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

Abstract

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 (AsPh 4 + vs BPh 4 -) 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, Sis better hydrated than S + , but the difference, ∆G +-, 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 S 0 species. BPh 4is better hydrated than AsPh 4 + and, contrary to the TATB assumption, ∆G +markedly depends on the details of charge distributions. The set8 charges equally diluted on all atoms lead to ∆G +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 AsPh 4 + and BPh 4at 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.

Single-ion hydration thermodynamics from clusters to bulk solutions: Recent insights from molecular modeling

“…As a result, similar trends have been observed in the hydration free energies of ion solvation by different water models, as exemplified on the large ions of the TATB system mentioned earlier [84]. This fact has been used to define the so-called net potential, f net G , which represents electrostatic potential in the center of an uncharged solute [108,109] f net…”

“…However, the assumption that charge asymmetric water molecules will respond symmetrically to large cations and anions is certainly not guaranteed. The reliability of the TATB was investigated by Schurhammer et al [84] using molecular dynamics simulations with two simple molecular models (TIP3P [85] and TIP5P [86]) of water. The results revealed significant differences between interactions of water with the cation and anion, especially for the more charge-asymmetric TIP3P water model.…”

Absolute hydration free energies of ions, ion–water clusters, and quasichemical theory

“…But because the values obtained that way would not include a contribution from the potential of the phase, those values would be different from values extracted from the ion-cluster studies analyzed here. The computational testing of that TATB hypothesis has lead to energetic uncertainties of nearly the same size as the energetic contributions of issue here [60]. Therefore, the TATB hypothesis must be currently viewed as not satisfactorily proven.…”

“…A classic alternative to the ion-cluster experimental studies for obtaining the absolute hydration free energies of ions is the tetraphenyl arsonium tetraphenyl borate (TATB) hypothesis [60]. The molecular intuition is that these oppositely charged ions have the same nonionic interactions with any solvent molecules.…”

Charge equilibration force fields for molecular dynamics simulations of lipids, bilayers, and integral membrane protein systems

“…Schurhammer and coworkers have also explored the variation in hydration free energies for the TPB − /TPA + system using molecular dynamics simulations and free energy perturbation calculations. 103 The authors find that TPB − is more favorably hydrated than TPA + , and that the difference in hydration free energy between the two is strongly dependent on the specific charge distribution; the range of differences in hy-dration energies is from 4.3 kcal/mol to 25 kcal/mol. Moreover, recent studies investigating the effects of charge asymmetry on hydration free energies of model asymmetric polar molecules by Mobley et al 104 demonstrate significant differences in hydration free energies of oppositely polarized molecules, with these differences approaching the order of 10 kcal/mol.…”