T. N. Parac-Vogt, L. Vander Elst et al.
FULL PAPER
Ph), 3.50 (s, 2 H, CH2–COOH), 3.57 (s, 4 H, 2ϫCH2–COOH),
3.69 (s, 4 H, 2ϫCH2–CO–NH), 6.60–6.92 (AAЈBBЈ, 8 H, 2ϫPh)
ppm. 13C NMR (D2O): δ = 173.2, 172.1, 169.4, 154.4, 131.2, 130.6,
diameter tubes with a Bruker AMX-300 spectrometer. The tem-
perature was regulated by air or nitrogen flow controlled by a BVT
2000 unit. No field frequency lock was used. 17O transverse relax-
ation times of distilled water (pH = 6.5–7) were measured using a
CPMG sequence and a subsequent two-parameter fit of the data
points. The 90° and 180° pulse lengths were 25 and 50 µs, respec-
tively. 17O T2 values of water in complex solution were obtained
from line-width measurement. Concentrations of the samples were
115.7, 57.2, 54.7, 51.9, 51.4, 51.3, 40.8, 33.9 ppm. IR: ν = 1635
˜
(CO amide I), 1510 (CO amide II) cm–1. ESI-MS(+) (C30H41N5O10:
Mcalcd. = 631): m/z = 632 [M + H]+, 654 [M + Na]+.
DTPA-(HTA)2: Yield: 79% (630 mg). C30H38N5O12Na3(H2O)
(747.64): calcd. C 48.18, H 5.39, N 9.37; found C 48.63, H 5.60, N
less than 25 m {[Gd-DTPA-(TA)2]
= 20.1 m, [Gd-DTPA-
1
8.97. H NMR (D2O): δ = 2.61 (t, 4 H, 2ϫN–CH2), 2.95 (t, 4 H,
(HTA)2] = 20.0 m and [Gd-DTPA-(PAE)2] = 20.3 m}. The data
2ϫN–CH2), 3.10 (m, 4 H, 2ϫCH2–NH–CO), 3.37 (m, 4 H,
2ϫCH2–Ph), 3.50 (s, 2 H, CH2–COOH), 3.56 (s, 4 H, 2ϫCH2–
COOH), 3.68 (s, 4 H, 2ϫCH2–CO–NH), 6.56–6.82 (m, 6 H, Ph)
ppm. 13C NMR (D2O): δ = 179.6, 174.4, 171.4, 152.3, 149.5, 128.9,
117.5, 116.7, 115.7, 59.4, 57.8, 52.1, 48.1, 46.5, 40.9, 35.5 ppm. IR:
were treated as described elsewhere.[26–28,34]
Transmetallation Kinetics: The technique is based on the measure-
ment of the evolution of the water proton paramagnetic longitudi-
nal relaxation rate (R1p) of a buffered solution ([KH2PO4] =
0.026 molL–1, [Na2HPO4] = 0.041 molL–1, pH = 7) containing the
gadolinium(III) complex (2.5 m) and ZnCl2 (2.5 m).[37] The
measurements were performed with a spin analyzer Minispec PC-
120 (Bruker, Karlsruhe, Germany) at 20 MHz and 310 K. The sam-
ples (0.3 mL) were contained in 7-mm o.d. PyrexTM tubes and kept
at 310 K in a dry block between measurements (up to 4 d).
ν = 1740 (CO acid), 1647 (CO amide I), 1521 (CO amide II) cm–1.
˜
ESI-MS(+) (C30H41N5O12: Mcalcd. = 663): m/z = 664 [M + H]+,
686 [M + Na]+.
Synthesis of the Gadolinium(III) Complexes: All complexes were
synthesized according to the following general procedure. A solu-
tion of hydrated GdCl3 salt (1 mmol) in H2O (1 mL) was added to
the ligand (1 mmol) dissolved in pyridine (30 mL), and the mixture
was heated at 70 °C for 3 h. Because of the basicity of pyridine, the
addition of extra base for the deprotonation of the ligand was not
necessary.The solvents were evaporated under reduced pressure,
and the crude product was then refluxed in ethanol for 1 h. After
cooling to room temp., the complex was filtered off and dried in
vacuo. The absence of free gadolinium(III) ions was checked with
xylenol orange indicator.[36]
Acknowledgments
T. N. P.-V., K. K. and K. B. thank the K. U. Leuven for financial
support (VIS/01/006.01/20002-06/2004 and GOA 03/03). T. N. P.-V.
acknowledges the F. W. O.-Flanders (Belgium) for a Postdoctoral
Fellowship. C,H,N microanalyses were performed by Mrs. Petra
Bloemen. This work was supported by the ARC Program (con-
tracts number 95/00-194 and 00-05/258) of the French Community
of Belgium. L. V. E., S. L., C. T. and R. N. M. kindly acknowledge
the support and sponsorship concerted by COST Action D18
“Lanthanide Chemistry for Diagnosis and Therapy”, and the
EMIL NoE of the FP6 of the EC.
Analytical Data for the Gadolinium(III) Complexes
Gd-DTPA-(PAE) : Yield: 35% (315 mg). IR: ν = 1733 (CO ester),
˜
2
1622 (CO amide I), 1589 (COO– asym. stretch), 1388 (COO– sym.
stretch) cm–1. ESI-MS(+) (C36H46GdN5O12: Mcalcd. = 897): m/z =
898 [M + H]+.
Gd-DTPA-(TA) : Yield: 53% (417 mg). IR: ν = 1627 (CO amide I),
˜
2
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1595 (COO– asym. stretch), 1399 (COO– sym. stretch) cm–1. ESI-
MS(+) (C30H38GdN5O10: Mcalcd. = 785): m/z = 786 [M + H]+, 809
[M + Na]+.
Gd-DTPA-(HTA) : Yield: 95% (770 mg). IR: ν = 2923, 2852 (CH
˜
2
alkyl), 1628 (CO amide I), 1602 (COO– asym. stretch), 1408 (COO–
sym. stretch) cm–1. ESI-MS(+) (C30H38GdN5O12: Mcalcd. = 817):
m/z = 840 [M + Na]+.
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Sodium and Potassium Ion Content Measurements: The potassium
and sodium ion content of the solutions was checked by flame pho-
tometry (IL 943, Instrumentation Laboratories, Massachusetts,
USA). Na+ content (mmol per mol of the complex): Gd-DTPA-
(PAE)2: 0.7; Gd-DTPA-(TA)2: 0.0; Gd-DTPA-(HTA)2: 0.0. K+
content: no K+ could be detected in any of the complexes.
Proton T1 Measurements: Proton nuclear magnetic relaxation dis-
persion (NMRD) profiles were recorded at 310 K between 0.24 mT
and 0.24 T with a Field Cycling Relaxometer (Stelar Spinmaster
FFC-2000, Stelar S. R. L., Mede, Italy) on solutions (0.6 mL) con-
tained in 10-mm o.d. tubes. Proton relaxation rates were also mea-
sured at 0.47, 1.5 and 7.05 T on Minispec PC-120, mq-60 and
AMX-300 spectrometers (Bruker, Karlsruhe, Germany), respec-
1
tively. H NMRD data were fitted according to the theoretical in-
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and to the outer-sphere contribution described by Freed.[32] Calcu-
lations were performed with a previously described software.[26]
17O NMR Measurements: 17O NMR measurements of solutions
were performed on samples (2 mL) contained in 10-mm external
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