Integrated QM/polarizable MM/continuum approaches to model chiroptical properties of strongly interacting solute–solvent systems

Abstract

Solvent effects on chiroptical properties and spectroscopies can be huge, and affect not only the absolute value but the sign of molecular chiroptical responses. Therefore, the definition of reliable theoretical models and computational protocols to calculate chiroptical responses and assist the assignment of the chiral absolute configuration cannot overlook the effects of the surrounding environment. Continuum solvation methodologies are successful in case of weakly interacting solute–solvent couples, whereas in case of strongly interacting systems, such as those dominated by explicit hydrogen bonding interaction, a change of strategy is required to gain a reliable modeling. In this review, a recently developed integrated Quantum-Mechanical/Polarizable molecular mechanics (MM)/polarizable continuum model (PCM) method is discussed, which combines a fluctuating charge approach to the MM polarization with the PCM. Its theoretical fundamentals, and issues related to the calculation of chiroptical responses are summarized, and the application to few representative test cases in aqueous solution is discussed.