Phosphate Triester Hydrolysis Promoted by an N2S(thiolate)Zn Complex: Mechanistic Implications for the Metal-Dependent Reactivity of Peptide Deformylase
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- 作者：David P. Goldberg ; Robert C. diTargiani ; Frances Namuswe ; Ellen C. Minnihan ; SeChin Chang ; Lev N. Zakharov ; and Arnold L. Rheingold
- 刊名：Inorganic Chemistry
- 出版年：2005
- 出版时间：October 17, 2005
- 年：2005
- 卷：44
- 期：21
- 页码：7559 - 7569
- 全文大小：258K
- 年卷期：v.44,no.21(October 17, 2005)
- ISSN：1520-510X
文摘
The zinc(II) complex (PATH)ZnOH, where PATH is an N2S(thiolate) ligand, has been investigated for its ability topromote the hydrolysis of the phosphate triester tris(4-nitrophenyl) phosphate (TNP). The hydrolysis of TNP wasexamined 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 thesecond-order rate constants were derived from linear plots of the observed pseudo-first-order rate constants versuszinc complex concentration at different pH values. A pH-rate profile yielded a kinetic pKa of 8.52(5) for the zinc-bound water molecule and a pH-independent rate constant of 16.1(7) M-1 s-1. Temperature-dependent studiesshowed linear Eyring behavior, yielding the activation parameters 
H
= 36.9(1) kJ mol-1 and S = -106.7(4)J mol-1 K-1. Interpretation of the kinetic data leads to the conclusion that hydrolysis of TNP takes place througha hybrid mechanism, in which the metal center plays a dual role of providing a nucleophilic hydroxide and activatingthe substrate through a Lewis acid effect. The synthesis and structural characterization of the related nickel(II) andiron(II) complexes [(PATH)2Ni2]Br2 (2) and (PATH)2Fe2Cl2 (3) are also described. Taken together, these data suggesta possible explanation for the low reactivity of the zinc(II) form of peptide deformylase as compared to the iron(II)form.
C. The reaction is first order in both zinc(II) complex and substrate, and thesecond-order rate constants were derived from linear plots of the observed pseudo-first-order rate constants versuszinc complex concentration at different pH values. A pH-rate profile yielded a kinetic pKa of 8.52(5) for the zinc-bound water molecule and a pH-independent rate constant of 16.1(7) M-1 s-1. Temperature-dependent studiesshowed linear Eyring behavior, yielding the activation parameters H = 36.9(1) kJ mol-1 and S = -106.7(4)J mol-1 K-1. Interpretation of the kinetic data leads to the conclusion that hydrolysis of TNP takes place througha hybrid mechanism, in which the metal center plays a dual role of providing a nucleophilic hydroxide and activatingthe substrate through a Lewis acid effect. The synthesis and structural characterization of the related nickel(II) andiron(II) complexes [(PATH)2Ni2]Br2 (2) and (PATH)2Fe2Cl2 (3) are also described. Taken together, these data suggesta possible explanation for the low reactivity of the zinc(II) form of peptide deformylase as compared to the iron(II)form.