Synthesis of two N′ -2 -pyridylmethyl and N′ -2-hydroxypropyl derivatives of diethylenetriaminepentaacetic acid and the stabilities of their complexes with Ln 3+, Ca 2+, Cu 2+ and Zn 2+

Abstract

Two N′-2-pyridylmethyl and N′-2-hydroxypropyl derivatives of H 5dtpa (diethylene- N,N′ ,N′′-triamine- N, N, N′, N′′, N′′-pentaacetic acid), H 4L 1= N′-(2-pyridylmethyl)- N, N, N′′ N′′-diethylenetriaminetetraacetic acid and H 4L 2= N′-(2-hydroxypropyl)- N, N, N′′ N′′diethylenetriaminetetraacetic acid were synthesized. Their protonation constants were determined by potentiometric titration in 0.10 mol dm −3 Me 4NNO 3 and by NMR pH titration at 25.0±0.1°C. Stability and selectivity constants were determined to evaluate the possibility of using the corresponding gadolinium(III) complexes as 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 lanthanide(III), copper(II), zinc(II) and calcium(II) complexes were investigated quantitatively by potentiometry. The stability constants of lanthanides(III) complexes with H 4L 1 and H 4L 2 increase from La(III) to Nd(III) and then plateau at Sm(III) and Gd(III), before increasing again to Yb(III). The stability constant of the gadolinium(III) complex is larger than those of Ca(II), Zn(II) and Cu(II) complexes for these two ligands. The selectivity constants and modified selectivity constants of H 4L 1 and H 4L 2 for Gd 3+ over endogenously available metal ions were calculated. Effectiveness of these two ligands in binding divalent and trivalent metal ions in biological media is assessed by comparing p M values at physiological pH 7.4. Spin-lattice relaxivity R 1 for the Gd(III) complex was also determined. The observed relaxivity values of [GdL 1] − and [GdL 2] − became invariant with respect to pH changes over the range of 2–10 and 3–10, respectively. 17O NMR shifts showed that the [DyL 1] − and [DyL 2] − complexes have 1.50 and 2.51 inner-sphere water molecules, respectively. Water proton spin-lattice relaxation rates for the [GdL 1] − and [GdL 2] − complexes were also consistent with inner-sphere gadolinium(III) coordination.