Hydrogen Isotope Labeling of Pharmaceuticals Via Dual Hydrogen Isotope Exchange Pathways Using CdS Quantum Dot Photocatalyst
Isotopic labeling is a powerful technique extensively used in the pharmaceutical industry. By tracking isotope-labeled molecules, researchers gain unique and invaluable insights into the pharmacokinetics and pharmacodynamics of new drug candidates. Hydrogen isotope labeling is particularly important as hydrogen is ubiquitous in organic molecules in biological systems, and it can be introduced effectively through late-stage hydrogen isotope exchange (HIE). However, hydrogen isotope methods that simultaneously label multiple sites with varying types of C-H bonds in the different types of molecules are still lacking. Herein, we demonstrate a heterogeneous photocatalytic system using a CdS quantum dot catalyst that proceeds via a unique dual HIE pathway mechanism─one occurs in the reaction solution and the other on the catalytic surface─to address it. This unique mechanism unlocked several unique labeling capabilities, including simultaneous labeling of multiple and challenging sites such as secondary α-amino, α-ethereal, allyl, and vinyl sites, providing great versatility in practical uses for pharmaceutical labeling.
Authors
- Moses Adeyemo (ORCID: https://orcid.org/0000-0002-0493-3145)
- Joseph Frimpong (ORCID: https://orcid.org/0000-0002-1400-4876)
- Zheng Huang (ORCID: https://orcid.org/0000-0003-0876-5369)
- Daohua Liu (ORCID: https://orcid.org/0000-0003-2155-0741)
- Jingwei Li (ORCID: https://orcid.org/0000-0003-2534-5091)
- Dan Lehnherr (ORCID: https://orcid.org/0000-0001-8392-1208)
- Frédéric A. Perras (ORCID: https://orcid.org/0000-0002-2662-5119)
- Rajendra Maity (ORCID: https://orcid.org/0009-0000-3082-093X)
- Eric M. Phillips (ORCID: https://orcid.org/0000-0003-3530-8876)
- Long Luo (ORCID: https://orcid.org/0000-0001-5771-6892)
- Timothy Quainoo (ORCID: https://orcid.org/0000-0003-3565-6723)
- Sumei Ren (ORCID: https://orcid.org/0000-0002-5163-0489)
- Otto Dungan (ORCID: https://orcid.org/0009-0007-9426-4611)
- Zhen–Fei Liu (ORCID: https://orcid.org/0000-0002-2423-8430)
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Iowa State University (US)
- Wayne State University (US)
- University of Utah (US)
- Ames National Laboratory (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-11-23
- DOI
- https://doi.org/10.1021/jacs.4c13857
- Citations
- 10
- Primary Topic
- Chemical Reactions and Isotopes
- Type
- article
- Field-Weighted Citation Impact
- 2.08
Funders
- U.S. Department of Energy
- Alfred P. Sloan Foundation
- Wayne State University
- National Institute of General Medical Sciences
- Division of Chemistry