9 Metal Nanoparticles for Hydrogen Isotope Exchange
285
Fig. 9.4 Quantitative whole-body autoradiography (QWBA) showing the site of administration of
a radioactive drug [4]. Reprinted with permission from Ref. [4]. Copyright 2018 Wiley
Receptor affinity can be easily measured by saturation experiments which provide
the half maximal inhibitory concentration (IC 50 ) of the unlabeled molecule [29].
Tritiated compounds can also be used in later phases of drug development process
such as adsorption, distribution, metabolism and excretion (ADME) studies. Among
them, ex vivo imaging techniques such as whole-body autoradiography (WBA) can
be used to determine the in situ localization of radiolabeled xenobiotics in laboratory
animals (Fig. 9.4) [30].
9.2 Current Approach to the Synthesis of Deuterated
and Tritiated Molecules
The synthesis of molecules labeled with hydrogen isotopes can be achieved
throughout two pathways. First, one can envisage the use of isotopically labeled
building blocks for the synthesis of the desired molecules. This approach is the most
reliable one because of the high control on the site of the isotope incorporation and
the high level of isotopic enrichment achievable. However, the necessity of reworking
a synthetic pathway in order to incorporate a labeled fragment may be difficult, especially for complicated compounds such as biomolecules. Moreover, in the case of
tritiations, high amounts of radioactive wastes are produced. In this context, direct
exchange of hydrogen with its isotopes represents a fascinating alternative to classical
synthesis. In fact, Hydrogen Isotope Exchange (HIE) is easier, cheaper and leads to
less radioactive wastes because it can be done directly on the compound of interest
(late stage functionalization) [31]. On the other hand, HIE methods are still under
development, and not all functionalities are nowadays compatible. In the example
reported in Fig. 9.5, [32] deuterated paroxetine was prepared through a five-step
synthesis with an overall yield of 20%. The same molecule could be deuterated (on
285
Fig. 9.4 Quantitative whole-body autoradiography (QWBA) showing the site of administration of
a radioactive drug [4]. Reprinted with permission from Ref. [4]. Copyright 2018 Wiley
Receptor affinity can be easily measured by saturation experiments which provide
the half maximal inhibitory concentration (IC 50 ) of the unlabeled molecule [29].
Tritiated compounds can also be used in later phases of drug development process
such as adsorption, distribution, metabolism and excretion (ADME) studies. Among
them, ex vivo imaging techniques such as whole-body autoradiography (WBA) can
be used to determine the in situ localization of radiolabeled xenobiotics in laboratory
animals (Fig. 9.4) [30].
9.2 Current Approach to the Synthesis of Deuterated
and Tritiated Molecules
The synthesis of molecules labeled with hydrogen isotopes can be achieved
throughout two pathways. First, one can envisage the use of isotopically labeled
building blocks for the synthesis of the desired molecules. This approach is the most
reliable one because of the high control on the site of the isotope incorporation and
the high level of isotopic enrichment achievable. However, the necessity of reworking
a synthetic pathway in order to incorporate a labeled fragment may be difficult, especially for complicated compounds such as biomolecules. Moreover, in the case of
tritiations, high amounts of radioactive wastes are produced. In this context, direct
exchange of hydrogen with its isotopes represents a fascinating alternative to classical
synthesis. In fact, Hydrogen Isotope Exchange (HIE) is easier, cheaper and leads to
less radioactive wastes because it can be done directly on the compound of interest
(late stage functionalization) [31]. On the other hand, HIE methods are still under
development, and not all functionalities are nowadays compatible. In the example
reported in Fig. 9.5, [32] deuterated paroxetine was prepared through a five-step
synthesis with an overall yield of 20%. The same molecule could be deuterated (on