Research Project
6028238
This project has the goal of defining the chemistry possible at the active sites of molybdenum enzymes. Every living organism relies on one or more of the approximately forty known molybdenum enzymes for sustained health. In addition to these roles, molybdenum enzymes are key participants in the global biogeochemical cycling of the elements carbon, nitrogen and sulfur. The molybdenum coordination environment at the catalytic sites of these enzymes has recently become more well-defined as a result of X-ray crystal structure determinations for several enzymes. However, in one case dimethylsulfoxide reductase (DMSOR), definition of the Mo site has become more confused because three different Mo coordination environments are observed. Hypotheses have been presented to explain the disagreement between DMSOR active site structures from Rhodobacter sphaeroides and two independent determinations of R. capsulatus. There is a clear need for improved active site model compounds to test some of these hypotheses. New model compounds for the active site of DMSOR have been developed. The distinctive feature of these models is the incorporation of dithiolene substituents that are nearly identical to the pterin substituent in the enzymes. The anticipated result is that these models will possess electronic structure and chemical reactivity very similar to that of the enzyme active sites. These models will be valuable for establishing reactivity types and identifying spectroscopic signatures for interpreting analogous results from the molybdenum enzymes. The new models are synthesized by a coupling reaction between a molybdenum-tetrasulfide reagent and an alkyne bearing the N-heterocycles pterin or quinoxaline. The parent model compounds are obtained with Mo in a formal +4 oxidation state and access to Mo(V) and Mo(VI) compounds by chemical oxidation will be explored. Attention will be given to identifying other oxidation products relevant to known or suspected oxidation reactions of the enzyme. Reduction reactions involving the N-heterocyclic substituents will be explored, both as a means to forming the pyran ring component of the active site as well as to duplicate the reduction treatment applied to protein crystals which is suspected to produce the peculiar active site structure observed by X-ray diffraction. It is expected that studies of these models whose electronic structure closely resembles that of the molybdenum active site will yield significant results that will: a) provide the basis for understanding the diversity of DMSOR X-ray structures; b) reveal the special purpose of the pterin in the active site of all molybdopterin enzymes; c) provide spectroscopic and structural benchmarks to aid in interpretation of analogous results from the enzymes and d) provide examples of fundamental chemistry needed to make progress in understanding the active site chemistry of molybdenum and tungsten enzymes.
