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

TY - JOUR

T1 - An octadentate bis(semicarbazone) macrocycle: a potential chelator for lead and bismuth radiopharmaceuticals

AU - Lange, Jaclyn L

AU - Davey, Patrick R W J

AU - Ma, Michelle T

AU - White, Jonathan M

AU - Morgenstern, Alfred

AU - Bruchertseifer, Frank

AU - Blower, Philip J

AU - Paterson, Brett M

PY - 2020/11/14

Y1 - 2020/11/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85095461634&partnerID=8YFLogxK

U2 - 10.1039/d0dt02673e

DO - 10.1039/d0dt02673e

M3 - Article

C2 - 33079111

SN - 1477-9226

VL - 49

SP - 14962

EP - 14974

JO - Dalton transactions (Cambridge, England : 2003)

JF - Dalton transactions (Cambridge, England : 2003)

IS - 42

ER -