The Influence of the Hydrogen Isotope Effect on the Kinetics of Amoxicillin and Essential Elements Interaction

Chemical incompatibility between active pharmaceutical ingredients (APIs) and mineral supplements may affect their bioavailability and effectiveness. Water, as the main component of physiological fluids, plays a crucial role in these interactions. Natural waters vary in the deuterium. Estimation of the kinetic isotope effect (KIE) provides valuable information on reaction mechanisms in solvents with different D/H ratios and with the replacement of protium with deuterium in API molecules. Studies of the kinetics of interactions between zinc ions and amoxicillin in water with a natural isotopic composition (D/H = 145 ppm) and in heavy water (99.9% D2O) offer a model for predicting similar interactions in vivo. The presence of chiral centers in the amoxicillin molecule allowed the use of polarimetry to study the influence of the solvent isotopic composition, temperature, and pH on the rate of interaction. In heavy water, a twofold decrease in the rate of amoxicillin binding to hydrated zinc ions was observed compared to natural water at 20 °C. Arrhenius kinetics confirmed the observed KIE: Ea = 112.5 ± 1.3 kJ/mol for D2O and 96.0 ± 2.1 kJ/mol for H2O. For the first time, kinetic polarimetric studies demonstrated differences in the mechanisms of binding of d- and s-element cations to amoxicillin.