Problems in Bioinorganic and Metal Cluster Chemistry

这个无机、生物无机和有机金属化学项目的奖项支持哈佛大学化学系Richard H. Holm博士在生物无机化学和金属簇方面的研究。将进行四项调查。在第一个专题领域，将研究二甲基亚砜还原酶、硝酸还原酶和甲酸脱氢酶催化位点的精确最小合成表示。酶转化的途径和促进这些途径的可行性的因素将被探讨。第二个研究领域涉及与氢化酶有关的镍和铁的生物化学。将制备用于稳定两种金属的硫酸桥接排列的四胱胺基环肽。二氢吸收和进化的动力学将在得到的模型化合物中进行研究。第三个领域包括过氧化物桥接血红素-铜的合成和铁与铜之间的磁偶联的研究，这是血红素-铜氧化酶的一个重要性质。含卟啉的铁铜配合物与过氧化物和酶抑制剂氰化物的相互作用也将被研究。最后，将合成中尺度金属硫属化合物簇并对其进行表征。这些团簇将含有铼和硫或硒，并将通过桥接相互作用连接起来。金属在多种酶的活性中起着重要作用，但控制其活性的因素尚不完全清楚。在这里，将合成模拟多种酶的化合物，并研究结构和电子变化对作用方式的影响。一个潜在的结果是在分子水平上描述好氧生物中氰化物毒性的基础。参与研究的研究生将学习各种先进的光谱方法，并将从参与包括其他机构合作者的项目中受益。

This award in the Inorganic, Bioinorganic, and Organometallic Chemistry program supports research in bioinorganic chemistry and in metal clusters by Dr. Richard H. Holm of the Chemistry Department, Harvard University. Four lines of investigation will be pursued. In the first topical area, accurate minimal synthetic representations of the catalytic sites of the enzymes dimethylsulfoxide reductase, nitrate reductase, and formate dehydrogenase will be examined. Pathways for enzymatic transformations and the factors contributing to the feasibility of these pathways will be explored. The second area of research involves biologically related nickel and iron chemistry pertinent to the enzyme hydrogenase. Tetracysteinyl cyclic peptides designed to stabilize the thiolate-bridged arrangement of the two metals will be prepared. The kinetics of dihydrogen uptake and evolution will be studied in the resulting model compounds. The third area includes synthesis of a peroxide-bridged heme-copper species and investigation of magnetic coupling between iron and copper, an imporant property of heme-copper oxidases. Interactions of porphyrin-containing iron-copper complexes with peroxide and the enzyme inhibitor cyanide will also be studied. Finally, mesoscale metal chalcogenide clusters will be synthesized and characterized. The clusters will contain rhenium and sulfur or selenium and will be linked by bridging interactions.Metals play important roles in the activity of a wide range of enzymes, but factors controlling their activity are not entirely understood. Here compounds modeling a number of enzymes will be synthesized and the effect of structural and electronic changes on mode of action will be studied. One potential outcome is a molecular level description of the basis of cyanide toxicity in aerobic organisms. Graduate students involved in the investigation will learn a wide variety of advanced spectroscopic methods and will benefit from involvement in a program that includes collaborators at other institutions.