Solvent Effects on Optical Rotation: On the Balance between Hydrogen Bonding and Shifts in Dihedral Angles

Area of Science:

• Computational chemistry
• Theoretical organic chemistry

Background:

• Accurate prediction of optical rotation is crucial for understanding chiral molecules.
• Traditional methods often struggle to capture complex solvent effects.

Purpose of the Study:

• To investigate the influence of solvent environments on the optical rotations of fluorinated molecules.
• To evaluate the effectiveness of a combined implicit and explicit solvent model (microsolvation) for predicting optical rotations.

Main Methods:

• Calculated optical rotations using time-dependent density functional theory (TDDFT) with CAM-B3LYP functional and aug-cc-pVDZ basis set.
• Employed the polarizable continuum model (PCM) for implicit solvent effects.
• Utilized a microsolvation approach (explicit solvent molecules) combined with PCM for detailed solvent interactions.

Main Results:

• The microsolvation model improved agreement with experimental optical rotation signs and magnitudes compared to gas-phase and PCM-only calculations.
• This model successfully reproduced experimental optical rotation signs for molecules in water and chloroform.
• Identified specific hydrogen bonding interactions in microsolvation that significantly influence conformational preferences and optical rotation.

Conclusions:

• A microsolvation approach, combined with PCM, provides a reliable method for predicting optical rotations.
• This advanced computational method offers better accuracy for chiral molecule characterization in various solvent environments.