(271a) Predition of the Distribution of Neutral Compounds and Ions in Micelles and Biomembranes with Cosmomic

The understanding and quantification of the distribution of molecules in micellar systems and biomembranes is of substantial importance for formulation, separation, pharmaceutical and environmental research and development. Direct measurements usually can only provide overall partition coefficients, but do not provide detailed information about the distribution of the molecules in the inhomogeneous systems. Therefore simulation techniques are of special interest. The standard approach is for such simulations is molecular dynamics (MD), but these simulations are extremely time consuming, especially when solutes free energy profiles are desired. Furthermore their results strongly depend on the chosen force field.

A much more computational efficient alternative (COSMOmic) for the prediction of micellar partition coefficients and the generation of such distribution profiles has been developed as an extension of the quantum chemically based COSMO-RS method, which meanwhile has become a kind of standard for fluid phase thermodynamics in homogeneous liquids. Recent third party comparisons have demonstrated that COSMOmic can produce information of at least the same quality as MD simulation at computational costs which are roughly three orders of magnitude lower, thus enabling such simulations to be included in routine workflows.

Very recently the applicability of COSMOmic to the distribution of ions has been analyzed. It turns out that by addition of a simple zeta-potential the partition coefficients of anions and cations in biomembranes can be nicely quantified. Unfortunately it turns out that the zeta potential cannot be predicted from first principles or MD simulations, and thus needs to be fitted for each system to experimental partition coefficients of a few test ions.