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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Cotton Chemistry and Utilization Research » Research » Publications at this Location » Publication #255725

Title: Phosphate Triester Hydrolysis Promoted by an N2S (thiolate) Zinc Complex: Mechanistic Implications for the Metal-Dependent Reactivity of Peptide Deformylase

item GOLDBERG, D. - Johns Hopkins University
item DI TARGIANI, R. - Johns Hopkins University
item NAMUSWE, F. - Johns Hopkins University
item MINNIHAN, E. - Johns Hopkins University
item Chang, Sechin
item ZAKHAROV, L. - University Of California
item RHEINGOLD, A. - University Of California

Submitted to: Inorganic Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2005
Publication Date: 9/16/2005
Citation: Goldberg, D., Di Targiani, R., Namuswe, F., Minnihan, E., Chang, S., Zakharov, L., Rheingold, A. 2005. Phosphate Triester Hydrolysis Promoted by an N2S (thiolate) Zinc Complex: Mechanistic Implications for the Metal-Dependent Reactivity of Peptide Deformylase. Inorganic Chemistry. 44(21):7559-7569.

Interpretive Summary: The long term objective of this research concerns the synthesis and reactivity of a new family of nitrogen/sulfur metal complexes that are designed to be structural and functional models of certain of these important biological centers. In this paper, we have focused synthesis of the iron(II) and nickel(II) complexes, this results suggests that the parent form of the nitrogen/sulfur containing ligand will not be suitable because monomeric species do not appear favored in reactions with simple metal halides. Additionally, the kinetic studies described that the different reactivities of zinc- and iron(II)- peptide deformylase enzyme on hydrolysis of zinc hydroxide complex may arise from the iron(II) center’s strong preference for five-coordination geometry.

Technical Abstract: The zinc(II) complex (PATH)ZnOH, where PATH is an N2S(thiolate) ligand, has been investigated for its ability to promote the hydrolysis of the phosphate triester tris(4-nitrophenyl) phosphate (TNP). The hydrolysis of TNP was examined as a function of PATH-zinc(II) complex concentration, substrate concentration, and pH in a water/ethanol mixture (66:33 v/v) at 25 °C. The reaction is first order in both zinc(II) complex and substrate, and the second-order rate constants were derived from linear plots of the observed pseudo-first-order rate constants versus zinc complex concentration at different pH values. Interpretation of the kinetic data leads to the conclusion that hydrolysis of TNP takes place through a hybrid mechanism, in which the metal center plays a dual role of providing a nucleophilic hydroxide and activating the substrate through a Lewis acid effect. The synthesis and structural characterization of the related nickel(II) and iron(II) complexes [(PATH)2Ni2]Br2 and (PATH)2Fe2Cl2 are also described. Taken together, these data suggest a possible explanation for the low reactivity of the zinc(II) form of peptide deformylase as compared to the iron(II) form.