George A Lindsay Collegiate Professor of Chemistry and Biophysics
About
Although they are only present at part-per-million to part-per-billion levels, trace metals are absolutely essential for life. Our research is focused on understanding the many roles that trace metals (especially Mn, Fe, Co, Ni, Cu and Zn) play in biology.
A portion of our work focuses on the biochemistry of metalloenzymes (proteins with metals at their active sites). Metalloenzymes catalyze reactions with a speed and selectivity that is unrivaled by conventional catalysts. We want to understand how metalloenzymes work. Our approach is to correlate metal-site structure with enzymatic function.
In addition to their enzymatic roles, essential trace elements play numerous other roles in biology and fluctuations in metal concentration are associated with numerous disease states. We have developed techniques that allow us to follow the distribution and chemical speciation of first row transition metals in intact tissue. Using an X-ray nanoprobe, we have been able to map sub-cellular distributions of metal ions with spatial resolutions as good as 100nm. The ultimate goal of this work is to develop the new field of inorganic physiology - the study of the transport, storage and distribution of metal ions in biology.
Finally, a major focus of our recent work has been on the characterization of "molecular movies" where we follow the structural evolution of photoactive metal sites following photoexcitation. In order to follow structure, we use a combination of X-ray absorption, X-ray emission, and X-ray scattering. With modern X-ray free-electron lasers, we can use these tools to interrogate molecular structure with a time-resolution of 50 fs or better.
We make extensive use of synchrotron radiation, using the unique resources available at synchrotron laboratories in the U.S. (Brookhaven, Argonne, Stanford and Berkeley) and abroad ( Japan , France ). A key technique is X-ray absorption spectroscopy. This is one of the only ways to obtain detailed structural information for non-crystalline systems. In addition to X-ray methods, we make use of a wide range of other spectroscopies, including EPR, IR and paramagnetically-shifted NMR.
Research Interests
- Biophysical Chemistry and Inorganic Spectroscopy, Physical Bioinorganic Chemistry
Selected recent publications
“Watching Excited State Dynamics with Optical and X-ray Probes: The Excited State Dynamics of Aquocobalamin and Hydroxocobalamin”, J. Am. Chem. Soc., 2023, 145, 14070-14086 https://doi.org/10.1021/jacs.3c04099
“Ultrafast X-ray Absorption Spectroscopy Reveals Excited State Dynamics of B12 Coenzymes Controlled by the Axial Base.”, J. Phys. Chem. B, 2024, 128, 1428–1437. https://doi.org/10.1021/acs.jpcb.3c07779
“Determining the coordination environment and electronic structure of polymer-encapsulated cobalt phthalocyanine under electrocatalytic CO2 reduction conditions using in situ X-Ray absorption spectroscopy”, Dalton Trans., 2020, 49, 16329-16339. https://doi.org/10.1039/D0DT01288B
“Revving up a Designed Copper Nitrite Reductase Using Noncoded Active Site Ligands” ACS Catal. 2024, 14, 4362–4368. https://doi.org/10.1021/acscatal.3c06159
“Probing a silent metal: A Combined X-ray Absorption and Emission Spectroscopic Study of Biologically Relevant Zinc Complexes”, Inorg. Chem., 2020, 59, 13551-13560. https://dx.doi.org/10.1021/acs.inorgchem.0c01931
“An interprotein Co-S coordination complex in the B12-trafficking pathway, J. Am. Chem. Soc. 2020 142, 16334–16345. https://doi.org/10.1021/jacs.0c06590
“The Photoactive Excited State of the B12-Based Photoreceptor CarH”, J. Phys. Chem. B, 2020, 124, 10732-10738. https://dx.doi.org/10.1021/acs.jpcb.0c09428
