Harry B. Gray
Assistant: Pat Anderson
Professor Gray's interdisciplinary research program addresses a wide range of fundamental problems in inorganic chemistry, biochemistry, and biophysics. Electron-transfer (ET) chemistry is a unifying theme for much of this research.
Great progress has been made in understanding how covalent bridges mediate long-range ET reactions. Questions remain, however, regarding the contributions of solvents to long-range interactions between electron donors and acceptors. Gray's research has shown that electron tunneling in aqueous glasses is much less efficient than tunneling across saturated covalent bridges. Investigations of ET reactions between excited metal complexes and electron acceptors in rigid protic and aprotic media are probing the factors that control distant couplings through solvents.
Over the past twenty years the Gray group has been measuring the kinetics of long-range ET reactions in metalloproteins labeled with inorganic redox reagents. Current research is aimed at understanding how intermediate protein radicals accelerate long-range ET. New techniques have been developed for measuring ET rates in crystals of Ru-, Os-, and Re-modified azurins, as well as crystals of Fe(III)-cytochrome c doped with Zn(II)-cytochrome c. This method of integrating photosensitizers into protein crystals has provided a powerful new tool for studying biochemical reaction dynamics.
Electron exchange with metal cofactors deeply buried in the interiors of redox enzymes is often quite slow. Researchers in the Gray group have succeeded in accelerating the delivery of electrons and holes to the buried active site of cytochrome P450 by tethering a photochemical redox sensitizer to P450 substrate analogs. This approach is now being exploited in studies of several other redox enzymes (e.g., nitric oxide synthase, catechol oxidase, amine oxidase).
The Gray group is also using ET chemistry to probe the dynamics of protein folding. A continuing challenge in this is field understanding how a heterogeneous ensemble of unfolded polypeptides evolves into a collection of neatly folded proteins. Laser-induced ET reactions are being used both to trigger and to probe the folding of redox active proteins. Research also is aimed at using fluorescence energy transfer to probe the heterogeneity of protein ensembles during folding.