The Nature of the Co-C Bond Cleavage Processes in Methylcob(II)Alamin and Adenosylcob(III)Alamin

Abstract

Abstract. Unfortunately, there are still signifi cant disagreements between experimental and theoretical data of rate constants, energy barriers for Co-C bond cleavage process and coordination numbers of vitamin B 12 coenzyme species in spite of the remarkable efforts done by research community. Therefore, no grounded mechanisms for Co-C vitamin B 12 coenzyme bond breaking process and subsequent reactions have been found up to now. The infl uence of the mixing orbitals e.g. Pseudo-Jahn-Teller and similar effects on the reactions paths of bond-cleavage mechanisms of vitamin B 12 co-factors must be taken into account by utilizing multi-reference methods, in particular multiconfi gurational self-consistent fi eld (MCSCF) method. Then, the change in total energy along the normal coordinate Q for the stretching mode including Co-C and Co-N bonds in vitamin B 12 cofactors is expected due to a "vibronic" coupling term, which couples an excited state and ground state by a second order derivative potential-energy operator. The strong state mixing effect is expected to lead to low energy barriers and to Co-C and Co-N axial bond cleavage events in agreement with experimental data. Afterward, the updated mechanisms of vitamin B 12 bio-processes can be determined.Keywords: vitamin B 12 , mechanism, bio-catalysis, Pseudo-Jahn-Teller effect, DFT, MCSCF. Received: December 2015/ Revised fi nal: February 2016/ Accepted: February 2016 IntroductionVitamin B 12 cofactor is one of eight B vitamins and is involved in mammalian cellular metabolism, infl uencing amino acid and DNA synthesis [1] and hematopoiesis. The best known human physiological function of vitamin B 12 is its role in promoting normal health in the brain and nervous system. Vitamin B 12 anemia can cause such neurologic dysfunction as weakness, fatigue, light-headedness, rapid heartbeat, rapid breathing, pale skin color, bruising, and bleeding (including bleeding gums). The more severe vitamin B 12 anemia dysfunctions are characterized by tingling or numbness of the fi ngers and toes, diffi culty walking, mood changes, depression, memory loss, disorientation and, in most severe cases, dementia [2]. Vitamin B 12 defi ciency has even been considered in playing a role in the development of Alzheimer's disease [3][4][5][6][7].The vitamin B 12 cofactor contains a cobalt atom surrounded by an equatorial corrin ring. Covalently linked to the central atom is a dimethylbenzimidazole that occupies one of the axial coordination positions. The opposite coordinate is available for several ligands in bio-medium or in solution; however, known biologically active structures containing adenosyl-or methyl have been considered most often (Figure 1).

Disposal of Poisonous Organic Halides by Using the Electrochemical Method: DFT Simulation

“…For non-adiabatic ET the DFT calculation of the electronic structure of the substrate is not valid and no conclusion regarding the reactivity of the substrate ions can be made [22,23]. More sophisticated electronic structure methods, like MCSCF must be applied to these studied processes [22,24,25]. Although, the true nature of the ET can be determined using the experimental data, along with theoretical ones [21].…”

The Miracle of Vitamin B12 Biochemistry

“…All calculations of vitamin B12 cofactor-dependent processes performed using the DFT or the QM/MM method based on the DFT have failed to explain these bioprocesses or contained problematic issues. It has been shown on several occasions that the Pseudo-Jahn-Teller Effect is very prominent in the vitamin B12 cofactors [126,127,[141][142][143][144]. In particular, the explanation for the failure of DFT in studying the vitamin B12-dependent bioprocesses can be drawn from work by Isaac Bersuker [164], who showed that the DFT method could not handle compounds in which Pseudo-Jahn-Teller is prominent.…”

“…Theoretical methods [100][101][102][103][104] have been used to study the properties and action of vitamin B12 cofactors in enzymatic processes [105][106][107][108][109][110]. In particular, spectroscopic processes, the trans effect, substrate implication in vitamin B12 bioreactions, and the processes of breaking the Co-C and Co-N axial bonds have been studied [102,[111][112][113][114], mainly by using the DFT method [115][116][117][118][119] or by using the QM/MM method, in which the QM part is treated as the DFT method [120][121][122][123][124] by using the models [125][126][127][128][129] of the vitamin B12 cofactors [130][131][132][133]. The authors claimed that the DFT method [134][135][136][137][138] was suitable for studies of vitamin B12 bioprocesses [139,140].…”

The Mechanism of the Toxic Organic Halides Disposal under the Catalytic Influence of the Vitamin B12

“…The methylcobalamin and adenosylcobalamin cofactors are the basic structures for the catalytic action of vitamin B12. In the center of these structures is the cobalt ion, which is linked by four coordinative bonds to the coring ring (Figure 1), which structure is planar [29]. The permanent axial ligand to the central cobalt atom in the relaxed state (in vitro) is dimethylbenzimidazole, which is linked to the corrin ring through a side chain.…”

“…In the position of the other axial ligand is one of the methyl or 5'-deoxy-5'-adenosyl radicals. In their biochemical processes, the central cobalt atom of the cofactors changes its oxidation state from +3 to +1, and vice versa [29] (Figure 1). As it has been shown, the effective particle in the process of annihilation of toxic organic halide compounds is the cofactor of vitamin B12 in which the oxidation state of the central cobalt atom is +1, and the axial ligands are decoupled from the central atom [14].…”