Intracellular Ruthenium-Promoted (2+2+2) Cycloadditions

Area of Science:

• Chemical Biology
• Biomedical Research
• Organic Synthesis

Background:

• Metal-mediated reactions are crucial in chemical biology and biomedicine.
• Current intracellular reactions primarily focus on uncaging or redox processes.
• Developing new intracellular catalytic transformations is essential for advancing cell biology and medicine.

Purpose of the Study:

• To demonstrate the feasibility of multicomponent alkyne cycloaromatizations inside live mammalian cells.
• To utilize ruthenium catalysts for novel intracellular chemical transformations.
• To synthesize valuable compounds like anthraquinones and aggregation-induced emission (AIE) materials within cells.

Main Methods:

• Employing ruthenium catalysts to mediate multicomponent alkyne cycloaromatizations in live mammalian cells.
• Investigating both intramolecular and intermolecular cycloaddition reactions of diynes with alkynes.
• Synthesizing anthraquinone derivatives and AIE-active molecules intracellularly.

Main Results:

• Successfully performed multicomponent alkyne cycloaromatizations within live mammalian cells using ruthenium catalysts.
• Achieved intracellular synthesis of diverse anthraquinones via intermolecular cycloadditions.
• Generated anthraquinone-based aggregation-induced emission (AIE) materials that are cell-impermeable.
• Demonstrated control over product intracellular distribution by modifying the ruthenium complex.

Conclusions:

• Ruthenium-catalyzed multicomponent alkyne cycloaromatizations represent a powerful new tool for intracellular synthesis.
• This methodology enables the creation of complex molecules, including AIEgens, directly within living cells.
• The ability to tune catalyst properties offers a strategy for controlling intracellular product localization, with significant implications for chemical biology and drug development.