Texas A&M University - 1993
University of Texas, San Antonio 1988
NATO Postdoctoral Fellow
École Normale Supérieure, Paris - 1993-1994
NSF Postdoctoral Fellow
California Institute of Technology, Postdoctoral Researcher - 1994-1995
Assistant Professor of Chemistry
University of California, Irvine - 1995-2001
Associate Professor of Chemistry
University of California, Irvine - 2001-2005
Professor of Chemistry
University of California, Irvine - 2005-2009
Professor and Chair, Department of Chemistry and Biochemistry
Baylor University - 2009-present
Some of the research topics include Flavonol Complexes, Melanin/Melanoma,and Biocoordination of HNO. In the Flavonol Complexes area, we are investigating a family of heterocyclic dyes with "pre-aromatic" constructs, in that oxidation generates pseudo-aromatic tautomers. These dyes are structurally related to the naturally occurring flavonals, which are widely studied antioxidants found in the skin of fruit and berries. In the Melanin/Melanoma area, we are interested in the coordination and redox chemistry of the black pigment melanin, the color in your hair and skin, especially as it relates to melanoma cancer. And in the Biocoordination of HNO, we have reported extensively on the stable HNO adduct of deoxymyoglobin, HNO-Mb, generated by reduction of nitrosyl myoglobin or by the trapping of free HNO by deoxyMb, characterized by NMR, resonance Raman and X-ray absorption spectroscopies. Recent work has demonstrated that stable HNO-adducts of other oxygen-binding globins may be generated by trapping of free HNO.
Nature is an amazing chemist that is constantly synthesizing and transforming the world around us. Much of this work is done by enzymes, amazing little catalysts made of protein, just like you and me. Unlike industrial catalysts, enzymes work in water at mild temperatures and pressures. In many cases, enzymes with very similar active sites perform very different functions-- for example, identical Fe-heme cofactors bind and transport oxygen in hemoglobin and myoglobin, reduce oxygen in the cytochromes P450s and cytochrome oxidase, or nitrogen oxides in the nitrite and nitric oxide reductases. The substrate specificities and reactivity of the heme in the various enzymes is controlled by the protein environment around it, and small changes can have large effects. Likewise, the flow of electrons to a redox-active heme is also largely controled by the protein matrix it is contained in. Nature has amazing control over these electron transfers; redox sites are typically oriented so as to "aim" the electron towards its acceptor site, and triggering the flow to a specific chemical event.
Like nature, we try to use a controlled flow of electrons to initiate redox catalysis in hybrid heme enzymes. By varying the structures and environments of the hemes, we hope to make unique catalysts for different reactivities. These tailor-made enzymes are intended to perform useful chemical transformations driven simply by electricity or light. For example, by affixing the oxygen-binding protein myoglobin to an electrode we can make it catalyze the multi-electron reduction of nitrite to ammonia, a reaction that is important in plant metabolism. Using a P450, we can reduce carbon tetrachloride to methane, and amazing eight electron reduction that detoxifies this potent halocarbon. Binding photo-active Ru complexes to the surface of a protein allows us to photo-initiate electron flow into the heme active-site, and to control the reactions that occur there on the time-scale of a laser-pulse.
We are also interested in the redox chemistry of melanin, the black pigment in hair and skin. Melanins are catecholic pigments formed in melanocytes by oxidative polymerization of tyrosine. Melanins have very interesting photochemical properties; they are redox-active and tight binders of metal ions. Our recent work shows that they both mediate and generate reduced oxygen species. We are exploring the unique chemistry of melanins as a means of targeting melanoma, a cancer of the cells that make melanin.