Bifunctional chelators for copper radiopharmaceuticals: the synthesis of [Cu(ATSM)-amino acid] and [Cu(ATSM)-octreotide] conjugates

Abstract

Two new bifunctional chelators that are derivatives of the bis(thiosemicarbazone) ATSMH(2) proligand have been prepared, one with two phenyl carboxylate substituents on the exocyclic nitrogens (L(1)H(2)) and one with a single phenyl carboxylate (L(2)H(2)). The new ligands have been characterised by NMR spectroscopy, mass spectrometry and in the case of L(1)H(2) by X-ray crystallography. The copper, nickel and zinc complexes of the new ligands have been synthesised and characterised. Electrochemical measurements show that the copper(II) complexes undergo a reversible reduction attributable to a Cu(II)/Cu(I) process. The new proligands have been tethered to the N-alpha-Boc-protected amino acid..