Identification of the Molecular Structure of Mandelic Acid in Solid and Aqueous Solutions by Raman Spectra in the C-H/C-D Stretching Region

Identifying the molecular structures of drugs are important for understanding the molecular interactions between drugs and proteins. Especially in situ measurement of drug structures that interact with proteins in aqueous solutions or cells is a challenge. In this work, mandelic acid (MA) was used as a model molecule to prove that the Raman spectra in the C-H or C-D stretching region can be employed to identify the molecular structure through theoretical and experimental Raman spectra and molecular dynamics simulations methods. Using the experimental and theoretical Raman spectra of MA rotamers, C α -H was determined to be trans (higher than 2950 cm −1 ) and nontrans (below 2950 cm −1 ) from the α-OH group for solid DL-MA (~2961 cm −1 ) and D -MA (~2898 cm −1 ), respectively, which agreed well with the results from X-ray diffraction. Molecular dynamic (MD) simulations and Raman band of the MA aqueous solution revealed that the C α -H group was determined to be nontrans from the α-OH group, the structure of the carboxyl group was cis (~2910 cm −1 ), the carboxyl group was roughly vertical to the C α -benzene bond, and the benzene ring was approximately coplanar with the C α -H bond. Our work also paves that the Raman spectra in the C-D or C-H stretching region could be used as fingerprint regions to study the structure of drugs.