Studies of Biologically Relevant Oxidation Processes with Singlet Oxygen

描述(申请人提供)：将探索单线态氧与金属结合的硫代硫酸盐、芳基膦和一些酚类抗氧化剂的化学。这一领域的研究成果很少。其基本目的有两个：(1)解决氧化化学中的一些基本机理问题，特别是关于在所谓的“活性氧物种”引发的氧化反应中形成的过氧化中间体的反应性；(2)探索单线态氧--一种高活性氧物种--与所选择的生物分子的化学。氧化学中的活性中间体通常很难检测到，因为它们本身就是强大的氧化剂。我们正在使用单线态氧来观察和可能分离这些物种，并在适用的情况下，研究它们作为氧化剂的潜力。具体地说，将研究单线态氧与金属硫酸盐的化学，特别是与S结合的半胱氨酸。我们将探索不同的反应途径，如亚硫酸盐的形成，亚硫酸盐，C-S键断裂或金属中心的氧化加成。我们将确定决定这些硫酸盐对氧化损伤的敏感性的因素(金属的氧化状态、质子态与非质子态环境、立体结构)。硫代配体经常作为多核络合物的桥梁，也将探索此类物种与单线态氧的化学作用。在这类体系中，配体氧化和金属中心的氧反应都是可能的反应途径。我们将讨论第一个金属的氧化如何影响第二个金属中心的反应性这一根本问题。我们还将调查其他不寻常的过氧化氢的化学成分。我们计划研究磷二氧杂环氧烷的化学，作为一个高活性的杂原子过氧化氢的例子。该物种作为一种类似氧原子的氧原子转移剂，还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反应性中间体的反应性的因素。最后，我们将研究有效的酚类抗氧化剂反式白藜芦醇与单线态氧的化学作用。白藜芦醇与自由基的化学作用是众所周知的。然而，白藜芦醇与单线态氧的化学作用尚未被探索，但了解白藜芦醇是否与单线态氧形成高活性的过氧化物种是评估其健康益处的关键。我们将确定在白藜芦醇和单线态氧相互作用过程中形成的产物和任何活性中间体。

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.