Humanity's understanding of many of the chemical reactions that sustain terrestrial life owes in large part to concerted applications of biochemical, spectroscopic, theoretical, and synthetic methods to identify, characterize, and model the active sites of metalloproteins. In keeping with the established tradition of bioinorganic chemists of throwing everything including the kitchen sink at problems, KML's educational and postdoctoral training was spent stocking a methodological toolbox (bolded above) that spans the "bioinorganic armamentarium" (partially listed above).

Students and postdocs trained in the Lancaster group will be trained in similar fashion: find a nail, then reach into bag of hammers. At present the laboratories are equipped for preparative biochemistry and air-free inorganic/organometallic synthesis. This infrastructure will provide feedstock for spectroscopic and theoretical studies taking advantage of resources that are in-house (UV/vis, stopped-flow, spectroelectrochemistry, quantum calculations, NMR), on-campus (XAS/XES, ESR), or afforded by collaborators (MCD, resonance Raman, etc.).



The Haber-Bosch process has afforded vast quantities of bio-available nitrogen, permitting Earth to sustain a tremendous population. However, not all of this nitrogen makes it from the soil to the dinner table; much of the nitrates are washed into aquifers, and likewise a great deal of ammonia is oxidized to nitrites/nitrates in a process termed "nitrification." These oxidized nitrogen species ultimately make their way back into the atmosphere, but not always as dinitrogen – microorganisms also release greenhouse agents such as N2O and gaseous nitrogen oxides.


We are pursuing studies of these oxidative processes; specifically, we are interested in the role played by Archaea in nitrification. Mounting evidence indicates that Archaea are the dominant nitrifying organisms in both marine and terrestrial environments, although the bio(inorganic)chemistry is largely unknown. Clues from bioinformatics suggest Archaeal nitrification is distinguished from the Bacterial chemistry by substitution of copper enzymes for known iron-based homologues. We are characterizing these putative copper-based nitrification enzymes from the marine crenarchaeota Nitrosopumilus maritimus. Students will take these studies from the DNA to the protein to the spectrometer, diffractometer, etc., affording a bona fide and holistic bioinorganic experience.



For the synthetically inclined, Nature offers a playbook billions of years in the making. The protein matrix is essential for metalloenzyme function. For example: an outer-sphere hydrogen bonding network confers low reorganization energy to blue copper proteins, permitting efficient electron transfer reactivity. In other cases, distal histidine imidazole sidechains promote dioxygen binding in hemoglobin and myoglobin while inhibiting heme poisoning by carbon monoxide.

We are currently inspired by this latter strategy to design coordination complexes to serve as traps with specificity for and that will confer stability to reactive small molecules. One target is nitroxyl, HNO. This enigmatic molecule has shown promise in promoting recovery following cardiac arrest and is slated to become an important therapeutic agent. We are presently using outer-sphere coordination to find a "perfect fit" and challenge the established inner-sphere "requirements' for isolation of HNO complexes. Thus, the Lancaster group also welcomes dyed-in-the-wool synthetic chemists seeking to push the limits of ligand design.




Metalloenzymes and abiotic transition metal catalysts often display a frustrating commonality: studies of the active catalyst are often concealed, either by spectator sites, the matrix, or both. However, these catalysts can frequently be distinguished by elemental identity, spin state, and oxidation state. Conveniently, these are spectroscopic handles that can be exploited in synchrotron-based X-ray absorption and emission studies. Currently we maintain collaborations with the Cornell High Energy Synchrotron Source (CHESS) and the Stanford Synchrotron Radiation Lightsource (SSRL), permitting access to advanced X-ray based spectroscopic methods. We are interested in taking the "bioinorganic approach" to heterogeneous and homogeneous catalysis. We will identify and characterize active species. We will optimize current catalysts for small-molecule activation through ligand design informed by these spectroscopic studies.