Molecular Probes for the Chemistry of Peroxynitrite

描述(申请人提供)：过氧亚硝酸盐(ONOO)是一种破坏性的 生物氧化剂，与广泛的 人类疾病状态的范围。一种新型脱毒催化剂 过氧亚硝酸盐(通过与良性硝酸根离子异构化)应提供 有价值的探索，以了解复杂的相互作用的反应性氧化剂 生物系统。此外，这些试剂可能被证明是重要的 药剂。这项建议概述了一项发展 用于ONOO快速选择性异构化为N03-的铁基催化剂。 建议的“过氧亚硝酸酶”是一般的双核铁络合物。 式[Fe(III)2(u-O)L(X)X(Y)](Cl)(4)z。这些阳离子二铁物种是 预计将参与过亚硝酸根的高效催化循环 混合价态Fe(III)/Fe(IV)中间体催化的异构化反应变异 配体X和L的作用是容易的，并且应该能够使催化最优化 活性和催化剂稳定性。对这两个问题的机械性调查 [Fe(III)2(u-O)L(X)X(Y)](Cl)(4)z与Fe(III)2(u-O)的化学计量和催化反应 为了确定重要的中间体，将进行过氧亚硝酸根 并充分描述催化循环的特征。

DESCRIPTION (provided by applicant): Peroxynitrite (ONOO) is a destructive biological oxidant which contributes to cellular damage associated with a wide range of human disease states. New catalysts for the detoxification of peroxynitrite (by isomerization to the benign nitrate anion) should provide valuable probes for understanding the complex interplay of reactive oxidants in biological systems. In addition these reagents could prove important as pharmaceutical agents. This proposal outlines a strategy for the development of iron-based catalysts for the rapid and selective isomerization of ONOO to N03-. The proposed "peroxynitritases" are binuclear iron complexes of the general formula [Fe(III)2(u-O)L(x)X(y)](Cl)(4)z. These cationic di-iron species are expected to participate in an efficient catalytic cycle for peroxynitrite isomerization mediated by mixed valent Fe(III)/Fe(IV) intermediates. Variation of the ligands X and L is facile, and should enable optimization of catalytic activity and catalyst stability. Mechanistic investigations of both the stoichiometric and catalytic reactions of [Fe(III)2(u-O)L(x)X(y)](Cl)(4)z with peroxynitrite will be undertaken in order to identify important intermediates and to fully characterize the catalytic cycle.