Investigation of 3,3’-diindolylmethane solubility in 14 solvents from 272.45 to 324.25 K: Experimental measurement, thermodynamic analysis, and molecular simulation

The solubility of 3,3′-Diindolylmethane in 14 different solvents (272.45–324.25 K) was determined using the gravimetric method. The results show that its solubility increases with rising temperature across the studied solvent range. At 298.15 K, the solubility of 3,3′-Diindolylmethane in the solvents follows the order: 2-pentanone > ethyl acetate > methyl acetate > ethyl formate > acetonitrile > n-pentanol > n-butanol > n-propanol > ethanol > isopropanol > isopentanol > methanol > isobutanol > toluene. Five thermodynamic models were employed to correlate the experimental data, among which the modified Apelblat model provided the best fit. In addition, electrostatic potential energy surface analysis was conducted to preliminarily evaluate possible solute solvent interactions. Results from density functional theory calculations and the KAT-LSER model indicate that 3,3′-Diindolylmethane primarily acts as a hydrogen-bond donor, and its solubility is synergistically influenced by the hydrogen-bond acceptor ability, polarity, and hydrophobicity of the solvents. Furthermore, the mixing thermodynamic properties of the dissolution process were calculated using a Wilson-based model, revealing that the dissolution of 3,3′-Diindolylmethane in the studied solvents is a spontaneous, endothermic, and entropy-driven process.