First-principles computation of electronic circular dichroism spectra of solvated molecules using RISM-SCF-cSED

Abstract

We propose a practical first-principles protocol for computing electronic circular dichroism (ECD) spectra of chiral molecules in aqueous solution by combining time-dependent density functional theory (TDDFT) with the reference interaction site model self-consistent field with constrained spatial electron density (RISM-SCF-cSED), and, when necessary, molecular dynamics-based conformational sampling. After demonstrating the approach for D-lactic acid in water as a benchmark system with limited conformational variability, we apply a similar workflow to a solvated biomolecule, the terminally capped alanine tetramer (Ac-Ala4-NMe). One of the achievements of this study is that incorporating an explicit solute water hydrogen-bonding structure through RISM-SCF-cSED enables quantitative reproduction of the ECD spectrum of the rigid α-helical state. These results establish RISM-SCF-cSED/TDDFT combined as a general and computationally efficient platform for predicting ECD spectra of solvated molecules.