Challenges in predicting ΔrxnG in solution: Hydronium,hydroxide, and water autoionization

Standard non‐semiempirical continuum‐dielectric orbital‐based methods horribly overpredict, by 26‐50 kcal mol⁻¹, the Gibbs energy for the water autoionization reaction 2 H₂O_(l) → H₃O⁺_(aq) + OH^–_(aq). Here, we demonstrate these errors, fully investigate the reasons for these errors, and show that the use of 4 explicit solvent within the continuum (the “semicontinuum,” “cluster‐continuum,” or “hybrid” technique) can reduce the error of a standard continuum model from 50 to 2 kcal mol⁻¹. Results from pure cluster, pure continuum (several versions including semiempirical ones), and semicontinuum modeling are each presented and discussed. We recommend use of 3 waters around hydronium and 4 waters around hydroxide with standard continua whenever these ions are involved in reaction. To the possible surprise of some, time‐consuming molecular‐dynamics simulations are not needed to reproduce this problematic energy.