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

Abstract

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 Δ(δ,δ,δ,δ)/Λ(λ,λ,λ,λ) and Δ(λ,λ,λ,λ)/Λ(δ,δ,δ,δ) diastereomers, and the Co2+ complex exists as the Δ(δ,δ,δ,δ)/Λ(λ,λ,λ,λ) and Δ(λ,λ,λ,δ)/Λ(δ,δ,δ,λ) 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 °C for 10 min.

Structure and bonding trends of bisthiosemicarbazones: An overview

“…The addition of cobalt (II) acetate in methanolic solution of tetraazacyclododecane (H 2 L) resulted into the formation of complex [Co (HL)] + , which was then precipitated as tetraphenylborate salt [Co (HL)](BPh 4 ) 11 (Figure 3), by adding NaBPh 4 . [ 137 ] The formation of complex cation was confirmed from the peak at m/z = 544.22 in mass spectrum. Two discrete diastereomeric units, [Co1(HL)] + and [Co2(HL) + , are crystallized in complex 11 and present as racemic mixture (Figure 2a and b).…”

“…The condensation of thiosemicarbazide with cyclohexane‐1,2‐dione and (4,10‐Dimethyl‐1,4,7,10‐tetraazacyclododecane‐1,7‐diyl) bis (propan‐2‐one), respectively, yields bisthiosemi‐ carbazones with cyclohexane rings ( D1, D2 ) and macrocyclic rings ( D3 ) (Chart 16). [ 113,130,137 ]…”

“…[136] The condensation of thiosemicarbazide with cyclohexane-1,2-dione and (4,10-Dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl) bis (propan-2-one), respectively, yields bisthiosemi-carbazones with cyclohexane rings (D1, D2) and macrocyclic rings (D3) (Chart 16). [113,130,137] It has been observed that generally, for the synthesis of ketone-based bisthiosemicarbazone, acidic condition had to be maintained by adding few drops of acid, [88,106,109] whereas in case of aldehyde-based bisthiosemicarbazone, condensation of aldehyde and thiosemicarbazide can take place without the addition of acid. [121,124] 5 | SPECTROSCOPIC TECHNIQUES Various spectroscopic techniques like infrared (IR), ultraviolet-visible (UV-visible), nuclear magnetic resonance (NMR), and electron spin resonance (ESR) were used to characterize the bisthiosemicarbazones and their complexes.…”

“…The addition of zinc (II) acetate in methanolic solution of tetraazacyclododecane (H 2 L) resulted into the formation of complex, [Zn (HL)] + , which was then precipitated as tetraphenylborate salt [Zn (HL)](BPh 4 ) 54 (Figure 8), by adding NaBPh 4 .The complex has a distorted octahedral geometry. The formation of complex F I G U R E 8 Molecular structure of [Zn (HL)] + 54 (adapted from reference [137] ). cation was confirmed from the peak at m/z = 549.22 in mass spectrum.…”

Hexadentate technetium-99m bis(thiosemicarbazonato) complexes: synthesis, characterisation and biodistribution

“…13 Several bis(thiosemicarbazones) have also been investigated as delivery vehicles for radionuclides of copper, indium and gallium. 14–20 Radiolabelling with Cu 2+ occurs rapidly at room temperature and the complexes are stable (log K >17), neutral and membrane permeable. 21 Modification of the terminal groups on bis(thiosemicarbazones) has been shown to alter the biodistribution and cellular uptake of Cu 2+ bis(thiosemicarbazonato) complexes without changing the coordination environment.…”