Quantum Computing for Electronic Circular Dichroism Spectrum Prediction of Chiral Molecules

TL;DR

This paper introduces a quantum computing framework for predicting electronic circular dichroism spectra of chiral molecules, achieving high accuracy and scalability compared to classical methods, and demonstrating its effectiveness on drug molecules.

Contribution

It presents a novel hybrid quantum/classical approach using variational quantum algorithms for ECD spectrum prediction, enabling scalable and accurate calculations for larger molecules.

Findings

Quantum ECD spectra closely match classical reference results.

The method scales to molecules with active spaces of 20-24 qubits.

Accurate reproduction of spectral features and chiroptical properties.

Abstract

Electronic circular dichroism (ECD) spectroscopy captures the chiroptical response of molecules, enabling absolute configuration assignment that is vital for enantioselective synthesis and drug design. The practical use of ECD spectra in predictive modeling remains restricted, as existing approaches offer limited confidence for chiral discrimination. By contrast, theoretical ECD calculations demand substantial computational effort rooted in electronic structure theory, which constrains their scalability to larger chemically diverse molecules. These limitations underscore the need for computational approaches that retain first principles physical rigor while enabling efficient and scalable prediction. Motivated by recent advances in quantum algorithms for chemistry, we introduce a variational quantum framework combined with the quantum equation of motion formalism to compute molecular properties and predict ECD spectra, implemented within a multi GPU or QPU accelerated hybrid quantum/classical workflow. We demonstrate its efficient applicability on 12 clinically relevant chiral drug molecules accessing expanded active spaces. The proposed framework is assessed by comparison with established classical wavefunction based methods, employing Coupled Cluster Singles and Doubles (CCSD) for ground-state energy benchmarks and Complete Active Space Configuration Interaction (CASCI) as the reference method for excited state energies and chiroptical properties within the same active orbital space. Notably, the quantum computed ECD spectra, obtained from chemically relevant active spaces mapped onto quantum circuits of approximately 20 to 24 qubits, exhibit near quantitative agreement with classical reference calculations, accurately reproducing spectral line shapes, Cotton effect signs, and relative peak intensities.