Probing the conformations of lactic acid in aqueous solution through methine CH stretching vibrations: a Raman and MP2 study.

Lactic acid plays important roles in biological metabolism and molecular recognition, yet its conformational distribution in aqueous solution remains under debate because of the complex hydrogen-bonding interactions with surrounding water molecules. In this work, Raman spectroscopy combined with MP2/6-311+G(d,p) calculations was employed to investigate the conformational preferences of aqueous lactic acid through its CH stretching vibrations. To resolve the long-standing spectral overlap between methyl and methine vibrations, methyl-deuterated lactic acid was employed, enabling direct observation of the methine CH stretching vibration. Based on Raman spectra calculated for 11 optimized lactic acid-(H2O)8 clusters using cluster-in-a-liquid solvation model, the methine CH stretching vibration is highly sensitive to molecular conformation, whereas the methyl antisymmetric stretching vibration is nearly conformation-independent and therefore serves as a reliable internal spectral reference. Polarized Raman spectroscopy confirmed the assignment of the Raman band near 3000 cm-1 to the methyl antisymmetric stretching vibration, while the methine stretching band was directly observed at ∼2925 cm-1 in methyl-deuterated lactic acid. By comparing the experimentally measured frequency difference between these two vibrations with theoretical predictions, the G+TC and A-TC⁎ conformers were identified as the dominant structures in aqueous solution, and this assignment was further supported by the fingerprint-region Raman spectra. These results establish a general Raman spectroscopic strategy for conformational analysis based on the frequency difference between conformation-sensitive and conformation-insensitive CH stretching vibrations, which is demonstrated here for aqueous lactic acid.