additionally, regression coefficients demonstrate a negative quadratic effect (β =-0.00825) and a positive contribution of chain length (β = 0.1469), indicating that intermediate chain lengths optimize gelation efficiency. Solvent effects, on the other hand, seem secondary but influence the gelation window, especially through interactions involving hydrogen bonds. These results show that intrinsic molecular design is the primary driver of gelation, with solvent parameters serving as boundary requirements that determine the accessible self-assembly region. In order to better understand and optimize amphiphilic gelators for hydrophobic solvent applications, this work develops a prediction framework based on descriptors.