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

Area of Science:

• Computational Chemistry
• Biochemistry
• Organic Chemistry

Background:

• Thiamine (vitamin B1) is essential for metabolic processes.
• Understanding its oxidation to thiochrome is crucial for biochemical studies.
• Previous studies lack detailed mechanistic insights into this transformation.

Purpose of the Study:

• To elucidate the oxidation mechanism of thiamine to thiochrome using DFT.
• To investigate the role of different oxidizing agents and water solvation.
• To identify key intermediates and reaction pathways.

Main Methods:

• Density Functional Theory (DFT) calculations.
• wB97X-D functional with 6-311+G** and SDD basis sets.
• Solvent effect modeling using Self-Consistent Reaction Field (SCRF) with Polarizable Continuum Model (PCM).

Main Results:

• Identified a common, stable 2(3H)-thiazolone intermediate in three distinct reaction systems.
• Observed simultaneous cleavage of C-H and O-O bonds (methyl peroxy radical) or C-H and O-H bonds (cyanogen bromide, mercury(ii) chloride).
• Described the subsequent three-step conversion of the intermediate to N-protonated thiochrome, facilitated by proton transfers via water hydrogen bonds.

Conclusions:

• The oxidation of thiamine to thiochrome proceeds through a conserved 2(3H)-thiazolone intermediate.
• Water molecules play a significant role in stabilizing intermediates and facilitating proton transfer steps.
• DFT calculations provide a detailed mechanistic understanding of thiamine oxidation in aqueous solution.