Complementary DNA strands allow novel reaction products to be easily identified.

Although chemists have been studying chemical reactions for a few hundred years, they have probably only scraped the surface of all possible reactions, what is known as the 'reactivity space'. But now a team of chemists from Harvard University, Cambridge, US, led by David Liu, has developed a sort of chemical speed dating, where a range of different molecules can be brought together to see if they react.

The work could help researchers delve deeper into reactivity space.

Chemical speed dating is based on DNA-templated synthesis, in which synthetic molecules are created by attaching their chemical precursors to complementary strands of DNA. The technique was developed by Liu and his colleagues, who had previously used it to carry out planned chemical reactions. However, they soon realised that this technique also offered a way to conduct more speculative chemical syntheses.

'We were intrigued by a different approach to reaction discovery that does not focus on any specific combination of substrates but instead can simultaneously examine many combinations,' explains Liu.

The chemists split 24 different DNA-attached compounds into two pools. The specific sequence of each DNA strand codes for its attached compound and is also complementary to a strand in the other pool. When the two pools are combined, the complementary DNA strands pair with each other, bringing their attached compounds into close enough proximity to react. In this way, 144 potential reactions can be carried out simultaneously. After separating the compounds that reacted from those that didn't, the chemists could identify the reactants via their still-attached DNA sequences.

Using this technique, Liu's team explored palladium-catalysed reactions between organic molecules and identified a novel reaction between a terminal alkyne and a terminal alkene, which resulted in the synthesis of a 20-membered macrocyclic trans-enone. Further research demonstrated that this reaction could also take place efficiently on much larger scales.

Liu and his team are now planning to investigate novel reactions involving a range of compounds, including transition-metal complexes, Lewis acids and organic reagents.

Jon Evans