Favorable Symmetric Structures of Radiopharmaceutically Important Anionic (2-) Cyclen-Based Ligands

Cyclen-based ligands belong to the most preferred ones in radiopharmacy, where they are mainly applied for transferring radioisotopes through the human body. A crucial criterion is the stability of their metal-ligand complexes, which depends on the stabilization of the free ligand in solution. However, these flexible ligands can have numerous conformations and for a reliable evaluation of the dissociation energy the most stable one(s) in solution must be known. In the present study the low-energy conformational space of four anionic (2-) cyclen-based ligands has been elucidated in aqueous solution by a joint molecular mechanics (MM)/Density Functional Theory (DFT) proce-dure. The results revealed a significant preference of C2 symmetric structures, more-or-less resem-bling to the arrangements in their metal complexes. The computed dissociation energies agree with the experimentally found stability trend for the Pb2+ complexes with ligands containing pico-linate pendant arms. For complexes with mixed donor groups (carboxyl, amide, pyridine) signifi-cant thermodynamic stabilities were predicted.

KOVACS Attila; 

2025-09-19

MULTIDISCIPLINARY DIGITAL PUBLISHING INSTITUTE (MDPI)

JRC141708

https://www.mdpi.com/2073-8994/17/9/1466,    https://publications.jrc.ec.europa.eu/repository/handle/JRC141708,   

10.3390/sym17091466 (online),