Investigation of the robustness of Rayleigh optical activity for the assignment of absolute configurations of chiral molecules

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Puente, Andrew R. and McArthur, Duncan and Alexakis, Emmanouil I. and MacKenzie, Lewis E. and Cameron, Robert P. and Barron, Laurence D. and Polavarapu, Prasad L. (2026) Investigation of the robustness of Rayleigh optical activity for the assignment of absolute configurations of chiral molecules. Journal of Physical Chemistry A, 130 (10). pp. 2238-2251. ISSN 1089-5639 (https://doi.org/10.1021/acs.jpca.5c08390)

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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.

ORCID iDs

Puente, Andrew R., McArthur, Duncan ORCID logoORCID: https://orcid.org/0000-0001-8603-8349, Alexakis, Emmanouil I., MacKenzie, Lewis E. ORCID logoORCID: https://orcid.org/0000-0002-8151-0525, Cameron, Robert P. ORCID logoORCID: https://orcid.org/0000-0002-8809-5459, Barron, Laurence D. and Polavarapu, Prasad L.;
CORE (COnnecting REpositories)