Water-Dispersible Ruthenium Nanocatalyst for Carbonyl Reduction With D₂ or T₂ in Aqueous Media

Area of Science:

• Catalysis
• Nanomaterials Science
• Organic Chemistry

Background:

• Biologics are increasingly important therapeutic agents.
• Efficient methods for incorporating hydrogen isotopes into complex molecules are needed.
• Current methods often lack efficiency or require harsh conditions.

Purpose of the Study:

• To develop a catalytic system for direct hydrogen isotope incorporation in aqueous media.
• To synthesize and characterize water-dispersible ruthenium nanoparticles (Ru NPs) for catalytic applications.
• To explore the utility of these Ru NPs for labeling complex molecules and biologics.

Main Methods:

• Synthesis of water-dispersible ruthenium nanoparticles stabilized by sSPhos.
• Catalytic reduction of carbonyl compounds using deuterium and tritium gas.
• Characterization of deuterated products using isotopic enrichment analysis.
• Mechanistic studies to elucidate deuterium incorporation pathways.
• Application of the method to active pharmaceutical ingredients and antibody-drug conjugate linkers.

Main Results:

• Successfully synthesized and characterized water-dispersible Ru NPs.
• Achieved high isotopic enrichment of deuterated alcohols from various aldehydes.
• Demonstrated regioselective labeling of complex molecules like losartan and peptide linkers.
• Confirmed the method's applicability using deuterium and tritium labeling experiments.

Conclusions:

• Water-dispersible Ru NPs are effective catalysts for hydrogen isotope labeling in aqueous media.
• The developed methodology offers a versatile approach for synthesizing labeled complex polar molecules and biologics.
• This work advances the field of isotopic labeling for pharmaceutical and biological applications.