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Don’t Throw Away Those Cannabis Leaves – They’re Packed With Rare Compounds

Stellenbosch University researchers identify rare phenolic compounds in Cannabis leaves for the first time.

Chemists at Stellenbosch University (SU) have uncovered the first evidence of a rare group of phenolic compounds, known as flavoalkaloids, in Cannabis leaves.

Phenolic compounds particularly flavonoids are highly valued in the pharmaceutical field because of their antioxidant, anti-inflammatory, and anti-carcinogenic effects.

In their study, the researchers analyzed three commercially cultivated Cannabis strains from South Africa and identified 79 distinct phenolic compounds. Of these, 25 had never before been reported in Cannabis, and 16 were tentatively classified as flavoalkaloids. Notably, these rare compounds were found primarily in the leaves of just one strain.

 
Challenges of studying plant phenolics

Dr Magriet Muller, an analytical chemist in the LC-MS laboratory of the Central Analytical Facility (CAF) at Stellenbosch University and first author on the paper, says the analysis of plant phenolics is challenging due to their low concentration and extreme structural diversity.

“Most plants contain highly complex mixtures of phenolic compounds, and while flavonoids occur widely in the plant kingdom, the flavoalkaloids are very rare in nature,” she explains.

“We know that Cannabis is extremely complex – it contains more than 750 metabolites – but we did not expect such high variation in phenolic profiles between only three strains, nor to detect so many compounds for the first time in the species. Especially the first evidence of flavoalkaloids in Cannabis was very exciting.”

Developing new analytical methods

As part of her postgraduate work in SU’s Department of Chemistry and Polymer Science, she designed advanced analytical techniques that integrate comprehensive two-dimensional liquid chromatography with high-resolution mass spectrometry to achieve detailed characterization of phenolic compounds.

“We were looking for a new application for the methods that I developed, after successfully testing them on rooibos tea, grapes, and wine. I then decided to apply the methods to Cannabis because I knew it was a complex sample, and that Cannabis phenolics have not been well characterized,” she explains.

According to Prof. André de Villiers, her study leader and main author on the paper, he was blown away by the chromatographic results that Muller obtained: “The excellent performance of two-dimensional liquid chromatography allowed separation of the flavoalkaloids from the much more abundant flavonoids, which is why we were able to detect these rare compounds for the first time in Cannabis.” He leads the analytical chemistry research group in SU’s Department of Chemistry and Polymer Science.

Prof. De Villiers says it is obvious there is still much to gain from studying Cannabis, as the bulk of research in this field to date has been focused on the pharmacological properties of the mood-altering cannabinoids.

“Our analysis again highlights the medicinal potential of Cannabis plant material, currently regarded as waste. Cannabis exhibits a rich and unique non-cannabinoid phenolic profile, which could be relevant from a biomedical research perspective,” he concludes.

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Scientists Discover a Cheaper, More Powerful Catalyst for Clean Hydrogen Energy

Scientists used a nanoparticle “megalibrary” to uncover a low-cost, high-performing alternative to iridium, unlocking a faster path to affordable hydrogen energy.

The Search for Iridium Alternatives

For years, scientists across the globe have been working to replace iridium, a precious and extremely costly metal that plays a key role in producing clean hydrogen fuel. Recently, researchers succeeded in identifying a substitute using a groundbreaking tool, and they did it in just one afternoon.

Developed at Northwestern University, the tool is known as a megalibrary. Described as the world’s first nanomaterial “data factory,” a single megalibrary holds millions of carefully designed nanoparticles arranged on a chip no larger than a fingertip.

Working together with the Toyota Research Institute (TRI), the Northwestern team used this platform to pinpoint promising catalysts for hydrogen generation. After identifying a candidate, they then scaled it up and proved that the material could perform inside an actual device, all in remarkably short time.

A Megalibrary for Materials Discovery

The megalibrary allowed scientists to test countless combinations of four metals that are abundant, inexpensive, and already known for their catalytic properties. From this massive screening effort, the researchers uncovered an entirely new material. In laboratory trials, it not only matched but, in some cases, outperformed commercial iridium-based catalysts, while costing only a fraction of the price.

The implications reach far beyond lowering the price of green hydrogen. The success also highlights the potential of the megalibrary approach itself, which could revolutionize how new materials are discovered across a wide range of fields.

A New Way to Find the Best Materials

“We’ve unleashed arguably the world’s most powerful synthesis tool, which allows one to search the enormous number of combinations available to chemists and materials scientists to find materials that matter,” said Northwestern’s Chad A. Mirkin, the study’s senior author and primary inventor of the megalibrary platform. “In this particular project, we have channeled that capability toward a major problem facing the energy sector. That is: How do we find a material that is as good as iridium but is more plentiful, more available and a lot cheaper? This new tool enabled us to find a promising alternative and to find it rapidly.”

A nanotechnology pioneer, Mirkin is the George B. Rathmann Professor of Chemistry at Northwestern’s Weinberg College of Arts and Sciences; professor of chemical and biological engineering, biomedical engineering and materials science and engineering at the McCormick School of Engineering; and executive director of the International Institute for Nanotechnology. Mirkin co-led the work with Ted Sargent, the Lynn Hopton Davis and Greg Davis Professor of Chemistry at Weinberg, professor of electrical and computer engineering at McCormick and executive director of the Paula M. Trienens Institute for Sustainability and Energy.

Hydrogen’s Iridium Problem

As the world moves away from fossil fuels and toward decarbonization, affordable green hydrogen has emerged as a critical piece of the puzzle. To produce clean hydrogen energy, scientists have turned to water splitting, a process that uses electricity to split water molecules into their two constituent components hydrogen and oxygen.

The oxygen part of this reaction, called the oxygen evolution reaction (OER), however, is difficult and inefficient. OER is most effective when scientists use iridium-based catalysts, which have significant disadvantages. Iridium is rare, expensive and often obtained as a byproduct from platinum mining. More valuable than gold, iridium costs nearly $5,000 per ounce.

“There’s not enough iridium in the world to meet all of our projected needs,” Sargent said. “As we think about splitting water to generate alternative forms of energy, there’s not enough iridium from a purely supply standpoint.”

A Nanoparticle Army on a Chip

Mirkin, who introduced the megalibraries in 2016, decided with Sargent that finding new candidates to replace iridium was a perfect application for his revolutionary tool. While materials discovery is traditionally a slow and daunting task filled with trial and error, megalibraries enable scientists to pinpoint optimal compositions at breakneck speeds.

Each megalibrary is created with arrays of hundreds of thousands of tiny, pyramid-shaped tips to print individual “dots” onto a surface. Each dot contains an intentionally designed mix of metal salts. When heated, the metal salts are reduced to form single nanoparticles, each with a precise composition and size.

“You can think of each tip as a tiny person in a tiny lab,” Mirkin said. “Instead of having one tiny person make one structure at a time, you have millions of people. So, you basically have a full army of researchers deployed on a chip.”

The Winning Catalyst Emerges

In the new study, the chip contained 156 million particles, each made from different combinations of ruthenium, cobalt, manganese and chromium. A robotic scanner then assessed how well the most promising particles could perform an OER. Based on these tests, Mirkin and his team selected the best-performing candidates to undergo further testing in the laboratory.

Eventually, one composition stood out: a precise combination of all four metals (Ru52Co33Mn9Cr6 oxide). Multi-metal catalysts are known to elicit synergistic effects that can make them more active than single-metal catalysts.

“Our catalyst actually has a little higher activity than iridium and excellent stability,” Mirkin said. “That’s rare because oftentimes ruthenium is less stable. But the other elements in the composition stabilize ruthenium.”

Proving Stability and Cost Benefits

The ability to screen particles for their ultimate performance is a major new innovation. “For the first time, we were not only able to rapidly screen catalysts, but we saw the best ones performing well in a scaled-up setting,” said Joseph Montoya, a senior staff research scientist at TRI and study co-author.

In long-term tests, the new catalyst operated for more than 1,000 hours with high efficiency and excellent stability in a harsh acidic environment. It is also dramatically cheaper than iridium about one-sixteenth of the cost.

“There’s lots of work to do to make this commercially viable, but it’s very exciting that we can identify promising catalysts so quickly not only at the lab scale but for devices,” Montoya said.

Beyond Hydrogen: The Bigger Picture

By generating massive high-quality materials datasets, the megalibrary approach also lays the groundwork for using artificial intelligence (AI) and machine learning to design the next generation of new materials. Northwestern, TRI and Mattiq, a Northwestern spinout company, have already developed machine learning algorithms to sift through the megalibraries at record speeds.

Mirkin says this is only the beginning. With AI, the approach could scale beyond catalysts to revolutionize materials discovery for virtually any technology, such as batteries, biomedical devices and advanced optical components.

“We’re going to look for all sorts of materials for batteries, fusion and more,” he said. “The world does not use the best materials for its needs. People found the best materials at a certain point in time, given the tools available to them. The problem is that we now have a huge infrastructure built around those materials, and we’re stuck with them. We want to turn that upside down. It’s time to truly find the best materials for every need without compromise.”

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Challenging a Century-Old Belief: Scientists Rewrite the Rules of Light-Driven Chemistry

Researchers have uncovered a new mechanism in photochemistry showing that a molecule’s microenvironment can strongly influence how it reacts to light.

A global team of scientists, led by researchers at QUT, is overturning a long-standing belief in photochemistry with findings that could influence areas from healthcare to advanced manufacturing.

Their study, published in the Journal of the American Chemical Society, proposes that the ability of light to drive chemical reactions depends on more than just how strongly a molecule absorbs it.

The group, directed by principal investigator Distinguished Professor Christopher Barner-Kowollik with lead authors Dr. Joshua Carroll and Fred Pashely-Johnson from QUT’s Soft Matter Materials Group, has uncovered a previously overlooked mechanism. They found that the local molecular environment plays a crucial role in shaping how molecules react when exposed to light.

“Since light consists of a spectrum of colours, it has been expected for many years that the colour that is absorbed the most by a molecule will be the most efficient at triggering any photoreactions,” Dr. Carroll said.

“Our experiments confirmed that the microenvironment around each individual absorbing molecule can lead to vastly different properties.”

Red-Shifted Light and the ‘Red-Edge Effect’

The QUT team found that these effects can lead to longer excited-state lifetimes, making certain molecules more reactive under lower-energy, red-shifted light.

The behaviour was linked to a known phenomenon in fluorescence science called the ‘red-edge effect’ and its influence on photochemical reactivity was confirmed through advanced experimental techniques including fluorescence spectroscopy and photochemical action plots.

Fluorescence spectroscopy is a technique used to study the fluorescent properties of substances – that is how they absorb light at one wavelength and then emit light at a longer wavelength. Photochemical action plots show how effective different wavelengths of light are at driving a specific photochemical reaction.

An International Effort

The QUT research team also comprised Dr. Maciej Klein and Associate Professor Ajay Pandey as well as Professor Andreas Unterreiner and Theresa Stephan from the Karlsruhe Institute of Technology (KIT) and Dr. Michael Walter from the University of Freiburg in Germany.

The potential impact of the observed and rationalised effect will enable researchers to develop more sophisticated photochemical technologies in fields such as photodynamic therapy, 3D printing, organic chemistry, solar energy, and many more.

“By controlling microenvironments, through solvent choice or molecular design, we can tune how light affects molecules, allowing for more precision in photochemical drug delivery, polymer engineerin,g and light harvesting.”

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