A. Decker, M.S. Chow, J.N. Kemsley, N. Lehnert, E. I. Solomon, JACS 2006 in press.

Non-heme iron (NHFe) enzymes catalyze a wide variety of reactions that are biologically and industrially important. My research involves the use of spectroscopic (CD, MCD, Abs, EPR) and computational (DFT) techniques to study the electronic and geometric structures of the non-heme iron active sites in the anticancer drug Bleomycin, the pterin-dependent monooxygenases Phenylalanine Hydroylase and Tyrosine Hydroxylase, and the industrially important enzyme Nitrile Hydratase. By studying the changes that take place at the active sites during catalytic turnover we hope to gain insight into the molecular mechanisms that govern the reactivity of these systems.

We are very interested in studying the putative high-valent oxygen intermediates of these NHFe systems. One example is Activated Bleomycin (ABLM), a low spin ferric peroxide, and the last bleomycin intermediate detected prior to DNA strand cleavage. Using VTVH MCD and XAS, our group has previously determined the electronic and geometric structure of ABLM.

We are able to study the kinetics of the ABLM reaction using circular dichroism spectropscopy and have recently shown that the ABLM reaction with and without H-atom donor substrates has a deuterium isotope effect ~3, indicating that ABLM is capable of H-atom abstraction.