Bioinorganic Chemical Biology

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Although there are many motivations and definitions of chemical biology the one that drives the program of research in my laboratory is that it is a theme and an approach "to discover new chemistry." Our unifying guiding hypothesis is global, open-ended, and invigorating; by understanding how biological evolution has circumvented the fundamental chemical limitations imposed by terrestrial temperature, pressure, environment, and element distribution considerable new chemistry can be discovered. This approach allows for discovery and innovation in that not only are new techniques and tools used, and developed, to help solve important health related problems, but solutions to deeper scientific issues are uncovered. Current chemical biology research in the Bohle group follows three general themes: A; the first is related the unusual biochemistry often employed by parasites, with the heme metabolism in pathogens such as plasmodia (malaria), B; the bioinorganic chemistry of rarely utilized elements such as arsenic and tungsten, and C; the final area to the study of bio-inspired nitrogen chemistry. A. Parasites such as plasmodia have a highly evolved biology which allows them to have some of the most complicated life cycles and often have elegant biochemistry. Often they have sophisticated means to circumvent the host’s immune system; they are a logical place to apply the ideas of chemical biology. B. The biochemistry of underutilized elements remains a challenging area of chemical biology. Elements such as tungsten and arsenic are in fact relatively common and available, and yet evolution has rarely used either of them in any context. Our research into these topics is highly collaborative and at present focusses on their toxicology and medicinal value. Finally C, few first row elements have the remarkably variable oxidation state chemistry of nitrogen and its oxides. If we can understand how the nitrogen oxides are employed in organisms we can in principle use these ideas in commercial/industrial settings especially for pollution abatement strategies. Our approach to this research is to work on the fundamental problems in each of these themes. This style is ideally suited for the training of HQP and it does not tie us to a particular technique, method, or class of compounds. To illustrate this diversity my group can frequently be found working at Synchrotrons as well as preparing and characterizing new compounds. For the latter we use a wide range of spectroscopic and structural techniques, with X-ray diffraction being particularly useful. Theoretical methods are also drawn upon for both their predictive and supporting roles. At its best our work is highly collaborative with our chemistry having value for biologists and clinicians as well stimulating our efforts in bioinorganic chemical biology.