Study of Hydrogen Bonding Patterns of a Pharmaceutically Active Drug Molecule Paraldehyde: a Raman and DFT Study

Abstract

Abstract Raman spectra of neat paraldehyde (prldh) and its binary mixtures with methanol (M) with varying mole fractions of prldh from 0.1 to 0.8 were recorded in order to explore the hydrogen bonding patterns of prldh and their influence on spectral features of some selected vibrational bands of prldh in the region 400–1200 cm−1. Only few vibrational bands of paraldehyde show a significant change in their peak position in going from neat prldh to the complexes. One peculiar feature in this study is that the solvent band which occurs at ∼1034 cm−1 shows significant red shift of >4 cm−1 at higher mole fractions of prldh. This red shift is caused due to the hydrogen bonding between the O atom of the prldh ring and H atom of the methanol molecules. The Raman band at ∼1097 cm−1 band shows a blue shift of ∼5 cm−1 upon dilution and its linewidth also shows an increase of ∼5 cm−1 in going from neat prldh to extreme dilution. The line broadening upon dilution clearly indicates that the diffusion mechanism plays a dominant role in the dephasing of this vibrational mode. Density functional theoretic (DFT) calculations were performed employing B3LYP functional and high level basis set, 6-311++G(d,p) to obtain the ground state geometry of neat prldh and its hydrogen bonded complexes with methanol in gas phase. Basis set superimpose error (BSSE) correction was also introduced using the counterpoise method. In order to realize a condition quite close to the experiment, the polarizable continuum model (PCM, specific plus bulk solvation) calculations were also performed. For a detailed vibrational assignment of the normal modes, potential energy distribution (PED) calculation was also performed.