The aim of this proposed research is to modulate the microenvironments (secondary coordination spheres) about metal ions to direct their chemistry. The approach utilizes the principles of molecular architecture that have been delineated for active sites of metalloproteins. New modular non-heme ligand systems have been designed and synthesized that will address how the structure and morphology of metal binding pockets influence the functional and physical properties of metal complexes. The ligand systems can position functional groups into well-defined arrays to create specific chemical microenvironments. Moreover, weak intraligand and metal-ligand interactions will be employed to orient these arrays relative to the bound metal ions. Once these metal-ligand systems are characterized structurally and physically, they will be used to address how highly reactive oxidized and radical intermediates are regulated in biological systems, to probe structure-function relationships in oxidative catalysis, and understand how metal ions can control the self assembly of helical motifs. Metalloproteins perform chemical reactions that have not yet been achieved in synthetic systems. This chemical versatility follows at least in part from the ability of the proteins to regulate the reactivity of their metal centers by adjustment of their microenvironments. Thus the function and disfunction of biologically-important metalloproteins can be understood in the context of changes in their microenvironments. This type of analysis necessitates basic reactivity studies in which the effects of single components can be analyzed individually as described herein.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29GM050781-01
Application #
2188847
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1994-04-01
Project End
1999-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Kansas State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Manhattan
State
KS
Country
United States
Zip Code
66506
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