How is vitamin B1 oxidized to thiochrome? Elementary processes revealed by a DFT study

The oxidation reaction of thiamine (vitamin B1) to thiochrome was investigated by DFT calculations. Three reaction systems, [A] thiamine + methyl peroxy radical + (H₂O)₈, [B] thiamine + cyanogen bromide + HO⁻(H₂O)₈ and [C] thiamine + mercury(II) chloride + HO⁻(H₂O)₈, were investigated. wB97X-D/6-311+G** for [A] and [B] and wB97X-D/SDD&6-311(+)G** for [C] geometry optimizations were carried out with the solvent effect (water). The effect is of the self-consistent reaction field (SCRF) with the polarizable continuum model (PCM). In [A], the H₃C–O₂˙ adduct of thiamine undergoes simultaneous cleavage of the C–H and O–O bonds, leading to a very stable 2(3H)-thiazolone intermediate. The same intermediate was obtained after the cleavage of the C–H and O–H bonds of the HO adduct of thiamine in [B] and [C]. After the formation of the key intermediate, the N-protonated thiochrome was afforded via three steps. In reflection of the water-soluble character of vitamin B1, proton transfers along hydrogen bonds of the water cluster enhance those steps.