Complex formation equilibria of imipenem with some transition metal ions. Ternary complex formation reactions involving Cu(II) with imipenem and various bio-relevant ligands

Abstract

Imipenem is one of the β-lactam antibiotics (β-lactamase inhibitors), which are reported to be the most important class of drugs that are capable of inhibiting the bacterial enzyme to protect the β-lactam antibiotic from destruction. In view of the biological importance of imipenem as drug, the ligation behavior of imipenem is studied in order to get an idea about its potentiality towards some transition metals in in-vitro systems. The binary complex formation equilibria with the metal ions Cu(II), Ni(II), Co(II), Mn(II), and Zn(II) were investigated potentiometrically. The effects of dioxane as a solvent, on the protonation constant of imipenem and the formation constants of Cu(II)-imipenem complexes were discussed. The ternary copper(II) complexes involving imipenem and various biologically relevant ligands containing different functional groups, as amino acids, amides, dicarboxylic acids and DNA constituents were investigated. The stability constants of the complexes are determined. The mechanisms of complex formation are speculatively discussed based on the calculated stability constant values. The ternary complexes are formed by simultaneous reactions. The concentration distributions of various species formed in solution were also evaluated as a function of pH.