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

Area of Science:

• Radiochemistry
• Computational Chemistry
• Oncology

Background:

• Lead radioisotopes (203Pb and 212Pb) are being explored for targeted cancer therapy.
• Personalized radionuclide treatment offers a promising avenue for advanced, untreatable cancers.

Purpose of the Study:

• To investigate the bonding interactions of Pb2+ with various macrocyclic ligands.
• To assess the structural preferences and electronic characteristics of these complexes for potential therapeutic applications.

Main Methods:

• Density Functional Theory (DFT) calculations were employed to model molecular structures.
• The polarized continuum model was used to simulate aqueous solutions.
• Natural Energy Decomposition Analysis (NEDA) was performed to characterize bonding.

Main Results:

• The twisted square antiprismatic (TSAP) structure was preferred for most cyclen-based complexes.
• Bonding interactions were predominantly electrostatic, with variations in charge transfer (CT) based on ligand type.
• Carboxylate O and aromatic N donors demonstrated superior performance, with acetate pendant arms showing particular efficacy.

Conclusions:

• DFT calculations provide insights into Pb2+ complexation for radionuclide therapy.
• Ligand design, particularly the use of carboxylate O and aromatic N donors, is crucial for optimizing binding.
• While acetate pendant arms are effective, significant cooperative effects between different pendant arms were not observed.