Solute Partitioning in Micelles: Combining Molecular Dynamics Simulations, COSMOmic, and Experiments

The partition equilibria of solutes between micelles and an aqueous phase is a key factor in many applications. Depending on the task, many micelle-solute combinations are possible. Therefore, theoretical methods to predict the partition behavior in micellar systems are needed. Here, two predictive methods are evaluated and compared. First, it is shown how molecular dynamics simulations (MD) with the umbrella sampling method can be used to calculate free energy profiles in micellar systems. The second applied method is an extension of the COSMO-RS theory to anisotropic systems termed COSMOmic. Both methods are compared by means of free energy profiles and experimental micelle/water partition coefficients. A particular focus is on the partitioning of ionized solutes. As experimental data for partitioning in micelles especially for charged solutes is rare, partition coefficients were also determined experimentally. To get a general understanding of micelles examples of all micelle classes (classified by headgroup charge) are studied: nonionic Triton X-114 (TX114), zwitterionic miltefosine (HePC), anionic sodium dodecyl sulfate (SDS), and cationic cetyltrimethylammonium bromid (CTAB). The free energy profiles of neutral solutes obtained from MD simulations and COSMOmic are in an overall good agreement, and partition coefficients from both methods are in good agreement with experimental data. Depending on the system, the results for charged solutes show some deviations between the methods and experimental data.