Coacervate Droplets Drive Organocatalyzed Aqueous C-C Bond Formation via Interfacial Activation

Area of Science:

• Supramolecular Chemistry
• Catalysis
• Biomimetic Systems

Background:

• Membraneless organelles regulate biochemical reactions via liquid-liquid phase separation (LLPS).
• Coacervate microdroplets serve as synthetic analogues for reaction modulation in aqueous media.
• N-heterocyclic carbene (NHC) organocatalysis is crucial for various chemical transformations.

Purpose of the Study:

• To investigate coacervates as active promoters of aqueous NHC organocatalysis.
• To demonstrate base-free carbon-carbon (C-C) bond formation using coacervate-enabled Stetter reaction.
• To explore the mechanism of NHC precatalyst activation within coacervate systems.

Main Methods:

• Design and synthesis of an amphiphilic thiazolium precatalyst.
• Formation of model polyelectrolyte coacervates encapsulating organic droplets.
• Characterization of coacervate-organic droplet interfaces and catalytic activity.
• Investigation of electrostatic interactions driving precatalyst activation.

Main Results:

• Coacervates effectively sequester Stetter reactants at the organic droplet interface.
• Strong electrostatic interactions between thiazolium salt and polyanion activate the precatalyst.
• Coacervates facilitate carbene generation and drive base-free C-C bond formation.
• Coacervate droplets dissolve upon carbene formation, demonstrating dynamic restructuring during catalysis.

Conclusions:

• Coacervates provide a novel platform for activating organocatalysts in aqueous solutions.
• This study reveals a new mode of catalyst activation within phase-separated materials.
• Coacervates offer dynamic, sacrificial compartments for promoting challenging chemical reactions.