Efficient first-principles modeling of complex molecular crystals at sub-chemical accuracy

TL;DR

This paper introduces a new computational framework combining correlated wavefunction theory and many-body expansion to accurately predict the relative energies of complex molecular crystal polymorphs at a cost comparable to standard DFT, enabling high-throughput screening.

Contribution

It presents a novel, cost-effective cWFT-based method achieving sub-chemical accuracy for large molecular crystals, surpassing previous approaches in efficiency and applicability.

Findings

Accurately predicts lattice energies within experimental uncertainties for diverse molecular crystals.

Achieves sub-chemical accuracy for complex drug-like molecules and challenging polymorphs.

Provides openly available tools and parametrized DFT functional for high-throughput polymorph screening.

Abstract

Molecules can form myriad crystalline polymorphs, each with distinct properties affecting their performance across diverse applications, from pharmaceuticals to functional materials and more. Predicting the thermodynamically most stable polymorph from first principles remains a formidable challenge. It requires methods that scale to large, technologically-relevant molecules while achieving very high accuracy (below 1 kJ/mol) on relative lattice energies. Such accuracy, often termed sub-chemical accuracy, is generally beyond the reach of the workhorse density functional theory (DFT). In this work, we introduce a framework, combining advances in correlated wavefunction theory (cWFT) and the many-body expansion, to deliver accurate, cost-effective predictions of complex molecular crystals. For 23 organic molecules and 13 ice polymorphs, we predict crystal lattice energies to within experimental uncertainties at costs comparable to hybrid DFT, while being several orders of magnitude more efficient than previous cWFT approaches. We extend this approach to a set of large, drug-like molecules including axitinib and ROY, previously inaccessible to cWFT and where DFT is insufficient, achieving sub-chemical accuracy on the relative energies between challenging polymorphs. With the reference data generated throughout this work, we have been able to further parametrize a DFT functional with unprecedented accuracy aligning with our predictions. This cWFT framework as well as DFT functional are made openly available, providing new ranking tools to facilitate efficient high-throughput screening of molecular crystal polymorphs.