Problems in Bioinorganic and Oxygen Atom Transfer Chemistry

这个奖项由无机，生物无机和有机化学计划支持研究教授理查德H。哈佛大学的霍尔姆专注于钼/钨羟化酶和氧转移酶。 催化中心含有单核Mo或W原子，与一个或两个蝶呤-二硫杂环戊烯配体（通常称为蝶呤）结合。 实验方法包括合成低分子量的代表或类似物的催化位点的酶，这是充分的特点，然后才被研究的反应性调查。 天然配体以合成的二硫纶为代表，当与钼或钨结合时，其功能为烯-1，2-二硫纶，并且密切模拟由蝶呤-二硫纶产生的电子环境。 通过模拟系统，该项目研究了硝酸还原酶，甲酸脱氢酶，亚砷酸盐氧化酶，乙炔水合酶，亚硫酸盐氧化酶和醛氧化酶等酶的反应。 这涉及在氧化和还原状态下合成新的活性位点类似物，包括不常见的monodithiolene复合物，以及动力学测定和伴随的速率常数和活化参数的评价。 动力学和其他信息被用来推断可能的机制进行调查的反应。 还在研究中的是非生理金属铌、钽和钽在其较高氧化态下的合成和氧代转移反应性。 参与全球碳，氮和硫循环和催化单个氧原子转移的酶的基本组成部分将通过模拟复合物进行研究。 其中一些酶，如亚硫酸盐和黄嘌呤氧化酶，存在于人类中;它们的功能障碍会导致重大的健康风险。 研究生和博士后学生将在合成，表征和机制以及模型和生物系统之间的相互关系方面进行培训。

This award by the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Prof. Richard H. Holm of Harvard University focused on molybdenum/tungsten hydroxylases and oxotransferases. The catalytic centers contain mononuclear Mo or W atoms bound to one or two pterin-dithiolene ligands (often called molybdopterin). The experimental approach involves the synthesis of low molecular weight representations or analogs of the catalytic sites of enzymes, which are fully characterized before being studied in reactivity investigations. The natural ligand is represented by a synthetic dithiolene, which functions as an ene-1,2-dithiolate when bound to molybdenum or tungsten and closely simulates the electronic environment engendered by the pterin-dithiolene. Through analog systems, the project examines reactions of the enzymes nitrate reductase, formate dehydrogenase, arsenite oxidase, acetylene hydratase, sulfite oxidase, and aldehyde oxidase, among others. This involves the synthesis of new active site analogs in oxidized and reduced states, including uncommon monodithiolene complexes, and kinetics determinations with attendant evaluation of rate constants and activation parameters. Kinetic and other information is used to deduce probable mechanisms for the reactions investigated. Also under investigation are the synthesis and oxo transfer reactivity of the non-physiological metals niobium, tantalum, and rhenium in their higher oxidation states. The essential components of enzymes involved in global carbon, nitrogen, and sulfur cycles and catalyzing the transfer of a single oxygen atom will be studied through analog complexes. Some of these enzymes, such as the sulfite and xanthine oxidases, occur in humans; and their malfunction leads to significant health risks. Graduate and postdoctoral students will be trained in synthesis, characterization and mechanism and in regard to the interrelationships between model and biological systems.