Dinuclear Cobalt(II) Complexes as Metallo--lactamase Mimics

The -lactamase activity of two previously reported dinuclear cobalt(II) complexes is described. The two complexes, [Co2(CO2EtH2L1)(CH3COO)2](PF6) (CO2EtH3L1 = ethyl 4-hydroxy-3,5-bis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}benzoate) and [Co2(CO2EtL2)(CH3COO)2](PF6) (CO2EtHL2 = ethyl 4-hydroxy-3,5-bis{[(2-methoxyethyl)(pyridin-2-ylmethyl)amino]methyl}benzoate), differ in that the latter has methyl ether donors in contrast to potentially nucleophilic alkoxide donors in the former. They thus offer a direct comparison of potential ligand-centered nucleophiles. The complexes were treated with the antibiotic penicillin G and the commonly used lactamase substrate nitrocefin. On the basis of mass spectrometry, UV/Vis, and infrared spectroscopy measurements in solution, it was shown that only [Co2(CO2EtH2L1)(CH3COO)2](PF6) was capable of hydrolyzing both penicillin and nitrocefin, and that the hydrolysis-initiating nucleophile was an alkoxide donor. Analysis of kinetic data showed that nitrocefin binding occurs more rapidly {k1 = [(2.5x103)+/-(1.9x101)] M-1min-1} than its subsequent hydrolysis {k2 = [(1.6x10-1)+/-(8.1x10-4)] min-1}. The pH dependence of nitrocefin hydrolysis by [Co2(CO2EtH2L1)(CH3COO)2]+ displays two pKa values (6.88 +/- 0.74; 8.45 +/- 0.68), the first of which is attributed to the deprotonation of a CoII alcohol, and the second of which is proposed to arise from CoII-OH2. For [Co2(CO2EtL2)(CH3COO)2]+, only one relevant pKa1 (8.47 +/- 0.14) is evident, assigned to a terminal water molecule. By using variable-temperature/variable-field magnetic circular dichroism (VTVH MCD), it was demonstrated that the sign of the magnetic exchange coupling parameter (J) for the parent dinuclear cobalt(II) complexes changes upon binding of the substrate. This work presents one of the few cobalt(II) -lactamase model complexes that is capable of facile hydrolysis of -lactam substrates, an outcome that provides a good benchmark to investigate the reaction mechanism(s) applicable to the enzyme systems.