Theoretical Simulations of Optical Rotation and Raman Optical Activity of Molecules in Solution

Abstract

<p>Chiroptical spectroscopic techniques such as optical rotation (OR), electronic circular dichroism (ECD), and Raman optical activity (ROA) provide the means to probe molecular dissymmetry, which is the arrangement of atoms that is not superimposable on its mirror image. However, the application of chiroptical methods for conformational and configurational analysis of molecules (or molecular stereochemistry) requires the accurate and efficient computation of chiroptical response properties. Access to a battery of accurate methods, especially for OR, have just emerged over the last decade. A combination of quantum chemical electronic structure methods and chiroptical spectroscopy can now be used to establish a comprehensive understanding of molecular stereochemistry. A key challenge in stereochemical analysis is to compute the chiroptical response of molecules in solution, which is the focus of our research in optical activity.</p><p>Although the common perception is that chiroptical responses are solely determined by a chiral solute's electronic structure in its environment, we demonstrate that chiral imprinting effects on media, and molecular assembly effects can dominate chiroptical signatures. Both these effects are strongly influenced by intermolecular interactions that are essential to accurately describe chiroptical signatures of molecules. Chiroptical response of molecules spans a range of large positive and negative values, and hence, the measured chiroptical response represents an ensemble average of orientations. Thus, accurate prediction of chiroptical properties requires adequate conformational averaging. Here we show that OR and ROA of molecules in solution can be modeled using a combination of structure sampling and electronic structure methods. Method for computing chiroptical response in the condensed phase using continuum solvation models and point charge solvent model, although more efficient than explicit solvent treatments, are often inadequate for describing induced chirality effects. The lack of a priori knowledge of solvent-solute interactions and their influence on the chiroptical signature demands exploration of thermally averaged solute-solvent clusters and comparison with simpler solvent studies.</p>