A detailed study of the structures, thermodynamic stabilities and kinetics of the dissociation of Ga3+, In3+ and Cu2+ complexes formed with the heptadentate ligand AAZTA is reported. The stability constants (log KML) of the AAZTA complexes of Ga3+, In3+ and Cu2+ are 22.18, 29.58 and 22.27, respectively, which suggests that the seven‐membered‐ring skeleton is suited to the accommodation of these metal ions. The solid‐state structure of [Cu(H2AAZTA)]·H2O shows a distorted octahedral coordination. The equatorial coordination sites of Cu2+ are occupied by one of the ring N atoms, a water O atom, one of the carboxylate O atoms and the N atom of the iminodiacetate moiety. The other ring N atom and the carboxylate O atom of the iminodiacetate moiety coordinate to the Cu2+ in the axial positions. In the pH range 4.5–8.5, Ga3+ is present in the form of the highly stable [Ga(AAZTA)OH]2– (log βGaLH–1 = 17.69) The exchange reactions of [Ga(AAZTA)OH]2– with Cu2+ and transferrin are very slow and mainly occur through the spontaneous dissociation of the complex close to physiological conditions. The half‐life for the dissociation of [Ga(AAZTA)OH]2– is t1/2 = 23 h at pH = 7.5 and 25 °C in 0.025 M NaHCO3 and 0.15 M NaCl. The high conditional stability, fast formation and sufficiently slow dissociation of [Ga(AAZTA)OH]2– represent promising properties for the complexation and diagnostic applications of radioactive Ga isotopes.

The Gd(3+)-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) ions are similar, whereas the logKLnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log KMHL) of the sulphonamide nitrogen in the Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln(3+) ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes are formed via triprotonated *Ln(H3DO3A-SA) intermediates which rearrange to the final complex in an OH(-)-assisted deprotonation process. The transmetalation reaction of Gd(HDO3A-SA) with Cu(2+) is very slow (t1/2 = 5.6 × 10(3) h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The (1)H and (13)C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6%, respectively. Line shape analysis of the (13)C NMR spectra of La-, Y- , and Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The coordination sites of Cu(2+) are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.

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Three triaza macrocyclic ligands, HNOTP (1,4,7-triazacyclononane-N,N',N″-trimethylene phosphonic acid), HNO2AP (1,4,7-triazacyclononane-N-methylenephosphonic acid-N',N″-dimethylenecarboxylic acid), and HNOA2P (1,4,7-triazacyclononane-N,N'-bis(methylenephosphonic acid)-N″-methylene carboxylic acid), and their gallium(III) chelates were studied in view of their potential interest as scintigraphic and PET (Positron Emission Tomography) imaging agents. A H,P and Ga multinuclear NMR study gave an insight on the structure, internal dynamics and stability of the chelates in aqueous solution. In particular, the analysis ofGa NMR spectra gave information on the symmetry of the Ga coordination sphere and the stability of the chelates towards hydrolysis. The P NMR spectra afforded information on the protonation of the non-coordinated oxygen atoms from the pendant phosphonate groups and on the number of species in solution. TheH NMR spectra allowed the analysis of the structure and the number of species in solution. P andH NMR titrations combined with potentiometry afforded the measurement of the protonation constants (log K) and the microscopic protonation scheme of the triaza macrocyclic ligands. The remarkably high thermodynamic stability constant (log K=34.44 (0.04) and stepwise protonation constants of Ga(NOA2P) were determined by potentiometry and Ga andP NMR titrations. Biodistribution and gamma imaging studies have been performed on Wistar rats using the radiolabeled Ga(NO2AP) and Ga(NOA2P)chelates, having both demonstrated to have renal excretion. The correlation of the molecular properties of the chelates with their pharmacokinetic properties has been analysed.