A DFT study of the interaction of aspirin, paracetamol and caffeine with one water molecule

We have studied the interaction of water with three important analgesics, aspirin, paracetamol and caffeine using DFT calculations and FTIR-ATR spectroscopy. In our study, water is used as a probe molecule to reveal the various H-bonding sites on the electrostatic potential energy surface of the analgesics. We find that water forms a strong double H-bond with the COOH group of aspirin and that the oxygen of the ester group can become H-bond acceptors. Paracetamol forms the strongest H-bond with water at the hydroxyl group and weaker H-bonds with the C = O group and the N–H group. Caffeine forms the strongest H-bond with water at the top C = O group and can form additional H-bonds with the bottom C = O group and the nitrogen of the imidazole ring. These studies may help to better understand the solvation of these analgesics in water. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00894-022-05258-w.