Hydration of the Carboxylate Group in Anti-Inflammatory Drugs: ATR-IR and Computational Studies of Aqueous Solution of Sodium Diclofenac

[Image: see text] Diclofenac (active ingredient of Voltaren) has a significant, multifaceted 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 between the steric hindrance (the intramolecular N–H···O bond, etc.) carboxylate group (−CO(2)(–)) with water. Aqueous solution of sodium declofenac is investigated using attenuated total reflection-infrared (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 −CO(2)(–) group of the diclofenac anion undergoes strong specific interactions with the water molecules. The combined experimental and theoretical techniques provide significant insights into the spectroscopic manifestation of these interactions and the structure of the hydration shell of the −CO(2)(–) group. Moreover, the developed methodology for the theoretical analysis of the ATR-IR spectrum could serve as a template for the future IR/Raman studies of the strong interaction between the steric hindrance −CO(2)(–) group of bioactive molecules with the water molecules in dilute aqueous solutions.