Dinuclear cobalt(II) omplexes as metallo--lactamase mimics

Daumann, Lena J., Larrabee, James A., Comba, Peter, Schenk, Gerhard and Gahan, Lawrence R. (2013) Dinuclear cobalt(II) omplexes as metallo--lactamase mimics. European Journal of Inorganic Chemistry, 17: 3082-3089. doi:10.1002/ejic.201300280


Author Daumann, Lena J.
Larrabee, James A.
Comba, Peter
Schenk, Gerhard
Gahan, Lawrence R.
Title Dinuclear cobalt(II) omplexes as metallo--lactamase mimics
Formatted title
Dinuclear cobalt(II) complexes as metallo-β-lactamase mimics
Journal name European Journal of Inorganic Chemistry   Check publisher's open access policy
ISSN 1434-1948
1099-0682
Publication date 2013-06-01
Year available 2013
Sub-type Article (original research)
DOI 10.1002/ejic.201300280
Open Access Status Not yet assessed
Issue 17
Start page 3082
End page 3089
Total pages 8
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Language eng
Abstract 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.
Formatted abstract
The β-lactamase activity of two previously reported dinuclear cobalt(II) complexes is described. The two complexes, [Co2(CO 2EtH2L1)(CH3COO)2](PF6) (CO2EtH3L1 = ethyl 4-hydroxy-3,5-bis{[(2-hydroxyethyl) (pyridin-2-ylmethyl)amino]methyl}benzoate) and [Co2(CO 2EtL2)(CH3COO)2](PF6) (CO 2EtHL2 = 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 = [(2.5 × 103) ± (1.9 × 101)] M-1 min-1} than its subsequent hydrolysis {k2 = [(1.6 × 10-1) ± (8.1 × 10 -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)(CH 3COO)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) β-lactamase model complexes that is capable of facile hydrolysis of β-lactam substrates, an outcome that provides a good benchmark to investigate the reaction mechanism(s) applicable to the enzyme systems. Two dinuclear CoII complexes were tested for their ability to hydrolyze β-lactam substrates. The [Co 2(CO2EtH2L1)(CH3COO) 2]+ complex is reactive towards nitrocefin and penicillin, whereas [Co2(CO2EtL2)(CH3COO) 2]+ is unreactive. The difference between the two complexes is due to the presence of an alkoxide in the former.
Keyword Cobalt
Biomimetics
Lactams
Nucleophiles
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP0986613
CHE0848433
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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