Infoscience

Journal article

Gadolinium(III) complexes of 1,4,7-triazacyclononane based picolinate ligands: simultaneous optimization of water exchange kinetics and electronic relaxation

The two new tripodal picolinate H3ebpatcn (1-carboxyethyl-4,7-bis((6-carboxypyridin-2-yl)-methyl)-1,4,7-triazacyclononane) and H4pbpatcn (1-methylphosphonic-acid-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) ligands based on the 1,4,7-triazacyclononane anchor were prepared and their lanthanide complexes were characterized by NMR, fluorescence and potentiometric studies. The [Gd(ebpatcn)(H2O)] complex displays a relaxivity of r1 = 4.68 mM-1 s-1 at 45 MHz and 298 K, whereas r1 = 4.55 mM-1 s-1 was measured for [Gd(Hpbpatcn)(H2O)] under the same conditions. The modified scaffold of the ligands with respect to the previously reported H3bpatcn (1-(carboxymethyl)-4,7-bis[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane) leads to an optimization of the properties of these gadolinium complexes. The replacement of an acetate binding group of the H3bpatcn ligand with a propionate group (H3ebpatcn) or a phosphonate group (H4pbpatcn) leads to a faster exchange rate of the coordinated water molecule in both mono-aquo gadolinium complexes. The resulting water exchange rate is optimized for the future design of high relaxivity macromolecular gadolinium based contrast agents with a value measured by O17 NMRD of kex = 34 ¥ 106 s-1 for [Gd(Hpbpatcn)(H2O)] falling in the range of optimum values of (30 to 50) ¥ 106 s-1 predicted by the SBM theory. The water exchange rate kex 298 = 86 ¥ 106 s-1 of the complex [Gd(ebpatcn)(H2O)] is the fastest reported in the literature for a neutral complex with only one inner-sphere water molecule. The relatively high stability of these modified gadolinium complexes (pGd = 14.1 for Gd(pbpatcn) and 13.1 for Gd(ebpatcn)) is similar to that of the [Gd(bpatcn)(H2O)] complex (pGd = 13.6). The high luminescence efficiency is also retained for the terbium complex. However, whereas the longitudinal electronic spin relaxation time keeps a value for [Gd(ebpatcn)(H2O)], which is long enough not to affect the relaxivity in macromolecular complexes (transient ZFS amplitude D2 [1020 rad2 s-2] = 0.39), the O17 relaxation and the 1H NMRD indicate a rather fast electron spin relaxation for the phosphonate containing complex (D2 [1020 rad2 s-2]= 1.3).

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