Influence of microsolvation on vibrational circular dichroism spectra in dimethyl sulfoxide solvent: A Bottom-Up approach using Quantum cluster growth.

[Display omitted] • Conformers of solute-DMSO complexes generated using Quantum cluster growth method. • The effects of incremental DMSO solvation and dynamicity of –OH group were explored. • Predicted and experimental vibrational circular dichroism spectra matched well. • The final populations of conformers are sensitive to the choice of functional used. Chiroptical spectroscopic measurements serve as routine methods to assign the absolute configuration of chiral compounds and interpret their conformational behavior in solution. One common challenge is the use of strongly hydrogen-bonding solvents, which can significantly bias the conformational ensemble and affect the vibrational circular dichroism (VCD) active bands in solution. One such solvent is dimethyl sulfoxide (DMSO)—an excellent solvent for stubborn compounds—that must be explicitly considered in VCD analysis. Explicit consideration of solvent remains a critical challenge in chiroptical spectroscopy due to the need to explore solute–solvent conformational space and the computational expense in modeling these clusters. Interested in the recent development of the Quantum Cluster Growth (QCG) program by the Grimme lab, we set out to model and interpret previously reported VCD spectra for several molecules using their efficient program. Our purposes are two-fold: (1) to investigate the applicability of the QCG program to the problem of reproducing VCD spectra in DMSO solvent and (2) to identify limitations in using this approach. We find that we can conveniently model and analyze the VCD spectra of investigated molecules in DMSO. However, the final set of conformers used for VCD calculations are functional dependent and different sets of conformers can provide satisfactory quantitative agreement between experimental and predicted VCD spectra. We hope that this study provides guidance for future chiroptical studies in the challenging DMSO solvent. [ABSTRACT FROM AUTHOR]