Studies of Biologically Relevant Oxidation Processes with Singlet Oxygen

单线态氧的生物学相关氧化过程的研究

• 批准号: 7900343
• 负责人: MATTHIAS SELKE
• 金额: $ 18.06万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7900343
• 关键词: Address; Affect; Antioxidants; Area; Asses; Binding; Bioinorganic Chemistry; Biological; Chemistry; Complex; Cysteine; Dioxygen; Environment; Free Radicals; Health Benefit; Laboratories; Ligand Binding; Ligands; Metals; Nature; Oxidants; Oxygen; Pathway interactions; Peroxides; Phosphines; Predisposition; Process; Property; Reaction; Reactive Oxygen Species; Research; Resveratrol; Singlet Oxygen; Site; Structure; Sulfur; System; Transition Elements; cold temperature; dioxirane; interest; metal complex; metalloenzyme; oxene; oxidation; oxidative damage; tool; trans-resveratrol; triplet state

DESCRIPTION (provided by applicant): The chemistry of singlet oxygen with metal-bound thiolates, arylphosphines and some phenolic antioxidants will be explored. Very little research has been accomplished in this area. The basic aims are twofold (i) To solve a number of fundamental mechanistic questions in oxidation chemistry, especially concerning the reactivity of peroxidic intermediates formed during oxidations initiated by so-called "reactive oxygen species" and (ii) to explore chemistry of singlet oxygen - a highly reactive oxygen species - with seleced biomolecules. Reactive intermediates in oxygen chemistry are often difficult to detect because they themselves are powerful oxidants. We are using singlet dioxygen to observe and possibly isolate such species and, where applicable, to investigate their potential as oxidants. Specifically, the chemistry of singlet oxygen with metal thiolates, especially S-bound cysteine, will be investigated. We will explore the diverse reaction pathways such as formation of sulfenate, sulfinate, C-S bond cleavage or oxidative addition at the metal center. We will determine factors (oxidation state of metal, protic vs. aprotic environment, sterics) that determine the susceptibility of such thiolates toward oxidative damage. Thiolate ligands often serve as bridges in multinuclear complexes, and the chemistry of such species with singlet oxygen will be explored as well. Both ligand oxidation and reaction of dioxygen at the metal center are possible reactive pathways in such systems. We will address the fundamental question of how oxidation at the first metal affects reactivity at the second metal center. We will also investigate the chemistry of other unusual peroxides. We are planning to study the chemistry of phosphadioxiranes, as an example of a highly reactive heteroatom peroxide. This species acts as an "oxene"-like oxygen atom transfer agent, and undergoes several other reactions discovered by us. We will study the factors that govern the reactivity of this highly unstable reactive intermediate. Finally, we will study the chemistry of the powerful phenolic antioxidant trans-resveratrol with singlet oxygen. The chemistry of resveratrol with free radicals is well known. However, its chemistry with singlet oxygen has not been explored, yet knowing whether or not resveratrol forms highly reactive peroxidic species with singlet oxygen is essential to evaluate its health benefits. We will determine the products and any reactive intermediates formed during the interaction between resveratrol and singlet oxygen.

描述（由申请人提供）：将探索单线态氧与金属结合硫醇盐、芳基膦和一些酚类抗氧化剂的化学反应。这方面的研究很少。基本目标是双重的：（i）解决氧化化学中的一些基本机制问题，特别是关于由所谓的“活性氧”引发的氧化过程中形成的过氧化物中间体的反应性，以及（ii）探索单线态氧-高活性氧-与选定的生物分子的化学。氧化学中的活性中间体通常很难检测，因为它们本身就是强氧化剂。我们正在使用单线态分子氧来观察并可能分离这些物种，并在适用的情况下研究它们作为氧化剂的潜力。具体而言，单线态氧与金属硫醇盐，特别是S-结合半胱氨酸的化学，将进行研究。我们将探讨不同的反应途径，如形成亚磺酸盐，亚磺酸盐，C-S键断裂或在金属中心的氧化加成。我们将确定的因素（金属的氧化态，质子与非质子环境，立体），确定这种硫醇盐对氧化损伤的敏感性。硫醇配体通常作为多核配合物中的桥梁，这些物种与单线态氧的化学也将被探索。配体氧化和分子氧在金属中心的反应是这类体系中可能的反应途径。我们将解决的基本问题，如何在第一金属氧化影响反应性的第二金属中心。我们还将研究其他不寻常的过氧化物的化学性质。我们正计划研究磷杂环氧乙烷的化学，作为一个高度反应性的杂原子过氧化物的例子。这种物种作为一个“oxene”样的氧原子转移剂，并经历了我们发现的其他几个反应。我们将研究控制这种高度不稳定的活性中间体的反应性的因素。最后，我们将研究强大的酚类抗氧化剂反式白藜芦醇与单线态氧的化学。白藜芦醇与自由基的化学作用是众所周知的。然而，它与单线态氧的化学性质尚未被探索，但知道白藜芦醇是否与单线态氧形成高活性过氧化物物种对于评估其健康益处至关重要。我们将确定的产品和任何反应中间体之间的相互作用过程中形成的白藜芦醇和单线态氧。