Synthesis of two N '-2-pyridylmethyl and N '-2-hydroxypropyl derivatives of diethylenetriaminepentaacetic acid and the stabilities of their complexeswith Ln(3+), Ca2+, CU2+ and Zn2+

Two N'-2-pyridylmethyl and N'-2-hydroxypropyl derivatives of H(5)dtpa (diet hylene-N',N',N''-triamine-N,N,N',N"-pentaacetic acid), H4L1 = N'-(2-pyridyl methyl)-N,N,N"N"-diethylenetriaminetetraacetic acid and H4L2 = N'-(2-hydrox ypropyl)N,N,N"N"diethylenetriaminetetraacetic acid were synthesized. Their protonation constants were determined by potentiometric titration in 0.10 m ol dm(-3) Me4NNO3 and by NMR pH titration at 25.0 +/- 0.1 degreesC. Stabili ty and selectivity constants were determined to evaluate the possibility of using the corresponding gadolinium(III) complexes as magnetic resonance im aging contrast agents. Low stability or selectivity constants indicate high er possibility for releasing free Gd3+ ion and free ligand as well from gad olinium(III) complexes. The formations of lanthanide(III), copper(II), zinc (II) and calcium(II) complexes were investigated quantitatively by potentio metry. The stability constants of lanthanides(III) complexes with H4L1 and H4L2 increase from La(III) to Nd(III) and then plateau at Sm(III) and Gd(II I), before increasing again to Yb(III). The stability constant of the gadol inium(III) complex is larger than those of Ca(II), Zn(II) and Cu(II) comple xes for these two ligands. The selectivity constants and modified selectivi ty constants of H4L1 and H4L2 for Gd3+ over endogenously available metal io ns were calculated. Effectiveness of these two ligands in binding divalent and trivalent metal ions in biological media is assessed by comparing pM va lues at physiological pH 7.4. Spin-lattice relaxivity R-1 for the Gd(III) c omplex was also determined. The observed relaxivity values of [GdL1](-) and [GdL2](-) became invariant with respect to pH changes over the range of 2- 10 and 3-10, respectively. O-17 NMR shifts showed that the [DyL1](-) and [D yL2](-) complexes have 1.50 and 2.51 inner-sphere water molecules, respecti vely. Water proton spin-lattice relaxation rates for the [GdL1](-) and [GdL 2](-) complexes were also consistent with inner-sphere gadolinium(III) coor dination. (C) 2000 Elsevier Science Ltd. All rights reserved.