One pot, many reactions
Synthesis and functionalization
January 2, 2008
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| Enzymes confined to different areas by polymersomes allow three different reactions to be carried out in one pot. (Courtesy of Jan C. M. van Hest.) |
Chemists at Radboud University in The Netherlands have demonstrated how polymer nanoreactors can be used to perform one-pot multistep reactions [Vriezema et al., Angew. Chem. Int. Ed. (2007) doi: 10.1002/anie.200701125].
The nanoreactors allow each enzyme-catalyzed step to be confined to different compartments within the reaction mix.
In biological systems, many synthetic pathways run side by side at the same time with incredible efficiency and specificity. One of the ways this is achieved is by carrying out multiple reaction steps in different compartments.
This isolates the catalytic cycle, prevents interference from other compounds, and allows control over the flux of products and reactants into the compartments.
A number of approaches mimicking this concept have been developed, including encapsulating enzymes in nanoreactors based on liposomes or block-copolymer capsules. The capsules or polymersomes tend to be more stable than liposomes, but the diffusion of species through the shells tends to be slow.
Jan C. M. van Hest and colleagues have previously reported more porous polymerosomes that still provide robust protection for encapsulated enzymes.
“What makes our polymersomes special is the fact that they remain permeable for small organic molecules, whereas large molecules such as proteins are caged inside,” explains van Hest. “Enzymes can, therefore, still do their work while being protected against proteases.”
The group has now developed a way of incorporating enzymes into the polymer membrane of the capsules, as well as the central space. This allows them to localize three different enzymes in three different domains: the external solution, the polymersome membrane, and the internal encapsulated volume.
“Cascade reactions have therefore become possible, and we are a step closer to the natural organization of enzymes in multistep cascade reactions,” comments van Hest.
The team used a three-enzyme system, first to convert a substrate into glucose in the space outside the polymersomes. Glucose oxidase inside the nanoreactors can then convert the glucose into lactone and release H2O2, which is finally used by horseradish peroxidise in the polymer shell in a third reaction. All this in one pot.
“We are currently developing the technology in order to perform industrially relevant cascade reactions in which the order and positioning of the catalytic sites determines the outcome of the overall reaction,” adds van Hest.
He believes the cascade nanoreactors can be an efficient alternative to homogeneous and heterogeneous catalytic processes in the fine chemistry, biomedical, and pharma industries.
Jonathan Wood