Chemical Intuition in Chiroptical Spectroscopy

Despite a long history of use to probe chiral systems, it remains poorly understood how the observed optical activity of a molecule correlates with its structure. We are working to unravel this relationship by developing new electronic structure methods that can aid in characterizing the specific interactions that lead to chiroptical phenomena.

The chirality, or handedness, of a molecule can have a profound effect on its properties; a drug that is beneficial in one form may have a mirror image that is toxic. Similarly, a catalyst might react readily with one handedness of a molecule and not at all with the other. Optical activity, the rotation of plane polarized light after passing through a chiral medium, has been an invaluable tool for studying such compounds for more than two centuries. While this technique is widely used, it remains chemically unintuitive how the magnitude, or even the direction, of optical rotation (OR) is linked to the structure of a molecule. We are elucidating this structure-property relationship by developing and applying new electronic structure methods to study chiroptical phenomena.

A crucial open problem in this area is how to properly model the effect of solvation; most experimental measurements of OR are done in solution, but it is too costly to simulate the surrounding solvent molecules quantum mechanically. The solvent shell can have chirality induced by the solute, causing additional OR that goes unaccounted for in simulations of the solute alone. We are developing tools to simplify the treatment of solvated systems and assign OR contributions to specific functional groups in order to better distinguish between molecular and solvent effects. Another approach to attack this problem is developing methods to calculate OR of solid systems. While the OR in solution is the same in each direction due to isotropic averaging, solids give a different response along each crystal axis, making it easier to disentangle what chemical features are producing the OR. Calculating OR for solids, in particular molecular crystals, could make clearer the distinction between OR caused by molecular versus environmental/supermolecular chirality. We are also interested in isotopically chiral molecules. Seeding a chiral superstructure with isotopically chiral monomers can cause it to favor a particular handedness; we are analyzing if the OR of these monomers hints at the extent to which a given handedness is preferred and whether the OR can be tuned through site specific isotopic substitution.

T. Balduf, M. Caricato*, Helical Chains of Diatomic Molecules as a Model for Solid State Optical Rotation; J. Phys. Chem. C, 123, (2019) 4329.

T. Aharon, M. Caricato*, Configuration Space Analysis of the Specific Rotation of Helicenes; J. Phys. Chem. A, 123, (2019) 4406.

T. Aharon, P. Lemler, P. H. Vaccaro*, M. Caricato*, Comparison of Measured and Predicted Specific Optical Rotation in Gas and Solution Phases: A Test for the Polarizable Continuum Model of Solvation; Chirality, 30, (2018) 38

M. Caricato*, Orbital Analysis of Molecular Optical Activity Based on Configuration Rotatory Strength; J. Chem. Theory Comput., 11, (2015) 1349.