Characterization of the aqueous iron(III) chelation chemistry of a potential Trojan Horse antimicrobial agent: chelate structure, stability and pH dependent speciation

The aqueous solution equilibria of a β-lactam antimicrobial agent containing a 3-hydroxy, 4-pyridinone group (L PF) binding to Fe(III) in aqueous solution has been characterized through spectrophotometric and potentiometric titrations. The metal-free ligand has four observable protonation constants, pKa1 = 2.6, pKa2 = 3.43, pKa3 = 6.43, and pKa4 = 9.62. L PF forms a 3:1 ligand:Fe(III) complex in aqueous solution through coordinate-covalent bond formation exclusively involving the bidentate hydroxypyridinone moiety. This 3:1 L PF:Fe complex was found to have a stability constant of log β130 = 33.46. A speciation diagram for the L PF system demonstrates that in the region of physiological pH the tris-(L PF)Fe(III) complex, Fe(LPF) 3 6− , predominates. This complex exhibits two irreversible reduction waves in solution at −30 mV versus NHE, corresponding to a ligand-based reduction, and at −385 mV versus NHE, corresponding to an irreversible Fe3+/Fe2+ reduction of the Fe(LPF) 3 6− complex.