Problems in Bioinorganic and Oxygen Atom Transfer Chemistry

这项由无机化学、生物无机化学和金属有机化学项目颁发的奖项支持哈佛大学理查德·H·霍尔姆教授专注于钼/钨羟基酶和氧转移酶的研究。催化中心含有单核Mo或W原子，它们与一个或两个蝶呤-二硫杂环烯配体(通常称为钼杂蝶呤)结合。实验方法包括合成酶的催化部位的低分子量表示或类似物，在反应活性研究之前对其进行充分表征。天然配体由合成的二硫杂环戊烯代表，当它与钼或钨结合时，它的功能是烯-1，2-二硫杂环戊二烯，并与蝶呤-二硫杂环烯产生的电子环境非常相似。通过模拟系统，该项目检查了硝酸还原酶、甲酸脱氢酶、亚砷酸氧化酶、乙炔水合酶、亚硫酸盐氧化酶和乙醛氧化酶等酶的反应。这包括在氧化和还原状态下合成新的活性中心类似物，包括罕见的单二硫烯络合物，以及动力学测定以及随之而来的速度常数和活化参数的评估。动力学和其他信息被用来推断所研究的反应的可能机理。还在研究非生理金属Nb、Ta和Re在其较高氧化态的合成和氧转移反应活性。参与全球碳、氮、硫循环和催化单个氧原子转移的酶的基本成分将通过模拟络合物进行研究。其中一些酶，如亚硫酸盐和黄嘌呤氧化酶，存在于人类体内；它们的故障会导致重大的健康风险。研究生和博士后将接受综合、表征和机理以及模型和生物系统之间的相互关系方面的培训。

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.