Sep 2022
1. Introduction to the Theory and Applications of Molecular Quantum Mechanics
An introduction to the basic concepts and principles of modern electronic structure theory as well as theoretical aspects of photochemistry. Special emphasis will be placed on density functional theory (DFT), time dependent DFT (TD-DFT), and ab initio methods such as CASSCF. Application of DFT/TD-DFT methods to study electronically excited states and to construct potential energy surfaces (PESs) will be presented.
2. Quantum Chemical Modeling of Co-C Bond Activation in B12-Dependent Enzymes
The origin of the enormous catalytic activity of coenzyme B12-dependent enzymes continues to be an outstanding problem in bioinorganic chemistry. During enzymatic catalysis the Co-C bond of coenzyme B12 (AdoCbl) is cleaved homolytically, leading to the formation of the 5’-deoxyadenosyl radical and cob(II)alamin. The rate of enzymatically accelerated homolytic cobalt-carbon bond cleavage of AdoCbl exceeds the rate observed in aqueous solution by about 12 orders of magnitude as a consequence of the coenzyme interaction with the substrate in the presence of apoenzyme. Despite the great effort that has been devoted to this problem, the mechanism of the catalytic activation is poorly understood. To the extent it has been addressed experimentally, evidence from model systems indicate that steric hindrance around coordinated alkyl ligands leads to a higher homolysis rate. Different models have been suggested, but none can be considered as fully satisfactory in light of a large body of experimental results.
I will summarize recent progress in computational modeling of the catalytic activation of cobalt-carbon bond cleavage. The growing interest in modeling the structure and electronic properties of AdoCbl has demonstrated that computer simulations, in particular density functional theory (DFT) can be an important part of coenzyme B12 research.
3. Photolytic properties of cobalamins: a theoretical perspective
I will discuss recent theoretical developments and summarize the current understanding of the photolytic properties of cobalamins (vitamin B12 derivatives) from a computational point of view. The primary focus will be on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co–C bond leads to formation of singlet-born alkyl/cob(II)alamin radical pairs (RPs). Potential energy surfaces (PESs) associated with cobalamin low-lying excited states as functions of both axial bonds, provide the most reliable tool for initial analysis of their photochemical and photophysical properties. Due to the complexity, and size limitations associated with the cobalamins, the primary method for calculating ground state properties is density functional theory (DFT), while time-dependent DFT (TD-DFT) is used for electronically excited states. For alkyl cobalamins, energy pathways on the lowest singlet surface, connecting metal-to-ligand charge transfer (MLCT) and ligand field (LF) minima, can be associated with photo-homolysis of the Co–C bond observed experimentally. Additionally, energy pathways between minima and seams associated with crossing of S1/S0 surfaces, are the most efficient for internal conversion (IC) to the ground state. Depending on the specific cobalamin, such IC may involve simultaneous elongation of both axial bonds (CNCbl), or detachment of axial base followed by corrin ring distortion (MeCbl). The possibility of inter-system crossing, and the formation of triplet RPs would be also presented based on Landau–Zener theory. Finally, I will discuss photolytic properties of B12-dependent enzymes including ethanolamine ammonia-lyase (EAL), glutamate mutase (GLM), methionine synthase (MetH) and CarH photoreceptor.
Prof. Pawel M. Kozlowski holds a permanent, tenured faculty appointment in the Department of Chemistry at the University of Louisville, Kentucky. He obtained PhD in 1992 from University of Arizona under supervision of Prof. L. Adamowicz and was a post-dock with Prof. E. Davidson (Indiana University) and Prof. P. Pulay (University of Arkansas). After that, he was staff scientist with Prof. T. Spiro at Princeton University for three years before he started tenure track appointment at Louisville in 1999. He received tenure and was promoted to associate professor in 2005 and after to full professor in 2011, respectively. In 2017, he also received honorary title “Professor of Pharmacy” from the Medical University of Gdańsk, Poland.
Over the past twenty years, he has developed an active, independent research program in the area of theoretical and computational chemistry. All of his current projects exploit the capability of modern quantum chemistry. To date he have published 173 scientific papers in the area of theoretical and computational chemistry in well-respected journals. He has also received several fellowships and awards including the Monbusho Fellowship, an award from the Japan Society for the Promotion of Science (JSPS) as well as the Fulbright Foreign Scholarship.