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

Abstract

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.

Optical Rotation Calculations for a Set of Pyrrole Compounds

“…For all molecules, the CC2 method gives smaller optical rotation magnitudes than CAM-B3LYP except for molecules 1 and 3 , as seen in Table . We note that the calculated optical rotations are in the gas phase whereas the experimental rotations were reported in CH 2 Cl 2 . − Therefore, differences between the calculations and experiments, specifically for molecules 3 and 5 , come from various factors that are not included in the calculations such as solvent effects − and vibrational contributions. ,− …”

“…In the DFT method, the CAM-B3LYP functional is used which has been demonstrated to be an appropriate functional for predicting both excitation energies and optical rotations − ,, where the long-range correction contributes significantly. The presence of a solvent, − the influence of vibrational contributions (both harmonic and anharmonic), ,− different conformations, ,− and temperature − are important factors to obtain accurate theoretical predictions and comparison between theoretical optical rotations and experiments. However, in this work we restrict ourselves to a screening study of the relatively large-size molecules, not studied theoretically before, in the gas phase for comparing the CAM-B3LYP and CC2 methods.…”

Optical Rotation Calculations for Fluorinated Alcohols, Amines, Amides, and Esters

“…Tables and show the large ADs between the calculated and experimental optical rotations for some of the investigated molecules, specifically for molecules containing the naphthalene and benzoate groups. We note that the calculations are performed in the gas phase, while the experimental rotations were measured in various solvents. − Thus, there are important contributions to the optical rotations such as solvent effects − and vibrational contributions ,− which are not considered in the calculations.…”

“…In this paper, we theoretically study the optical rotation of 45 fluorinated alcohols, amines, amides, and esters which have been measured experimentally. − For a detailed comparison between calculated and experimental optical rotations, one should consider solvent effects, − the influence of vibrational contributions (both harmonic and anharmonic), ,− different conformations, ,− and temperature. − However, in this work, we focus our investigation on the calculated optical rotation in the gas phase in a screening study of a relatively large set of molecules not studied theoretically before. This allows for comparing the performance of the DFT and CC2 methods using the aug-cc-pVDZ basis set for relatively large molecules that contain different elements such as N, O, F, and Br (where relativistic effects may play important roles for molecules containing Br , ).…”

Classical Magnetic Dipole Moments for the Simulation of Vibrational Circular Dichroism by ab Initio Molecular Dynamics

“…To reproduce experimental conditions, it is often necessary to include the influence of the molecular surrounding in the bulk phase or in a solution. In the context of static quantum chemistry, this is possible by implicit solvation models and microsolvation approaches with explicit solvent molecules, as has been done, for example, to study the VCD spectra of several biomolecules. − Such solute–solvent clusters can be extracted from molecular dynamics (MD) simulations, , but it would be desirable to directly employ MD without modifications of the molecular surrounding to capture the dynamic nature of the intermolecular interaction network and to cover the conformational flexibility in the bulk phase.…”