HHBEDpa: Octadentate Chelate after A. E. Martell.

HHBEDpa, a new octadentate chelator inspired by the 1960s ligand HBED of Arthur E. Martell, has been investigated for a selection of trivalent metal ions useful in diagnostic and therapeutic applications (Sc, Fe, Ga, In, and Lu). Complex formation equilibria were thoroughly investigated using combined potentiometric and UV-vis spectrophotometric titrations which revealed effective chelation and high metal-sequestering capacity, in particular for Fe, log = 36.62, [Fe(HBEDpa)]. X-ray diffraction study of single crystals revealed that the ligand is preorganized and forms hexa-coordinated complexes with Fe and Ga at acidic pH. Density functional theory (DFT) calculations were applied to probe the geometries and energies of all the possible conformers of [M(HBEDpa)] (M = Sc, Fe, Ga, In, and Lu). DFT calculations confirmed the experimental findings, indicating that [Fe(HBEDpa)] is bound tightly in an asymmetric pattern as compared to the symmetrically bound and more open [Ga(HBEDpa)], prone to hydrolysis at higher pH. DFT calculations also showed that a large metal ion such as Lu fully coordinates with HBEDpa, forming a binary octadentate complex in its lowest-energy form. Smaller metal ions form six or seven coordinate complexes with HBEDpa.