Hydrophobic Ions in TIP5P Water and at a Water−Chloroform Interface:  The Effect of Sign Inversion Investigated by MD and FEP Simulations

According to the TATB (tetraphenylarsonium tetraphenylborate) assumption, large isosterical ions of opposite charge have identical free energies of solvation in any solvent. In this context, we present a molecular dynamics study of the solvation of tetrahedral (AsPh4 + vs BPh4 -) and large spherical (S+ vs S-) ions in water using the recently developed TIP5P model. The results markedly differ from those obtained in TIP3P water and are in better agreement with the TATB hypothesis. According to free energy perturbation calculations, S- is better hydrated than S+, but the difference, ΔG +-, in hydration energies is much weaker in TIP5P (3.2 kcal/mol) than in TIP3P water (27.3 kcal/mol) which leads to an artifactually positive electrostatic potential at the center of the neutral S0 species. BPh4 - is better hydrated than AsPh4 + and, contrary to the TATB assumption, ΔG +- markedly depends on the details of charge distributions. The set8 charges equally diluted on all atoms lead to ΔG +- of 4.3 kcal/mol only, much less than the value obtained with the set1 ESP charges (25 kcal/mol). These values are much smaller than those obtained in TIP3P water, but still indicate some preference for the anion hydration. The differences are discussed from hydration patterns, electrostatic potentials and solute−solvent interactions. Simulations of AsPh4 + and BPh4 - at the (TIP5P)water−chloroform interface confirm the high surface activity of both ions, despite their “symmetrical structure”. These results are important for our understanding of the influence of water models on calculated hydration and association of hydrophobic species in pure and mixed liquid environments.