William B. Tolman
My research group is interested in the synthesis, physical characterization, and reactivity of novel inorganic and organometallic chemical complexes. The emphasis of our research is two-fold: (a) to understand the factors that influence the roles transition metal ions play in biology by elucidating the detailed chemistry of models of metalloprotein cores, and (b) to develop new types of multidentate and optically active ligands for the preparation of compounds that bind substrates stereoselectively, with the ultimate goal of establishing synthetically useful asymmetric transformations.
(a) The binding and subsequent reduction and/or decomposition of nitrogen oxides, dioxygen, and its redox partners superoxide and peroxide by copper ions is critically important in both biological and heterogeneous catalytic systems. The coordination and activation of dioxygen by transition metal ions imbedded in proteins is central to the utilization of O2 for respiration and for the oxidation of organic substrates in metabolic processes. Metalloproteins are also responsible for the catalytic comsumption of superoxide (O21-) and peroxide (O22-), ubiquitous redox partners of O2 whose concentrations in biological systems must be controlled in order to inhibit their deleterious reactivity with organic matter. Elucidation of the nature of metal/O2n- (n = 0, 1, or 2) adducts and their role in biocatalysis are thus central research goals in metallobiochemistry.
In biological denitrification, a key process in the global nitrogen cycle, anaerobic organisms utilize nitrate (NO3-) and nitrite (NO2-) as electron acceptors for metabolism and produce gaseous nitric oxide (NO), nitrous oxide (N2O), and/or N2 in a fascinating departure from the dioxygen utilization performed by other forms of life. Environmental consequences of the process include depletion of a key sources of nitrogen necessary for plant growth and production of N2O, a greenhouse gas also believed to contribute to the destruction of atmospheric ozone. Copper-containing enzymes catalyze several of the reductive chemical steps in denitrification, and various novel Cu-NxOy species have been postulated as intermediates. Similar species have been postulated to form upon treatment of other copper proteins with NO or NO2- as structure/function probes and, interestingly, upon spectroscopic monitoring of the reaction of Cu-exchanged zeolites with NO. The structures and reaction pathways traversed by these interesting Cu-NxOy adducts are poorly understood, however. This situation is exacerbated by a general lack of knowledge of the fundamental chemistry of copper-nitrogen oxide complexes.
My research program is directed towards providing the necessary chemical foundation with which to evaluate the plausibility of postulated intermediates and reaction pathways in copper-mediated dioxygen and nitrogen oxide transformations of biological and environmental importance. Ultimately, our work will provide a deeper understanding of the relationships between nitrogen oxide and dioxygen activation by metals in biology and will clarify basic features of energy transduction in divergent biological systems.
In our overall approach, in-depth studies of synthetic complexes specifically designed to mimic the structure, spectroscopic and physical properties, and reactivity of the targeted metalloprotein active site(s) are performed, yielding important insights into the structure and function of the biological system. A multi-faceted synthetic strategy is applied which involves the use of carefully chosen chelating, biomimetic, and sterically hindered ligands to stabilize reactive Cu-NxOy or Cu-O2 moieties in organic solvents and allow attenuation of structural and redox properties. A wide array of physical methods are used to comprehensively characterize all new materials and allow comparison to protein active sites. Reactivity and mechanistic studies directed toward unraveling chemistry relevant to the biological systems follows. Ultimately, this synthetic analog approach will probe chemical aspects of NxOy and O2 binding and reduction in a detailed fashion impossible to achieve with the biological system itself.
(b) In a second major research project underway in my group, we are studying transition metal complexes of a new class of optically active ligands with features that are fundamentally different from those of other known chiral ligands and that will be highly useful for promoting asymmetric synthetic transformations. The new ligands contain tris(pyrazolyl) units amenable for tridentate coordination to metal ions and have stereogenic centers which are forced to lie in close proximity to potential substrate binding sites in a C3-symmetric array. This three-fold symmetry is significantly different from the C2 symmetry found in molecules normally employed in stereoselective chemistry. We hypothesize that the novel sterically hindered and C3-symmetric chiral "fence" about a metal ion that is provided by the new ligands will effectively promote a high degree of enantioselectivity in subsequent chemical reactions. This fundamentally important idea is being tested by fully characterizing metal complexes of the new ligands by a plethora of physical and spectroscopic techniques and then subjecting them to reactivity studies designed to assess their ability to effect a variety of enantioselective conversions, including carbonyl additions, hydrosilylations, cyclopropanations, cycloadditions, and oxidations. This research ultimately will provide a fundamental understanding of the role of geometrical constraints inherent to a C3-symmetric system in promoting stereoselective reactions of metal reagents and should lead to the discovery of new and potentially useful asymmetric metal-mediated processes.