Mizzou researchers invent a new tool to help lower the cost of tomorrow’s medicine
Two University of Missouri scientists created AshPhos, a chemical tool that makes it more efficient to create carbon-nitrogen bonds
News Release
University of Missouri-Columbia
image:
Sachin Handa and Ashish Dusunge with their new chemical tool, AshPhos, in Handa's lab at the University of Missouri. Photo courtesy Sachin Handa
view moreCredit: Photo courtesy Sachin Handa
University of Missouri researchers and collaborators have developed a new chemical tool that could help lower the cost of prescription medications.
The tool, called AshPhos, is a ligand, or molecule, that makes it easier to create special carbon-nitrogen bonds. These bonds are the backbone of more than half of all medicines on the market today.
“What makes AshPhos special from other existing ligands is that it’s made from inexpensive and easy-to-find materials, and it is far better in terms of activity and efficiency,” said Sachin Handa, an associate professor of chemistry at Mizzou’s College of Arts and Science.
That’s by design.
The team, led by Handa and graduate student Ashish Dusunge, alongside Biohaven Pharmaceuticals, developed AshPhos with the goal of promoting sustainable chemistry.
“It’s eco-friendly because it’s made with less waste and uses materials from renewable sources,” Handa said. “It will also make medicine production cheaper, helping more people afford the medications they need.”
Handa, who grew up in India and was a first-generation high school student, knows firsthand the importance of providing affordable life-saving medication.
“Witnessing people in India struggle to access essential health care during my childhood continues to motivate me to use my expertise as a chemist to create solutions that benefit society as a whole,” he said.
Other potential applications
Looking ahead, researchers plan to explore the use of AshPhos beyond pharmaceutical applications.
One idea is to use AshPhos to create nanomaterials that can facilitate hydrogen evolution. Hydrogen is considered a clean energy source, and efficient methods for its production are crucial for transitioning toward renewable energy sources.
Another idea is to investigate how AshPhos could help degrade PFAS, or "forever chemicals.” By developing a catalyst using AshPhos and earth-abundant metals, Handa said they could provide a potential solution for breaking down these persistent pollutants.
While future applications are still under development, they showcase the versatility of AshPhos and highlight its potential to address critical challenges related to energy and environmental sustainability.
The mechanics of AshPhos
How does it work?
“Ligands such as AshPhos facilitate the formation of carbon-nitrogen bonds by stabilizing metal ions and guiding them in reactions, called Buchwald–Hartwig aminations,” said Handa, who was hired through the university’s MizzouForward initiative in 2023. “This is important for highly challenging bulky molecules that otherwise deactivate the catalyst in the absence of AshPhos.”
AshPhos, named in part for Dusunge, the first author of the study, works by binding to a metal atom, transforming it into a catalyst. This catalyst is essential for the reaction to proceed. The metal catalyst then brings together a “highly challenging” molecule containing carbon and another containing nitrogen, facilitating the formation of a carbon-nitrogen bond between them, Handa said.
In the case of AshPhos, the ligand attaches to a metal — palladium — to help it speed up chemical reactions more effectively.
“It acts as a 'boss' by directing the metal what to do, ensuring the metal stays active and selective during the process,” Handa said.
During this process, the ligand might temporarily detach from the metal, rendering it inactive. AshPhos can prevent this from happening by reattaching to the metal with a little heat, ensuring the catalyst remains active and the reaction continues.
“This reattachment ability is key to AshPhos’ effectiveness and makes it superior to many existing ligands,” Handa said. “Our ligand is very strong — it’s like locking a door with a key, ensuring it stays securely closed and won’t open.”
Innovations such as AshPhos are the hallmarks of Mizzou researchers, including Handa, whose work is powering the new Center for Energy Innovation.
“AshPhos ligand: Facilitating challenging aminations in five- and six-membered heteroaryl halides using cyclic secondary and bulky amines,” was published in JACS Au, a journal of the American Chemical Society. The article’s other co-author is David Leahy at Biohaven Pharmaceuticals.
Funding was provided by grants awarded to Handa from the U.S. National Science Foundation (CHE 2044778 and 2345856). AshPhos has received commercial interest from entities in both the U.S. and Europe.
Journal
JACS Au
Article Title
AshPhos Ligand: Facilitating Challenging Aminations in Five- and Six-Membered Heteroaryl Halides Using Cyclic Secondary and Bulky Amines
Purdue aims to speed evolution of pharma manufacturing in collaboration with Lilly and Merck
New academic-industry consortium to revolutionize pharmaceutical manufacturing with focus on advanced aseptic processing technology
Purdue University
WEST LAFAYETTE, Ind. — Purdue University, in collaboration with Eli Lilly and Company and Merck & Co. Inc., announced Friday (Jan. 17) the launch of the Young Institute Pharmaceutical Manufacturing Consortium, a collaborative effort to pioneer advances in making medicines.
Operating within Purdue’s William D. and Sherry L. Young Institute for Advanced Manufacturing of Pharmaceuticals, consortium partners will revolutionize pharmaceutical manufacturing with a focus on sterile injectables and innovative aseptic manufacturing technology to ensure quality, safety and compliance.
Pharmaceutical manufacturing is a key component of Purdue’s One Health initiative, which advances knowledge and innovation related to animal, human and environmental health and well-being through novel interdisciplinary research and industry partnerships.
“We’re on the frontier of Pharma 4.0 — autonomous experimentation, advanced robotics, big data, smart factories, AI and machine learning,” said Karen Plaut, Purdue’s executive vice president for research. “Through this partnership, we will have a global impact in solving complex problems in the pharmaceutical and biopharmaceutical manufacturing ecosystem.”
The consortium will elevate and enhance pharmaceutical and biopharmaceutical advanced manufacturing by developing disruptive innovative technologies, autonomous systems, and smart AI and digital technology, together with industrially relevant education and training for the next generation of scientific leaders and researchers. The collaboration also underscores a commitment to onshoring pharmaceutical manufacturing while bolstering domestic production.
“Addressing pharma manufacturing challenges requires a significant advancement in technology. With an alliance of this caliber, the consortium will explore greater emphasis on both current and future advanced chemistries and accelerate research of innovative discoveries,” said Elizabeth Topp, director of the Young Institute.
Topp, who will serve as the new consortium’s director, is a professor in the Department of Industrial and Molecular Pharmaceutics and the Davidson School of Chemical Engineering and is an expert in improving the shelf life and stability of pharmaceuticals.
The consortium will rely on the distinctive research strengths of Purdue, Lilly and Merck, leveraging the organizations’ collaborative research relationship and workforce development programs.
The members anticipate the consortium will attract broad participation throughout the sector from other pharmaceutical companies, pharma contract manufacturers, equipment manufacturers, startups and venture capital firms, and will result in a broad base of stakeholders to chart the industry’s future course.
The consortium will look to create systems equipped with automated visual inspection and in-line process and product quality monitoring, all of which will require a new generation of skilled pharmaceutical manufacturing engineers and scientists. Through research excellence and comprehensive training opportunities, this program is poised to continue strengthening the pharmaceutical sciences program and preparing talent to support the growth of the sector.
“Being a founding member of the Young Institute means building on the remarkable legacy of next-generation manufacturing,” said Arup Roy, senior vice president, technical services and manufacturing science at Lilly. “Together, we will transform the industry with advanced aseptic manufacturing technologies, innovative research, and top-notch education and training to bring pharmaceutical sciences into the future with sterile processing standards. Our work honors Bill Young’s visionary spirit to shape the future of manufacturing and make it a core industry competency for a lasting impact on global communities.”
Merck Senior Vice President of Manufacturing Dave Maraldo said generative AI, machine learning and quantum computing are the future of the manufacturing process.
“If our collaborative research efforts can use smart technology to accelerate the timeline from research to market, we can reduce costs and bring critical and effective therapies to patients with greater speed,” Maraldo said. “Harnessing innovation will help create a safe and sustainable future for the industry, and most importantly, allow us to better serve patients.”
In addition to industry, the Young Institute Consortium will be supported by Purdue’s colleges of Engineering, Pharmacy and Science, which will strengthen its ability to establish strategic priorities for training and education, to foster student engagement and to advance expertise in the field.
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