Arts & Sciences

Chemistry professor receives NSF CAREER grant to make novel radiolabeled compounds with applications in new drug development

Dr. Joseph Clark, assistant professor of chemistry in the Klingler College of Arts and Sciences, has been awarded a National Science Foundation CAREER grant, the National Science Foundation’s most prestigious awards in support of early-career faculty. The $650,000 grant will be used to develop new reactions for precision labeling of small molecules, which can allow scientists to track the fate of a drug molecule in the body.

The reactions being studied will enable a specific quantity of tritium and/or deuterium to be placed at an exact location of a small molecule. The research has implications in new drug development where tritium labeled molecules have potential applications in radioligand binding assays and absorption, distribution, metabolism, and excretion (ADME) studies.

The objective of this project is to develop new reactions to incorporate a precise quantity of a deuterium or tritium isotope into a small molecule. Tritium is a radioactive isotope of hydrogen and is widely used as a radioactive tracer element in biological and chemical research. Small molecules containing tritium are widely used in new drug development because they can allow scientists to track the fate of a drug molecule in the body.

“Reaction development for precision labeling is lagging, especially given the sudden supply crisis for commercially available 14C building blocks,” Clark said. “It will take years to rectify this crisis and is therefore a critical moment for investment in research aimed at developing precision labeling techniques. If 14C radiolabeling has limited or no availability, tritium radiolabeled drug molecules serve as the only ‘gold-standard’ alternative for use in ADME studies.”

For nearly five years, the Clark Lab has been investigating new techniques for the precision deuteration of small molecules and will use this award to make fundamental advances in the preparation of novel tritium transfer reagents. These reagents will be employed in the proposed selective tritium labeling reactions and advance understanding of how to place an exact quantity of tritium into a precise location of a small molecule. This process will also enable additional understanding into the factors controlling selectivity in the precision deuteration of small molecules containing 1,3-diene, allene or enyne functionality, and explore the synthesis of compounds precisely deuterated at the allylic position. The synthesis of precisely labeled molecules will also enable new spectroscopic advances to characterize and quantify tritium labeled product mixtures.

In addition to the scientific merit, this NSF CAREER award will also fund an annual workshop at the University of Puerto Rico at Cayey. The goal is to inspire students to pursue careers in chemistry. The workshop will educate students about pursuing graduate studies in chemistry and will offer opportunities for students to interview for summer internships in the Clark Lab to perform research in proposed projects included in the award. Each year, the workshop will allow for Clark Lab alumni to present their investigations in front of Ph.D. scientists from Puerto Rico, representing several universities and major pharmaceutical companies in both the United States and Puerto Rico.

“We are thrilled for Dr. Clark about this prestigious grant, which is a recognition of the promise his lab has shown and the results already delivered to date,” said Dr. Heidi Bostic, dean of the Klingler College of Arts and Sciences. “Dr. Clark’s approach to collaborative research and addressing the needs of our community is also a great example of the work being done in the Klingler College of Arts and Sciences and at Marquette. His partnership with the University of Puerto Rico at Cayey will offer invaluable experiences for chemistry students at both institutions and help to foster renewed interest in the natural sciences in Puerto Rico following the devastating effects of Hurricane Maria in 2017.”

The Faculty Early Career Development (CAREER) Program is a foundation-wide activity that offers the National Science Foundation’s most prestigious awards in support of early-career faculty who have the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization. Activities pursued by early-career faculty should build a firm foundation for a lifetime of leadership in integrating education and research. NSF encourages submission of CAREER proposals from early-career faculty at all CAREER-eligible organizations and especially encourages women, members of underrepresented minority groups, and persons with disabilities to apply.