Cadmium(II) complexes: Mimics of organophosphate pesticide degrading enzymes and metallo-β-lactamases

Daumann, Lena J., Gahan, Lawrence R., Comba, Peter and Schenk, Gerhard (2012) Cadmium(II) complexes: Mimics of organophosphate pesticide degrading enzymes and metallo-β-lactamases. Inorganic Chemistry, 51 14: 7669-7681. doi:10.1021/ic300687y


Author Daumann, Lena J.
Gahan, Lawrence R.
Comba, Peter
Schenk, Gerhard
Title Cadmium(II) complexes: Mimics of organophosphate pesticide degrading enzymes and metallo-β-lactamases
Journal name Inorganic Chemistry   Check publisher's open access policy
ISSN 0020-1669
1520-510X
Publication date 2012-07-03
Sub-type Article (original research)
DOI 10.1021/ic300687y
Volume 51
Issue 14
Start page 7669
End page 7681
Total pages 13
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2013
Language eng
Formatted abstract
Cadmium(II) complexes of ethyl 4-hydroxy-3,5-bis(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl)-benzoate (CO2EtH3L1) and ethyl 4-hydroxy-3,5-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)benzoate(CO2EtHL2) are described. The two ligands possess an ethyl ester (CO2Et-) at the position para to the phenolic −OH; CO2EtHL2, with methyl ether donors in contrast to potentially nucleophilic alkoxide donors in CO2EtH3L1, offers a direct comparison of potential ligand-centered nucleophiles. The complex with CO2EtH3L1 was characterized using 1H and 13C NMR
spectroscopy, mass spectrometry and microanalysis; X-ray crystallography defined a tetranuclear structure [Cd4(CO2EtH2L1)2(CH3COO)3.75Cl0.25(H2O)2](PF6)2. Functional studies of the cadmium(II) complexes were undertaken with the substrates bis(2,4-dinitrophenyl)phosphate (BDNPP), and nitrocefin to assess their phosphatase and β-lactamase activities, respectively. The complexes with CO2EtH3L1 and CO2EtHL2 are competent phosphoesterase mimics with KM = 9.4 ± 2.1 mM and 10.1 ± 3.4 mM, kcat = 9.4 ± 0.2 × 10−3 s−1 and 9.7 ± 2.7 × 10−3 s−1, respectively. Use of a solvent mixture containing H2 18O/H2 16O in the reaction with BDNPP showed that for the complex with CO2EtH3L1 the 18O label was incorporated in the reaction product suggesting that the nucleophile involved is a Cd−OH moiety and not a metal bound alkoxide; for CO2EtHL2 the presence of the methyl-ether dictates that the active nucleophile must also be a hydroxide. The cadmium(II) complex with CO2EtH3L1 was furthermore found to be a competent β-lactamase mimic with kcat = 1.39 × 10−2 ± 3 × 10−3 s−1, KM = 0.11 ± 0.03 mM, and pKa = 7.9 ± 0.1. Mass spectral evidence suggested that the active nucleophile in this reaction is the alkoxide; lack of β-lactamase activity of the complex with CO2EtHL2 supports this assignment. Similar to enzymecatalyzed reactions, a blue reaction intermediate in the β-lactamase reaction of the CO2EtH3L1 complex was also identified. It is proposed that the Cd(II) complexes of CO2EtH3L1 and CO2EtHL2 react identically as phosphatases, with a terminal hydroxide as the nucleophile; the former exhibits β-lactamase activity with the alkoxide as a nucleophile, while the latter, without a potentially nucleophilic alkoxide, is inactive.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Publication Date: July 3 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 10 Jul 2012, 15:17:54 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences