Thermodynamic and Kinetic Evaluation of Ampicillin Complexation with Nickel(II) and Copper(II) Ions

This study examined the apparent thermodynamic and kinetic behavior of ampicillin complexation with Ni(II) and Cu(II) in a water–ethanol medium at 25 and 35 °C. Potentiometric titration curves for an acid blank, free ampicillin, and equimolar metal–ampicillin mixtures were compared, and apparent formation constants were estimated from the reported half-neutralization treatment. At 25 °C, the apparent log β values were 7.19 for Ni(II)–ampicillin and 4.07 for Cu(II)–ampicillin. Both systems had negative standard Gibbs energy changes at the two temperatures studied. The Ni(II) system was exothermic and entropically unfavorable (ΔH° = −59.80 kJ mol?¹; ΔS° = −62.93 J mol?¹ K?¹), whereas the Cu(II) system was exothermic with a favorable entropy contribution (ΔH° = −14.07 kJ mol?¹; ΔS° = 30.72 J mol?¹ K?¹). Time-dependent pH measurements yielded linear plots of ln[H?] against time under the selected experimental conditions. The apparent first-order rate constant increased slightly with temperature for Cu(II) but decreased for Ni(II). Consequently, the Ni(II) data show anti-Arrhenius behavior over this narrow temperature interval and should not be interpreted as a conventional positive activation energy. The results indicate stronger apparent binding of Ni(II) than Cu(II), but rigorous publication-level formation constants require nonlinear speciation fitting, replicate titrations, and uncertainty estimates. This revised interpretation distinguishes observations supported by the data from mechanistic hypotheses.