Tuning the Properties of Rigidified Acyclic DEDPA 2- Derivatives for Application in PET Using Copper-64
Torralba-Maldonado, Daniel (Universitat Autònoma de Barcelona. Departament de Química)
Marlin, Axia (University of Wisconsin-Madison)
Lucio-Martínez, Fátima (Universidade da Coruña)
Freire-García, Antía (Universidade da Coruña)
Whetter, Jennifer (University of Wisconsin-Madison)
Brandariz, Isabel (Universidade da Coruña)
Iglesias, Emilia (Universidade da Coruña)
Pérez-Lourido, Paulo (Universidade de Vigo)
Ortuño Mingarro, Rosa María (Universitat Autònoma de Barcelona. Departament de Química)
Boros, Eszter (University of Wisconsin-Madison)
Illa, Ona (Universitat Autònoma de Barcelona. Departament de Química)
Esteban-Gómez, David (Universidade da Coruña)
Platas-Iglesias, Carlos (Universidade da Coruña)

Date:	2024
Abstract:	We present a detailed investigation of the coordination chemistry toward [ nat Cu/ 64 Cu]copper of a series of HDEDPA derivatives (HDEDPA = 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing cyclohexyl (HCHXDEDPA), cyclopentyl (HCpDEDPA) or cyclobutyl (HCBuDEDPA) spacers. Furthermore, we also developed a strategy that allowed the synthesis of a HCBuDEDPA 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 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 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. The nature of the rigid central spacer in acyclic chelators has a significant impact in the properties of their toward [ nat Cu/ 64 Cu]copper complexes.
Grants:	Agencia Estatal de Investigación PID2022-138335NB-I00 Agencia Estatal de Investigación PID2022-139826OB-I00 Agencia Estatal de Investigación RED2022-134091-T Agència de Gestió d'Ajuts Universitaris i de Recerca 2020/FI-SDUR-00055 Agencia Estatal de Investigación FPU21/06305
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Dissociation ; Ligands ; Mechanisms of action ; Reaction products ; Stability
Published in:	Inorganic chemistry, Vol. 63, Issue 46 (November 2024) , p. 22297-22307, ISSN 1520-510X

DOI: 10.1021/acs.inorgchem.4c04050
PMID: 39508185

11 p, 3.5 MB

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