Theoretical Study of Metal-Ligand Interactions in Lead Complexes with Radiopharmaceutical Interest.

The Pb and Pb lead radioisotopes are attracting growing interest as they can aid in the development of personalized, targeted radionuclide treatment for advanced and currently untreatable cancers. In the present study, the bonding interactions of Pb with twelve macrocyclic ligands, having an octa and nona coordination, were assessed using Density Functional Theory (DFT) calculations. The molecular structures in an aqueous solution were computed utilizing the polarized continuum model. The preference for the twisted square antiprismatic (TSAP) structure was confirmed for ten out of the eleven cyclen-based complexes. The characteristics of the bonding were assessed using a Natural Energy Decomposition Analysis (NEDA). The analysis revealed a strong electrostatic character of the bonding in the complexes, with minor variations in electrical terms. The charge transfer (CT) had a comparable energetic contribution only in the case of neutral ligands, while in general, it showed notable variations regarding the various donor groups. Our data confirmed the general superiority of the carboxylate O and aromatic N donors. The combination of the selected efficient pendant arms pointed out the superiority of the acetate pendant arms and the lack of significant cooperation between the different pendant arms in the probed ligands. Altogether, the combination led only to a marginal enhancement in the total CTs in the complexes.