EFFECTS OF DIAZONIUM SALTS ON METALLOPROTEINS

重氮盐对金属蛋白质的影响

• 批准号: 3438492
• 负责人: Michael PATRICK Doyle
• 金额: $ 7.26万
• 依托单位: TRINITY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438492
• 关键词: alkylation; chemical carcinogen; chemical models; copper; diazo compound; electron transport; fatty acids; hemerythrin; hemoglobin; hemoprotein; hydrolysis; metalloproteins; nitrogen compounds; nitrosourea; salts; stoichiometry

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.

目的是定义和表征脂肪族的反应， 重氮盐与金属蛋白质。 作为过渡中间体， 在烷基化反应中，脂肪族重氮离子被认为是 由含氮化合物形成的终极致癌物-氮 邦德 然而，芳烃重氮盐在某些情况下进行电子转移， 血红素蛋白导致它们转化为σ-芳基铁（III）络合物 原卟啉IX，并预计类似的转换与他们的 脂肪族对应物。 重氮盐将在原位产生， 重氮化合物通过质子化和已知形成的N-亚硝基脲 重氮盐水解。 详细的动力学和产物分析 重氮化合物和血红蛋白之间的反应将进行， 建立电子转移的化学计量和机理 过程 电中性重氮化合物在水溶液中的迁移 pH控制的亲水环境到疏水环境中 血红蛋白血红素口袋，质子化和电子转移导致 形成原卟啉IX的σ-烷基铁（III）络合物， 预期 这些环境之间存在交叉屏障 对于重氮化合物，类似于对于芳烃重氮盐所建议的， 将在模型系统的帮助下进行研究。 敏感自由基 将采用涉及自由基加成反应的捕获实验 来确定电子转移后发生的化学反应 步 预期的化学反应和反应性 σ-烷基铁（III）配合物以及脂肪族 重氮离子与代表性血红素蛋白、血红蛋白和铜 将研究蛋白质。