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

摘要

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, pK _(a1) = 2.6, pK _(a2) = 3.43, pK _(a3) = 6.43, and pK _(a4) = 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(L ~(PF)) 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 Fe ~(3+)/Fe ~(2+) reduction of the Fe(L ~(PF)) 3 ~(6-) complex.