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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM069236-02
Application #
6806512
Study Section
Special Emphasis Panel (ZRG1-F04 (20))
Program Officer
Lograsso, Philip
Project Start
2003-09-15
Project End
2006-09-14
Budget Start
2004-09-15
Budget End
2005-09-14
Support Year
2
Fiscal Year
2004
Total Cost
$42,976
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Kodanko, Jeremy J; Morys, Anna J; Lippard, Stephen J (2005) Synthesis of diethynyltriptycene-linked dipyridyl ligands. Org Lett 7:4585-8
Kodanko, Jeremy J; Xu, Dong; Song, Datong et al. (2005) Iron substitution for sodium in a carboxylate-bridged, heterodinuclear sodium-iron complex. J Am Chem Soc 127:16004-5