Lanthanide (Eu3 +, Tb3 +, Gd3 +) hybrid system with functionalized diethylenetriamine pentaacetic acid: Coordination bonding assembly, luminescence and MRI contrast agent property

Article abstract of DOI:10.1016/j.inoche.2012.01.005

A bridge molecule (abbreviated as DTPA-AM, DTPA-bi(4′-acrylamide)) orignated from the diethylenetriamine pentaacetic acid (DTPA) derivative (DTPAA, diethylene-triaminepentaacetic anhydride) after the modification by acrylamide though its amino group group. Subsequently, the lanthanide (Eu^{3 +}, Tb^{3 +}, Gd^{3 +}) polymer hybrid material systems have been assembled with coordination bonds, which present luminescence for Eu ^{3 +}, Tb^{3 +} system and MRI (magnetic resonance imaging) contrast agent property for Gd^{3 +} system, respectively.

Full text of DOI:10.1016/j.inoche.2012.01.005

Inorganic Chemistry Communications 18 (2012) 43–46
Contents lists available at SciVerse ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
3
+
3+
3+
Lanthanide (Eu , Tb , Gd ) hybrid system with functionalized
diethylenetriamine pentaacetic acid: coordination bonding assembly, luminescence
and MRI contrast agent property
Bing Yan ⁎, Chao Sheng, Lei Guo
Department of Chemistry, Tongji University, Shanghai 200092, P. R. China
a r t i c l e i n f o
a b s t r a c t
Article history:
A bridge molecule (abbreviated as DTPA-AM, DTPA-bi(4′-acrylamide)) orignated from the diethylenetria-
Received 25 November 2011
Accepted 5 January 2012
Available online 12 January 2012
mine pentaacetic acid (DTPA) derivative (DTPAA, diethylene-triaminepentaacetic anhydride) after the mod-
3+
3+
3+
ification by acrylamide though its amino group group. Subsequently, the lanthanide (Eu , Tb , Gd
)
polymer hybrid material systems have been assembled with coordination bonds, which present lumines-
3
+
3+
3+
cence for Eu , Tb
tem, respectively.
system and MRI (magnetic resonance imaging) contrast agent property for Gd
sys-
Keywords:
Lanthanide hybrid system
Coordination bond
Luminescence
©
2012 Elsevier B.V. All rights reserved.
MRI contrast agent property
Lanthanide complexes with organic ligands belong to the impor-
tant versatile active species in all kinds of practical functional mate-
rials and their applied fields. Some of them can present the sharp
in the organic or inorganic polymeric host. Lanthanide ions or their
complex are introduced into polymer host for a long time [14]. We
have summarized the three methods to construct the lanthanide
polymeric hybrids [15-18]. The first is most extensive, in which poly-
mer unit behaves as the ligands to coordinate to central lanthanide
ions [15,16]. The second is the covalently bonded polymer chain to
other functional unit to assemble lanthanide polymer and polymer
chain does not coordinate to lanthanide ions directly [17]. The third
is the copolymerization reaction between monomer of polymer and
the other functional component [18]. These polymer hybrids can
show the controlled structure and active functionalization, which is
favorable to the property and application for active lanthanide com-
plex. For example, the introduction of polymer unit in photoactive
lanthanide hybrid system can enhance the luminescent lifetime and
quantum efficiency [19]. Besides, the Gd3 complex MRI agents and
polymer chain are composed to improve the stability and change
the hydrophobicity in biological systems, which can benefit the relax-
ation efficiency (much more paramagnetic ion) and rotation time
(much higher molecular weight) [20].
3
+
3+
3+
3+
3+
line emission in visible (Eu , Tb , Sm , Dy , Pr ) or near in-
frared region (Nd , Er3+, Tm3+, Yb ) [1-3], which can be used
widely in many fields for their unique optical properties such as elec-
troluminescence device, fluoroimmunoassays and polymer optical fi-
3
+
3+
3
+
3+
bers [4-6]. Besides, the all Ln
Lu , have unpaired electrons and are thus paramagnetic. Especially
ions, with the exception of La
and
3
+
3
+
Gd
complexes have been spectacularly successful as extracellular
or blood pool T1 agents but their relative insensitivity to changes in
environment coupled with the fact that they are never completely si-
lent limits their applicability in the design of responsive MRI agents
[7,8]. The molar absorption coefficients of organic ligands are many
+
times as large as that of trivalent lanthanide ion, intramolecular trans-
3
+
fer process within the complex systems from ligands to Ln
ions is
much more effective than direct excitation of Ln3 [9,10], which can-
not only protect metal ions from vibrational coupling but also can in-
crease the light absorption through the “antenna effect” [11]. On the
+
3
+
other hand, Gd
complexes with amino polycarboxylic acids (such
In this text, diethylenetriamine pentaacetic acid (DTPA) is a com-
mon chelated ligand for Gd3 MRI complex, which possess more co-
ordination of N atom and O atom than ethylenediaminetetraacetic
acid (EDTA), which is firstly modified to be the derivative DTPAA
(diethylene-triaminepentaacetic anhydride) [21]. Yields 84%. Anal.
+
as DOTA (tetraazacyclododecanetetraacetic acid), DTPA (diethylene-
triaminepentaacetic acid), etc.) have been extensively used as MRI
agents (magnetic resonance imaging) [12,13].
All these lanthanide complex species are limited to be extensive
application for their poor thermal and optical stability, which can be
improved to fabricate these lanthanide functional complex species
Calcd. (%) for C14
C 46.80, H 5.07, N 12.02. H NMR (DMSO-D6, 400 MHz): δ 10.51
CO); 3.00–2.90 (t, 8H, NCH CH2-
19 3 8
H N O (357.32): C 47.06, H 5.36, N 11.76; Found:
1
(
−COOH); 3.34, 3.45 (m, 10H, NCH
2
2
N) (see Fig. 1a). Then the DTPAA is modified with AM (acrylamide) to
achieve the derivative DTPA-AM (DTPA-bi(4′-acrylamide)). Yields
⁎
Corresponding author. Tel.: +86 21 65984663; fax: +86 21 65982287.
E-mail address: byan@tongji.edu.cn (B. Yan).
29 5
83%. Anal. Calcd. (%) for C20H N O10 (499.47): C 48.09, H 5.85, N
1387-7003/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2012.01.005

44
B. Yan et al. / Inorganic Chemistry Communications 18 (2012) 43–46
O
O
O
O
O
O
a HOOC
HOOC
(CH CO) O Py
COOH
COOH
3
2
N
N
N
N
N
N
o
COOH
55-60 C
COOH
b O
O
O
O
O
HOOC
CONH
COOH
DMF
N
N
N
+
2
H
2
C
CH C NH2
O
O
N
N
N
CONH
O
C
5-60 o
COOH
5
C
COOH
C
O
HC CH
2
H
2
C
CH
c
-OOC
CONH
COO-
-OOC
COO-
N
N
COO-
N
Ln(NO3)3 6H O
2
N
N
COO-
N
CONH
O
C
CONH
CONH
O
C
o
H O / 25 C
2
C
O
C
O
Ln3+
HC CH2
H C CH
2
HC CH2
H C CH
2
O
d
e
-OOC
CONH
-OOC
COO-
COO-
N
N
COO-
N
CH2 = CH-C-NH2
N
N
COO-
N
CONH
CONH
C
CONH
O
C
o
BPO / 60 C
C
O
Ln3+
O
C
O
Ln3+
HC CH2
H C CH
HC
CH2
H C CH
2
2
H
H
O
Ln3+
H
O
C
O
C
H
N
N
N
N
O
N
O
HC CH
H C CH
2
2
CO
O
CO
O
OC
O
Fig. 1. Reaction scheme of the formation of DTPAA (a), DTPA-AM (b), Ln-DTPA-AM complex (c), Ln-DTPA-PAM hybrids (d) and possible coordination mode of lanthanide ions.
1
4
4.02; Found: C 47.88, H 5.63, N 14.18. 1H NMR (DMSO-D6,
group [22]. Fig. S2 presents the FT-IR spectra of DTPA-AM and the cor-
responding lanthanide complexes. The disappearance of the anhy-
00 MHz): δ 10.50 (−COOH); 10.15 (s, 2H, NH); 8. 92 ( s, 2H,
−
1
CONH) 3.35, 3.47 (m, 10H, NCH
2
CO); 3.00–2.90 (t, 8H, NCH
C NMR (DMSO-D6, 100 MHz): δ 34.6, 35.2, 38.5
2
CH
2
N),
dride group at 1755–1745 cm
and the new bands appear at
indicating the modification of
1
3
−1
−1
2
(
.05 (4H, s).
CHCH ), 169.5 (COOH), 170.7, 171.5, 172.5 (CONH) (Fig. 1b). The
lanthanide hybrids with DTPA-AM are synthesized by homogeneous
precipitation. Yields 85%. Anal. Calcd. (%) for 11Eu
666.43): C 36.05, H 4.24, N 10.51, Eu 22.80; Found: C 36.20, H 4.03,
N 10.33, Eu 22.98. C20 11Gd (671.71): C 35.76, H 4.20, N
0.43, Gd 23.41; Found: C 35.90, H 4.00, N 10.27, Gd 23.18.
11Tb (673.39): C 35.67, H 4.19, N 10.40, Tb 23.60; Found:
1730 cm
and 1701 cm
,
2
―O―O―O― group to C O one. The other two characteristic absorp-
−
1
−1
tion bands at 3022 cm
to νN-H and 1200 cm
to νC-N still can be
can be checked,
−
1
C
20
H
28
5
N O
observed. Besides, δN-H absorption at 1634 cm
(
which is attributed to the in-plane absorption of amide group. The
FT-IR spectra of lanthanide complex hybrids with DTPA functiona-
lized bridge molecule and PAM unit all show the similar feature.
Here Gd-DTPA-PAM is set up as an example. The absorption band of
28 5
H N O
1
C
20 28 5
H N O
−
1
C 35.50, H 3.97, N 10.24, Tb 23.89 (Fig. 1c). The final lanthanide poly-
mer hybrids are prepared with the polymerization of AM, whose con-
tents of Ln and N elements are determined for they are the content in
the polymerization reaction: Eu 5.74%, N 2.65 &; Gd 6.11%, N 2.70%;
Tb 6.20%, N 2. 73%. From the data, it can be estimated that the
molar ratio of Ln to N is close to 5 (Fig. 1d). All the elemental data
take agreement with the estimation data from the aim products.
Fig. 1 presents the scheme for the synthesis of the precursors and
the final lanthanide hybrid system. The whole DTPA-PAM can provide
five coordinated oxygen atoms and three coordination nitrogen
atoms to form the eight coordination position around Ln3 . The five
N―H group at 3010 cm
of hybrids is similar to that of free DTPA-
−
1
AM at 3000 cm . While the in-plane absorption band of amide II
−
1
−1
at 1640 cm
has shifted to 1585 cm , suggesting that the forma-
tion of the second amide of hybrid system from the first amide of
−
1
free ligand. The absorption bands at 1730 cm
of νC = O and
−
1
1200 cm
of νC-N have shifted to the lower wave numbers of 1691
and 1090 cm , respectively. This reveals that the coordination inter-
action of O and N atom to Ln ions has taken place [23].
−
1
Fig. S3 shows the ultra-violet diffuse reflectance spectra of the lan-
thanide hybrids with DPTAA and PAM chain. All the complex hybrids
present the strong wide absorption bands in the region of
200–300 nm, which is ascribed as the n→π* transition of hetero
atoms (carbonyl O, amino N) belonging to the ligands. Figs. 2 and 3
show the excitation and emission spectra of europium and terbium
hybrids with DTPAA and PAM unit. In monitoring with the emission
wavelength of 614 and 544 nm, there exists a wide absorption excita-
tion band at the region of 250–450 nm with the maximum excitation
peak of 369 nm for Eu hybrids and 371 nm for terbium hybrids, re-
spectively. Besides, no apparent sharp excitation bands can be
+
O atoms are from three carboxylates and two amide groups. Fig. 1e
shows the predicted coordination environment surrounding Ln3
+
.
Fig. S1 compares the FT-IR spectra of DTPA and DTPAA. Among the
−
1
absorption bands in 1755–1745 cm
can be ascribed as the charac-
−
1
teristic band of anhydride. The absorption at 1634 cm
and
is originated from the vibration bands C O and N―H
groups, respectively. In addition, there exists an absorption band at
−
1
2
993 cm
−
1
1
219 cm , corresponding to the vibration absorption of C―N

B. Yan et al. / Inorganic Chemistry Communications 18 (2012) 43–46
45
5D
7F
2
0.10
λem = 614 nm
0
Gd-DTPA-PAM
Linear Fit of Gd-DTPA-PAM
λex = 369 nm
0
0
0
0
0
.08
.06
.04
.02
.00
5D
7F
0,1
0
5D
7F
3,4
0
300
400
500
600
700
Wavelength/nm
0
.000 0.002 0.004 0.006 0.008 0.010 0.012 0.014
Concentration (mM Gd)
Fig. 2. Excitation and emission spectra of Eu-DTPA-PAM hybrids.
1
Fig. 4. MRI relaxation rate (1/T ) for Gd-DTPA-PAM hybrids in water.
checked in the long wavelength region, suggesting the self-excitation
3
+
3+
of f–f transition of Eu
or Tb
is too weak compared to the excita-
sequence on a Bruker Avance III 400 NMR spectrometer at 9.4 T. In
each case, six samples are prepared separately with concentrations
varying from 0 to 0.0125 mM Gd3 in water. To investigate the po-
tential of the obtained Gd-containing materials as MRI contrast
agents, proton relaxivity measurements are performed. The ability
of proton relaxation enhancement of a paramagnetic compound is
tion of organic unit in the whole hybrid systems. Therefore, the wide
excitation band originated from the organically modified unit DTPAA-
PAM, which is favorable for the energy transfer and luminescence of
ion. As a result, the emission lines of Eu-DTPAA-PAM hybrids
are assigned to the transitions from the
+
3
+
Eu
5
7
0 J
D → F (J=1, 2, 3, 4) tran-
3
+
sitions at about 578, 589, 614, 652 and 700 nm for Eu
and
commonly expressed by the term relaxivity r , defined as the slope
1
Tb-DTPAA-PAM hybrids are 489, 544, 590, 622 nm for Tb3 . Further,
+
−1 −1
of Eq. (1) in the units of mM
s
:
it is found that among these emission bands of the complexes of che-
3
+
lated Eu , red emission intensities of electric dipole transition of
ð1=T1Þobs ¼ ð1=T Þ þ r ½Mꢀ
ð1Þ
1
d
1
5
7
D
0
2
→ F at about 614 nm are all stronger than the other emission in-
5
7
tensities of magnetic dipole transition of
dipole transitions D → F and D → F respectively. And the emis-
D
0
→ F
1
and other electric
where (1/T1)obs and (1/T1)d are the observed values in the presence
and absence of the paramagnetic species, and [M] is the concentration
5
7
5
7
0 3 0 4
sion of terbium hybrids presents the strongest intensities for green
emission. These facts take agreement with the amorphous characters
of the hybrid materials and also indicate effective energy transfer
takes place for the formation of conjugated systems between the li-
gands and the chelated Ln3 ions in obtained polymeric hybrid mate-
rials. Then we can draw the conclusion that the effective energy
transfer has taken place between the DTPAA and the chelated Ln3
of the paramagnetic species [26]. Relaxivity (r ) is calculated from the
1
slope of the plot of the relaxation rate (1/T ) as a function of Gd con-
1
centration, shown in Fig. 4. The relaxivity values of Gd-DTPA-PAM is
−
1 −1
6.26± 1.03 mM
s
. The results present that the relaxivity of the
+
obtained materials is comparable to that of Gd-DTPA chelates
[27,28]. So, this kind of material can be expected to be a potential can-
didate for tailoring desired properties to the positive contrast agents
for MRI.
+
ions. The decay curves of all the europium and terbium hybrid mate-
5
rials at room temperature are measured, which are 440 μs for
0
D of
3
+
5
3+
Eu
and 386 μs for
D
4
of Tb , respectively. Further, we can selec-
Acknowledgements
5
tively determine the emission quantum efficiencies of the D
state of europium ion for Eu
spectra and lifetime of the 5
0
excited
hybrids on the basis of the emission
emitting level, which is 20.2% [24,25].
The longitudinal relaxation times (T ) of aqueous solutions of Gd-
DTPA-PAM are measured by a standard inversion-recovery pulse
3
+
This work is supported by the National Natural Science Founda-
tion of China (20971100) and Program for New Century Excellent
Talents in University (NCET-08-0398). The authors thank to Prof.
Shi-Ping Yang and Dr. He Hu for their help with the MRI
measurements.
D
0
1
5D
7F
5
4
Appendix A. Supplementary material
λem = 544 nm
λex = 371 nm
Supplementary data to this article can be found online at doi:10.
1
016/j.inoche.2012.01.005.
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