Toward a Molecular Dynamics Force Field for Simulations of 40% Trifluoroethanol–Water

Various computational models of trifluoroethanol (TFE) and water have been explored with the goal of finding a system for molecular dynamics (MD) simulations that reliably predict properties of 40% TFE-water (v/v) and can be used in studies of peptide-solvent nuclear cross-relaxation. Models derived by modification of TFE parameters developed by Fioroni et al. (J. Phys. Chem. B 2000, 104, 12347), in combination with either TIP4P-Ew or TIP5P-E water, were most successful. Simulations of 40% TFE-TIP4P-Ew water evidenced separation of the system into large TFE-rich and water-rich domains. With TIP5P-E water, simulations showed aggregation of each solvent component into small clusters. Nuclear spin dipolar interactions between solvent fluorines and the methyl hydrogens of acetate ion dissolved in 40% TFE-water were calculated. The cross-relaxation parameter σHF reckoned for the TFE-TIP5P-E system agreed with experiment while the value calculated using the TFE-TIP4P-Ew system was too low. While the TFE-TIP5P-E model of 40% TFE-water leads to good predictions of the system density, translational diffusion coefficients, and a solvent-solute cross-relaxation parameter, this model performs poorly in predicting the enthalpy of mixing. Preliminary studies of 20% TFE-water and 50% TFE-water suggest that the model will perform with the same characteristics for mixtures that have compositions near 40% TFE-water.