The Synthesis of a Bis(thiosemicarbazone) Macrocyclic Ligand and the Mn(II), Co(II), Zn(II) and 68Ga(III) Complexes

A 1,4,7,10-tetraazacyclododecane (cyclen) variant bearing two thiosemicarbazone pendant groups has been prepared. The ligand forms complexes with Mn2+, Co2+ and Zn2+. X-ray crystallography of the Mn2+, Co2+ and Zn2+ complexes showed that the ligand provides a six-coordinate environment for the metal ions. The Mn2+ and Zn2+ complexes exist in the solid state as racemic mixtures of the Delta(delta,delta,delta,delta)/?(lambda,lambda,lambda,lambda) and Delta(lambda,lambda,lambda,lambda)/?(delta,delta,delta,delta) diastereomers, and the Co2+ complex exists as the Delta(delta,delta,delta,delta)/?(lambda,lambda,lambda,lambda) and Delta(lambda,lambda,lambda,delta)/?(delta,delta,delta,lambda) diastereomers. Density functional theory calculations indicated that the relative energies of the diastereomers are within 10 kJ mol(-1). Magnetic susceptibility of the complexes indicated that both the Mn2+ and Co2+ ions are high spin. The ligand was radiolabelled with gallium-68, in the interest of developing new positron emission tomography imaging agents, which produced a single species in high radiochemical purity (>95%) at 90 degrees C for 10 min.

Automated summary

A new variant of 1,4,7,10-tetraazacyclododecane (cyclen) with two thiosemicarbazone pendant groups was prepared and successfully formed complexes with Mn2+, Co2+, and Zn2+. X-ray crystallography revealed a six-coordinate environment provided by the ligand for the metal ions, with different diastereomers observed in the solid state for each metal complex. Density functional theory calculations indicated that the diastereomers had similar relative energies.