Metal–antibiotic interactions: potentiometric and spectroscopic investigation of cloxacillin and dicloxacillin complexes in aqueous solution

This study investigates the complexation of selected 3d transition metals (Co(II), Ni(II), Cu(II)) and lanthanide(III) ions (Nd(III), Eu(III), Tb(III)) with cloxacillin (Clox) and dicloxacillin (Diclox) in aqueous solution. The investigation combines potentiometric titrations and spectroscopic methods to provide insight into the coordination behavior of these isoxazolylpenicillins. The results show that complex stability follows the order Co(II) ≈ Ni(II) < Cu(II) and increases along the lanthanide series (Nd(III) < Eu(III) < Tb(III)). Dicloxacillin, containing two chlorine substituents in the isoxazolyl ring, forms consistently more stable complexes than cloxacillin, indicating a noticeable effect of ligand substitution on metal binding. Speciation analysis indicates the formation of mono- and bis-ligand species at near-neutral pH and hydroxo-ligand complexes at higher pH. Spectroscopic data confirm coordination mainly via the deprotonated carboxylate group, with additional involvement of amide functionalities. The observed spectral changes are consistent with potentiometric models and indicate stronger interactions in dicloxacillin systems. These findings demonstrate that small structural differences between the ligands significantly affect metal binding and speciation, providing new insight into β-lactam-metal interactions.