ИСТИНА

Diclofenac (Voltaren©) has a significant, multi-faceted role in medicine, pharmacy, and biochemistry. Its physical properties and impact on biomolecular structures still attract essential scientific interest. However, its interaction with water has not been described yet at the molecular level. In the present study, we shed light on the interaction of the carboxylate group (–CO2–) with steric hindrance (the presence of the intramolecular N-H···O bond and the existence of the chlorine atom in vicinity of the –CO2– group) with water. Aqueous solution of sodium declofenac is investigated using ATR-IR and computational approaches, i.e. classical molecular dynamics (MD) simulations and density functional theory (DFT). Our coupled classical MD simulations, DFT calculations, and ATR-IR spectroscopy results indicated that the –CO2– group of the diclofenac anion undergoes strong specific interactions with the water molecules. The combined experimental and theoretical techniques provide significant insights the spectroscopic manifestation these interactions and the structure of the first hydration shell of the –CO2– group. Moreover, the developed methodology for the theoretical analysis of the ATR-IR spectrum could serve as a template for future IR/Raman studies of the strong interaction of the –CO2– group with steric hindrance of bioactive molecules with the water molecules in dilute aqueous solutions.