Molecular structure, spectroscopic signature and reactivity analyses of paracetamol hydrochloride monohydrate salt using density functional theory calculations

The aim of this study was to understand the role of the intermolecular hydrogen bond interactions present in paracetamol hydrochloride monohydrated salt. Paracetamol hydrochloride monohydrate salt (PRA-HCl) and paracetamol (form I) were investigated via vibrational (FT-IR and FT-Raman) spectroscopy and density functional theory (DFT) to gain insight into the hydrogen bond patterns present in these crystalline materials. Two different density functionals, wB97X-D and M062X, were used for the comparison of the results. The geometrical parameters of PRA-HCl and form I obtained using these functional were compared with the crystallographic data, which proved the existence of intra-molecular and intermolecular hydrogen bonds. The C10?O2 group of form I forms an intramolecular hydrogen bond, while the O1-H18 group of PRA-HCl forms an intermolecular hydrogen bond with a chloride ion (Cl-), resulting in the elongation of the bond length and shift to a lower wavenumber for the O1-H18 group. To examine the potency of hydrogen bonding, quantum theory of atoms in molecules (QTAIM) calculations were performed and the results suggested that O1-H18Cl22 is a strong intermolecular hydrogen bond. The chemical reactivity parameters reveal that the PRA-HCl and PRA-OXA cocrystals are more reactive and softer (low HOMO-LUMO energy gap) in comparison to paracetamol (form I).