Synthesis, thermodynamics and relaxivity studies for the complexation of Gd 3+, Ca 2+, Cu 2+ and Zn 2+ by N,N″-bis(amide) derivatives of diethylenetriaminepentaacetic acid

Abstract

Three bis(amide) derivatives of Hsdtpa [(carboxymethyl)iminobis(ethylenenitrilo)tetraacetic acid], H 3L 1 = bis(adamantanamide), H 3L 2 = bis(2-methoxybenzylamide), and H 3L 3 = bis(2-methoxyphenethylamide) were synthesized. Their protonation constants were determined by potentiometric titration in 0.10 mol dm −3 KCl and by NMR pH titration at 25.0±0.1°C. Stability and selectivity constants are measured to evaluate the possibility of using the corresponding gadolinium(III) complexes for magnetic resonance imaging contrast agents. Low stability or selectivity constants indicate higher possibility for releasing free Gd 3+ ion and free ligand as well from gadolinium(III) complexes. The formations of gadolinium(III), copper(II), zinc(II), and calcium(II) complexes were investigated quantitatively by the potentiometry. The stability constant for gadolinium(III) complex is larger than those for Ca(II), Zn(II), and Cu(II) complexes for these three octadentate ligands. The selectivity constants and modified selectivity constants of the amides for Gd 3+ over endogenously available metal ions were calculated. Effectiveness of all three ligands in binding divalent and trivalent metal ions in biological media is assessed by comparing pM values at physiological pH 7.4. Spinlattice relaxivity R 1 for Gd(III) complexes was also determined. The observed relaxivity were found to decrease with increasing pH in the acid range below pH 3 and relaxivity values were become invariant with respect to pH changes over the range of 3–10.