Biodegradable Grubbs-Loaded Artificial Organelles for Endosomal Ring-Closing Metathesis

The application of transition-metal catalysts in livingcells presentsa promising approach to facilitate reactions that otherwise wouldnot occur in nature. However, the usage of metal complexes is oftenrestricted by their limited biocompatibility, toxicity, and susceptibilityto inactivation and loss of activity by the cell's defensivemechanisms. This is especially relevant for ruthenium-mediated reactions,such as ring-closing metathesis. In order to address these issues,we have incorporated the second-generation Hoveyda-Grubbs catalyst(HGII) into polymeric vesicles (polymersomes), which were composedof biodegradable poly(ethylene glycol)-b-poly(caprolactone-g-trimethylene carbonate) [PEG-b-P(CL-g-TMC)] block copolymers. The catalyst was either covalentlyor non-covalently introduced into the polymersome membrane. Thesepolymersomes were able to act as artificial organelles that promoteendosomal ring-closing metathesis for the intracellular generationof a fluorescent dye. This is the first example of the use of a polymersome-basedartificial organelle with an active ruthenium catalyst for carbon-carbonbond formation.

Automated summary

The application of transition-metal catalysts in living cells is a promising approach to facilitate reactions not naturally occurring. However, the usage of metal complexes is often restricted by limited biocompatibility, toxicity, and susceptibility to inactivation by cell's defense mechanisms. In this study, a second-generation Hoveyda-Grubbs catalyst was incorporated into polymeric vesicles, acting as artificial organelles, to facilitate intracellular ring-closing metathesis reactions. This is the first example of using polymersome-based artificial organelles with an active ruthenium catalyst for carbon-carbon bond formation.