Insights into Actinium Complexes with TetraacetatesAcBATA versus AcDOTA: Thermodynamic, Structural, and Labeling Properties

In the current research, we conducted a comparative study of the Ac3+ complex with H4DOTA and H4BATA. The stability constants of the [AcBATA]− and [AcDOTA]− complexes were studied directly by extraction methods. We discovered that the thermodynamic properties of the [AcBATA]− complex are superior to those of [AcDOTA]−. Moreover, the fast kinetics of H4BATA complexation with Ac3+ during the radiolabeling experiment was observed already at room temperature. Ac3+ was placed inside the macrocyclic cavity of the [AcBATA]− complex, preventing the release of the cation. According to DFT studies, two possible conformations were found, where two pendant arms coordinate with the metal cation on one side of the azacrown cavity and two on the other side, or three pendant arms are located on one side and one on the other. Finally, high inertness in vitro and in vivo of [AcBATA]− was discovered, making the H4BATA ligand highly preferable for application as a component of actinium-based radiopharmaceuticals.