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.