Thermodynamic Redox Properties of Cobamides

The electrochemistry of the B12 derivative aquocobalamin (4 ) has been particularly well studied [90,94-99] where the one-electron reduction of 4 gives Bi2r (23) and then Bi2s (40 ) (see Fig. 4). Typicahy, electrochemical studies of aquocobalamin (4 ) were carried out in aqueous solution. 

A standard potential vs. pH diagram correlates the thermodynamics of the aquocobalamin (4+)-Bi2r (23)-Bi2s (40 ) system (see Fig. 5). The interconversion between the different oxidation states of B -derivatives can usually be monitored effectively by UV-vis spectroscopy, and the relevant data were obtained from potentiostatic measurements, which were followed by UV-vis spectroscopy [90,94], Within the pH range - 1 to 11 and applied potentials = 0.5 V and -1.2 V vs. SCE, seven solution cobalamins are thermodynamically predominant spanning a range of the three formal oxidation states of Bi2 [90]. 

Aquocobalamin (4+) and HOCbl (5) differ by protonation of the upper ( S) axial ligand with pKa (4+) = 7.8 [90]. The Co(II)-corrin Bi2r (23) represents the base-on form of the Co(II) oxidation level (i.e., the nucleotide loop is coordinated intramolecularly), this is converted into the base-off (23-H ) by protonation of the DMB-base, with pfCa (23-H+) = 2.9 [90]. At the Co(I)-level, cob(I)alamin B s (40 ) is first protonated at the nucleotide base to give 40-H. For the pKa of 40-H, an original value of 4.7 was determined [90,94,96], but more recently this has been estimated to be 5.6 [101,102]. A second protonation then occurs at the Co(I)center to give the Co(III)-hydride [92] 40-H2, with pKa (4O-H2+) = 1 [90,94,103]. 

This shift by about 110-140 mV to a more negative potential for the reduction, of (base-on) B r (23) when compared to that of the protonated base-off form 23-H+, reflects the selective stabilization of the Co(II)-corrin 23 by intramoleciflar nucleotide coordination [75,90]. A dependence of the standard potentials of the Co(III)-/Co(II)-redox couples occurs at approximately 60 mV per pH unit, at pH 7.8 for HOCbl (5)/Bi2r (23) and at pH 2.9 for 4 /23-H and this reflects the effect of the removal by protonation of one axial ligand. An analogous dependence of the potential occurs between pH 2.9 and ca. 5.6 for 23/40-H as well as below pH 1 for the Co(II)-/Co(I)-redox couple 23-H /40-H2. At all pH-values the disproportionation of Co(II)-corrins to Co(III)- and Co(I)-corrins is thermodynamically disfavored (the disproportionation equilibrium constant is below 10 °) [90]. 

A complex interplay between the thermodynamic and kinetic factors of electron transfer reactions occur in the analogous studies of vitamin B12 (1), due to the strongly coordinating cyano ligand [87,90]. Coordination of (one or two) cyanide ligands to the Co(III)-center stabilizes it against reduction and the Co(III)-/Co(II)-standard potentials are shifted to more negative values [90, 104]. Cyanide ions transform 1 into (base-off) dicyano-cob(III)alamin (1-CN ) with an equilibrium constant of about 10 M [22,104]. 

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