In drug discovery, building complex molecules quickly is the name of the game.
Chemists want molecules with increasingly three-dimensional atomic structures because they may be more potent and selective inside the body, but the additional chemical steps needed to build that complexity cost time and money.
As it turns out, molecular complexity can be built in fewer steps using some surprisingly simple tools: off-the-shelf blue LED lights and a commercially available chemical building block familiar to sophomore organic chemistry students.
That's according to a new University at Buffalo-co-led study published Thursday (July 9) in Science.
The researchers mixed the familiar chemical building blocks - molecules with carbon-halogen bonds - with a light-activated catalyst. When illuminated by blue LED light, the catalyst temporarily transformed the molecules into more reactive forms. That allowed the researchers to modify two adjacent carbon atoms instead of the usual one.
We've used the relatively mild conditions of visible light to expand what chemists can do with a longtime organic chemistry staple. We hope this gives chemists a faster route to the complex molecules needed in drug discovery."
Patricia Z. Musacchio, PhD, corresponding author, assistant professor of chemistry, UB College of Arts and Sciences
The work was done in collaboration with Worcester Polytechnic Institute, where Musacchio previously worked, and Binghamton University. It was supported by the National Institute of General Medical Sciences, part of the National Institutes of Health, and the National Science Foundation ACCESS program.
Two for one
Carbon atoms form the backbone of most small-molecule drugs. By changing what's attached to those carbon atoms, chemists can alter a drug's shape and behavior.
That's what makes molecules with carbon-halogen bonds such valuable starting points. A halogen atom can be readily removed from a carbon atom and replaced with another group of atoms, a reaction commonly taught in undergraduate organic chemistry.
Traditionally, the reaction only changes the carbon atom that the halogen was attached to. The neighboring carbon remains unchanged.
Musacchio and her team's method changes that. The photocatalyst temporarily opens a window for adding new groups of atoms to the neighboring carbon as well.
"The advantage is getting two modifications from a single reaction, whereas you normally only get one modification," says the study's other corresponding author, Jennifer Hirschi, PhD, associate professor of chemistry at Binghamton University. "More changes in fewer steps is crucial when creating small-molecule drugs."
Boxes of light
Musacchio's lab is filled with blue LEDs - the same lights used for indoor gardens and fish tanks.
The lights sit inside small compartments on shelves that the team has dubbed "Buffalo boxes." Inside these boxes, the blue LEDs activate the catalyst in each vial, beginning the reaction that ultimately allows two neighboring carbon atoms to be modified instead of one.
Using visible light is gentler than many traditional photochemical approaches that use higher-energy ultraviolet (UV) light.
"UV light could degrade or decompose the organic molecules that we're making, so the visible light is a much more mild approach," Musacchio says.
Musacchio says the approach could eventually be adapted for other types of molecular transformations as well. The team plans to work with pharmaceutical companies to explore how the method can be tailored to specific drug targets.
"The hope is to not only make drugs faster, but also make more complex drugs that can target more challenging medicinal goals," she says.
Other co-authors include David Watson, professor in the UB Department of Chemistry, as well as UB chemistry graduate students Yufei Zhang, Hammed Bisiriyu, Alon Nudler and Benjamin Parasch.
Source:
Journal reference:
Zhang, Y., et al. (2026) Vicinal disubstitution of alkyl C-X synthons via alkene radical cation generation. Science. DOI: 10.1126/science.aef0766. https://www.science.org/doi/10.1126/science.aef0766
Facts Only
* Researchers at the University at Buffalo, Worcester Polytechnic Institute, and Binghamton University conducted a study.
* The study was published in *Science* on July 9.
* The methodology involved mixing carbon-halogen bonded molecules with a light-activated catalyst.
* Illumination by blue LED light temporarily transformed the molecules into more reactive forms.
* This transformation allowed modification of two adjacent carbon atoms instead of one.
* The method used the relatively mild conditions of visible light.
* The process leverages familiar chemical building blocks, such as molecules with carbon-halogen bonds.
* The reaction changes the ability to add new groups to neighboring carbon atoms.
* The team utilized blue LEDs housed in compartments called "Buffalo boxes" to activate the catalyst in vials.
* The work was supported by the National Institute of General Medical Sciences, the National Institutes of Health, and the National Science Foundation ACCESS program.
Executive Summary
Researchers at the University at Buffalo, in collaboration with Worcester Polytechnic Institute and Binghamton University, developed a method to modify adjacent carbon atoms in molecules using blue LED light and readily available chemical building blocks. The method involves mixing carbon-halogen bonded molecules with a light-activated catalyst. Illumination by blue LED light causes the catalyst to temporarily transform the molecules, allowing for modification at two adjacent carbon atoms simultaneously, instead of the traditional single atom reaction.
The technique utilizes visible light, which is considered milder than higher-energy ultraviolet (UV) light, mitigating concerns about degradation or decomposition of the organic molecules. The researchers found that this process allows for two modifications in a single step, which is presented as crucial for creating complex small-molecule drugs efficiently. The setup involves placing blue LEDs inside compartments, dubbed "Buffalo boxes," where they activate the catalyst in various vials containing the reactants.
The research aims to provide chemists with a faster route to synthesizing complex molecules required in drug discovery and hopes the method can be adapted for targeting challenging medicinal goals by partnering with pharmaceutical companies.
Full Take
The core innovation lies in bypassing the traditional limitations of chemical reactivity by leveraging light-activated catalysis to achieve vicinal disubstitution in a single step. The shift from modifying a single carbon center to simultaneously affecting two adjacent centers addresses a known bottleneck in complex molecule synthesis: increasing structural complexity efficiently. The use of visible light instead of harsher UV radiation suggests an attempt to address both synthetic efficiency and environmental/molecular preservation concerns, positioning the method as potentially more sustainable for fine chemical synthesis.
The finding that two modifications can occur from a single reaction offers significant theoretical leverage in medicinal chemistry, where precise three-dimensional structure dictates biological activity. The question arises whether this general principle of double modification via photocatalysis can be systematically scaled across diverse organic transformations beyond simple C-C bond manipulation, as suggested by the researchers' hope to adapt it for various molecular transformations. Furthermore, the context suggests a tension between immediate synthetic speed and the long-term requirements for biological specificity; the potential benefit is not just speed but achieving *more* complexity in ways that address "more challenging medicinal goals."
The implication is that access to highly complex pharmaceutical structures might be accelerated through synthetic pathways that exploit non-traditional activation methods. This shifts the focus from incremental efficiency gains in step count to fundamentally redefining how molecular architecture can be accessed, prompting inquiry into whether this approach introduces new, unexplored chemical space or merely optimizes existing routes within established frameworks. What are the long-term consequences for synthetic methodology if seemingly simple tools unlock deeper molecular manipulation capabilities?
Sentinel — Human
The article presents a scientific finding using an academic tone, supported by named researchers and a formal citation, suggesting it originated from established scientific reporting channels.