Rapid and accurate molecular deprotonation energies from quantum alchemy

TL;DR

This study demonstrates that quantum alchemy via APDFT can rapidly and accurately estimate deprotonation energies in small organic molecules, significantly reducing computational costs while maintaining high accuracy.

Contribution

The paper introduces a hybrid APDFT approach that combines different levels of theory to achieve high accuracy in deprotonation energy predictions at a fraction of the computational cost.

Findings

APDFT converges quickly to reliable deprotonation energies.

CCSD-based APDFT reproduces energies within 1.4 kcal/mol.

Hybrid approach reaches 2 kcal/mol accuracy at 2% of the cost.

Abstract

We assess the applicability of Alchemical Perturbation Density Functional Theory (APDFT) for quickly and accurately estimating deprotonation energies. We have considered all possible single and double deprotonations in one hundred small organic molecules drawn at random from QM9 [Ramakrishnan et al, JCTC 2015]. Numerical evidence is presented for 5'160 deprotonated species at both HF/def2-TZVP and CCSD/6-31G* level of theory. We show that the perturbation expansion formalism of APDFT quickly converges to reliable results: using CCSD electron densities and derivatives, regular Hartree-Fock is outperformed at second or third order for ranking all possible doubly or singly deprotonated molecules, respectively. CCSD single deprotonation energies are reproduced within 1.4 kcal/mol on average within third order APDFT. We introduce a hybrid approach were the computational cost of APDFT is reduced even further by mixing first order terms at a higher level of theory (CCSD) with higher order terms at a lower level of theory only (HF). We find that this approach reaches 2 kcal/mol accuracy in absolute deprotonation energies compared to CCSD at 2% of the computational cost of third order APDFT.