Hydrogen Isotope Labeling of Pharmaceuticals Via Dual Hydrogen Isotope Exchange Pathways Using CdS Quantum Dot Photocatalyst
Rajendra Maity, Otto M. Dungan, Frédéric A. Perras, Jingwei Li, Daohua Liu, Sumei Ren, Dan Lehnherr, Zheng Huang, Eric M. Phillips, Moses Adeyemo, Joseph Frimpong, Timothy Quainoo, Zhen–Fei Liu, Long Luo
Abstract
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.