Investigation of Ln³⁺ complexation by a DOTA derivative substituted by an imidazothiadiazole: synthesis, solution...

We investigated the coordination properties of original macrocyclic Ln³⁺ complexes comprising an imidazothiadiazole heterocycle. The thermodynamic stability of the Gd³⁺ complex was determined by a combination of potentiometric and photophysical measurements. The kinetic inertness was assessed in highly acidic media. The solution structure of the Ln³⁺ complex was unambiguously determined by a set of photophysical measurements and ¹H, ¹³C, ⁸⁹Y NMR data in combination with DFT calculations, which proved coordination of the heterocycle to Ln³⁺. The ability of the imidazothiadiazole moiety to sensitize Tb³⁺ luminescence was investigated. Finally, the relaxation properties were investigated by recording ¹H nuclear magnetic relaxation dispersion (NMRD) profiles and ¹⁷O measurements. The water exchange rate is similar to that of GdDOTA as the less negative charge of the ligand is compensated for by the presence of a bulky heterocycle. Relaxivity is constant over a large range of pH values, demonstrating the favorable properties of the complex for imaging purposes.