Work

Tuning the Properties of Rigidified Acyclic DEDPA2– Derivatives for Application in PET Using Copper-64

Year: 2024

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide We present a detailed investigation of the coordination chemistry toward [ nat Cu/ 64 Cu]copper of a series of H 2 DEDPA derivatives (H 2 DEDPA = 6,6′-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing cyclohexyl (H 2 CHXDEDPA), cyclopentyl (H 2 CpDEDPA) or cyclobutyl (H 2 CBuDEDPA) spacers. Furthermore, we also developed a strategy that allowed the synthesis of a H 2 CBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl ring, which can be used for conjugation to targeting units. The X-ray structures of the Cu(II) complexes evidence distorted octahedral coordination around the metal ion in all cases. Cyclic voltammetry experiments (0.15 M NaCl) evidence quasi-reversible reduction waves associated with the reduction of Cu(II) to Cu(I). The complexes show a high thermodynamic stability, with log K CuL values of 25.11(1), 22.18(1) and 20.19(1) for the complexes of CHXDEDPA 2–, CpDEDPA 2– and CBuDEDPA 2–, respectively (25 °C, 1 M NaCl). Dissociation kinetics experiments reveal that both the spontaneous- and proton-assisted pathways operate at physiological pH. Quantitative labeling with 64 CuCl 2 was observed at 0.1 nmol for CHXDEDPA 2– and CpDEDPA 2–, 0.025 nmol for CBuDEDPA 2– and 1 nmol for CBuDEDPA-NHBoc 2–, with no significant differences observed at 15, 30, and 60 min. The radio-complexes are stable in PBS over a period of 24 h.

Source: Inorganic Chemistry

DOI: 10.1021/acs.inorgchem.4c04050