METAL CATALYZED BIOCHEMICAL TRANSFORMATIONS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们的研究计划的主要推力是在有机，无机和生物化学的界面。许多生物化学转化以及重要的合成和工业过程都是由金属催化的。最近的努力集中在新的仿生催化剂的设计和这些过程的分子机制，大规模的膜蛋白质小分子结构的设计和组装，生物硬材料的组装策略，以及过氧亚硝酸盐在生物系统中的作用的分子探针。 血红素辅基存在于参与氧代谢的多种酶中。已知肺、肝和上皮组织的细胞色素P450在致癌物活化、药物和异生物质解毒、类固醇和前列腺素代谢以及最近的细胞内信号分子NO的产生中发挥核心作用。该计划的目标是阐明这些过程的有机和无机化学。我们双管齐下的方法是（i）采用细胞色素P450的底物，旨在揭示反应机制中看不见的中间体的性质，以及（ii）开发模型系统作为这些过程的化学范式。这项工作的一个具体应用是设计可能具有药理学用途的选择性抑制剂。 合成的氧代金属卟啉配合物的表征已经开始为开发新的催化剂和选择性分子检测器提供合理的基础。因此，金属卟啉催化剂的尺寸和形状的相对小的变化可以引起各种底物的相对反应性的大的变化。同样的标准允许开发能够催化不对称环氧化和羟基化的手性卟啉。在迄今为止发现的最有利的情况下，发现苯乙烯的环氧化以95%的对映体过量发生。这类和其他家族的手性卟啉的合成和评价正在进行中。特别是，我们正在设计的技术，将提供一个理解为什么一个不对称催化剂给出了一个高的对映体过量，而一个非常相似的结构没有。

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. The major thrust of our research program is at the interface of organic, inorganic, and biological chemistry. Many biochemical transformations as well as important synthetic an industrial processes are catalyzed by metals. Recent efforts have focused on the design of new, biomimetic catalysts and the molecular mechanisms of these processes, the design and assembly of large scale membrane-protein-small molecule constructs, strategies for the assembly of biogenic hard materials, and molecular probes of the role of peroxynitrite in biological systems. The heme prosthetic group is found in a variety of enzymes involved in oxygen metabolism. The cytochromes P450 of lung, liver and epithelial tissue are known to play a central role in carcinogen activation, drug and xenobiotic detoxification, steroid and prostaglandin metabolism, and, most recently, the production of the intracellular signal molecule NO. The goals of this program have been to elucidate the organic and inorganic chemistry of these processes. Our two-pronged approach has been (i) to employ substrates for cytochrome P450 designed to reveal the nature of unseen intermediates in the reaction mechanism and (ii) to develop model systems as chemical paradigms for these processes. One specific application of the work is the design of selective inhibitors which could have pharmacological uses. The characterization of synthetic oxo-metalloporphyrin complexes has begun to provide a rational basis for the development of new catalysts and selective molecular detectors. Thus, relatively small changes in the size and shape of a metalloporphyrin catalyst may cause large changes in the relative reactivity of various substrates. The same criteria have allowed the development of chiral porphyrins capable of catalytic asymmetric epoxidation and hydroxylation. In the most favorable case found to date, the epoxidation of styrene was found to occur with a 95% enantiomeric excess. The synthesis and evaluation of this and other families of chiral porphyrins are now in progress. In particular, we are devising techniques that will provide a understanding of why one asymmetric catalyst gives a high enantiomeric excess while a very similar structure does not.