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 H(3)ebpatcn (1-carboxyethyl-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) and H(4)pbpatcn (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)(H(2)O)] complex displays a relaxivity of r(1) = 4.68 mM(-1) s(-1) at 45 MHz and 298 K, whereas r(1) = 4.55 mM(-1) s(-1) was measured for [Gd(Hpbpatcn)(H(2)O)] under the same conditions. The modified scaffold of the ligands with respect to the previously reported H(3)bpatcn (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 H(3)bpatcn ligand with a propionate group (H(3)ebpatcn) or a phosphonate group (H(4)pbpatcn) 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 O(17) NMRD of k(ex) = 34 x 10(6) s(-1) for [Gd(Hpbpatcn)(H(2)O)] falling in the range of optimum values of (30 to 50) x 10(6) s(-1) predicted by the SBM theory. The water exchange rate k(ex)(298) = 86 x 10(6) s(-1) of the complex [Gd(ebpatcn)(H(2)O)] 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)(H(2)O)] 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)(H(2)O)], which is long enough not to affect the relaxivity in macromolecular complexes (transient ZFS amplitude Delta(2) [10(20) rad(2) s(-2)] = 0.39), the O(17) relaxation and the (1)H NMRD indicate a rather fast electron spin relaxation for the phosphonate containing complex (Delta(2) [10(20) rad(2) s(-2)] = 1.3).
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CEA, INAC, Service de Chimie Inorganique et Biologique (UMR-E 3 CEA-UJF, FR 3200 CNRS), Laboratoire de Reconnaissance Ionique et Chimie de Coordination, CEA-Grenoble, 38054 Grenoble, Cedex 09, France.
Giraud
Marion
M
Gateau
Christelle
C
Fries
Pascal H
PH
Helm
Lothar
L
Mazzanti
Marinella
M
D005682:Gadolinium / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007700:Kinetics; D028581:Lanthanoid Series Elements / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010848:Picolinic Acids / Q000737:chemistry*; D011199:Potentiometry; D011522:Protons; D013050:Spectrometry, Fluorescence; D014867:Water / Q000737:chemistry*
C545633:(1-carboxyethyl-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane); C545632:(1-methylphosphonic-acid-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane); D006571:Heterocyclic Compounds; D028581:Lanthanoid Series Elements; D008024:Ligands; D010848:Picolinic Acids; D011522:Protons; D014867:Water; C075712:1,4,7-triazacyclononane; D005682:Gadolinium; C030614:picolinic acid