The long-term objective of this proposal is the development of a catalyst for the selective oxidation of hydrocarbons to alcohols. In biology, Cytochrome P450, Methane Monooxygenase and Bleomycin all catalyze this oxidation with a high level of control and selectivity that hasnot been duplicated synthetically. Though the industrial applications of such a catalyst are enormous, the biological implications are just as important. The primary use of Bleomycin is as an anti-cancer drug, the site-specific C-H bond oxidation leads to DNA degradation in cancerous cells. The development of a system that allows for detailed mechanistic studies in vitro could lead to a deeper understanding of Bleomycin action in vivo. Thus, new models must be prepared that mimic not only the reactivity of Bleomycin, but also the mechanistic features of the drug. To achieve this goal, a new ligand framework for non-heme iron hydroxylation has been proposed, which takes inspiration from spectroscopic studies of the biologically-derived drug. A softer coordination environment will allow reversible oxygen coordination and stabilization of various intermediates analogous to those observed in Bleomycin. The experimental design allows for control over steric and electronic parameters that influence the reactivity at the iron site, such that systematic variation can lead to a catalyst that mimics the observed reaction patterns of Bleomycin.
NIH ExPorter
NIH ExPorter