N-Heterocyclic Carbenes as Ligands to 198Au(I)-Radiolabeled Compounds: A New Platform for Radiopharmaceutical Design
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| Titel: | N-Heterocyclic Carbenes as Ligands to 198Au(I)-Radiolabeled Compounds: A New Platform for Radiopharmaceutical Design |
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| Autoren: | Sarah Spreckelmeyer, Sophie R. Thomas, Franziska Schuderer, Catarina I. G. Pinto, Ana Luiza de Andrade Querino, Felix A. Böhm, Mihyun Park, Christopher Geppert, Christian Gorges, Filipa Mendes, Angela Casini |
| Quelle: | Journal of Medicinal Chemistry. 68:17516-17526 |
| Verlagsinformationen: | American Chemical Society (ACS), 2025. |
| Publikationsjahr: | 2025 |
| Schlagwörter: | 301305 Medical chemistry, Heterocyclic Compounds/chemistry, Methane/analogs & derivatives, 104020 Radiochemistry, Ligands, 301207 Pharmazeutische Chemie, Article, ddc, Gold/chemistry, 104020 Radiochemie, SDG 3 - Good Health and Well-being, Drug Design, SDG 3 – Gesundheit und Wohlergehen, Imidazoles/chemistry, Radiopharmaceuticals/chemistry, Humans, 104003 Anorganische Chemie, 301207 Pharmaceutical chemistry, 104003 Inorganic chemistry, 301305 Medizinische Chemie |
| Beschreibung: | The radionuclide 198Au, with a half-life of 2.7 days, emits γ radiation ideal for diagnostic purposes and generates β- particles suitable for effective cancer radiotherapy, making it a perfect nuclide for "theranostics". However, the application of coordination compounds of Au(I)/Au(III) in medicine is limited by their instability in vivo. Here, we explore N-heterocyclic carbene (NHC) organometallic chemistry to stabilize 198Au(I) in radiopharmaceuticals. Thus, Au(I) NHC compounds featuring different scaffolds were selected for 198Au radiolabeling. Eventually, two compounds featuring imidazole (AuNHC-1) and theophylline (AuTMX2) scaffolds were successfully radiolabeled (radiochemical purity = 92.9% and 40.2%, respectively). Instead, two peptidic Au(I) benzimidazolylidene derivatives, capable of blood-brain barrier translocation in vitro, were subjected to ligand exchange reactions under the applied radiolabeling conditions. The obtained proof-of-concept results showed that NHCs are suitable ligands to achieve isotope exchange in Au(I) complexes. Overall, our work reveals the still untapped potential of organometallic chemistry in radiopharmaceutical design. |
| Publikationsart: | Article |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.5c01073 |
| Zugangs-URL: | https://ucrisportal.univie.ac.at/de/publications/3d892232-6eae-4751-8242-95f3faa8ed61 https://doi.org/10.1021/acs.jmedchem.5c01073 https://mediatum.ub.tum.de/1796552 |
| Rights: | CC BY |
| Dokumentencode: | edsair.doi.dedup.....7d6c41b15d953d10eb6f324efb4ecd24 |
| Datenbank: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | The radionuclide 198Au, with a half-life of 2.7 days, emits γ radiation ideal for diagnostic purposes and generates β- particles suitable for effective cancer radiotherapy, making it a perfect nuclide for "theranostics". However, the application of coordination compounds of Au(I)/Au(III) in medicine is limited by their instability in vivo. Here, we explore N-heterocyclic carbene (NHC) organometallic chemistry to stabilize 198Au(I) in radiopharmaceuticals. Thus, Au(I) NHC compounds featuring different scaffolds were selected for 198Au radiolabeling. Eventually, two compounds featuring imidazole (AuNHC-1) and theophylline (AuTMX2) scaffolds were successfully radiolabeled (radiochemical purity = 92.9% and 40.2%, respectively). Instead, two peptidic Au(I) benzimidazolylidene derivatives, capable of blood-brain barrier translocation in vitro, were subjected to ligand exchange reactions under the applied radiolabeling conditions. The obtained proof-of-concept results showed that NHCs are suitable ligands to achieve isotope exchange in Au(I) complexes. Overall, our work reveals the still untapped potential of organometallic chemistry in radiopharmaceutical design. |
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| ISSN: | 15204804 00222623 |
| DOI: | 10.1021/acs.jmedchem.5c01073 |