A team of chemists from the Korea Advanced Institute of Science and Technology has made a breakthrough in molecular editing, using light to replace an oxygen atom with a nitrogen atom in a furan molecule. This innovative technique, known as the ‘pencil-and-eraser’ method, could revolutionize the way drugs are synthesized, as it allows for precise, targeted changes to complex molecules. Photocatalysis plays a key role in this process, and the findings are outlined in a study published in the journal Science.
Precise Molecular Editing with Light
Professor Lee Won-young and his colleagues from the leading American chemistry institute Korea Advanced Institute of Design teardown research team have developed a groundbreaking technology to remove one individual atom among atoms that constitute one molecule, and additionally replace it with another. This “pencil-and-eraser” method, as they call it, has been noted to be especially important given that attempts at such precise molecular editing were difficult previously and generally included high temperatures or irradiation — not ideal circumstances for the research.
In their latest study, they broke the furan ring—a fairly common organic functionality—using nothing but light as a photocatalyst. They were able to radicalize the furan by inserting a single electron oxidation onto the furan, using light. This, in turn, enabled the addition of an amine followed by a chain of electron and proton transfer between the product and the photocatalyst. In the end, what was created was a similar ring aldehyde intermediate, but with a nitrogen atom in place of one of the oxygen atoms.
New Horizons in the Synthesis of Drugs
This finding could be very important, as it may revolutionize drug synthesis. This is of great importance in the case regarding drugs, as Ellie Plachinski and Tehshik Yoon from the University of Wisconsin–Madison state mild structural variation of a molecule can result in a dramatic decrease or increase in its activity.
Before this advancement, whenever chemists wanted even a slight alteration in just one region of the molecule or to replace an atom, they had to synthesize complex molecules from the beginning. It was a long and resource-heavy process. This capability to ‘write and erase’ the chemistry of molecules will allow chemists to tailor-make molecules for the purpose of creating new drugs and improving existing ones.
Dealing with Molecular Delocalization Problems
Delocalization, where the electrons of a molecule reside in multiple atoms has been one of the central problems with molecular editing. However, this also means that it is hard to hit and replace one atom only the whole molecule will be broken up. However, in this study, the researchers used light to Photocatalyst to bypass this.
The idea emerged from a 1971 paper by chemists Axel Couture and Alain Lablache-Combier, who had learned to convert one furan compound into an N-polypyrrole by shining it with ultraviolet light, leading to higher overall yields. Drawing from this knowledge, the scientists in the latest study came up with a more efficient and process-driven way of swapping out an oxygen atom for a nitrogen atom at another position on a furan molecule, which researchers believe could enable more breakthroughs to take place in molecular editing.
