# Investigation of the Robustness of Rayleigh Optical Activity for the Assignment of Absolute Configurations of Chiral Molecules

## TL;DR

This paper explores how Rayleigh optical activity can be used to determine the structure of chiral molecules.

## Contribution

The study computationally models RayOA and shows it is more robust for assigning molecular configurations than other methods.

## Key findings

- RayOA is less sensitive to conformational flexibility and solvent effects than other chiroptical methods.
- Chiral propellers can be designed to have strong RayOA signals.
- Preresonance enhancement occurs when RayOA measurements approach electronic transition wavelengths.

## Abstract

Experimental measurements of Rayleigh optical activity
(RayOA)
for liquid phase chiral molecules have been recently reported for
the first time, nearly 50 years after it was theoretically formulated.
Inspired by these experimental data, we computationally model the
RayOA of several chiral molecules to assess the usefulness of this
newly reported experimental method for assigning their absolute configurations.
We consider the influence of factors that can often preclude the routine
assignment of absolute configurations, including conformational flexibility,
solute–solvent clusters, and dispersion interactions. We find
that RayOA is not as sensitive to these factors as other commonly
used chiroptical spectroscopies, namely, specific rotation, electronic
circular dichroism, vibrational circular dichroism, and vibrational
Raman optical activity, which suggests that RayOA may be best suited
for routine absolute configuration assignment. Additionally, we report
on a class of chiral propellers that could be tailored to have large
magnitudes of RayOA. We also find that there can be preresonance RayOA
enhancement when the wavelength of RayOA measurement approaches that
of electronic transitions. Thus, RayOA may potentially find a strong
foothold within the chemical community due to its potential robustness
and ease of computational treatment for absolute configuration determinations.