Toward Equilibrium Charges: Environment‐Consistent Atomic Charge Models for Nonpolarizable Force Fields

Electrostatic interactions in nonpolarizable force fields are represented by fixed atomic charges, despite their sensitivity to molecular environments. We use the self‐consistent polarization (SCP) method to derive environment‐consistent charges for seven aliphatic alcohols, from methanol to tert‐butanol, in water, methanol, pure alcohol liquids, and n ‐octanol. SCP calculations on MD‐derived solvation clusters reveal solvent‐induced polarization of hydroxyl‐group charges, dominated by direct polarization and environmental back‐polarization. Hydroxyl charges are transferable across alcohols and hydrogen‐bonding solvents, whereas aliphatic carbon and hydrogen charges depend on substitution pattern. SCP‐derived charges improve hydration free energies when transformed from bulk to vacuum values at the water–vacuum interface, achieving mean deviations of c.a. 0.3 kcal mol −1 of experiment. The reproduction of mixing enthalpies for alcohol‐water mixtures was also improved with SCP charges. These results support equilibrium‐derived charges as an intermediate description between additive and explicitly polarizable force fields.