Light-driven reductive cyclization catalyzed by vitamin B₁₂-based artificial photoenzymes

Area of Science:

• Biochemistry
• Organic Chemistry
• Photochemistry

Background:

• Vitamin B12 (cobalamin) has a unique light-sensitive metal-carbon bond.
• This photolabile bond is vital for B12-dependent microbial photoreceptors but not yet exploited by enzymes.
• No enzymes are known to utilize cobalamin's photoreactivity for catalysis.

Purpose of the Study:

• To develop artificial photoenzymes using cobalamin.
• To catalyze the intramolecular cyclization of unactivated alkyl halides with tethered alkenes.
• To investigate the effect of a protein environment on cobalamin's photoreactivity.

Main Methods:

• Assembly of cobalamin-serum albumin conjugates.
• Utilizing visible light for photolytic cleavage of the cobalamin metal-carbon bond.
• Catalysis of intramolecular cyclization reactions.

Main Results:

• Demonstrated cobalamin-serum albumin conjugates as artificial photoenzymes.
• Achieved 4.5x enhanced reactivity for a model substrate due to protein encapsulation.
• Successfully cyclized various alkyl halides to form molecular scaffolds.
• Performed a tandem Giese reaction with methyl acrylate.

Conclusions:

• Cobalamin-serum albumin conjugates function as effective artificial photoenzymes.
• Protein encapsulation significantly enhances cobalamin-mediated photoreactions.
• Developed a novel method for synthesizing diverse molecular scaffolds using light-activated cobalamin.