Quantitative modeling of acid-base equilibria

Abstract

Simulating acid-base equilibria from first principles is a tremendous challenge, as it requires modeling bond-breaking events in a complex hydrogen-bonding environment. The quantum mechanical behavior of the protons is often important, complicating simulations even further. We show that by combining state-of-the-art machine-learning potentials, accelerated sampling of the dissociation process, and an efficient estimation of nuclear quantum corrections it is possible to reliably compute the dissociation constants of different species in water. We demonstrate the transferability of this workflow, applying it successfully to the autoionization of water and to the entire ladder of the aqueous dissociation of phosphoric acid. The definition of the dissociation constant, the choice of order parameters, sampling artifacts and finite-size effects, as well as quantum nuclear effects all play a non-trivial role in determining the outcome of the calculation, so that cutting corners is likely to introduce biases that can only be compensated by fortuitous cancellations of errors.