Subat Michael, Woinaroschy Kristina, Gerstl Corinna, Sarkar Biprajit, Kaim Wolfgang, König Burkhard
Institute for Organic Chemistry, University of Regensburg, Universitätsstr.31, D-93053 Regensburg, Germany.
Inorg Chem. 2008 Jun 2;47(11):4661-8. doi: 10.1021/ic702413q. Epub 2008 May 8.
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.
先前已报道了1,4,7,10 - 四氮杂环十二烷（[12]aneN4或环烯）与不同长度（双联吡啶和三联吡啶）的杂环间隔基（三嗪、吡啶）或氮杂冠醚侧基形成的单核和双核锌（II）、铜（II）和镍（II）配合物，已在生理条件（pH 7 - 9，25℃）下对其催化双（4 - 硝基苯基）磷酸酯（BNPP）水解的性能进行了测试。所有锌（II）配合物在生理条件下均能促进BNPP的水解，而铜（II）和镍（II）的配合物对水解反应没有显著影响。在25℃下，通过初始斜率法（产物转化率<5%）测定了缓冲溶液（0.05 M Bis/Tris、TRIS、HEPES或CHES，I = 0.1 M，NaCl）中的水解动力学。单核配合物ZnL1、ZnL3和ZnL6的二级pH无关速率常数（kBNPP，M⁻¹ s⁻¹）分别为6.1×10⁻⁵、5.1×10⁻⁵和5.7×10⁻⁵，这表明杂环部分使水解速率比母体锌（[12]aneN4）配合物（kBNPP = 1.1×10⁻⁵ M⁻¹ s⁻¹）提高了多达六倍。活性物种是Zn（II） - OH⁻配合物，其中与Zn（II）配位的OH⁻作为亲核试剂。对于双核配合物Zn2L2、Zn2L4和Zn2L5，反应速率由金属中心之间的协同程度决定，而协同程度由间隔基长度决定。具有较短间隔基的Zn2L2和Zn2L4水解BNPP的速度比Zn2L5快1至2个数量级。Zn2L4和Zn2L2在pH 7、8和9时的二级速率常数k显著高于先前报道的相关配合物。高BNPP水解活性可能与芳香间隔基部分与底物之间的π - 堆积和疏水相互作用有关。配合物Zn2L4和Zn2L2在pH 7和8时表现出水解活性，这使得在生理条件下能够水解活化的磷酸酯。
