Cobalt Porphyrinoid Complexes in Catalysis: Mechanistic Insights into Carbene Transfer and Biocatalysis Applications
Creators: name: Musselman, Bradley
Publisher: name: My University
Year: 2022
Subjects: subject: Inorganic and Bioinorganic Chemistry
subject: Organometallic and Bioorganometallic Chemistry
subject: Catalysis
subject: Carbene Transfer
subject: Porphyrinoid
subject: Chemistry
subject: Science

description: Artificial heme enzymes have, in recent years, proven to be useful for catalyzing a wide array of carbene and nitrene transfer reactions in water with high activity and stereoselectivity. A commonly employed, and effective, technique to develop these artificial enzymes is to mutate amino acids near the active site of the metal cofactor through directed evolution. However, a less common but productive strategy to further explore new avenues in carbene transfer biocatalysis is to tailor modifications at the cofactor itself. There are few limited examples in the literature for modifications of the ancillary porphyrin ligand all of which to date have favorable effects on carbene transfer giving access to more challenging substrates and providing high yields under mild conditions. In this work, I sought to investigate the influence of the ancillary ligand on chemocatalytic and biocatalytic carbene transfer using cobalt “porphyrinoid” complexes, where porphyrinoids are tetrapyrrolic macrocycles structurally related to porphyrin. Porphyrinoid complexes have vastly different electronic effects on the metal due to changes in the ligand charge and metal coordination cavity. I first investigated the viability of cobalt corrole complexes in the Co(II) and Co(III) oxidation states for styrene cyclopropanation compared to the analogous cobalt porphyrin catalyst. Co(III) corrole catalysts were found to suffer from a deactivation pathway to preferentially make a N-bridged carbene byproduct opposed to the active, axial carbene mode. Using a sterically encumbered corrole complex, I showed that the N-bridged mode can be disfavored in the Co(III) state but can make a stable carbene-radical in the Co(II) state. The difference in reactivity suggests that the diazo substrate can be deactivated by ligand-assisted decomposition to make the N-bridging mode. In the third chapter, I investigated the tetradehydrocorrin (TDHC) cofactor with the weakest ligand field strength of the porphyrinoid series as the electronic opposite of a corrole. The cofactor was reconstituted into the heme-protein myoglobin (Mb) and was screened for carbene-transfer catalysis. Unfortunately, the pure reconstituted protein (rMb) and a variant rMb(H64V,V68A) were inactive for catalysis likely due to the facile deactivation of the key carbene-radical intermediate. N-H insertion activity was improved by the addition of oxymyoglobin as a cocatalyst which surprisingly participates in redox chemistry with rMb. Based on the formation of the Co(I) state of TDHC during catalysis, it’s likely that rMb does not act as a carbene transferase as intended but acts as an alkyl transferase akin to cobalamin dependent enzymes. In the last chapter, I collaborated with Dr. Shafaat (OSU) on the magnetic circular dichroism (MCD) characterization of high spin M121A NiII azurin (Az) and M121A NiII-CH3 Az which were used to model key intermediates in the carbon monoxide dehydrogenase and acetyl coenzyme A protein complex (CODH/ACS). CODH/ACS is an important enzyme that naturally fixates CO2 and a methyl group into coenzyme A to make acetyl CoA, an important metabolite used as a source of energy and/or a source of carbon in cellular biomass. The mechanism for the formation of Ni-CH3 intermediates in ACS is not fully understood, so the Shafaat group developed a protein model of ACS using nickel-substituted azurin. My contribution to this work included the MCD characterization of this key NiII-CH3 intermediate and a frontier molecular orbital analysis of M121A NiII-CH3 Az to show how the NiII-acyl intermediate in ACS could be formed.