South Korea successfully researches the world's first 'single atom editing' technique

For thousands of years, humans have had to go through a series of steps to change a single atom in a molecule. But now, that's all going to change!

Look at the chemical formulas of these two molecules. They differ by just one atom.

On the left is Furan , an aromatic, 5-atom heterocyclic organic compound, with one carbon (C) replaced by oxygen (O). Swap this oxygen atom for nitrogen (N), and you get Pyrrole - the compound on the right:

Furan and Pyrrole.

Although only an extremely tiny atom, this difference is considered "fatal".

Because Furan is inherently toxic, it can even cause cancer in humans. But Pyrrole is a pharmaceutical substance, used as an anti-cancer drug, pain reliever and cardiovascular treatment drug.

Luckily, you can't mistake them for each other, because at room temperature and pressure, Furan is a clear liquid, while Pyrrole is red (sorry chemistry teachers who are always losing their labels). But that's how one atom can completely change the properties of a chemical compound.

Sadly, changing just one atom of these heterocyclic compounds is never easy. For example, to make Pyrrole, you would need to use this reaction:

Or this reaction:

Or at least this reaction:

There is a way to produce Pyrrole directly from Furan, which is to react it with ammonia (NH ₃ ). But this reaction requires high temperatures up to 500 degrees Celsius, along with the presence of expensive catalysts such as SiO ₂ and Al ₂ O ₃ . In addition, the low reaction efficiency makes this method of synthesizing Pyrrole difficult to achieve economic feasibility.

Yet, that is still the way humans are forced to use to produce Pyrrole in particular and many other pharmaceuticals in general. For thousands of years, from the age of the alchemists to modern chemical methods, humans have always had to take a roundabout way, using many reaction steps just to change a single atom in a molecule.

But from now on, everything will change!

Single-atom editing was once a chemist's dream.

Uniatomic reaction techniques with aromatic compounds

In a groundbreaking new study published in the journal Science, a team of scientists from the Korea Advanced Institute of Science and Technology (KAIST) said they have successfully developed the world's first single-atom editing technique , allowing for direct changes to a single atom in a molecule.

Testing this method on Furan, they successfully converted the compound into Pyrrole, by replacing the oxygen atom with a nitrogen atom, at room temperature and atmospheric pressure. Such single-atom modifications were once a dream of chemists.

It has even been likened to the "hand of God", which can create complex compounds, using a simple method, as easy as assembling a Lego piece.

Professor Yoonsu Park, study author from Korea Advanced Institute of Science and Technology (KAIST).

" Aromatic compounds have such high stability energies that changing one atom into another was once considered impossible," said study author Professor Yoonsu Park of KAIST.

To do that, Professor Park's team used a strategy called "photocatalysis ," which uses light as a catalyst for the reaction.

By using an acridinium catalyst to fire blue light at Furan, Professor Park temporarily cleaved its aromatic ring, allowing an NH amine group to be inserted in place of the O atom.

Then, through a condensation process, the final compound will push the oxygen atom out, pairing with hydrogen to form water (H ₂ O), leaving only the N atom in the aromatic ring to form the Pyrrole compound.

" Here, we have presented a photocatalytic strategy that swaps an oxygen atom of furan with a nitrogen group, directly converting furan into a pyrrole analogue in a single intermolecular reaction ," said Professor Park.

The reaction that Korean scientists used.

Why is this discovery revolutionary for the pharmaceutical industry?

Commenting on the new research, Mark Levin, an organic chemist at the University of Chicago, USA, said:

" Existing methods for this type of heterocyclic cycloaddition reaction often require harsh conditions, such as extremely high temperatures or ultraviolet radiation. This limits their applicability in the synthesis of complex organic compounds, due to low product yields and limited substrate range.

The new reaction by the Korean researchers is the first protocol that allows the direct conversion of furan to pyrrole under milder conditions , making it much more practical for many applications in synthetic chemistry."

In a dedicated article in the "Perspectives" section , where Science magazine invites independent, well-known and reputable scientists in the field to comment on a research that has a great impact or is revolutionary, two chemists Ellie F. Plachinski and Tehshik P. Yoon from the University of Wisconsin-Madison, USA, said:

" The properties of a biologically active molecule depend heavily on the precise arrangement of its constituent atoms. For example, changing the identity of a single atom in a heterocyclic ring—a molecular ring containing at least one element other than carbon—can influence the efficacy of a drug."

' This research has very strong potential to create continuous chemical synthesis processes, transform complex molecules, and advance pharmaceutical discoveries ,' Plachinski and Yoon emphasize.

Single-atom editing could create a myriad of drugs that could be added to the human pharmacopoeia.

For his part, Professor Park said: " This breakthrough has enabled the selective modification of five-membered organic ring structures , which will open new doors for building libraries of potential drug candidates, a key challenge in the pharmaceutical industry. I hope this platform technology will be used to revolutionize drug development processes."

Like Furan and Pyrrole, many drugs have very complex chemical structures but their medicinal properties come from a single atom. Atoms such as oxygen and nitrogen play a central role in enhancing the pharmacological effects of these drugs, especially their anti-viral effects.

Professor Park's team is now testing a series of similar processes for single-atom modifications of various Furan and Pyrrole-based compounds. The next step is to design industrial-scale reactors to test the technique on a large scale.

If we succeed in being able to edit every atom inside a molecule, and on an industrial scale, we will be able to create any drug we want, in unlimited quantities.