Short-Range Solvation Effects on Chiroptical Properties: A Time-Dependent Density Functional Theory and ab Initio Molecular Dynamics Computational Case Study on Austdiol

The description of solvation effects on the chiroptical properties of chiral molecules is still a difficult challenge in the field of computational spectroscopy; this issue is critical in stereochemical characterization, since a reliable assessment of absolute configuration requires high accuracy. The present case study reports the huge effect of solvation on the chiroptical properties of austdiol, a fungal metabolite of known stereochemistry. Standard protocols based on time-dependent density functional theory calculations failed to reproduce its experimental chiroptical properties in methanol. When short-range solvation effects are explicitly considered by means of ab initio molecular dynamics, the correlation between calculated and experimental data is greatly improved because of a better description of the chiral environment around the ketone chromophore, showing that the modeling of subtle solvent-induced perturbations may require the most accurate computational methods.