BYLINE: Tracy Crane, Department of Chemistry

Newswise — Researchers at the University of Illinois Urbana-Champaign have reported a breakthrough in nickel catalysis that harnesses a rare oxidation state of nickel that has proved challenging to control yet is highly valued for its potential to facilitate important chemical reactions.

The researchers, led by Liviu Mirica, a professor of chemistry at Illinois, explain in a recently published paper in Nature Catalysis how they have overcome a long-standing challenge in the field of nickel catalysis by developing a new method for synthesizing thermally stable Ni(I) compounds that opens new avenues for building complex molecules.

“We have developed shelf-stable Ni(I) compounds that could dramatically change the playing field of nickel catalysis. And that’s why we have an international patent for it, and we’re working with pharmaceutical companies and chemical vendors who want to license it,” Mirica said.

Nickel-catalyzed cross-coupling reactions are widely used to form carbon–carbon and carbon–heteroatom bonds, essential steps in producing pharmaceuticals, agrochemicals, and advanced materials. Traditionally, these reactions rely on two forms of nickel – Ni(0) or Ni(II) – as catalysts. Catalytically competent Ni(I) sources have remained elusive, but attractive.

“This form of nickel is highly desirable partly because it may open up new avenues of reactivity that have remained elusive with traditional sources of nickel,” said Sagnik Chakrabarti, co-author and former graduate student in the Mirica group who worked on the project with graduate students Jubyeong Chae and Katy A. Knecht.

Mirica said previous approaches by chemists have used specialized ligands that limit the generality of Ni(I) in a reaction the way one would use Ni(II) or Ni(0) sources. By tapping into the unique properties of organic compounds called isocyanides, the Mirica group has developed a simple system that gets the chemistry to work.

In their study, they demonstrated how the commercially available isocyanides function as simple supporting ligands, which connect to the nickel atom and form stable, powerful catalysts that can be used to snap molecular pieces together with exceptional speed and precision, opening an untapped chemical space for reaction discovery.

Their Ni(I) complexes are readily available, shelf-stable, easily prepared, and easily handled catalysts that are efficient for a wide variety of chemical reactions. This is unique because most Ni(I) complexes tend to be rather unstable, which has limited their use in catalytic settings.

“We were able to put Ni(I), ‘nickel one’, in a bottle so people can use it on a wider scale for various synthetic applications,” Mirica said.

In the study, the researchers demonstrate that these new catalysts work in several of the most important reactions used to make pharmaceuticals, electronics, advanced materials, and more. They report the synthesis, characterization, and catalytic activity of two classes of Ni(I) isocyanide complexes: coordinatively saturated homoleptic compounds and coordinatively unsaturated Ni(I)-halide compounds. One is slightly more reactive than the other.

Their complexes exhibit rapid ligand substitution and demonstrate exceptional performance in Kumada, Suzuki–Miyaura, and Buchwald–Hartwig cross-coupling reactions, according to the study, and notably, they exhibit chemo-selectivity, displaying their versatility.

According to Mirica and Chakrabarti this new class of catalysts could be a game changer in nickel catalysis. Chakrabarti said there could be new reactions that could be discovered by directly introducing Ni(I) into reactions.

“And in fact, in the paper, we do talk about a new class of reactions that we developed and that has not been achieved with Ni catalysts before,” he said. “It’s just a snippet of reactivity, not like a full vignette in itself, but it still shows that by synthesizing something that’s different from what’s out there, we can maybe coax unique reactivity.”

The research team also found that a tiny amount goes a long way. 

“The interesting thing that we found is that we can use very, very tiny amounts of the nickel catalyst, which is unusual in Ni catalysis, which typically needs higher amounts of the catalyst,” Mirica said.

The study also highlights the structural diversity of isocyanides and their potential as spectator ligands for reaction discovery. Their study showed that this chemistry is not limited to just the one class of isocyanide they used, the tert-butyl isocyanide, but it’s broadly applicable to other classes of isocyanides as well.

“So, the generality in using a bunch of different isocyanides bodes well for the future development of this chemistry,” Chakrabarti said.

Future work in the Mirica group will explore the fundamental structure and bonding of these unusually stable compounds, their new reactivity, and the differences in reactivity between alkyl and aryl isocyanide-supported complexes, which, according to their study, exhibit divergent catalytic behavior.

Original release:

Health Canada is warning Canadians to check their medication after two lots of MAR-Amlodipine 5 mg tablets were recalled, as some bottles may contain the wrong drug.

Marcan Pharmaceuticals Inc. says certain bottles labelled as MAR-Amlodipine may contain midodrine 2.5 mg tablets, a medication used to treat low blood pressure.

Meanwhile, MAR-Amlodipine, the actual medication that is meant for the bottles, is prescribed to treat high blood pressure and chest pain.

Health Canada says taking midodrine instead of amlodipine could lead to serious health risks, including dangerously high blood pressure, dizziness, fainting, slow heartbeats and potential organ damage.

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Children may face a higher risk of harm if they take the incorrect medication.

The affected product is MAR-Amlodipine 5 mg, DIN 02371715, from lots 2472021 and 2472021A, with an expiry date of July 2027, according to the public advisory.

The correct amlodipine tablets are white to off-white, flat and eight-sided, with a line across the middle. One side is marked “210” and “5,” while the other side is blank.

The incorrect midodrine tablets are white, round and marked with “M2” on one side.

Health Canada is urging patients to immediately check their bottles and return them to a pharmacy if they contain any round tablets or if there is uncertainty about the contents.

Patients are advised not to take the round tablets.

Those experiencing symptoms such as dizziness, unusually high blood pressure or slow heartbeats are advised to contact a health-care professional or call 911.

Immediate medical attention is recommended for chest pain, sudden headaches, trouble speaking, or numbness or weakness.

Health Canada says it is monitoring the recall and the company’s investigation and will notify the public if additional risks are identified.

Consumers with questions can contact Marcan Pharmaceuticals Inc. directly, and health-care professionals are being asked to carefully check bottles before dispensing and report any issues.

&copy 2026 Global News, a division of Corus Entertainment Inc.

Newswise — New psychoactive substances, originally developed as potential analgesics but abandoned due to adverse side effects, may still have pharmaceutical value if researchers could nail down the causes of those side effects. A new study from the University of Illinois Urbana-Champaign used deep learning and large-scale computer simulations to identify structural differences in synthetic cannabinoid molecules that cause them to bind to human brain receptors differently from classical cannabinoids.

“The largest class of NPS are often sold as the street drugs Fubinaca, Chimica and Pinaca,” said chemical and biomolecular engineering professor Diwakar Shukla. “In addition to the adverse side effects, the formulas used to produce NPS vary, making them challenging to detect in standard drug screenings.”

New psychoactive substances are synthetic compounds; one class mimics the effects of classical cannabinoids. However, the study found that NPS tend to activate distinct signaling pathways in the human brain compared to classical cannabinoids. Specifically, they often trigger what’s called the “beta arrestin pathway” rather than the “G protein pathway.” This switch in signaling can lead to more severe psychological effects.

The study’s findings are published in the journal eLife.

“New psychoactive substances bind very strongly to cannabinoid receptors in the brain and are slow to unbind, making them difficult to observe and simulate in standard laboratory or computer experiments,” Shukla said. “It can take a huge amount of computer time to see these rare binding and unbinding events.”

In the lab, graduate student Soumajit Dutta used a new simulation approach, the Transition-Based Reweighting Method, to estimate the thermodynamics and kinetics of slow molecular processes. The team found that TRAM can also be used to observe the rare, slow molecular processes involved in the unbinding of NPS from cannabinoid receptors — by efficiently sampling these events that would otherwise require massive computing resources.

The researchers also used the Folding@Home platform, which enables millions of volunteers worldwide to donate computing power. This approach allowed the team to run many simulations in parallel, stitching the results together and using algorithms to decide which simulations to run next. It allows for the study of very long or rare events that would be nearly impossible with a single computer or a small cluster.

Together, these methods allowed the researchers to uncover new physical insights into how NPS interact with receptors — insights that were previously out of reach due to computational limitations — pointing the way toward the design of safer cannabinoid-based drugs that could avoid harmful side effects.

By revealing the NPS signal via pathways associated with more adverse effects, researchers can now focus on designing new molecules that avoid triggering these pathways for medical use. Shukla said their findings could direct more researchers to aim for compounds that bind less tightly or unbind more readily, potentially reducing the drugs’ harm.

The National Institutes of Health award R35GM-142745 and the National Science Foundation supported this research. Shukla is also affiliated with chemistry, bioengineering, the National Center for Supercomputing Applications, the Center for Digital Agriculture and the Carl R. Woese Institute for Genomic Biology.

Original release: