Multistep synthesis of a novel copper complex with potential for Alzheimer’s disease diagnosis
Fatma Dellal, Diego Santo Domingo Porqueras, Stacy Narayanin-Richenapin, Marine Thimotee, Vanessa Delahaye, Yacine Diouf, Karolina Piasta, Elżbieta Gumienna-Kontecka, Henryk Kozlowski, Maryline Beyler, Raphael Tripier, Alban Moyeux, Olivier Gager, Valérie Besnard & Milena Salerno
Journal of Biological Inorganic Chemistry, 2023, 28, 777-790, Doi: 10.1007/s00775-023-02028-8
 

Positron emission tomography (PET) imaging of Aβ plaques, is recognized as a tool for the diagnosis of Alzheimer’s disease. As a contribution to the development of new strategies for early diagnosis of the disease, using PET medical imaging technique, a new copper complex, the [Cu(TE1PA-ONO)]⁺ was synthesized in ten steps. The key step of our strategy is the coupling of a monopicolinate-N-alkylated cyclam-based ligand with a moiety capable of recognizing Aβ plaques via a successful and challenging Buchwald-Hartwig coupling reaction. To our knowledge, it is the first time that such a strategy is used to functionalize polyazamacrocyclic derivatives. The thermodynamic stability constants determined in MeOH/H₂O solvent indicate that the attachment of this moiety does not weaken the chelating properties of TE1PA-ONO ligand in relation to parent HTE1PA. The novel complex described here is able to recognize amyloid plaques in brain sections from Alzheimer's disease patients and shows low toxicity to human neuronal cells.