VITAMIN B12 CATALYSIS

We are developing catalytic methods that mimic an enzymes' characteristic by combining the robust nature of simple chemical substances with the enzyme’s selectivity, speed, specificity. We believe that vitamin B12 (cobalamin) is the ideal candidate for devising such efficient systems for several reasons:

  1. In nature vitamin B12 plays the role of vitamin B 12 cobalamin cofactor for adenosylcobalamin- and methylcobalamin-dependent enzymes catalyzing various reactions: rearrangement, methylation, dehalogenation. It is involved in both bond forming and bond breaking reactions therefore vitamin B12 it is suitable for both production and decomposition methodologies.
  2. As a natural compound, vitamin B12 is easily consumed by nature. Even more important is the fact that it is a vital nutrient and it cannot be overdosed. Again, from an industrial point of view (for example drugs’ production or water purification) it is ideally suited. Even, if the catalyst remains post-process, it is happily returned to nature.
  3. Vitamin B12 possesses the ability to catalytically generate highly reactive intermediates with practically limitless application in organic chemistry. All vitamin B12-catalyzed processes rely on the redox chemistry of the central cobalt cation (+3), which can be easily reduced giving radical Co(II) or supernucleophilic Co(I) species. Most of vitamin B12- catalyzed reactions involve Co(I) form as it readily reacts with electrophiles such as halides or activated olefins forming covalent Co-C bond (Scheme 2). This bond is prone to cleavage upon thermolytic, photolytic, or electrolytic conditions, ultimately leading to carbon-radicals or carbon-ionic species that can undergo further chemical transformations.
  4. We, as well as other researchers, have undoubtedly proved that cobalamin as a catalyst can be activated by light, so this source of energy can be definitely utilized.
  5. It is much less expensive in comparison to precious metal catalysts such as: Pd, Pt, Rh, Ru, Ir and their use will be naturally avoided.
  6. It is a highly functionalized corrinoid possessing a cobalt cation in the central macrocyclic cavity. Metal leakage or abstraction is basically impossible from this very stable cobalt complex.

VITAMIN B12 BIOLOGICAL APPLICATIONS

Vitamin B12 is an essential nutrient cofactor for all mammals but its biosynthesis is restricted to some microorganisms. The molecule cannot be synthesized within the human body and must be consumed via nutritional means. In mammals, the established B12 delivery mechanism made this molecule an attractive candidate as a drug carrier - an auxiliary drug motif responsible for transportation of therapeutics to the place of its action and as such has received a lot of interest. To utilize its uptake properties and to prepare a potential hybrid drug, vitamin B12 has to be chemically modified and then conjugated to the required therapeutic. These require suitable building blocks and methods for their connection.

Consequently, the elaboration of new, stable but reactive B12 derivatives can meet the interest of medicinal chemists and biologists working on the biochemistry and enzymology of vitamin B12 and may lead to the development of new B12 containing bioactive molecules. It will open new possibilities in vitamin B12 chemistry: broaden the arsenal of vitamin B12 applications and allow for the delivery of biologicaly active oligonucleotides into prokaryotic cells.

For example, we are working on the design and synthesis of vitamin B12-oligmer conjugates and evaluate their antibacterial activity.