Synthesis of new acyclic chelators H4aPyta and H6aPyha and their complexes with Cu2+, Ga3+, Y3+, and Bi3.

In this article, we present the synthesis and characterization of new acyclic pyridine-containing polyaminocarboxylate ligands H4aPyta and H6aPyha, which differ in structural rigidity and the number of chelating groups. Their abilities to form complexes with Cu2+, Ga3+, Y3+, and Bi3+ cations, as well as the stability of the complexes, were evaluated by potentiometric titration method, radiolabeling with the corresponding radionuclides, in vitro studies, mass spectrometry, and HPLC. The structures of the resulting complexes were determined using NMR spectroscopy and DFT calculations. The results obtained made it possible to evaluate the influence of the structural features of the complexes on their stability. The developed chelators H4aPyta and H6aPyha were proved to be promising for further research in the field of radiopharmaceuticals.

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.

Novel Hybrid Benzoazacrown Ligand as a Chelator for Copper and Lead Cations: What Difference Does Pyridine Make.

A synthetic procedure for the synthesis of azacrown ethers with a combination of pendant arms has been developed and the synthesized ligand, characterized by various techniques, was studied. The prepared benzoazacrown ether with hybrid pendant arms and its complexes with copper and lead cations were studied in terms of biomedical applications. Similarly to a fully acetate analog, the new one binds both cations with close stability constants, despite the decrease in both constants. The calculated geometry of the complexes correlate with the data from X-ray absorption and NMR spectroscopy. Coordination of both cations differs due to the difference between the ionic radii. However, these chelation modes provide effective shielding of cations in both cases, that was shown by the stability of their complexes in the biologically relevant media towards transchelation and transmetallation.

Zinc and copper complexes with azacrown ethers and their comparative stability in vitro and in vivo.

Copper-based radiopharmaceuticals are of high interest these days owing to the decay properties of copper radioisotopes. In contrast, labeled zinc compounds have been less studied for applications in nuclear medicine. In this study, the stability of labeled zinc and copper complexes with two azacrown ether ligands was investigated and compared. Then, the in vitro and in vivo stability of the studied zinc complexes was demonstrated, with the complexes showing promise for biomedical applications. In contrast, analogous copper complexes quickly dissociated in the presence of serum proteins. Furthermore, a simple method for the production of radiochemically pure 65Zn was proposed, and the opportunity for its use as a surrogate radionuclide for research into potential zinc-containing radiopharmaceuticals was demonstrated.

Benzoazacrown compound: a highly effective chelator for therapeutic bismuth radioisotopes.

A new benzoazacrown ligand H4BATA was synthesized and its complexation ability towards bismuth cations was evaluated. Binding of cation occurs at room temperature in a few minutes and formed complex exhibits the same level of inertness as highly stable complex with the well-known H4DOTA in biologically relevant and challenging media under in vivo conditions.