Design and Synthesis of Dinucleating Nitrogen Ligands

描述(申请人提供)：非血红素二铁活性部位普遍存在于自然界中的金属化合物中。这些活性部位的合成类似物进一步加深了我们对控制这些酶活性的基本原理的理解。拟议的研究概述了合成新的空间位阻双核氮配体的一般战略，用于创建这些二铁活性中心的合成类似物，在这种情况下是甲烷氧化酶甲烷单加氧酶(MMO)的活性中心。这项工作的影响范围从获得关于这些双金属中心的知识到开发小分子碳氢化合物氧化催化剂，这些小分子催化剂可能会影响与精细化学品和药品生产有关的健康领域。 建议的研究包括设计合成一组结构多样化的双核氮配体的一般策略。这些双络合配体的结构将基于两个杂环胺官能团，吲哚和异吲哚。钯催化的碳-碳键形成过程的能力将被用来在短时间内组装这些配体，并将这些螯合部分安装在空间要求高的环境中，连接两个单齿胺功能的碳骨架将很容易改变，从而产生一系列不同的配体。合成策略将通过从同一中间体产生多个配体集来增强多样性。分子模拟的结论是，控制手性C2对称和中位二胺的相对立体化学将控制这一新型配体的空间环境和配位几何构型。

DESCRIPTION (provided by applicant): Non-heme diiron active sites are prevalent in metalloenyzmes throughout Nature. Synthetic analogues of these active sites have furthered our understanding of the fundamental principles that control the reactivity of these enzymes. The proposed study outlines a general strategy for the synthesis of novel, sterically encumbered dinucleating nitrogen ligands for use in the creation of synthetic analogues of these diiron active sites, in this case the active site of the methane-oxidizing enzyme methane monooxygenase (MMO). The implications of this work span from knowledge gained about these dimetallic centers to the development of small molecule catalysts for hydrocarbon oxidation that could impact the health field concerning the production of fine chemicals and pharmaceuticals. The research proposed involves the design of a general strategy for the synthesis of a structurally diverse set of dinucleating nitrogen ligands. The structure of these bischelating ligands will be based upon two heterocyclic amine functionalities, the indoline and isoindoline. The power of palladium catalyzed carbon-carbon bond forming processes will be employed to assemble these ligands in short order and install these chelating moieties inside sterically demanding environments, The carbon framework that links the two monodentate amine functionalities will be readily varied, resulting in the production of a diverse set of ligands. The synthetic strategy will enhance diversity by generating multiple ligand sets from the same intermediate. Molecular modeling concludes that controlling the relative stereochemistry of the chiral C2 symmetric and meso diamines produced will control the steric environment and coordination geometry of this novel ligand set.