| Project Detail |
Towards a bio-inspired sustainable chemistry
The Stetter reaction, a bio-inspired process catalysed by N-heterocyclic carbenes (NHCs), can form carbon-carbon (C-C) bonds in water without the use of metals or organic solvents. Insoluble organic substrates form hydrophobic organic droplets in water, which promotes the reaction despite NHC sensitivity to hydrolysis. In this context, the MSCA-funded BioCataDrops project is studying the Stetter reaction in coacervates (polymer-rich aqueous microdroplets considered to be primitive models of the first living cells). The premise is that coacervates can serve as microreactors for the synthesis of C-C bonds using newly designed organocatalysts. The project will demonstrate the formation of C-C bonds using a Stetter reaction model to explore the molecular mechanism and to study the impact of the internal polarity of coacervates on the reaction kinetics.
"Bio-inspired catalysis in aqueous coacervate droplets: towards a softer chemistry
Recent advancements in modern synthetic chemistry have aligned with the imperative of reducing environmental impact, driving the emergence of a more sustainable chemistry, inspired by nature. In organic chemistry, the formation of C-C bonds is pivotal but often necessitates the use of both metal and organic solvents. However, a non-enzymatic approach to forge C-C bonds in water has been demonstrated through the Stetter reaction, a bio-inspired process catalyzed by N-heterocyclic carbenes (NHC) and thiamin cofactor mimics. Due to their limited water solubility, organic substrates generate water-isolated organic droplets, effectively promoting the Stetter reaction despite NHCs sensitivity to hydrolysis. Our objective is to investigate the Stetter reaction within polymer-rich aqueous microdroplets known as ""coacervates,"" which emulate primitive models of early living cells. Similar to micellar chemistry, these droplets possess a hydrophobic inner core, facilitating the spontaneous uptake and accumulation of organic molecules. We hypothesize that coacervates can serve as microreactors for C-C bond synthesis, catalyzed by newly designed azolium-based organocatalysts compatible with coacervates. Our aim is to demonstrate in-situ C-C bond formation via a model Stetter reaction and explore the molecular mechanism, akin to an ""on-water"" environment, while considering the impact of coacervates internal polarity on reaction kinetics, yield, and selectivity. Altogether, our findings will broaden horizons in sustainable bio-inspired chemistry, enhancing the soft chemistry toolbox and potentially inaugurating a new realm of research: bio-inspired organic synthesis within coacervates. Significantly, the chemical synthesis of complex molecules in coacervates could also shed light on mechanisms that could have led to the formation of Life’s molecules in protocells before enzymes emerged. |
