Equilibrium and NMR relaxometric studies on the s-triazine-based heptadentate ligand PTDITA showing high selectivity for Gd3+ ions

A complete potentiometric and NMR relaxometric solution study on the heptadentate 2,2′,2′,2′-[(6-piperidinyl-1,3,5-triazine-2,4- diyl)dihydrazin-2-yl-1-ylidene]tetraacetic acid (PTDITA)ligand has been carried out. This ligand is based on the 1,3,5-triazine ring with two hydrazine-N,Ndiacetate groups in positions 2 and 4 and a piperidine moiety in position 6. The introduction of the triazine ring into the ligand backbone is expected to modify its flexibility and then to affect the stability of the corresponding complexes with transition-metal and lanthanide ions. Thermodynamic stabilities have been determined by pH potentiometry, UV spectrophotometry, and 1H NMR spectroscopy for formation of the complexes with Mg 2+, Ca 2+, Cu 2+, Zn 2+, La 3+, Gd 3+, and Lu 3+ ions. PTDITA shows a good binding affinity for Gd 3+ (logK = 18.49, pGd = 18.6)and an optimal selectivity for Gd 3+ over the endogenous Ca 2+, Zn 2+, and Cu 2+ (Ksel = 6.78 × 10 7), which is 3 orders of magnitude higher that that reported for Gd(DTPA)(K sel = 2.85 × 10 4). This is mainly due to the lower stability of the CuII-and ZnII(PTDITA)complexes compared to the corresponding DTPA complexes, which suggests an important role of the triazine ring on the selectivity for the Gd 3+ ion. The relaxometric properties of Gd(PTDITA)have been investigated in aqueous solution by measuring the 1H relaxivity as a function of the pH, temperature, and magnetic field strength (nuclear magnetic relaxation dispersion profile). Variable-temperature 17O NMR data have provided direct information on the kinetic parameters for exchange of the coordinated water molecules. A simultaneous fit of the data suggests that the high relaxivity value (r1 = 10.2 mM -1 s -1)is a result of the presence of two innersphere water molecules along with the occurrence of relatively slow rotation and electronic relaxation. The water residence lifetime, 298τM = 299 ns, is quite comparable to that of clinically approved magnetic resonance imaging contrast agents. The displacement of the inner-sphere water molecules by bidentate endogeneous anions (citrate, phosphate, and carbonate)has also been evaluated by 1H relaxometry. In general, the binding interaction is markedly weak, and only in the case of citrate, a ca. 35% decrease in relaxivity was observed in the presence of 60 equiv of the anion. Phosphate and carbonate also interact with the paramagnetic ion, likely as monodentate ligands, but formation of the ternary complex is accompanied by a modest increase of r1 due to the contribution of second-sphere water molecules

Solution properties of the Ln(III) complexes of a novel octadentate chelator with rigidified iminodiacetate arms

A novel octadentate ligand derived from the core structure of EGTA (ethyleneglycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid) with two piperidine-cis-dicarboxylic acid moieties spaced by a triethylenedioxy chain (L1) has been synthesised with the aim to assess the effect of the structural rigidity on the thermodynamic and kinetic stabilities of its Ln III complexes. The stability constants of [Ln(L1)]- complexes show a weaker binding affinity for Ln3+ ions of L1 than EGTA. On the other hand, the selectivity of L1 for Ca2+ over Mg 2+ is one of the highest ever reported. The kinetic inertness has been also investigated and faster rates of both acid catalysed and metal assisted decomplexation have been measured for [Gd(L1)]- as compared to [Gd(EGTA)]-. The 1H- and 13C NMR spectra of the diamagnetic La3+, Y3+ and Lu3+ complexes in aqueous media show pronounced stereochemical rigidity and the occurrence of a structural change across the lanthanide series. Finally, a complete 1H and 17O NMR relaxometric study indicates that [Gd(L1)]- possesses a nine-coordinate ground state with one inner coordination sphere water molecule characterized by a fast rate of exchange (298kex = 59 × 106 s-1)