Getting a lead on Pb2+-amide chelators for 203/212Pb radiopharmaceuticals
| Autor: | Neha Choudhary, Brooke McNeil, María de Guadalupe Jaraquemada-Peláez, Tom Kostelnik Kostelnik, Brian O. Patrick, Chris Orvig, Aidan Ingham |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Denticity
010405 organic chemistry Potentiometric titration 010402 general chemistry 01 natural sciences 0104 chemical sciences Inorganic Chemistry Metal chemistry.chemical_compound Crystallography chemistry visual_art Amide visual_art.visual_art_medium Proton NMR Chelation Chemical stability Isomerization |
| Zdroj: | Dalton Transactions. 50:11579-11595 |
| ISSN: | 1477-9234 1477-9226 |
| Popis: | Amide-based chelators DTPAm, EGTAm and ampam were synthesized to investigate which chelator most ideally coordinates [nat/203Pb]Pb2+ ions for potential radiopharmaceutical applications. 1H NMR spectroscopy was used to study each metal–ligand complex in the solution state. The 1H NMR spectrum of [Pb(DTPAm)]2+ revealed minimal isomerization and fluxional behaviour compared to [Pb(EGTAm)]2+ and [Pb(ampam)]2+, both of which showed fewer spectral changes indicative of less static behaviour. The solid-state coordination properties of each complex were also examined from single crystal structures that were studied by X-ray diffraction (XRD). In the solid-state, octadentate DTPAm coordinated Pb2+ to form an eight-coordinate hemidirected complex; octadentate EGTAm coordinated Pb2+ forming a ten-coordinate holodirected complex with a bidentate NO3− ion also coordinated to the metal centre; decadentate ampam completely encapsulated the Pb2+ ion to form a ten-coordinate holodirected complex with a C2 axis of symmetry. Potentiometric titrations were carried out to assess the thermodynamic stability of each metal–ligand complex. The pM values obtained for [Pb(DTPAm)]2+, [Pb(EGTAm)]2+ and [Pb(ampam)]2+ were 9.7, 7.2 and 10.2, respectively. The affinity of each chelator for Pb2+ ions was tested by [203Pb]Pb2+ radiolabeling studies to evaluate their prospects as chelators for [203/212Pb]Pb2+-based radiopharmaceuticals. DTPAm radiolabeled [203Pb]Pb2+ ions achieving molar activities as high as 3.5 MBq μmol−1 within 15 minutes, at 25 °C, whereas EGTAm and ampam produced lower molar activities of 0.25 MBq μmol−1 within 30 minutes, at 37 °C. EGTAm and ampam were therefore deemed unsuitable for [203/212Pb]Pb2+-based radiopharmaceutical applications, while DTPAm warrants further studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|