Integrated Control of the Primary and Secondary Coordination Spheres in Synthetic Monooxygenase Mimics: Probing Dioxygen Activation at a Single Metal Site.

项目摘要。拟议的研究计划描述了模拟的合成系统的发展 在单加氧酶活性部位内发现的性质，以探索金属介导的激活 氧气。利用的两个关键设计特征是结合了分子内氢键(H键) 次级配位圈内的网络和初级配位圈内氧化还原活性配体的使用 协调球体。将这些特征结合到一个单一的配基系统中代表着分子的进步 设计应允许分离模拟中间体结构的铁-氧物种 由P450在O2激活过程中产生。这种方法利用了带有氢键的三齿氧化还原活性配体 位于次级配位球体内的接受者。这种方法的一个优点是 另外的配体可以很容易地配位到金属中心；因此，可以有几种不同的变体 为功能准备、表征和筛选的。特别是，与轴向硫酸盐给体的铁络合物是 提出将模拟在环色素的活性部位内发现的许多结构特征 P450单加氧酶。与这些酶类似，所提议的络合物中的金属离子预计会 结合并活化氧(O2)以形成氢键稳定的过氧键(O22-)或氧代(O2-)单元，能够 使底物的C-H键功能化。因此，与O2和碳氢化合物底物的反应性研究是 还提出了使用光谱和计算对生成的产品进行表征的建议 技术包括UV-Vis、EPR、穆斯堡尔、FTIR光谱和密度泛函理论。 这些研究有望使人们更好地理解单加氧酶活性的生物化学。 以及地球上丰富的金属如何能够有效地激活惰性底物的C-H键。

Project Summary. The proposed research plan describes the development of synthetic systems that emulate the properties found within the active sites of monooxyenases in order to probe metal-mediated activation of dioxygen. Two key design features utilized are incorporation of intramolecular hydrogen bonding (H-bond) networks within the secondary coordination sphere and the use of redox-active ligands within the primary coordination sphere. Coupling these features into a single ligand system represents an advance in molecular design that should allow for the isolation of Fe–oxo species that mimic the structures of the intermediates produced by P450 during activation of O2. This approach utilizes tridentate redox-active ligands with H-bond acceptors positioned within the secondary coordination sphere. One advantage of the approach is that additional ligands can be readily coordinated to the metal center; thus, several different variants can be prepared, characterized, and screened for function. In particular, iron complexes with axial thiolate donors are proposed that would simulate many of the structural features found within the active sites of the cyctochrome P450 monooxygenases. Similar to these enzymes, the metal ions in the proposed complexes are expected to bind and activate dioxygen (O2) to form H-bond stabilized peroxo (O22–) or oxo (O2–) units capable of functionalizing C–H bonds of substrates. Therefore, reactivity studies with O2 and hydrocarbon substrates are also proposed in which the generated products will be characterized using spectroscopic and computational techniques that include UV-vis, EPR, Mössbauer, and FTIR spectroscopies and density functional theory. These studies are expected to lead to a greater understanding of the biochemistries of monooxygenase active sites and how earth abundant metals are capable of efficiently activating C–H bonds of inert substrates.