For thousands of years, humanity has always had to take the long way around, using many reaction steps just to change a single atom in a molecule. But from now on, everything will change!
Take a look at the chemical formulas of these two molecules. They differ by just one atom.
On the left is Furan, an aromatic organic compound with a five-membered ring, where one carbon (C) is replaced by oxygen (O). By changing this oxygen atom to nitrogen (N), you get Pyrrole – the compound on the right:
Furan and Pyrrole.
Although it’s just an extremely small atom, this difference is considered “critical.”
This is because Furan is a toxic substance that can even cause cancer in humans. However, Pyrrole is a therapeutic compound used as an anti-cancer drug, pain reliever, and treatment for cardiovascular diseases.
Fortunately, you can’t confuse them with each other, because at room temperature and atmospheric pressure, Furan is a clear liquid, while Pyrrole has a reddish color (apologies to those chemistry teachers who create exams that confuse labels). But that’s what just one atom can do to completely change the properties of a chemical compound.
Sadly, changing just one atom of these heterocyclic compounds has never been easy. For example, to create Pyrrole, you would need to employ this reaction:
Or this reaction:
Or at least this reaction:
There is a way to directly produce Pyrrole from Furan by reacting it with ammonia (NH3). However, this reaction requires high temperatures of up to 500 degrees Celsius and the presence of expensive catalysts like SiO2 and Al2O3. Furthermore, the low reaction yield makes this method of synthesizing Pyrrole economically unfeasible.
Nevertheless, this is still the method that humanity has had to use to produce Pyrrole specifically and many other therapeutic compounds generally. For thousands of years, from the era of alchemists to modern chemical methods, humans have always had to take the long way around, using many reaction steps just to change a single atom in a molecule.
But from now on, everything will change!
The process of single-atom editing was once the dream of chemists.
Single-Atom Reaction Technique with Aromatic Compounds
In a breakthrough study published in the journal Science, a team of scientists from the Korea Advanced Institute of Science and Technology (KAIST) reported that they have successfully developed the world’s first single-atom editing technique, allowing for direct changes to an atom in a molecule.
Testing this method with Furan, they successfully transformed this compound into Pyrrole by replacing the oxygen atom with a nitrogen atom, all at room temperature and atmospheric pressure. Such single-atom editing has long been a dream of chemists.
It is even likened to the “hand of God,” capable of creating complex compounds with a simple, easy method like assembling a Lego piece.
Professor Yoonsu Park, the study’s author from the Korea Advanced Institute of Science and Technology (KAIST).
Professor Yoonsu Park, the study’s author from KAIST, stated: “The aromatic compounds are so stable that changing one atom into another was once considered impossible.”
To achieve this, Professor Park’s research team employed a strategy called “photocatalysis,” which uses light as a catalyst for the reaction.
By using an acridinium catalyst to shine blue light on Furan, Professor Park temporarily disrupted its aromatic ring, allowing an NH amino group to be inserted in place of the O atom.
Then, through a condensation process, the final compound pushes the oxygen atom out, pairing with hydrogen to form water (H2O), leaving only the nitrogen atom within the aromatic ring to form Pyrrole.
“Here, we present a photocatalytic strategy for swapping one oxygen atom of furan with a nitrogen group, directly converting furan into a pyrrole analogue in a single intermolecular reaction,” Professor Park explained.
The reaction used by South Korean scientists.
Why This Discovery Is a Revolution for the Pharmaceutical Industry?
Commenting on the new research, Mark Levin, an organic chemist at the University of Chicago, USA, stated:
“Existing methods for this type of heterocyclic ring transformation reaction often require harsh conditions, such as extremely high temperatures or ultraviolet radiation. This limits their applicability in synthesizing complex organic compounds due to low product yields and a restricted substrate range.
The new reaction by the South Korean researchers is the first protocol allowing for the direct conversion of furan to pyrrole under milder conditions, making it much more practical for various applications in synthetic chemistry.”
In a dedicated piece in the “Perspective” section, where the journal Science invites independent, renowned, and reputable scientists to comment on impactful or revolutionary research, two chemists Ellie F. Plachinski and Tehshik P. Yoon from the University of Wisconsin-Madison, USA, said:
“The properties of a bioactive molecule depend heavily on the precise arrangement of its constituent atoms. For instance, changing the identity of a single atom in a heterocyclic ring—a molecular ring containing at least one non-carbon element—can affect the efficacy of drugs.”
“This research has very strong potential for creating continuous chemical synthesis processes, converting complex molecules, and advancing discoveries in the pharmaceutical field,” Plachinski and Yoon emphasized.
Single-atom editing can create countless additional drugs for the human pharmacopoeia.
For his part, Professor Park stated: “This breakthrough has enabled selective editing of five-membered organic ring structures, which will open new doors for building libraries of potential drug candidates, a significant challenge in the pharmaceutical industry. I hope this foundational technology will be used to revolutionize drug development processes.”
Like Furan and Pyrrole, many drugs have very complex chemical structures, but their therapeutic effects often come from just one single atom. Atoms like oxygen and nitrogen play a central role in enhancing the pharmacological effects of these drugs, especially against viruses.
Professor Park’s research team is currently testing a series of similar processes to single-atom edit various compounds based on Furan and Pyrrole. The next step is to design industrial-sized reactors to test the technique on a large scale.
If successful in the ability to edit each atom within a molecule and on an industrial scale, we could produce any drug we desire, in unlimited quantities.
