ScienceNot yet confirmed elsewhere1 publisher2 min readPublished
Levin's lab turns a stalled step into a blue-light route for swapping carbon for nitrogen in rings
Mark Levin's group at the University of Chicago used blue light and oxygen to swap a ring carbon for nitrogen in dozens of compounds, Science reports. Whether that widens how drug candidates are modified rests on property data for one compound.
The Scientist · Science desk
What happened
- Starting from ring molecules with an added nitrogen group, blue light, oxygen and tetramethylthiourea open the carbon ring, and a further treatment seals it with nitrogen in carbon's place.
- Earlier routes stalled when a reactive chemical switched into a state that could not rearrange, so the team added the reagent and let the molecule finish through a different reaction.
- The tested compounds included the heart-rhythm drug dronedarone and the active compounds vinpocetine, yohimbine and catharanthine.
- In early laboratory tests, one nitrogen-swapped vinpocetine was more soluble and had better metabolic properties than the original compound.
- The same analog had less effect on a key heart protein, and the report says that could lower the risk of dangerous heart rhythm problems.
Why it matters
- capability Medicinal chemists get a way to test carbon-to-nitrogen swaps on complex natural products, if the authors' claim of broader applicability holds up on compounds from other labs.
- constraint Each candidate has to carry the added nitrogen group before the light step, so the edit starts from a prepared precursor and the cost of preparing it belongs in any comparison with older routes.
- decision One favorable analog is a reason to try the swap on other candidates, and no basis yet for predicting it will improve them.
The authors tie the wider reach to the decision to work with the stalled state [5]. "By embracing rather than avoiding this otherwise parasitic spin state, we achieve a reaction with much more versatile applicability, enabling the interrogation of C-to-N replacement in genuinely complex natural products," the study authors said [6]. The paper, in Science, is Dong-Il Park et al., "Embracing triplet nitrenes for C-to-N replacement of complex bicyclic (hetero)aryl azides" [13].
Dozens of compounds show the swap runs [7]. Whether a swapped compound is a better drug is a separate test, and the report's evidence for it has one subject and one control: the vinpocetine analog against the original compound [9]. We think the firm result today is scope, and that the benefit case is a single lead that further analogs would have to support.
The report describes older approaches as often needing harsh chemicals or working only on specific types of molecules [2]. The thing this doesn't tell you is how much gentler the new conditions are: the report does not include a side-by-side of conditions, a solubility figure for the vinpocetine analog, or how the starting nitrogen group is installed.
Making the swap on dozens of compounds is a research result. The report says the technique has not yet been demonstrated for commercial drug manufacturing [11]. The team's stated target is medicinal chemistry. The team said: "We anticipate that this addition to the tool kit for C-to-N transmutation will find promising applications in medicinal chemistry." [12]
What to watch
- Property data with magnitudes (solubility, metabolic stability, heart-protein effect) for swapped analogs beyond the single vinpocetine case.
- A demonstration of the route for commercial drug manufacturing, the step the report says has not been done.
- Reports from other laboratories applying the blue-light swap to their own complex compounds.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence50
- Adoption
- Insufficient
- Hype gap+15
- Incentives
- Insufficient
- Confidence55
Claim ledger
Ranked by verification strength, evidence, and original report placement.
- [1]
Researchers led by Mark D. Levin at the University of Chicago developed a technique to replace a carbon atom with a nitrogen atom in ring-shaped molecules, described in a paper published in the journal Science.
- [2]
Older skeletal-editing approaches for swapping carbon for nitrogen often require harsh chemicals or only work on specific types of molecules.
- [3]
The process has three main steps: ring-shaped molecules containing an added group of nitrogen atoms are exposed to blue light in the presence of oxygen and a reagent called tetramethylthiourea, which sets off reactions that open the carbon ring and rearrange its atoms, and a further chemical treatment seals the ring back together, leaving the new nitrogen atom in place of the old carbon atom.
- [4]
The starting materials are ring-shaped molecules containing an added group of nitrogen atoms.
- [5]
Earlier approaches stalled right after the light hit the molecule because a reactive chemical switched into a state in which it could no longer rearrange; instead of trying to prevent that state, the researchers added the reagent, which allowed the molecule to complete the swap through a different reaction.
- [6]
"By embracing rather than avoiding this otherwise parasitic spin state, we achieve a reaction with much more versatile applicability, enabling the interrogation of C-to-N replacement in genuinely complex natural products,"
- [7]
The team tried the technique on several families of ring-shaped molecules commonly found in pharmaceuticals and performed the carbon-to-nitrogen swap across dozens of different compounds.
- [8]
The compounds included the heart-rhythm drug dronedarone and the pharmacologically active compounds vinpocetine, yohimbine and catharanthine.
- [9]
In early laboratory tests, one new nitrogen-swapped version of vinpocetine was more soluble and showed improved metabolic properties compared with the original compound.
- [10]
The new nitrogen-swapped version of vinpocetine also had less of an effect on a key heart protein, potentially reducing the risk of dangerous heart rhythm problems.
- [11]
The technique has not yet been demonstrated for commercial drug manufacturing.
- [12]
"We anticipate that this addition to the tool kit for C-to-N transmutation will find promising applications in medicinal chemistry."
- [13]
The paper is Dong-Il Park et al., Embracing triplet nitrenes for C-to-N replacement of complex bicyclic (hetero)aryl azides, Science (2026), DOI 10.1126/science.aef3511.
Sources
1 independent publisher whose own reporting we read for this story.
- phys.orgA new way to replace carbon with nitrogen atoms could lead to better medicines
1 article · October 13, 2026
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