Modern Strategies for Carbon Isotope Exchange

Abstract

In contrast to stable and natural abundant carbon‐12, the synthesis of organic molecules with carbon (radio)isotopes must be conceived and optimized in order to navigate through the hurdles of radiochemical requirements, such as high costs of the starting materials, harsh conditions and radioactive waste generation. In addition, it must initiate from the small cohort of available C‐labeled building blocks. For long time, multi‐step approaches have represented the sole available patterns. On the other side, the development of chemical reactions based on the reversible cleavage of C−C bonds might offer new opportunities and reshape retrosynthetic analysis in radiosynthesis. This review aims to provide a short survey on the recently emerged carbon isotope exchange technologies that provide effective opportunity for late‐stage labeling. At present, such strategies have relied on the use of primary and easily accessible radiolabeled C1‐building blocks, such as carbon dioxide, carbon monoxide and cyanides, while the activation principles have been based on thermal, photocatalytic, metal‐catalyzed and biocatalytic processes.

Platform for Multiple Isotope Labeling via Carbon–Sulfur Bond Exchange

“…Hydrogen isotope exchange (HIE, Figure 1A) is by far the best-established technology as it is utilized on a daily basis in the pharmaceutical industry. 3 Recently, carbon isotope exchange (CIE) was recognized as a modern tool for latestage labeling with 11 C, 13 C, and 14 C. 4 In addition, fluorine exchange (FIE, for positron emitter 18 F) 5 and examples of iodine exchange (IIE) have been described, as well. 6 A general pitfall of these technologies is that they are element-specific, meaning that they are optimized for one single element.…”

Carbon-Atom Exchange between [MC2]+ (M = Os and Ir) and Methane: on the Thermodynamic and Dynamic Aspects

“…Isotope labeling serves as a key tool in quite a few fields, such as modern chemistry, biology, and ecological sciences. − For example, radioisotope (tritium or carbon-14) labeling is commonly used to trace biological metabolic pathways and the conversion of substances in chemistry . On the other hand, stable isotope (deuterium and carbon-13) labeling is commonly used as internal standards for efficient analysis, such as liquid chromatograph mass spectrometer or magnetic resonance imaging techniques. , The H/D exchange and 12 C/ 13 C exchange reactions are commonly used for the preparation of internal standards in the condensed phase. − Furthermore, these exchange reactions can also be used to investigate the reaction mechanism in the gas phase, where idealized conditions can effectively reduce the heterogeneity of the active center morphology and the complexity of the chemical environment in the condensed phase. Gas-phase studies of isotope exchange reactions in clusters of finite atomic number may be an effective way to reveal isotope exchange mechanisms and to resolve structure–performance relationships at a molecular level. , In contrast to the abundant studies of isotope exchange reactions in the condensed phase, − reports on gas-phase isotope exchange reactions are scarce, focusing mainly on H/D, − 12 C/ 13 C, − 14 N/ 15 N, and 16 O/ 18 O − exchange reactions.…”

“…Isotope labeling serves as a key tool in quite a few fields, such as modern chemistry, biology, and ecological sciences. − For example, radioisotope (tritium or carbon-14) labeling is commonly used to trace biological metabolic pathways and the conversion of substances in chemistry . On the other hand, stable isotope (deuterium and carbon-13) labeling is commonly used as internal standards for efficient analysis, such as liquid chromatograph mass spectrometer or magnetic resonance imaging techniques. , The H/D exchange and 12 C/ 13 C exchange reactions are commonly used for the preparation of internal standards in the condensed phase. − Furthermore, these exchange reactions can also be used to investigate the reaction mechanism in the gas phase, where idealized conditions can effectively reduce the heterogeneity of the active center morphology and the complexity of the chemical environment in the condensed phase.…”

Carbon Dioxide Radical Anion by Photoinduced Equilibration between Formate Salts and [11C, 13C, 14C]CO2: Application to Carbon Isotope Radiolabeling

“…Carbon-11 ( 11 C, t 1/2 = 20.4 min, β + emitter) is a reference in positron emission tomography (PET) imaging, but it has a remarkably short half-life and can only be produced extemporaneously on the nanomolar scale . On the other hand, carbon-14 ( 14 C, t 1/2 = 5730 years, β – emitter) is a pivotal tool for tracking the fate of organic compounds and a gold standard for human-ADME studies and crop science development, but the costs related to the source, its handling, and the generation of long-lasting waste prevent the use of excess reagent . Consequently, despite the fact that [ 14 C]­CO 2 (1600 $ mmol –1 ) and [ 11 C]­CO 2 are primary sources of both isotopes, such inherent challenges have prevented the use of labeled CO 2 •– technologies.…”