MECHANISM OF MN-OXO/HYDROGEN ATOM ABSTRACTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。分子价金属-氧类化合物在生物、合成和工业等领域有着广泛的应用。血红素和非血红素高价金属-氧配合物已被认为是许多金属酶（如细胞色素P450、过氧化物酶、脂肪加氧酶、甲烷单加氧酶、光合反应中心）和相关合成体系（如金属卟啉氧化、salen基不对称环氧化）的机制中可能的关键中间体。虽然被广泛引用，但通常缺乏高价M=O配合物参与的直接证据，这些物种已从产品分析，动力学数据或其他间接方法推断为关键中间体。我们开发了一种连续流x射线荧光光谱仪，可用于记录时间分辨的x射线吸收光谱。作为第一个测试，我们已经用它来研究锰催化烯烃环氧化过程中形成的中间体（广泛的药物合成的一个重要步骤）。我们的结果表明，解释一大类Mn催化的氧转移反应的标准机制必须重新评估，因为没有任何可检测的Mn=O中间体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Molecular high-valent metal-oxo species are implicated in a wide variety of important biological, synthetic, and industrial applications. Both heme and non-heme high-valent metal-oxo complexes have been cited as possible crucial intermediates in the mechanisms of many metalloenzymes (e.g. Cytochrome P450, peroxidases, lipoxygenase, methane monooxygenase, photosynthetic reaction center), and related synthetic systems (e.g. metalloporphyrin oxidations, salen-based asymmetric epoxidations). Although widely invoked, direct evidence for the participation of a high-valent M=O complex is often lacking, and these species have been inferred as key intermediates from product analyses, kinetic data, or other indirect methods. We have developed a continuous flow x-ray fluorescence spectrometer that can be used to record time-resolved x-ray absorption spectra with msec resolution. As a first test, we have used this to investigate the intermediate formed during Mn catalyzed olefin epoxidation (an important step in a wide range of pharmaceutical syntheses). Our results suggest that the standard mechanisms for explaining a large class of Mn-catalyzed oxo transfer reactions must be reevaluated in light of the absence of any detectable Mn=O intermediates.