FREE RADICALS IN BIOLOGICAL REDOX PROCESSES

描述：（改编自申请人的摘要） 生物环境通常会引起破坏性的化学反应，因为它们的 反应性和非特异性化学。然而，最近，一种新的 已经鉴定了其中产生活性自由基物质的酶 从氨基酸或修饰的氨基酸侧链在正常过程中， 催化作用这些顺磁性物质似乎是 这些酶的功能。这些激进分子的一些原则 正在出现，并可以总结如下：a）氧化还原活性 侧链通常发生在靠近金属中心， B）一旦形成，所述自由基在产生自由基物质中起作用， 通过从底物中提取氢原子的催化作用;和c） 蛋白质包括稳定反应性自由基物质， 非特异性化学反应理解这些原则的手段 在分子一级实施是该项目的一个长期目标。到 这样做，申请人打算把重点放在02-进化（锰）4 YZ中心， 光系统II，它具有动力学特性，使它们能够捕获特定的 催化过程中的中间体，以及半乳糖氧化酶， 氧化还原连接配体交换过程和取代诱导自旋密度 已经提出了调制。该项目的一个主要目标是发展和 推广低频FTIR差分技术， 金属-底物配体、金属辅因子和辅因子振动模式 成为可能。采用这种方法将需要工具 与定向诱变，同位素取代， 无机模型化合物、电化学和计算研究。他们 打算继续他们在自由基酶类上的磁共振工作， 发展处理与原子核超精细相互作用中的自由基对的方法 在他们的附近，并通过完善他们的理解的因素， 控制自由基酶类中的自旋密度分布。

DESCRIPTION: (Adapted from the applicant's abstract) Free radicals in biological millieu generally provoke destructive chemistry, owing to their reactivity and non-specific chemistry. Recently, however, a new class of enzymes has been identified in which reactive radical species are generated from amino-acid or modified amino-acid side chains during the normal course of catalysis. These paramagnetie species appear to be integral to the proper function of these enzymes. Some of the principles by which these radicals operate are emerging and can be summarized as follows: a) the redox-active side-chain usually occurs in close proximity to a metal center that is involved in generating the radical species; b) once formed, the radical functions in catalysis by abstracting hydrogen-atoms from substrate; and c) the role of the protein includes stabilizing the reactive radical species so as to prevent non-specific chemistry. Understanding the means by which these principles are implemented at the molecular level is a long-term objective of the project. To do this, the applicants intend to focus on the 02-evolving (Mn)4YZ Center in Photosysytem II, which has kinetic properties that allow them to trap specific intermediates in the catalytic process, and on galactose oxidase, for which redox-linked ligand exchange processes and substitution-induced spin-density modulation have been proposed. A principal aim of the project is to develop and generalize low-frequency FTIR difference techniques so that direct observation of metal-substrate ligand, metal cofactor, and cofactor vibrational modes becomes possible. Employing this methodology will require instrument development in combination with directed mutagenesis, isotope-substitution, inorganic model compound, electrochemical, and computational studies. They intend to continue their magnetic-resonance work on the radical-enzyme class by developing methods to treat radical-pairs in hyperfine interaction with nuclei in their immediate vicinity and by refining their understanding of the factors that control spin density distributions in the radical enzyme class.