Charge Asymmetries in Hydration of Polar Solutes

Abstract

We study the solvation of polar molecules in water. The center of water's dipole moment is offset from its steric center. In common water models, the Lennard-Jones center is closer to the negatively charged oxygen than to the positively charged hydrogens. This asymmetry of water's charge sites leads to different hydration free energies of positive versus negative ions of the same size. Here, we explore these hydration effects for some hypothetical neutral solutes, and two real solutes, with molecular dynamics simulations using several different water models. We find that, like ions, polar solutes are solvated differently in water depending on the sign of the partial charges. Solutes having a large negative charge balancing diffuse positive charges are preferentially solvated relative to those having a large positive charge balancing diffuse negative charges. Asymmetries in hydration free energies can be as large as 10 kcal/mol for neutral benzene-sized solutes. These asymmetries are mainly enthalpic, arising primarily from the first solvation shell water structure. Such effects are not readily captured by implicit solvent models, which respond symmetrically with respect to charge.

Rapid Prediction of Solvation Free Energy. 2. The First-Shell Hydration (FiSH) Continuum Model

“…The two coefficients, c + and c -, used for positive and negative σ i were previously trained on the electrostatic free energy from FEP simulations for a set of model systems consisting of pairs of neutral hexagonal bracelets with mirrored charge distribution (Figure 1). 20 Tests on pairs of model systems with different geometries indicated the generality of the approach and the transferability of the calibrated coefficients. 23 However, the c + and c -coefficients derived previously were for highly simplified model systems made of a single atom type.…”

“…[34][35][36][37] The charge asymmetry phenomenon is dominated by first solvation shell effects. 20 Water molecules orient differently around positively and negatively charged atoms, resulting in changes in the dielectric boundaries ( Figure 1). This leads to different effective Born radii and an asymmetric dependence of the reaction field energies on solute charge.…”

“…Charge asymmetries are captured by explicit water simulations, but the usual continuum electrostatics calculations fail miserably in capturing this phenomenon. 20,38 We have recently presented a proof of concept, in which charge asymmetry of solvation can be handled in…”

“…19 Around polar solute surfaces, water molecules interact strongly with the solute but orient differently around positively and negatively charged atoms, a phenomenon known as the charge asymmetry of water. 20 It is imperative for implicit solvation models to be able to capture the effects of first shell water ordering.…”

Restoring Charge Asymmetry in Continuum Electrostatics Calculations of Hydration Free Energies

“…The other atoms have zero partial charge. Using the terminology of Mobley et al 5 the bracelets with a full -1 charge on one atom are called N-bracelets. Those with a full +1 charge on one atom are called P-bracelets.…”