Equilibrium, Kinetic and Structural Properties of Gallium(III) and Some Divalent Metal Complexes Formed with the New DATAm and DATA5m Ligands

Edit Farkas, Johannes Nagel, Bradley P. Waldron, David Parker, Imre Tóth, Ernő Brücher, Frank Rösch, Zsolt Baranyai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The development of 68Ge/68Ga generators has made the positron-emitting 68Ga isotope widely accessible and raised interest in new chelate complexes of Ga3+. The hexadentate 1,4-di(acetate)-6-methyl[amino(methyl)acetate]perhydro-1,4-diazepane (DATAm) ligand and its bifunctional analogue, 1,4-di(acetate)-6-pentanoic acid[amino(methyl)acetate]perhydro-1,4-diazepane (DATA5m), rapidly form complexes with 68Ga in high radiochemical yield. The stability constants of DATAm and DATA5m complexes formed with Ga3+, Zn2+, Cu2+, Mn2+ and Ca2+ have been determined by using pH potentiometry, spectrophotometry (Cu2+) and 1H and 71Ga NMR spectroscopy (Ga3+). The stability constants of Ga(DATAm) and Ga(DATA5m) complexes are slightly higher than those of Ga(AAZTA). The species distribution calculations indicated the predominance of Ga(L)OH mixed-hydroxo complexes at physiological pH. The 1H and 71Ga NMR spectroscopy studies provided information about the coordinated functional groups of ligands and on the kinetics of exchange between the Ga(L) and Ga(L)OH complexes. The transmetalation reactions between the Ga(L) complexes and Cu2+ citrate (6<pH<8.5) occur through both spontaneous and OH-assisted dissociation of the Ga(L)OH species. At pH 7.4 and 25 °C, the half-lives of the dissociation of Ga(DATAm), Ga(DATA5m) and Ga(AAZTA) were 11, 44 and 24 h, respectively. Similar half-lives have been obtained for the ligand-exchange reactions between the Ga(L)OH complexes and transferrin. The equilibrium and kinetic data indicate that the Ga(DATA5m) complex is a good 68Ga-based radiodiagnostic candidate.

Original languageEnglish
Pages (from-to)10358-10371
Number of pages14
JournalChemistry - A European Journal
Volume23
Issue number43
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • NMR spectroscopy
  • gallium
  • kinetics
  • molecular imaging
  • reaction mechanisms
  • thermodynamics

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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