Formation and characterization of gallium(III) complexes with monoamide derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid: A study of the dependency of structure on reaction pH

Dinesh Shetty, Soo Young Choi, Jae Min Jeong, Lathika Hoigebazar, Yun Sang Lee, Dong Soo Lee, June Key Chung, Myung Chul Lee, Young Keun Chung

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17 Scopus citations

Abstract

Two monoamide derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) conjugated with methylamine (4) or benzylamine (5) were synthesized by treating di-tert-butyl 1,4,7-triazacyclononane-1,4-diacetate (1) with 2-chloro-N-benzyl- or -N-methylacetamide, followed by an acid cleavage reaction. Complexes of 4 and 5 chelated to Ga3+ to give Ga-4 and Ga-5, respectively, in reaction solutions at different pH values (3 and 5). Complexes Ga-4 and Ga-5 were characterized by single-crystal X-ray diffraction and multinuclear NMR spectroscopy. In the solid state, these complexes were isostructural, and the coordination spheres of the metal ions exhibited distorted octahedral geometries. In the case of the Ga-4 complex, which was formed at both pH values, the metal ion is coordinated to the amide nitrogen atom of the modified pendent arm of 4. However, in the case of Ga-5, the metal ion is coordinated to a nitrogen or an oxygen atom of the amide linkage when the pH of the reaction soultion was 5 or 3, respectively. No significant difference was found between the 1H NMR spectra of the complexes formed at pH = 3 and 5. However, 71Ga NMR spectra showed a broad resonance signal and a narrow singlet for the complex synthesized at the lower pH, but only a single narrow singlet for the complex prepared at neutral pH. Variable-temperature 1H NMR spectra showed that complexes Ga-4 and Ga-5 are rigid in solution. The stability of these complexes in the physiological pH range and at high temperature suggests that NOTA can be used as a bifunctional chelating agent to label biomolecules with radioactive gallium by direct conjugation of the complex to target molecules. This finding could open up a wide range of applications for NOTA-type bifunctional chelating agents by eliminating the multi-step synthesis routes required to introduce extra linker groups to the labelling agent.

Original languageBritish English
Pages (from-to)5432-5438
Number of pages7
JournalEuropean Journal of Inorganic Chemistry
Issue number34
DOIs
StatePublished - Dec 2010

Keywords

  • Amides
  • Chelates
  • Gallium
  • NMR spectroscopy
  • X-ray diffraction

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