Revolutionizing Drug Discovery: Transforming Abundant Molecules into Lifesaving Compounds

Chemistry and Biomolecular Sciences
Professor Stephen Newman and PhD student Adam Cook are seen in the uOttawa Centre for Catalysis Research and Innovation, in front of a gas chromatograph (GC).
Professor Stephen Newman and PhD student Adam Cook are seen in the uOttawa Centre for Catalysis Research and Innovation, in front of a gas chromatograph (GC).
Have you ever wondered how simple molecules hold the key to life-saving drugs? Step into the world of catalytic chemistry with Professor Stephen Newman and PhD student Adam Cook as they rewrite the rules of drug discovery, one innovative reaction at a time.

In the intricate world of chemistry and molecular sciences, Professor Stephen Newman and his team are on a mission that transcends the laboratory walls. They are pioneers in the quest for more efficient, environmentally friendly, and safer methods to produce the building blocks of drugs and agrochemicals – the small molecules that constitute the backbone of organic chemistry.

Working closely with pharmaceutical manufacturing industries, Professor Newman's team is dedicated to finding innovative ways to enhance the production of these small molecules, which act as the foundation for more complex and essential products. Their goal is not just to make chemistry more accessible but also to simplify and make it environmentally sustainable.

At the heart of their groundbreaking work is catalysis – a fundamental technique that facilitates the combination of simpler building blocks of organic molecules to create larger, more complex molecules. Catalysts serve as facilitators, lowering the barrier to chemical reactions without being consumed in the process. One catalytic reaction that stands out in the history of chemistry is the Suzuki-Miyaura coupling reaction. Named after two Japanese chemists who discovered it over 50 years ago, the Suzuki reaction has been a catalyst for transformative changes in the field. It's an organic reaction classified as a cross-coupling reaction, where boronic acid and an organohalide are the coupling partners, and a palladium complex acts as the catalyst.

Scientists embraced the Suzuki reaction for creating bioactive molecules, hoping to discover new drugs. However, a hurdle emerged as the molecules that the Suzuki reaction creates are often too flat to function effectively. Most drugs work by interacting with complex, 3-dimensional biomolecules in the body such as proteins. Over the last two decades, researchers sought ways to harness the Suzuki reaction to create molecules with more drug-like architecture and properties.

Enter Adam Cook, a 5th-year Ph.D. student, who joined Professor Newman's team in 2019. Adam's focus has been on investigating new reactions using modern techniques and technology. His crucial contribution involves using alcohol-based building blocks directly in the Suzuki reaction, sidestepping the need to first transform these readily available feedstock molecules into more activated and unnatural intermediates. This innovation not only simplifies the process but retains the 3D complexity essential for drug efficacy. Adam's research has redefined the Suzuki reaction, offering a more direct route from abundant raw materials to intricate bioactive molecules. By leveraging alcohol substrates, Adam's approach efficiently accesses different scaffolds, providing pharmaceutical industries with the 3D complexity vital for effective drug interactions with enzymes. This innovative method, developed in the high-throughput labs in uOttawa’s Centre for Catalysis Research and Innovation, was published in the new Nature series journal, Nature Synthesis in 2023, and is expected to have significant impact.

Looking to the future, Professor Newman and his team aim to deepen their understanding and push the boundaries of this transformative process. Adam's discovery works efficiently with a specific class of alcohol, and the next challenge is to explore its applicability to a broader range of alcohols or other feedstock chemicals with carbon–oxygen bonds. Additionally, the team is delving into the possibility of forming new bonds, particularly carbon–nitrogen bonds, by altering one of the substrates in the reaction.

As they unravel the potential of these catalytic transformations, Professor Newman and his team are not only advancing the science of chemistry; they are unlocking a new era in drug discovery, where simplicity, efficiency, and environmental sustainability converge to create a brighter future for medicine and beyond.

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