Kozlowski, Pawel M

Project: Modelling the reaction mechanism pertaining to corrin macrocycle such as vitamin B₁₂ and its derivatives

The research projects in our laboratory can be classified into three major areas including photochemistry and reactivity in aerobic and anaerobic conditions, enzymatic catalysis of coenzyme B₁₂-dependent enzymes, and methyl transfer reactions. The brief description of the projects is below.

Photochemistry of vitamin B₁₂ derivatives and its dependent enzymes: Vitamin B₁₂ is complex bioorganic molecule which exhibits puzzling chemistry. It has two biologically active forms which acts as a cofactors in numerous enzymatic reactions. However, there are some other derivatives of vitamin B₁₂ such as aquacobalamin and hydroxocobalamin. Our group is employing the state of art quantum mechanical calculations to develop a more detailed understanding of vitamin B₁₂ photochemistry which has multidisciplinary applications, such as light activated drug delivery, use as a riboswitch for transcription factor proteins, and as a mimic for enzymatic catalysis. However, the mechanism of photodissociation in presence of O₂ is also a crucial reaction. Our group is applying number of computational approaches to understand this type of complex problem.

Enzymatic catalysis of coenzyme B₁₂-dependent enzymes: Coenzyme B₁₂ dependent enzymes catalyze the complex chemical reactions including the heteroatom atom eliminations, carbon-skeletal rearrangement and intermolecular amino group migration. Coenzyme B₁₂ acts as source of radical and catalyze the reactions. Understanding this type of catalysis reactions will help to design the biomimetic catalysts.

Methyl transfer reactions: Methyl transfer is an important biochemical reaction in nature that occurs in humans and mammals. Our group applies different levels of theory to understand the mechanism related to the interconversion of folate to methyl tetrahydro folate.

Computational methods:

We are applying state of art quantum mechanical calculations to solve complex biochemical problems. Our current method of understanding includes the use of different level of theory including quantum mechanics (QM), combined QM and molecular mechanics (QM/MM) and molecular dynamics (MD). In accordance we need the computing time to be able to use the

Students:

• Abdullah Al Mamun (Uofl, Chemistry PhD student)
• Megan J. Toda (Uofl, Chemistry PhD student)
• Arghya Ghosh (Uofl, Chemistry PhD student)
• Aida Bazarganpour (Uofl, Chemistry PhD student)
• Saurav Parmar, Added 01/08/2021

Required software:

• Gaussian
• Nwchem
• Gamess

Some recent publications of our group:

• Mamun, A. A.; Toda, M. J.; Lodowski, P.; Jaworska, M.; Kozlowski, P. M., Mechanism of Light Induced Radical Pair Formation in Coenzyme B₁₂-Dependent Ethanolamine Ammonia-Lyase. ACS Cat. 2018, 8, 7164-7178.
• Lodowski, P.; Ciura, K.; Toda, M. J.; Jaworska, M.; Kozlowski, P. M., Photodissociation of ethylphenylcobalamin antivitamin B₁₂. Chem. Chem. Phys., 2017, 19, 30310-30315. 
• Lodowski, P.; Toda, M. J.; Ciura, K.;Jaworska, M.; Kozlowski, P. M., Photolytic Properties of Antivitamins B₁₂. Chem.2018, 57, 7838-7850.