Chemical precedent studies probing quantum-mechanical tunneling in hydrogen abstractions facilitated by coenzyme B(12)

Recently, there have been numerous reports regarding the possible involvement of quantum mechanical tunneling in enzyme reactions that involve hydrogen transfer. The first chapter of this dissertation reviews the recent literature in this area, focusing on coenzyme B₁₂ systems.; The next three chapters of this dissertation focus on the experimental quantification of an enzyme's involvement in tunneling, which can only be studied by a comparison of the same reaction both inside and outside of the enzyme. The solution thermolysis reaction of coenzyme B₁₂ has been ethylene glycol, the same reaction that is observed in coenzyme B₁₂-dependent diol dehydratase. We have compared our solution data to the literature enzyme data and to another well studied enzyme, methylmalonyl-CoA mutase. In order to further our knowledge in this system, we have also synthesized 8-methoxyadenosylcobalamin, a methoxy analog of coenzyme B₁₂. This methoxy analog has demonstrated reaction kinetics. A third system was also studied utilizing neopentyl cobalamin. at lower, enzyme relevant temperatures. These systems have allowed us to conclude that in coenzyme B₁₂ systems, enzymes may exploit quantum mechanical tunneling but have not evolved to enhance it.