Synthesis and Chemistry of Carboxylate-Bridged Polymetallic Complexes

这个无机、生物无机和有机金属化学项目的奖项为麻省理工学院化学系Stephen J. Lippard博士对羧酸桥接金属二聚体的研究提供了持续的支持。含有这些单元的金属蛋白负责许多生物功能，包括氧运输、甲烷羟基化和磷酸酯的水解。在本研究中，将进行三方面的研究：二铁配合物的氧化化学作为甲烷单加氧酶羟化酶组分活性位点的模型；模拟脲酶和金属磷酸酶的金属水解酶化学；和糖异构化反应模型d -木糖异构酶。重点将放在设计具有足够内部预组织的双核配体，以便它们折叠成适合金属结合的形状。一类配体是二羧酸盐，其中两个Kemp的三酸酐-氯化物分子通过桥接1,3-二氨基二甲氧基、1,4-二氨基酞或双（氨基甲基苯基）卟啉基团连接。对称和不对称取代氨基酸盐配体，与羧酸盐等电子，也将进行研究。还将尝试使用多组分配体，通过一个桥接羧酸间隔剂连接两个末端双齿单位，使单羧酸桥接体系功能化。将对合成的化合物进行测试，看看它们在多大程度上模拟了生物原型的结构、物理性质和反应性，包括催化循环中的中间体。许多具有重要生物学意义的羟化酶、水解酶和异构酶的功能都是由于一个反应中心包含两个相连的金属原子和周围的羧酸基。为了了解这些酶如何工作的细节，模型化合物将被设计、合成并测试其催化活性。

This award in the Inorganic, Bioinorganic, and Organometallic Chemistry Program provides continued support for research on carboxylate-bridged metal dimers by Dr. Stephen J. Lippard, Chemistry Department, Massachusetts Institute of Technology. Metalloproteins containing such units are responsible for many biological functions, including oxygen transport, methane hydroxylation, and hydrolysis of phosphate esters. In this study, three lines of investigation will be pursued: oxidation chemistry of diiron complexes as models for the active site of the hydroxylase component of methane monooxygenase; metallohydrolase chemistry that mimics urease and metalophosphatase; and sugar isomerization reactions to model D-xylose isomerase. Emphasis will be placed on designing dinucleating ligands that have sufficient internal preorganization so that they fold into shapes that create the appropriate cavities for metal binding. One class of ligands is dicarboxylates in which two Kemp's triacid anhydride-chloride moities are linked by a bridging 1,3-diaminoxylene, 1,4-diaminophthalazine, or bis(aminomethylphenyl)porphyrin group. Symmetric and unsymmetrically substituted amidinate ligands, that are isoelectronic with carboxylate, will also be investigated. Attempts will also be made to functionalize mono-carboxylate bridged systems using a multicomponent ligand with two terminal bidentate units joined by one bridging carboxylate spacer. The compounds synthesized will be tested to see the extent to which they mimic the structures, physical properties, and reactivities of the biological prototypes, including intermediates in catalytic cycles. Many biologically-important hydroxylases, hydrolases, and isomerases function because of a reaction center that contains two linked metal atoms and a surrounding carboxylate group. In order to understand the details of how these enzymes work, model compounds will be designed, synthesized, and tested for catalytic activity.