H4HBEDpa: Octadentate Chelate after A. E. Martell.

H4HBEDpa, 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 (Sc3+, Fe3+, Ga3+, In3+, and Lu3+). 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 Fe3+, log KFeL = 36.62, [Fe(HBEDpa)]-. X-ray diffraction study of single crystals revealed that the ligand is preorganized and forms hexa-coordinated complexes with Fe3+ and Ga3+ 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 = Sc3+, Fe3+, Ga3+, In3+, and Lu3+). 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 Lu3+ fully coordinates with HBEDpa4-, forming a binary octadentate complex in its lowest-energy form. Smaller metal ions form six or seven coordinate complexes with HBEDpa4-.