Previously reported mono- and dinuclear Zn(II), Cu(II), and Ni(II) complexes of 1,4,7,10-tetrazacyclododecane ([12]aneN4 or cyclen) with different heterocyclic spacers (triazine, pyridine) of various lengths (bi- and tripyridine) or an azacrown-pendant have been tested for the hydrolysis of bis(4-nitrophenyl)phosphate (BNPP) under physiological conditions (pH 7-9, 25 degrees C). All Zn(II) complexes promote the hydrolysis of BNPP under physiological conditions, while those of Cu(II) and Ni(II) do not have a significant effect on the hydrolysis reaction. The hydrolysis kinetics in buffered solutions (0.05 M Bis/Tris, TRIS, HEPES, or CHES, I=0.1 M, NaCl) at 25 degrees C were determined by the initial slope method (product conversion<5%). Comparison of the second-order pH-independent rate constants (kBNPP, M(-1) s(-1)) for the mononuclear complexes ZnL1, ZnL3, and ZnL6, which are 6.1x10 (-5), 5.1x10(-5), and 5.7x10(-5), respectively, indicate that the heterocyclic moiety improves the rate of hydrolysis up to six times over the parent Zn([12]aneN4) complex (kBNPP=1.1x10(-5) M(-1) s(-1)). The reactive species is the Zn(II)-OH- complex, in which the Zn(II)-bound OH- acts as a nucleophile. For dinuclear complexes Zn2L2, Zn2L4, and Zn2L5, the rate of reaction is defined by the degree of cooperation between the metal centers, which is determined by the spacer length. Zn2L2 and Zn2L4 possessing shorter spacers are able to hydrolyze BNPP 1 to 2 orders of magnitudes faster than Zn2L5. The second-order rate constants k of Zn2L4 and Zn2L2 at pH 7, 8, and 9 are significantly higher than those of previously reported related complexes. The high BNPP hydrolytic activity may be related to pi-stacking and hydrophobic interactions between the aromatic spacer moieties and the substrate. Complexes Zn2L4 and Zn2L2 show hydrolytic activity at pH 7 and 8, which allows for the hydrolysis of activated phosphate esters under physiological conditions.

中文翻译：

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1,4,7,10-四氮杂环十二烷金属配合物在生理条件下作为磷酸二酯水解的有效促进剂。

先前报道的1,4,7,10-四氮杂十二烷（[12] aneN4或cyclen）的单核和双核Zn（II），Cu（II）和Ni（II）配合物具有不同的杂环间隔基（三嗪，吡啶）在生理条件（pH 7-9，25摄氏度）下，已经测试了各种长度的（联吡啶和三吡啶）或氮杂皇冠吊坠用于水解双（4-硝基苯基）磷酸酯（BNPP）。所有的Zn（II）配合物在生理条件下均能促进BNPP的水解，而Cu（II）和Ni（II）的配合物对水解反应没有显着影响。通过初始斜率法（产物转化率＜5％）测定在25℃的缓冲溶液（0.05M Bis / Tris，TRIS，HEPES或CHES，I ＝ 0.1M，NaCl）中的水解动力学。二阶pH无关速率常数（kBNPP，单核络合物ZnL1，ZnL3和ZnL6的M（-1）s（-1））分别为6.1x10（-5），5.1x10（-5）和5.7x10（-5）。与母体Zn（[12] aneN4）配合物（kBNPP = 1.1x10（-5）M（-1）s（-1））相比，杂环部分最多可将水解速率提高六倍。反应性物质是Zn（II）-OH-络合物，其中与Zn（II）结合的OH-充当亲核试剂。对于双核络合物Zn2L2，Zn2L4和Zn2L5，反应速率由金属中心之间的配合程度定义，而配合程度由间隔物长度决定。具有较短间隔基的Zn2L2和Zn2L4能够比Zn2L5更快地水解BNPP 1至2个数量级。Zn2L4和Zn2L2在pH 7、8和9下的二阶速率常数k明显高于先前报道的相关配合物。高的BNPP水解活性可能与芳香族间隔基团和底物之间的π堆积和疏水相互作用有关。配合物Zn2L4和Zn2L2在pH 7和8时显示水解活性，从而可以在生理条件下水解活化的磷酸酯。