Kinetics and Mechanisms: Oxidation of Some Selected sulfur Compounds of Physiological and Environmental Importance

无机化学、生物无机化学和金属有机化学项目的这一奖项支持波特兰州立大学鲁本·西莫伊教授的研究，该研究旨在阐明一些具有生理和环境重要性的选定有机硫化合物的氧化动力学和机理。这些机理数据将用于使有机硫化合物观察到的生理效应合理化，并预测其毒性。因此，这项提案将集中于硫代酰胺、硫代氨基甲酸酯、二硫代氨基甲酸酯和氨基硫醇。常用的生理氧化剂有分子氧、过氧化氢、过氧酸、高氯、高溴、超氧阴离子、羟基和过氧亚硝酸根。由于二氧化氯最近被广泛用作氧化剂和水消毒剂，它也将被用作部分农业有机硫化合物的氧化剂。有机硫化合物在形成硫代化合物的硫酸盐和尿素类似物之前，预计会形成S氧化物、二氧化物和三氧化物。这项提议的主要主题将是合成和表征(X-射线结构，反应性，化学性质)这些假定的硫氧酸。还将评估它们的生物活性，以确定在有氧环境中产生活性氧物种的可能性，以及探索通过DNA损伤实验量化的可能的毒性影响。反映S-亚硝硫醇在生理环境中重要性的工作将研究亚硝硫醇形成的相关化学(形成和分解的动力学和机理)。从机理上理解硫醇亚硝化反应应该能够设计出具有更好的药代动力学特性的RSNO。这项研究跨越了物理化学和生物物理化学领域，通过获得可以用来合理解释观察到的特定生物活性有机硫化合物的生理效应的机理和动力学数据。这笔助学金的很大一部分涉及对本科生和研究生进行这种跨学科研究的培训。国际和平协会的实验室目前正在培训一些来自弱势背景的博士生，所要求的资金中的很大一部分将用于教育代表不足的少数群体。

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Reuben Simoyi at Portland State University to elucidate the kinetics and mechanisms of the oxidation of some selected organosulfur compounds of physiological and environmental importance. The mechanistic data will be used in rationalizing the organosulfur compounds' observed physiological effects and to predict toxicities. This proposal will thus concentrate on thioamides, thiocarbamides, thiocarbamates, dithiocarbamates and aminothiols. The general physiological oxidants that will be used are molecular oxygen, hydrogen peroxide, peracids, HOCl, HOBr, and superoxide, hydroxyl and peroxynitrite radicals. Due to the recent wide-spread use of chlorine dioxide as an oxidant and water disinfectant, it will also be used as an oxidant of selected agricultural organosulfur compounds. The organosulfur compounds are expected to form S-oxides, dioxides and trioxides before forming sulfate and a urea analogue of the thio-compound. The major theme of this proposal will be to synthesize and characterize (X-ray structure, reactivity, chemical properties) these postulated sulfur oxo-acids. Their biological activities will also be evaluated for the possibility of deriving reactive oxygen species in aerobic environments as well as probing for possible toxicity effects as quantified by DNA damage experiments. Work reflecting the importance of S-nitrosothiols, RSNO's, in the physiological environment will study the relevant chemistry of formation of nitrosothiols (kinetics and mechanism of formation and decomposition). A mechanistic understanding of thiol nitrosation should enable the design of RSNO's with better pharmacokinetics properties. This research straddles the areas of physical chemistry and biophysical chemistry by deriving mechanistic and kinetic data that can be utilized to rationalize the observed physiological effects of specific biologically-active organosulfur compounds. A large component of this grant involves the training of undergraduate and graduate students to perform this cross-disciplinary research. The PI's laboratory is presently training a number students at the doctoral level from disadvantaged backgrounds, and a major portion of this requested funding will be used to educate under-represented minorities.