Mechanism of Hydrotropic Action of Hydrotrope Sodium Cumene Sulfonate on the Solubility of Di-t-Butyl-Methane: A Molecular Dynamics Simulation Study

Hydrotropes are special class of amphiphilic molecules that have an ability to solubilize the insoluble or sparingly soluble molecules in water. To find out the mechanism of hydrotropic action of hydrotropes on hydrophobic molecules, we have carried out classical molecular dynamics simulation of hydrophobic solute di-t-butyl-methane (DTBM) and hydrotrope sodium cumene sulfonate (SCS) in water with a regime of SCS concentrations. Our study demonstrates that, above the minimum hydrotrope concentration (MHC), the self-aggregation of SCS starts, and it creates a micellar-like environment in which the hydrophobic tail part of SCS points inward while its hydrophilic sulfonate group points outward to make favorable contact with water molecules. The formation of the hydrophobic core of SCS cluster creates a hydrophobic environment where the hydrophobic DTBM molecules are encapsulated. Interestingly, the determination of average water-SCS hydrogen bonds further suggests that the aggregate formation of SCS molecules has a negligible influence on it. Moreover, the calculations of Flory-Huggins interaction parameters also reveal favorable interactions between hydrotrope SCS and solute DTBM molecules. The implications of these findings on the mechanism of hydrotrope assisted enhanced solubility of hydrophobic molecules are discussed.