Predicting Octanol/Water Partition Coefficients of Alcohol Ethoxylate Surfactants Using a Combination of Molecular Dynamics and the Conductor-like Screening Model for Realistic Solvents

We
present a hybrid modeling strategy for the prediction of octanol/water
partition coefficients for alcohol ethoxylate surfactants of varying
chain lengths. The strategy makes use of molecular dynamics (MD) simulations
for the generation of molecular conformations in the presence of a
solvent. A clustering of the conformations from the MD trajectories
was carried out based on principal component analysis of their dihedral
angles. Representative conformations thus selected were then used
in the conductor-like screening model for realistic solvents (COSMO-RS).
Each conformation has been assigned a weight using an equation derived
on the basis of its probability of occurrence in the MD trajectory.
Experimental partition coefficients were reproduced within conformation-independent
accuracy of COSMO-RS despite the size and flexibility of the ethoxy
chain otherwise posing a challenge on their solvation modeling.