Testing the Simplified Molecular Dynamics Approach to Improve the Reproduction of ECD Spectra and Monitor Aggregation

TL;DR

Researchers tested a simplified molecular dynamics approach to better reproduce ECD spectra and found it improved agreement with experimental data, especially for molecules with limited conformational flexibility.

Contribution

The study introduces a simplified molecular dynamics approach that enhances ECD spectrum reproduction by using unoptimized geometries and solvent effects.

Findings

Using explicit solvent molecules in MD simulations improved agreement between experimental and computed ECD spectra.

The MD approach confirmed that aggregation of luzulin A contributed to specific ECD spectral features.

Dimer formation in solution was identified as the cause of an anomalous ECD spectrum.

Abstract

A simplified molecular-dynamics-based electronic circular dichroism (ECD) approach was tested on three condensed derivatives with limited conformational flexibility and an isochroman-2H-chromene hybrid, the ECD spectra of which could not be precisely reproduced by the conventional ECD calculation protocol. Application of explicit solvent molecules at the molecular mechanics (MD) level in the dynamics simulations and subsequent TDDFT-ECD calculation for the unoptimized MD structures was able to improve the agreements between experimental and computed spectra. Since enhancements were achieved even for molecules with limited conformational flexibility, deformations caused by the solvent molecules and multitudes of conformers produced with unoptimized geometries seem to be key factors for better agreement. The MD approach could confirm that aggregation of the phenanthrene natural product luzulin A had a significant contribution to a specific wavelength range of the experimental ECD. The MD approach has proved that dimer formation occurred in solution and this was responsible for the anomalous ECD spectrum. The scope and limitations of the method have also been discussed.

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