An octadentate bis(semicarbazone) macrocycle: a potential chelator for lead and bismuth radiopharmaceuticals

A variant of 1,4,7,10-tetraazacyclododecane (cyclen) bearing two semicarbazone pendant groups has been prepared. The octadentate ligand forms complexes with Bi3+ and Pb2+. X-ray crystallography showed that the neutral ligand provides an eight-coordinate environment for both metal ions and intermolecular hydrogen bond interactions have influenced the coordination environments of both complexes in the solid state. NMR spectroscopy revealed a fluxional environment for both complexes. The ligand was radiolabeled with the α-emitting radioactive isotope 213Bi3+, which is used in systemic targeted radiotherapy. The resulting complex was stable in serum for at least 90 min (two decay half-lives). The Pb2+ complex has reasonably fast kinetics of formation (t1/2 = 20 min) at 25 °C and pH 7.4. The Bi3+ and Pb2+ complexes show kinetic stability in 1.2 M HCl (half-lives of 214 min and 47 min, respectively). This is the first description of a macrocycle bearing semicarbazone pendant groups and its utility in coordinating main group metals, specifically those with radiotherapeutic potential.

LANGE Jaclyn L;  DAVEY Patrick;  MA Michelle;  WHITE Jonathan;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  BLOWER Phil;  PATERSON Brett; 

2021-03-25

ROYAL SOC CHEMISTRY

JRC112448

1477-9226 (online),   

https://pubs.rsc.org/en/content/articlelanding/2020/DT/D0DT02673E#!divAbstract,    https://publications.jrc.ec.europa.eu/repository/handle/JRC112448,   

10.1039/d0dt02673e (online),