UToledo Chemist Receives Nearly $2M to Develop Safer Opioids

Medications are often derived from natural sources like roots, leaves and flowers.

But transforming a plant extract into the sort of capsule that lowers blood pressure or relieves a headache requires some complex chemistry.

Those multistepped processes are a specialty of The University of Toledo's Dr. Michael C. Young, who explores the interface between organic and inorganic chemistry as an associate professor in the College of Natural Sciences and Mathematics. The National Institute of General Medical Sciences recently awarded Young nearly $2 million to advance foundational steps in these processes with a goal of safer opioids.

He'll be focusing on the carbon-hydrogen bonds that are part and parcel of organic molecules, exploring ways to manipulate them for specific effects.

"Historically, we've only been able to add new functionality to organic molecules where nature gives us a handle to install it," Young explained. "So one of our goals is to develop methodology where we can actually manipulate any carbon-hydrogen bond, enabling us to add new functionality where nature didn't give us a handle."

Young's work contributes to a rich research community at UToledo, which is recognized among the top-tier research universities in the country with the prestigious Carnegie R1 Classification. University-wide laboratories advance scientific discovery while welcoming undergraduate students to engage in experience-based learning as early as their first semester on campus in line with the UToledo Advantage.

Young expects the five-year award to support at least two undergraduates, four graduate students and a postdoctoral researcher in his Wolfe Hall lab.

The methodologies the chemist and his team aim to develop won't apply only to opioids, but the class of powerful but highly addictive analgesics presents an obvious target in light of an ongoing opioid epidemic.

More than a half-million people have died of opioid overdoses in the United States since 2017, when the federal government declared the epidemic a public health emergency, according to the health policy nonprofit KFF. Opioid overdose deaths have been declining since a peak in 2023.

When it comes to developing a next generation of safer opioids, Young can point to numerous characteristics worth targeting by manipulating carbon-hydrogen bonds to introduce new functionality. First and foremost is toxicity: Opioid overdoses kill by suppressing a person's breathing.

But the researchers also face a challenge in the many unanswered questions about the positive and negative ways that opioids affect the human body.

"We still don't fully understand the biochemical mechanisms that lead an opioid to be effective versus toxic versus addictive," Young said. "That's important because if we understand what makes them toxic, we may be able to develop alternatives that are harder to overdose on. Or if we could figure out the basis for chemical addiction, we may be able to develop alternatives that are less addictive but just as effective."

Young's research could also streamline the multi-step process of synthesizing opioids in line with a key goal of green chemistry: fewer steps and less waste.

A streamlined synthesis is also significant for its potential to bring down the manufacturing costs, not only for a next generation of safer opioids but also for naloxone, the opioid reversal drug responsible for countless lives saved amid the epidemic.

"It takes four to seven semi-synthetic steps to make naloxone," Young said. "If we could make naloxone in fewer steps, we could bring down the manufacturing costs and ensure that it's more accessible to the people who need it."