@article{cbec54d621f641f88b996e02b62573ae,
title = "Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds",
abstract = "Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at a-amino sp3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D2O or T2O) as the source of hydrogen isotope. In this context, we also report a convenient synthesis of T2O from T2, providing access to high-specific-activity T2O. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 18 drug molecules, which meet the requirements for use in ligand-binding assays and absorption, distribution, metabolism, and excretion studies.",
author = "Loh, {Yong Yao} and Kazunori Nagao and Hoover, {Andrew J.} and David Hesk and Rivera, {Nelo R.} and Colletti, {Steven L.} and Davies, {Ian W.} and MacMillan, {David W.C.}",
note = "Funding Information: Research reported in this publication was supported by the National Institutes of Health (NIH) under award number R01 GM103558-04 (D.W.C.M., Y.Y.L., and K.N.). Y.Y.L. thanks the Agency for Science, Technology and Research (A*STAR) for a graduate fellowship. K.N. thanks the Japan Society for the Promotion of Science for an overseas postdoctoral fellowship. Additional funding was provided by kind gifts from Merck, Abbvie, BMS, and Janssen. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional data supporting the conclusions are available in the supplementary materials. Publisher Copyright: {\textcopyright} 2017, American Association for the Advancement of Science. All rights reserved.",
year = "2017",
month = dec,
day = "1",
doi = "10.1126/science.aap9674",
language = "English (US)",
volume = "358",
pages = "1182--1187",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6367",
}