EFFECTS OF DIAZONIUM SALTS ON METALLOPROTEINS

目的是定义和表征脂肪族化合物的反应。 含金属蛋白的重氮盐。作为暂态中间体 烷基化反应中，脂肪族重氮离子被认为是 由含氮化合物形成的最终致癌物质 邦德。然而，芳基重氮盐以一定的方式进行电子转移 导致其转化为Sigma-芳纶(III)络合物的血球蛋白 原卟啉IX，预计会有类似的转化 脂肪族对应物。重氮盐将由以下物质现场生成 通过质子化和由N-亚硝基形成的重氮化合物 重氮盐通过水解制得。详细的动力学和产品分析 重氮化合物和血红蛋白之间的反应将进行到 建立电子转移的化学计量学和机理 进程。电子中性重氮化合物的输运 PH控制的亲水环境对疏水环境的影响 血红蛋白的血红素口袋，质子化和电子转移引起的 原卟啉的Sigma-烷基(III)络合物的形成 预期中。这些环境之间存在交叉障碍 对于重氮化合物，类似于芳基重氮盐的建议， 将借助模型系统进行调查。敏感基团 将采用包括自由基加成反应的捕获实验 以确定电子转移后发生的化学事件 一步。预期的化学反应和反应性 Sigma-烷基(III)络合物及脂肪族化合物的相互作用 具有代表性的血红蛋白、氯氰菊酯和铜的重氮离子 将对蛋白质进行研究。

The objective is to define and characterize the reactions of aliphatic diazonium salts with metalloproteins. As transient intermediates in alkylation reactions, aliphatic diazonium ions are considered to be the ultimate carcinogens formed from compounds containing the nitrogen-nitrogen bond. However, arenediazonium salts undergo electron transfer with certain hemoproteins resulting in their conversion to Sigma-aryliron(III) complexes of protoporphyrin IX, and similar transformations are expected with their aliphatic counterparts. Diazonium salts will be generated in situ from diazo compounds by protonation and from N-nitrosoureas known to form diazonium salts by hydrolysis. Detailed kinetic and product analyses for reactions between diazo compounds and hemoglobin will be undertaken to establish the stoichiometry and mechanism of the electron transfer process. Transport of the electronically neutral diazo compound from a pH-controlled hydrophilic environment to the hydrophobic environment in the heme pocket of hemoglobin, where protonation and electron transfer cause formation of a Sigma-alkyliron(III) complex of protoporphyrin IX, is expected. The existence of a crossover barrier between these environments for diazo compounds, analogous to that suggested for arenediazonium salts, will be investigated with the aid of model systems. Sensitive radical trapping experiments involving radical addition reactions will be employed to determine the chemical events that occur after the electron transfer step. The chemical reactions and reactivities of anticipated Sigma-alkyliron(III) complexes as well as the interactions of aliphatic diazonium ions with representative hemoproteins, hemerythrin, and copper proteins will be investigated.