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The Reductive Cleavage Mechanism and Complex Stability of Glutathionyl‐Cobalamin in Acidic Media
Author(s) -
Sajan Abin,
Birke Ronald L.
Publication year - 2016
Publication title -
electroanalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 128
eISSN - 1521-4109
pISSN - 1040-0397
DOI - 10.1002/elan.201600341
Subject(s) - chemistry , adduct , corrin , protonation , unpaired electron , cobalamin , cleavage (geology) , stereochemistry , medicinal chemistry , crystallography , ion , ring (chemistry) , radical , organic chemistry , vitamin b12 , biochemistry , geotechnical engineering , fracture (geology) , engineering
The mechanisms of the electrode reduction of vitamin B 12a and the reductive cleavage of glutathionyl cobalamin (GSCbl) were investigated with digital simulations in acid media at pH 3.78 and 2.78. Even though the pH is quite acidic, the 1‐electron reduction of B 12a goes through the base‐on form in a step‐wise sequence forming base‐on vitamin B 12r which then is protonated to the base‐off form, and finally reduced in another 1‐electron step to vitamin B 12s Unlike the case of B 12a , the GSCbl is found to go by a 1‐electron overall mechanism. In this case, electronic structure calculations at the B3LYP/6‐311G(d,p) level for a model GSCbl complex show that the one‐electron adduct is a radical anion with the unpaired electron in a corrin ring π* orbital. When the axial 5,6‐dimethylbenzimidazole dissociates, the Co(III)‐S bond will break forming Vitamin B 12s and the GS• radical. This reductive cleavage mechanism is the same as in the case of alkylcobalmins and is relevant to the biological mechanism of the B 12 trafficking chaperone proteins, CblC, for processing GSCbl in B 12 dependent enzyme reactions. Finally, we determined conditional stability constants for the formation of the GSCbl complex, K obs , which are 4.4±0.5×10 3 M −1 and 9.9±0.1×10 2 M −1 at pH 3.78 and 2.78, respectively.