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

无机，生物无机和有机化学计划的这一奖项支持波特兰州立大学的Reuben Simoyi教授的研究，以阐明某些具有生理和环境重要性的有机硫化合物氧化的动力学和机制。 机理数据将用于合理化有机硫化合物的观察到的生理效应，并预测毒性。 因此，本提案将集中于硫代酰胺、硫代脲、硫代氨基甲酸酯、二硫代氨基甲酸酯和氨基硫醇。 将使用的一般生理氧化剂是分子氧、过氧化氢、过酸、HOCl、HOBr和超氧化物、羟基和过氧亚硝酸根自由基。 由于近年来二氧化氯作为氧化剂和水消毒剂的广泛使用，它也将被用作某些农业有机硫化合物的氧化剂。 预计有机硫化合物在形成硫代化合物的硫酸盐和脲类似物之前形成S-氧化物、二氧化物和三氧化物。 本提案的主要主题将是合成和表征（X射线结构，反应性，化学性质）这些假定的硫含氧酸。 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的可能性，并探讨通过DNA损伤实验量化的可能毒性效应。 反映S-亚硝基硫醇（RSNO）在生理环境中的重要性的工作将研究亚硝基硫醇形成的相关化学（形成和分解的动力学和机制）。巯基亚硝化的机理理解应该能够设计具有更好药代动力学性质的RSNO。这项研究跨越了物理化学和生物物理化学领域，通过推导可用于合理化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。这项赠款的一个很大组成部分涉及培训本科生和研究生进行这种跨学科的研究。PI的实验室目前正在培训一些来自弱势背景的博士生，所要求的资金的大部分将用于教育代表性不足的少数群体。

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.