Toledo Chemist Wins $2 Million to Rework the Chemistry Behind Opioids

A University of Toledo chemist has received nearly $2 million from the National Institute of General Medical Sciences to develop a set of chemical reactions that could eventually change how opioid compounds — and the overdose antidote naloxone — are built in the laboratory. Michael C. Young, an associate professor in the university's Department of Chemistry and Biochemistry, will use the five-year award to work on carbon-hydrogen bond functionalization, a class of methods that lets chemists modify molecules at positions nature does not conveniently expose.

The grant does not fund a clinical trial, a drug candidate or a treatment program. It funds the sort of foundational chemistry that sits many years upstream of all three, and that is precisely why the agency that wrote the check cares about opioids.

What carbon-hydrogen bonds have to do with addiction

Most organic molecules are scaffolding of carbon atoms hung with hydrogen atoms. Chemists can readily attach new chemical groups at carbon atoms that already carry a reactive handle — a bromine, an oxygen, a nitrogen. The carbon-hydrogen bonds themselves are comparatively inert, which is why drug synthesis often requires long, wasteful routes that work around them rather than through them.

"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 said in the university's announcement, describing the objective as extending the reach of synthetic chemistry beyond the positions that are easy to touch.

Applied to the opioid scaffold, that capability could matter in two places. The first is toxicity. Opioids kill in overdose by suppressing the drive to breathe, and the structural features that produce analgesia overlap with the features that produce respiratory depression. If chemists can install new functional groups at positions that have been chemically off-limits, they widen the space available for separating the two.

"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."

Why naloxone shows up in a safer-opioids grant

The second place is manufacturing. Naloxone, the opioid antagonist that has reversed hundreds of thousands of overdoses, is made through a semi-synthetic route that Young pegs at four to seven steps. Each step costs reagents, energy, purification and yield.

"It takes four to seven semi-synthetic steps to make naloxone," he 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."

That is a quieter argument than the search for a non-addictive painkiller, but it lands closer to the present. Naloxone access in the United States is now shaped less by whether the drug exists than by what it costs and who pays — the difference between a shelf of over-the-counter nasal sprays and a public health department's purchasing budget. Federal rules adopted this year barred grant money from paying for syringes, pipes and test strips, tightening the same budgets that buy reversal medication.

A grant that measures success in students

The award will support at least two undergraduates, four graduate students and a postdoctoral researcher in Young's lab in Wolfe Hall, according to the university. That staffing plan is the honest measure of what a chemistry grant accomplishes in five years: not a pill, but a group of trained chemists and a set of published reactions other labs can adopt.

Ohio has an unusual concentration of interest in this kind of upstream work. The state's opioid research and treatment landscape includes the Ohio Narcotics Intelligence Center, which tracks what is actually circulating in the drug supply, and a network of academic medical centers running trials of medication-assisted treatment protocols that are already standard care. The chemistry Young describes would arrive, if it arrives, well behind all of them.

More than a half-million Americans have died of opioid overdoses since the federal government declared a public health emergency in 2017, according to figures the university cited from KFF. Deaths have been falling since a 2023 peak, a trend public health researchers attribute to a mix of naloxone saturation, expanded treatment and shifts in the drug supply.

The long horizon problem

Research on non-addictive analgesics has a long record of expensive disappointment, and nobody involved in this grant is promising a product. The proposal is to develop methodology — general reactions that work across many molecules — and to streamline syntheses in ways that also reduce waste, a goal the university ties to green chemistry.

For readers tracking how the opioid crisis gets solved, that places this award in the category of things that matter in a decade rather than a season. The naloxone cost question is the exception, and it is the one worth watching: a cheaper synthesis route is a policy lever disguised as an organic chemistry problem.

People seeking treatment for opioid use disorder can find medication-assisted treatment through community health centers, opioid treatment programs and primary care prescribers, and naloxone is available without a prescription at most pharmacies.