Alkane Oxidation Catalysts

The selective oxidation of strong C–H bonds in inert alkane substrates is a significant chemical challenge. Ideally, this would be achieved by direct oxidation of an alkane to the corresponding alcohol using oxygen as the oxidant. However, this reaction is hampered by the high C–H bond dissociation energy of the substrate. Nature has evolved a variety of metalloenzymes that mediate these complex multi-electron, multi-proton transformations under ambient conditions. Our goal is to produce functional mimics of these enzymes by developing artificial metalloenzymes for alkane oxidation. By encapsulating a molecular catalyst in a protein environment, bimolecular decomposition is circumvented, and transient intermediates can be stabilized by the protein superstructure. Cs H-NOX is an ideal protein for artificial enzymes because it binds unnatural cofactors and amino acid substitutions are easily made. We are currently working to repurpose Cs H-NOX for alkane oxidation using an appropriate heme analog (such as a corrole or dipyrrin) as the catalyst.

In a complementary approach, the Lemon lab is developing small molecule mimics of enzyme active sites that catalyze the oxidation of strong C–H bonds, such as methane monooxygenase (MMO) and polysaccharide monooxygenase (PMO). Both of these enzymes contain a mononuclear copper center bound by a chelating histidine brace. The conservation of this unique ligand suggests that it enables copper centers to oxidize strong C–H bonds. In an effort to emulate this activity, we are synthesizing mimics of the histidine brace that include a hydrogen bonding moiety to stabilize reactive intermediates, mimicking the secondary coordination sphere of PMOs.