In practical applications, surfactant solutions are mostly used in mixtures of nonionic and ionic surfactants because they have improved characteristics compared to those of single surfactant solutions. By adjusting the composition of the micelles and the pH value, the solubilization of solutes can be enhanced. Nevertheless, the partitioning of solutes between nonionic/ionic mixed micelles and the aqueous phase is studied to a much lesser extent than for single surfactant solutions. Theoretical methods to predict partition equilibria in mixed micelles are of interest for screening studies. For those, the composition of the mixed micelle has to be known. Here we investigate mixtures of TX-114 (Triton X-114), Brij35 (C12E23), SDS (sodium dodecyl sulfate), and CTAB (cetyltrimethylammonium bromide). First, to investigate the surfactant compositions in the micelles, molecular dynamics (MD) self-assembly simulations were applied. Thereafter, the predictive COSMO-RS model, which applies the pseudophase approach, and its extension to anisotropic systems termed COSMOmic were compared for the prediction of partition equilibria in mixed micelles, where various molar ratios of the surfactants were considered. It could be demonstrated that both methods are applicable and lead to reasonable predictions for neutral molecules. However, taking into account the three-dimensional structure of the micelle is beneficial because the calculations with COSMOmic are in better agreement with experimental results. Because the partitioning behavior of ionizable molecules in mixed micelles is of particular interest, the partitioning of ionized isovanillin in mixed Brij35/CTAB micelles at different micelle compositions was calculated with COSMOmic. Using a thermodynamic cycle, the position-dependent pKa of isovanillin within the micelle is calculated on the basis of COSMOmic free energy profiles. As a result, the protolytic equilibrium of isovanillin within the micelles can be taken into account, which is crucial for the reliable prediction of partition coefficients.
