New hybrid cluster-continuum model for pKa values calculations: Case study of neurotransmitters’ amino group acidity

Abstract

Acid dissociation constant is a quantitative measure of chemical species ability to donate a proton to water molecule and plays important role in aqueous chemistry. Many computational strategies were conceived in order to properly address an acid dissociation equilibrium. In this work, we present new economical cluster-continuum method based on the density functional theory for the accurate calculation of pKa values. By analysing hydration properties of neutral and protonated 2-phenylethylamine sampled in the first principle molecular dynamics simulations, we were able to find key interactions between water molecules and amino group in the neutral and protonated state. This was used to design a reaction scheme, which was shown to yield excellent agreement between the computed and experimental pKa values of selected neurotransmitters. We believe that the proposed scheme can be generalized for computation of acidic properties of other primary and secondary amines.