Biomimetic Oxidations Involving Metal Peroxides

涉及金属过氧化物的仿生氧化

• 批准号: 6339481
• 负责人: JEFFREY C YODER
• 金额: $ 2.89万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-20 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6339481
• 关键词: active sites; aluminum; biomimetics; chemical bond; chemical models; chemical reaction; chemical structure function; chemical synthesis; gallium; hydrogen peroxide; metalloenzyme; oxidation; peroxides; zinc

The proposed research is designed to test the feasibility of the participation of metal hydroperoxo species in oxidations catalyzed by metalloenzymes such as cytochrome P450 and methane monooxygenase. It has been recently proposed that metal hydroperoxides can indeed function as active oxidants in biological systems, in contrast to the accepted mechanistic paradigm which holds that high-valent metal oxo species are required. These metal hydroperoxides have been suggested to oxidize alkanes via insertion of either "O" or "OH" directly into a C-H bead. Substrate oxygenation, therefore, occurs concomitant with O-O bond breackage and, importantly, without change in the metal's oxidation state. Existing transition metal peroxide complexes typically effect hydrocarbon functionalization via free-radical autoxidation, a pathway that is facilitated by metal-centered oxidation state changes, and thus few valid biomimetic systems exist. Main group metals can mimic the electrophilic nature of the enzyme active sites and are also typically redox-insert, thus it is proposed that peroxide complexes of the group 12 and 13 metals can be utilized to model the enzyme catalyzed oxidations. Discrete hydro- and alkylperoxide complexes of zinc(II), aluminum(III), and gallium(III) will be synthesized; the proposed compounds can be made from known species in one or two steps. Detailed mechanistic studies will be carried out on alkane oxidations effect by these species, including the measurement of reaction rate constants and determination of kinetic deuterium isotope effects. The results of these studies will be compared with data obtained from oxidations catalyzed by metalloenzymes to test the validity of assigning high oxidation reactivity to biological hydroperoxide species.

这项研究旨在测试金属过氧化氢物种参与金属酶(如细胞色素P450和甲烷单加氧酶)催化氧化的可行性。最近有人提出，金属氢氧化物在生物系统中确实可以作为活性氧化剂发挥作用，而不是公认的机理范式，即需要高价金属氧物种。这些金属氢氧化物被认为是通过将“O”或“OH”直接插入C-H珠中来氧化烷烃的。因此，底物氧化与O-O键断裂同时发生，更重要的是，金属的氧化状态不变。现有的过渡金属过氧化物络合物通常通过自由基氧化来影响碳氢化合物的功能化，这是一种由金属为中心的氧化状态变化促进的途径，因此几乎没有有效的仿生系统存在。主族金属可以模拟酶活性中心的亲电性质，也是典型的氧化还原插入，因此可以用12和13族金属的过氧化物络合物来模拟酶催化的氧化反应。将合成锌(II)、铝(III)和镓(III)的离散的氢和烷基过氧化氢配合物；所提议的化合物可以通过一到两步从已知物种中合成。将对这些物种的烷烃氧化效应进行详细的机理研究，包括反应速率常数的测量和动力学氚同位素效应的测定。这些研究的结果将与金属酶催化氧化的数据进行比较，以测试赋予生物氢过氧化氢物种高氧化活性的有效性。