References
1. Ebbing DD, Gammon SD (2005) Atoms, molecules, and ions. In: General chemistry, 8th edn.
Houghton Mifflin Company, Boston
2. Atzrodt J, Derdau V, Kerr WJ, Reid M (2018) Deuterium- and tritium-labelled compounds:
applications in the life sciences. Angew Chem Int Ed 57:1758–1784. https://doi.org/10.1002/
anie.201704146
3. Isin EM, Elmore CS, Nilsson GN et al (2012) Use of radiolabeled compounds in drug
metabolism and pharmacokinetic studies. Chem Res Toxicol 25:532–542. https://doi.org/10.
1021/tx2005212
4. Filer CN (2010) Direct metal-catalyzed tritiation of organic compounds. J Label Compd
Radiopharm 53:739–744. https://doi.org/10.1002/jlcr.1801
5. Nilsson GN, Kerr WJ (2010) The development and use of novel iridium complexes as catalysts
for ortho-directed hydrogen isotope exchange reactions. J Label Compd Radiopharm
53:662–667. https://doi.org/10.1002/jlcr.1817
6. Allen PH, Hickey MJ, Kingston LP, Wilkinson DJ (2010) Metal-catalysed isotopic exchange
labelling: 30 years of experience in pharmaceutical R&D. J Label Compd Radiopharm
53:731–738. https://doi.org/10.1002/jlcr.1825
7. Hesk D, Lavey CF, McNamara P (2010) Tritium labelling of pharmaceuticals by metalcatalysed exchange methods. J Label Compd Radiopharm 53:722–730. https://doi.org/10.
1002/jlcr.1800
8. Lockley WJS, Heys JR (2010) Metal-catalysed hydrogen isotope exchange labelling: a brief
overview. J Label Compd Radiopharm 53:635–644. https://doi.org/10.1002/jlcr.1851
9. Lockley WJS, Hesk D (2010) Rhodium- and ruthenium-catalysed hydrogen isotope exchange.
J Label Compd Radiopharm 53:704–715. https://doi.org/10.1002/jlcr.1815
10. Lockley WJS, McEwen A, Cooke R (2012) Tritium: a coming of age for drug discovery and
development ADME studies. J Label Compd Radiopharm 55:235–257. https://doi.org/10.
1002/jlcr.2928
11. Di Giuseppe A, Castarlenas R, Oro LA (2015) Mechanistic considerations on catalytic H/D
exchange mediated by organometallic transition metal complexes. C R Chim 18:713–741.
https://doi.org/10.1016/j.crci.2015.02.006
12. Atzrodt J, Derdau V, Kerr WJ, Reid M (2018) CÀH functionalisation for hydrogen isotope
exchange. Angew Chem Int Ed 57:3022–3047. https://doi.org/10.1002/anie.201708903
13. Hesk D (2020) Highlights of C(sp
2
)–H hydrogen isotope exchange reactions. J Label Compd
Radiopharm 63:247–265. https://doi.org/10.1002/jlcr.3801
14. Junk T, Catallo WJ (1997) Hydrogen isotope exchange reactions involving C–H (D, T) bonds.
Chem Soc Rev 26:401–406. https://doi.org/10.1039/CS9972600401
15. Valero M, Derdau V (2020) Highlights of aliphatic C(sp
3
)–H hydrogen isotope exchange
reactions. J Label Compd Radiopharm 63:266–280. https://doi.org/10.1002/jlcr.3783
16. Saljoughian M (2002) Synthetic tritium labeling: reagents and methodologies. Synthesis
(Stuttg) 2002:1781–1801. https://doi.org/10.1055/s-2002-33907
17. Atzrodt J, Derdau V, Fey T, Zimmermann J (2007) The renaissance of H/D exchange. Angew
Chem Int Ed 46:7744–7765. https://doi.org/10.1002/anie.200700039
18. Lockley WJS (2007) 30 Years with ortho-directed hydrogen isotope exchange labelling. J
Label Compd Radiopharm 50:779–788. https://doi.org/10.1002/jlcr.1421
19. Hesk D, McNamara P (2007) Synthesis of isotopically labelled compounds at ScheringPlough, an historical perspective. J Label Compd Radiopharm 50:875–887. https://doi.org/
10.1002/jlcr.1424
20. Heys JR (2007) Organoiridium complexes for hydrogen isotope exchange labeling. J Label
Compd Radiopharm 50:770–778. https://doi.org/10.1002/jlcr.1428
21. Parkin G (2007) Applications of deuterium isotope effects for probing aspects of reactions
involving oxidative addition and reductive elimination of H–H and C–H bonds. J Label
Compd Radiopharm 50:1088–1114. https://doi.org/10.1002/jlcr.1435
294
M. Reid
1. Ebbing DD, Gammon SD (2005) Atoms, molecules, and ions. In: General chemistry, 8th edn.
Houghton Mifflin Company, Boston
2. Atzrodt J, Derdau V, Kerr WJ, Reid M (2018) Deuterium- and tritium-labelled compounds:
applications in the life sciences. Angew Chem Int Ed 57:1758–1784. https://doi.org/10.1002/
anie.201704146
3. Isin EM, Elmore CS, Nilsson GN et al (2012) Use of radiolabeled compounds in drug
metabolism and pharmacokinetic studies. Chem Res Toxicol 25:532–542. https://doi.org/10.
1021/tx2005212
4. Filer CN (2010) Direct metal-catalyzed tritiation of organic compounds. J Label Compd
Radiopharm 53:739–744. https://doi.org/10.1002/jlcr.1801
5. Nilsson GN, Kerr WJ (2010) The development and use of novel iridium complexes as catalysts
for ortho-directed hydrogen isotope exchange reactions. J Label Compd Radiopharm
53:662–667. https://doi.org/10.1002/jlcr.1817
6. Allen PH, Hickey MJ, Kingston LP, Wilkinson DJ (2010) Metal-catalysed isotopic exchange
labelling: 30 years of experience in pharmaceutical R&D. J Label Compd Radiopharm
53:731–738. https://doi.org/10.1002/jlcr.1825
7. Hesk D, Lavey CF, McNamara P (2010) Tritium labelling of pharmaceuticals by metalcatalysed exchange methods. J Label Compd Radiopharm 53:722–730. https://doi.org/10.
1002/jlcr.1800
8. Lockley WJS, Heys JR (2010) Metal-catalysed hydrogen isotope exchange labelling: a brief
overview. J Label Compd Radiopharm 53:635–644. https://doi.org/10.1002/jlcr.1851
9. Lockley WJS, Hesk D (2010) Rhodium- and ruthenium-catalysed hydrogen isotope exchange.
J Label Compd Radiopharm 53:704–715. https://doi.org/10.1002/jlcr.1815
10. Lockley WJS, McEwen A, Cooke R (2012) Tritium: a coming of age for drug discovery and
development ADME studies. J Label Compd Radiopharm 55:235–257. https://doi.org/10.
1002/jlcr.2928
11. Di Giuseppe A, Castarlenas R, Oro LA (2015) Mechanistic considerations on catalytic H/D
exchange mediated by organometallic transition metal complexes. C R Chim 18:713–741.
https://doi.org/10.1016/j.crci.2015.02.006
12. Atzrodt J, Derdau V, Kerr WJ, Reid M (2018) CÀH functionalisation for hydrogen isotope
exchange. Angew Chem Int Ed 57:3022–3047. https://doi.org/10.1002/anie.201708903
13. Hesk D (2020) Highlights of C(sp
2
)–H hydrogen isotope exchange reactions. J Label Compd
Radiopharm 63:247–265. https://doi.org/10.1002/jlcr.3801
14. Junk T, Catallo WJ (1997) Hydrogen isotope exchange reactions involving C–H (D, T) bonds.
Chem Soc Rev 26:401–406. https://doi.org/10.1039/CS9972600401
15. Valero M, Derdau V (2020) Highlights of aliphatic C(sp
3
)–H hydrogen isotope exchange
reactions. J Label Compd Radiopharm 63:266–280. https://doi.org/10.1002/jlcr.3783
16. Saljoughian M (2002) Synthetic tritium labeling: reagents and methodologies. Synthesis
(Stuttg) 2002:1781–1801. https://doi.org/10.1055/s-2002-33907
17. Atzrodt J, Derdau V, Fey T, Zimmermann J (2007) The renaissance of H/D exchange. Angew
Chem Int Ed 46:7744–7765. https://doi.org/10.1002/anie.200700039
18. Lockley WJS (2007) 30 Years with ortho-directed hydrogen isotope exchange labelling. J
Label Compd Radiopharm 50:779–788. https://doi.org/10.1002/jlcr.1421
19. Hesk D, McNamara P (2007) Synthesis of isotopically labelled compounds at ScheringPlough, an historical perspective. J Label Compd Radiopharm 50:875–887. https://doi.org/
10.1002/jlcr.1424
20. Heys JR (2007) Organoiridium complexes for hydrogen isotope exchange labeling. J Label
Compd Radiopharm 50:770–778. https://doi.org/10.1002/jlcr.1428
21. Parkin G (2007) Applications of deuterium isotope effects for probing aspects of reactions
involving oxidative addition and reductive elimination of H–H and C–H bonds. J Label
Compd Radiopharm 50:1088–1114. https://doi.org/10.1002/jlcr.1435
294
M. Reid