and NOx catalysis





and metal-based drugs

Photo chemistry

and hybrid enzymes





and hybrid enzymes


Because of the sluggish redox response of proteins, electrochemical measurements are typically obtained by slow, equilibrium titrations which can't differentiate kinetic or reorganizational factors. We are using fast electrochemical techniques to initiate and follow multi-electron protein catalysis. In our hands, this has evolved into making new protein mutants to test specific aspects of electrochemical mechanisms, as well as new ways of engineering proteins to interface with electrode surfaces.


Likewise, we are developing photoactive heme protein hybrids as a way to look at very short-lived species generated during redox transformations. Our intent is to use these techniques to address long-standing issues in bioinorganic chemistry about redox control and catalysis at heme sites: for example, how does the heme coordination environment affect and control redox transformations in the time domain; and what are the sequential steps in heme-based oxidoreductase catalysis, such as in the multi-electron reduction of dioxygen.


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 interesting photochemical properties, they are redox-active and tight binders of metal ions, and 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.

To this end, we are developing new metal-based drugs which increase the oxidative stress in melanoma cell lines. An important finding is that certain fat-soluble metal-dithiocarbamates are selectively toxic to melanoma cancers, and this toxicity increases with the particular metal's ability to induce melanin's production of ROS, reactive oxygen species such as superoxide or hydroxy radicals. The anti-melanoma activity is also observed for the dithiocarbamate ligands themselves, dependent on the availability of metal ions in the media. The ultimate source of toxicity is, we believe, due to metal-uptake into the cells producing a melanin-based pro-oxidant response. We are also investigating how the metal-dithiocarbamates are decomposed within a cell, perhaps by S-oxygenation of the dithiocarbamate ligand, and developing other S-based ligands which may have similar anti-melanoma activity.

HNO/NO biochemistry

We are also interested in the biological inorganic chemistry of NO and its one-electron reduced sibling, HNO. A variety of metalloproteins have been suggested to mediate the physiological activity of HNO, for instance, the ferric heme proteins such as the peroxidases and the cytochromes P450 and Cu, Zn superoxide dismutase. Nitroxyl intermediates have long been proposed in biological denitrification processes in plants, bacteria and fungi which are catalyzed by a variety of metalloenzymes. Despite the obvious importance, there is relatively little substantive knowledge about the bonding of nitroxyl to transition metal ions. Only a few examples of nitroxyl-metal complexes have been characterized. We recently reported the synthesis and characterization of the HNO adduct of myoglobin, Mb-HNO, which provides a unique opportunity to understand the properties and fate of nitroxyl intermediates biological systems.