Bimetallic lanthanide complexes derived from macrocycle-appended m-xylyl derivatives: Synthesis and spectroscopic properties

Article abstract of DOI:10.1002/hlca.200900141

A series of bimetallic lanthanide complexes was prepared from a bimacrocyclic system in which two DO3A units are linked by a m-xylyl unit appended with either a NO₂ or an NH₂ group (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic

Full text of DOI:10.1002/hlca.200900141

Helvetica Chimica Acta – Vol. 92 (2009)
2427
Bimetallic Lanthanide Complexes Derived from Macrocycle-Appended
m-Xylyl Derivatives: Synthesis and Spectroscopic Properties
a
a
b
c
by Matteo P. Placidi ), Louise S. Natrajan ), Daniel Sykes ), Alan M. Kenwright ), and
a
b
Stephen Faulkner* ) )
a) School of Chemistry, University of Manchester, Oxford Road, Manchester M139PL, UK
b) University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX13TA, UK
(
phone: þ 44-1865-285148; e-mail: Stephen.Faulkner@chem.ox.ac.uk)
c) Department of Chemistry, University of Durham, South Road, Durham DH13LE, UK
Dedicated to Professor Jean-Claude Bꢀnzli on the occasion of his 65th birthday.
A series of bimetallic lanthanide complexes was prepared from a bimacrocyclic system in which two
DO3Aunits are linked by a m-xylyl unit appended with either a NO or an NH group (DO3A ¼ 1,4,7,10-
2
2
tetraazacyclododecane-1,4,7-triacetic acid). The Nd-, Eu-, Tb- and Yb-complexes were all luminescent:
time-resolved studies indicated that the lipophilic xylyl group restricts close approach of H O to the
2
metal centre.
Introduction. – Lanthanide complexes have been widely used in imaging and assay
applications for many years, particularly as a consequence of the widespread
application of luminescent complexes in ultrasensitive bioassays [1] and of Gd-
complexes as magnetic-resonance-imaging (MRI) contrast agents [2]. Luminescence
from lanthanide complexes is long-lived as a consequence of the forbidden nature of f –
f transitions, meaning that time-gating techniques can be used to distinguish long-lived
luminescence from fluorescent background signals [3]. However, the forbidden nature
of f – f transitions also means that lanthanide ions have very low extinction coefficients,
so that direct excitation requires the use of high-intensity light sources [4]: this
disadvantage can be overcome by using sensitising chromophores with large extinction
coefficients. Such excitation is normally mediated by the triplet state [5] via both
Fçrster [6] and Dexter [7] mechanisms, though other routes have also been implicated
[
8]. The energy of the emissive state of the lanthanide determines which chromophores
can be used and also has a considerable impact upon the luminescence lifetime and
quantum yield, since the sensitising donor state must be significantly higher in energy
than the emissive state of the lanthanide to avoid back energy transfer, and since
nonradiative quenching of the emissive state occurs most readily for ions with low-
energy emissive states (i.e., those that emit light in the near-IR part of the spectrum).
This means that, although Eu- and Tb-complexes have high luminescence quantum
yields when used with appropriate chromophores, the choice of chromophore is
restricted to those which absorb in the UV, or at the blue edge of the VIS spectrum [9].
By contrast, Yb and Nd can be used with a wide range of sensitisers, including those
ꢀ
2009 Verlag Helvetica Chimica Acta AG, Zꢁrich

2
428
Helvetica Chimica Acta – Vol. 92 (2009)
which absorb red light, but their complexes generally have low quantum yields for
luminescence [9].
There has been considerable recent interest in the properties of multimetallic
lanthanide complexes. Two approaches have been used to prepare such systems. In the
most common, complexes are assembled under thermodynamic control, meaning that
simple systems can be used to assemble complicated architectures (for reviews on this
topic, see [10]). Alternatively, kinetically stable complexes can be prepared through
complexation under kinetic control. We have used this second approach to prepare
heterometallic lanthanide complexes that are not accessible when working under
thermodynamic control (see, e.g., [11]).
Linked DO3A moieties can be used to form multimetallic complexes with a high
kinetic stability (DO3A ¼ 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid): we have
previously shown how p-xylyl and 2,6-dimethylphenol groups can be used to link two
such units together [12][13], while Gunnlaugsson and Harte [14] and Morrow and co-
workers [15] have both used related systems to catalyse phosphate ester hydrolysis. We
now report the preparation of [Ln (1)] and [Ln (2)] (Fig. 1), in which a substituted m-
2
2
xylyl (¼1,3-phenylenebis(methylene)) bridging unit is used to link two DO3A units
together.
Fig. 1. Structures of the synthesised [Ln (1)] and [Ln (2)]
2
2
Results and Discussion. – [Ln (1)] and [Ln (2)] were prepared as shown in the
2
2
Scheme. A modified literature procedure [16] was used to convert 5-nitrobenzene-1,3-
methanol (3) into 1,3-bis(bromomethyl)-5-nitrobenzene (4): heating in the presence of
HBr and H SO for 8 h produced the product in good yield. Reaction of 4 with the well-
2
4
known triester 5 [17] yielded the hexaester 6, which was isolated as the adduct with two
equiv. of NaCl. Single crystals of 6 · 2 NaBr· CH Cl proved suitable for crystallog-
2
2
raphy: the molecular representation of the structure is shown in Fig. 2. It can be seen
þ
that a Na ion is bound in each of the binding sites, and that access to the binding site is
restricted by the bulk of the m-xylyl linking unit.
Cleavage of the tert-butyl esters in the presence of CF COOH yielded the hexa-acid
3
H · 1, which was converted into its lanthanide complexes by treatment with the
6
appropriate lanthanide triflate salt to yield [Ln (1)] (Ln ¼ Nd, Eu, Gd, Tb, and Yb)
2

Helvetica Chimica Acta – Vol. 92 (2009)
Scheme. Synthesis of Ligands and Complexes
2429

2
430
Helvetica Chimica Acta – Vol. 92 (2009)
Fig. 2. Molecular structure of [Na · 6]2 (50% probability ellipsoids; lattice solvent molecules and
þ
2
chloride counterions omitted for clarity). Selected distances [ꢂ] and angles [8]: Na(1)ꢀO(1) 2.398(5),
Na(1)ꢀO(5) 2.414(5), Na(2)ꢀO(7) 2.348(5), Na(2)ꢀO(11) 2.415(5), Na(1)ꢀN(1) 2.538(6),
Na(1)ꢀN(2) 2.485(6), Na(1)ꢀN(3) 2.472(6), Na(1)ꢀN(4) 2.692(6), Na(2)ꢀN(5) 2.636(6),
Na(2)ꢀN(8)
2.493(6);
O(1)ꢀNa(1)ꢀO(5)
117.13(19),
112.2(2),
O(1)ꢀNa(1)ꢀN(3)
N(2)ꢀNa(1)ꢀN(1)
166.5(2),
73.0(2),
O(5)ꢀNa(1)ꢀN(3)
68.35(18),
N(3)ꢀNa(1)ꢀN(1)
O(7)ꢀNa(2)ꢀO(11) 114.09(19), O(7)ꢀNa(2)ꢀN(8) 167.9(2), N(7)ꢀNa(2)ꢀO(9) 64.74(18).
(
triflate ¼ trifluoromethanesulfonate). In all cases, mass spectrometry showed the
presence of the molecular ions, while the IR C¼O stretch was shifted to lower
ꢀ
1
frequency by ca. 70 cm , indicating binding of the lanthanide ions in both DO3A
1
pockets. The H-NMR spectrum of [Yb (1)] (Fig. 3,a) showed further evidence for
2
binding in a cyclen-derived pocket where each of the nearby H-atoms is nonequivalent:
the four peaks in the range 110 – 140 ppm may be assigned to nonequivalent axial H-
atoms at the cyclen ring, and to a SAP (square antiprismatic) isomer by analogy with
the literature [18], while the less intense peaks in the range 40 – 70 ppm correspond to
axial ring H-atoms in a minor (TSAP ¼ twisted square antiprismatic) isomer. It is clear
that the two isomers are in slow exchange on the NMR timescale.
Transfer hydrogenation of [Ln (1)] with NH NH in the presence of a Pd catalyst
2
2
2
yielded the amino-group-bearing complexes [Ln (2)]. Once again, the molecular ions
2
for all complexes were observed in their mass spectra. Further evidence for reduction
ꢀ1
was obtained from the absence of bands in the IR spectra at 1530 and 1350 cm ,
1
corresponding to NO group stretching vibrations in [Ln (1)]. The H-NMR spectrum
2
2
of the Yb-complex (Fig. 3,b) also showed significant changes relative to the starting
material – significant line broadening was observed for the major isomer, and no peaks
corresponding to the minor isomer were present.
H · 2 was also prepared by an alternative route (Scheme): transfer hydrogenation of
6
6
yielded the hexaester 7, which was deprotected with CF COOH to yield H · 2.
3
6
Complexes prepared from H · 2 proved identical in all respects to those prepared by
6
reduction of [Ln (1)].
2

Helvetica Chimica Acta – Vol. 92 (2009)
2431
Fig. 3. 1H-NMR Spectrum of a) [Yb (1)], and b) [Yb (2)]
2
2
Physical Properties of the Complexes. The luminescence properties of the
complexes are summarised in the Table. All the complexes proved to be luminescent:
with the exception of [Eu (2)], all gave rise to intense lanthanide-centred emission
2
following excitation through the arene chromophore.
The anomalous behaviour of [Eu (2)] is likely to be a consequence of nonradiative
2
quenching of the excited state through ligand-to-metal charge transfer (LMCT) [19].
This is confirmed by the excitation and emission spectra (Fig. 4) of [Eu (2)]. The
2
excitation spectrum bears little resemblance to the absorption spectrum; in the
excitation spectrum, f – f transitions are prominent despite their low extinction
coefficients, and nonradiative quenching pathways must dominate the fate of the
excited state of the lanthanide ions.

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432
Helvetica Chimica Acta – Vol. 92 (2009)
Table. Photophysical Properties of the Complexesa)
lex [nm]
lem [nm]
tH2O [ms]
tD2O [ms]
q
[
[
[
[
[
[
[
[
Eu (1)]
280
280, 397
280
280
337
337
337
337
617
617
545
550
500
1760
980
1.2
0.8
1.0
0.8
2
b
Eu (2)] )
2
Tb (1)]
1400
1820
0.09
0.10
1.60
0.90
2240
2980
0.38
0.33
5.31
5.83
2
Tb (2)]
545
2
Nd
2
(1)]
1055
1055
980
Nd (2)]
2
Yb (1)]
0.3
0.8
2
Yb (2)]
980
2
a) Lifetimes are ꢁ 10% and calculated q values ꢁ 20%. q Values are not reported for Nd complexes
b
since their lifetimes are highly dependent on structure. ) The low intensity of emission from this complex
results in a large uncertainty in the fitted decays, and hence in the value of q.
Fig. 4. Excitation and emission spectra of [Eu (2)]: note how the excitation spectrum shows bands
2
corresponding to direct excitation (e.g., at 397 nm), and the obvious ineffectiveness of sensitised emission
for the Eu complex. The figure also shows the different intensities following direct excitation of the
lanthanide (blue line) and chromophore excitation (red line).
Time-resolved luminescence spectroscopy was used to establish the luminescence
lifetimes of the complexes, and the hydration number of inner-sphere H O molecules in
2
the Yb complexes was determined from the luminescence decay constants in H O and
2
D O with the formula q ¼ A(k
ꢀ k
ꢀ B), where q is the number of bound H O
2
H2O
D2O
2
molecules at each Yb ion, k
and k
are the observed rate constants in H O and
H2O
D2O
2
ꢀ1
D O, respectively (in ms ), and A and B are specific to a given lanthanide [20]. The
2
observed values of q imply the binding of one H O molecule close to each metal centre
2
for the complexes; they are lower than might be expected for lanthanide complexes
with heptadentate ligands but are comparable with those observed for other N-benzyl-
substituted DO3A derivatives [12][21]. Calculations of q rely on the assumption that

Helvetica Chimica Acta – Vol. 92 (2009)
2433
all inner-sphere H O molecules are situated at the ꢃaverageꢄ distance from the metal
2
centre, but since through-space coupling to the solvent OꢀH oscillators falls off rapidly
with distance, it is possible that these values reflect the presence of two solvent
molecules on each centre (both in the inner sphere, but further away than the ꢃaverageꢄ
separation owing to the hydrophobicity of the benzyl substituent).
The Gd-complexes lend some support to this hypothesis. Inversion recovery
measurements of T for the H O H-atoms in aqueous solutions containing varying
1
2
concentrations of the complexes were used to establish the relaxivity (the results of
these measurements are plotted in Fig. 5). The relaxivities per mol of Gd of both
ꢀ
1
ꢀ1
[
1
5
Gd (1)] and [Gd (2)] were measured at 400 MHz and found to be 11.6 mmol
s
and
relaxivity of
.5 mmol s ). These results are broadly comparable with those observed with p-
2
2
ꢀ1
ꢀ1
3.8 mmol s , respectively (cf. [Gd(DO3A)] which has
a
ꢀ
1
ꢀ1
xylyl-bridged DO3A complexes [22], and are consistent with the binding of two H O
2
molecules to each metal ion and with a slow rotational correlation time for the complex
molecules. It is also worth noting that the relaxivity of [Gd (2)] is marginally greater
2
than that of [Gd (1)]: the amino-group H-atoms will also be in exchange on the NMR
2
timescale, and may also help facilitate exchange of metal-bound H O.
2
Fig. 5. Plots of 1/T vs. Gd-concentration for [Gd (1)] (solid line) and [Gd (2)] (broken line)
1
2
2
Conclusion. – From these results it is clear that m-xylyl-linked systems can be
prepared without difficulty, and that they have interesting photophysical and
relaxometric properties. Furthermore, the complexes are sufficiently robust to with-
stand conversion of [Gd (1)] to [Gd (2)] by hydrogenation, implying that the amino
2
2
complex will be an effective building block for more complicated assemblies.
Experimental Part
General. Cyclen (¼1,4,7,10-tetraazacyclododecane) was purchased from Strem Chemicals, while
other reagents, solvents, and starting materials were obtained from the Aldrich Chemical Company. All
chemicals were used as supplied. 1,4,7-Tri(tert-butyl) 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate was
synthesized according to a published procedure [17]. Column chromatography ¼ CC. Absorption

2
434
Helvetica Chimica Acta – Vol. 92 (2009)
spectra: in H O; T60U spectrometer (PG Instruments Ltd.), fused-quartz cells with a path length of
2
ꢀ
1
1
cm; lmax (e) in nm. FT-IR Spectra: Equinox-55-FRA106/5 instrument; pressed KBr disks; ˜n in cm .
1
13
NMR Spectra: Bruker-Avance-400 spectrometer, at 400 ( H) or 100 MHz ( C) for diamagnetic
compounds, variable-temp. unit set at 300 K, unless otherwise stated; Varian-Inova-500 spectrometer, at
1
5
00 MHz ( H) and 295 K for paramagnetic compounds; d in ppm rel. to Me Si as internal standard, J in
4
Hz. MS: Micromass-Platform-II spectrometer for pos. electrospray ionization (ESI) in MeCN or MeOH
solns.; or Micromass-TOF-Spec-2E spectrometer for MALDI with MeOH solns. and an ALPHA
maxtrix; in m/z (rel. %). Elemental analyses were performed by the microanalytical services at the
University of Manchester with a Carlo-Erba Instruments CHNS-O EA1108 elemental analyzer (C, H, N,
and S analysis) and a Fisons-Horizon-Elemental-Analysis-ICP-OED spectrometer for metals and
halogens.
Photophysical Measurements. Luminescence spectra of Eu and Tb complexes were measured on a
Perkin-Elmer-LS55 fluorimeter. In the case of the Nd and Yb complexes, the sample was excited with a
pulsed nitrogen laser (PTI 3301, 337 nm). Light emitted at right angles to the excitation beam was
focussed onto the slits of the monochromator (PTI 120), which was used to select the appropriate
wavelength. The growth and decay of the luminescence at selected wavelengths was detected with a Ge
photodiode (Edinburgh Instruments) and recorded with a digital oscilloscope (Tektronix TDS220)
before being transferred to the computer for analysis. Luminescence lifetimes were obtained by iterative
reconvolution of the detector response (obtained by means of a scatterer) with exponential components
for growth and decay of the metal-centred luminescence, with a spreadsheet running in Microsoft Excel.
The time-resolved emission spectra (TRES) of the complexes were obtained by measuring the growth
and decay of the luminescence at each of a series of wavelengths.
Crystallography. Data for 6 · 2 NaBr· CH Cl were collected at 100 K with an Oxford-Diffraction-
2
2
XCalibur2 diffractometer equipped with an Oxford-Cryosystems low-temp. device [23], by means of
MoK radiation and w scans. Data were corrected for Lorenz and polarisation factors, and absorption
a
corrections were applied to all data. The structure was solved by direct methods with SHELXS-97 [24].
The structure was completed by iterative cycles of DF syntheses and a full-matrix least-squares
refinement. Several C-atoms and one N-atom were restrained as approximately isotropic to prevent them
from going non pos. definite, and the MeCN and MeOH solvent C-, N-, and O-atoms were refined
isotropically. All other non-H-atoms were refined anisotropically. Difference Fourier syntheses were
employed in positioning idealised H-atoms and were allowed to ride on their parent C- or N-atoms. All
2
refinements were against F and used SHELXL-97 [25].
CCDC-728845 contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.
1,3-Bis(bromomethyl)-5-nitrobenzene (4) [15]. The 5-nitrobenzene-1,3-dimethanol (0.9 g, 4.9 mmol)
was dissolved in 48% HBr soln. (20 ml) and conc. H SO soln. (6.7 ml). The resulting soln. was stirred
2
4
under reflux for 8 h, and subsequently allowed to cool to r.t. H O (40 ml) was added, the pH adjusted to 7
2
with 1m NaOH, and the resulting orange precipitate washed with brine (3 ꢂ 20 ml). The product was
dissolved in CHCl (40 ml), the soln. dried (MgSO ) and concentrated, and the yellow solid purified by
3
4
CC (silica gel, hexane/AcOEt 8 :2): 4 (0.98 g, 65%). White powder. Alternatively, purification was
achieved by recrystallisation from a hot mixture of hexane/CH Cl 9 :1, that was cooled slowly to between
2
2
0
and 58. UV/VIS (MeOH): 228 (11400, p ! p*), 264 (4,300, n ! p*). IR: 1538 (NO ), 1342 (NO ), 1254
2
2
1
(
CH wagging), 667 (CꢀBr stretch). H-NMR (400 MHz, CDCl , 258): 4.52 (s, 2 CH Br); 7.75 (s, 1 arom.
2
3
2
13
H); 8.18 (s, 2 arom. H). C-NMR (102 MHz, CDCl , 258): 30.6 (BrCH ); 123.7, 135.3 (arom. CH); 140.2,
3
2
þ
þ
1
48.6 (arom. C). ESI-MS (pos., CH Cl ): 309 (5, M ), 228 (100, [M ꢀ Br] ). Anal. calc. for C H Br NO :
2
2
8
7
2
2
C 31.0, H 2.28, N 4.53; found: C 30.83, H 2.17, N 4.23.
,1’,4,4’,7,7’-Hexa(tert-butyl) 10,10’-[(5-Nitro-1,3-phenylene)bis(methylene)]bis[1,4,7,10-tetraazacy-
clododecane-1,3,7-triacetate] (6). Cs CO (1.33 g, 4.09 mmol) was added to a soln. of 1,4,7-tri(tert-butyl)
1
2
3
2
1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (5; 1.00 g, 1.68 mmol) in anh. MeCN (25 ml) under N . A
soln. of 4 (0.253 g, 0.819 mmol) in anh. MeCN (5 ml) was added under stirring to the soln., and the
mixture was heated to reflux temp. for 72 h. The soln. was cooled to r.t. and filtered to remove the inorg.
salts, and the MeCN was evaporated. The product was dissolved in CH Cl (30 ml) and the soln. washed
2
2
with sat. NaCl soln. (5 ꢂ 30 ml), dried (MgSO ), and concentrated: dark yellow oil. The hexaester was
4

Helvetica Chimica Acta – Vol. 92 (2009)
2435
purified by CC (neutral alumina, CH Cl , then slowly increasing MeOH/CH Cl (0.1 ml per 100 ml). The
2
2
2
2
product was eluted with MeOH/CH Cl 3 :97, the solvent evaporated, and the residue triturated in Et O
2
2
2
followed by hexane: 0.55 g (50%) of 6 · 2 NaBr· CH Cl . Yellow powder. Single crystals suitable for X-
2
2
ray-analysis were grown by slow vapour diffusion between CH Cl and hexane. UV/VIS (MeOH): 204
2
2
1
(
8900, p ! p*), 262 (4400, n ! p*). IR: 1716 (C¼O), 1534 (NO ), 1368 (NO ). H-NMR (400 MHz,
2
2
t
CDCl , 258): 1.35 (s, 6 Bu); 2.8 – 4.4 (br., 48 H, CH ring, CH CO, ArCH N); 7.9 – 8.6 (br., 3 arom. H).
C-NMR (102 MHz, CDCl , 258): 27.8, 28.0 (Me ); 50.0, 50.2, 50.6, 51.5, 51.7, 55.5, 55.8, 56.1, 56.3, 57.1
3
2
2
2
13
3
3
(
1
[
CH N); 81.8, 82.2, 82.6, 83.0 (Me C); 124.0, 124.3, 124.7, 139.4, 140.2, 148.5, 148.6 (arom. C); 169.3,
2 3
þ
þ
70.0, 172.5, 173.5 (C¼O). ESI-MS (pos., MeCN): 1176 (48, [M þ H] ), 1198 (42, [M þ Na] ), 600 (57,
2
þ
M þ H þ Na] ). Anal. calc. for C H BrN NaO · CH Cl : C 53.70, H 7.90, N 9.24, Na 1.69; found: C
60
105
9
14
2
2
5
3.90, H 8.00, N 9.13, Na 1.67.
,1’,4,4’,7,7’-Hexa(tert-butyl) 10,10’-[(5-Amino-1,3-phenylene)bis(methylene)]bis[1,4,7,10-tetraaza-
cyclododecane-1,3,7-triacetate] (7). To a soln. of hexaester 6 · 2 NaBr· CH Cl (0.480 g, 0.361 mmol) in
1
2
2
MeOH (5 ml), a catalytic amount of Pd/C (0.03 g) was added, and the mixture was heated to 608. Then
NH NH · H O (5 ml, 84 mmol) was added. After 10 h (TLC monitoring), the soln. was cooled to r.t., the
2
2
2
excess catalyst removed by filtration through a Celite slurry in MeOH, the filtrate concentrated, the
yellow oil dissolved in CH Cl (30 ml), the soln. washed with brine (8 ꢂ 30 ml), dried (MgSO ), and
2
2
4
concentrated, and the light yellow solid triturated in Et O and then hexane: 0.350 g (75%) of 7 ·
2
0
.5 NaBr. UV/VIS (MeOH): 244 (12100, sh, p ! p*), 295 (5200, n ! p*). IR: 1720 (C¼O), 1225
1
t
(
CꢀN). H-NMR (400 MHz, CDCl ): 1.42 – 1.47 (s, 6 Bu); 2.80 – 4.42 (m, 48 H, CH ring, CH CO,
3
2
2
13
ArCH N); 6.64 – 6.93 (m, 3 arom. H). C-NMR (102 MHz, CDCl ): 26.9, 27.1, 27.2 (Me C); 48.8, 52.6,
2
3
3
5
1
4.8, 55.2, 58.6, 64.8 (CH N); 80.0, 81.5, 81.8 (Me C); 114.5, 120.7, 137.2, 147.2 (arom. C); 169.6, 171.5,
2 3
2
þ
2þ
72.5 (C¼O). ESI-MS (pos., MeCN): 574 (98, [M þ 2 H] ), 585 (90, [M þ H þ Na] ), 597 (11, [M þ
2þ
þ
þ
H þ Na] ), 1148 (36, [M þ H] ), 1170 (12, [M þ Na] ). Anal. calc. for C H Br N Na O : C 55.40,
60
107
1.5
9
1.5 12
H 8.29, N 9.69 Na 2.65; found: C 54.31, H 8.54, N 10.17, Na 2.73.
0,10’-[(5-Nitro-1,3-phenylene)bis(methylene)]bis[1,4,7,10-tetraazacyclododecane-1,4,7-triacetic
Acid] (H · 1). Hexaester 6 · 2 NaBr· CH Cl (0.500 g, 0.376 mmol) was dissolved in CH Cl (4 ml) and
1
6
2
2
2
2
CF COOH (4 ml, 54.04 mmol) was added dropwise to the yellow soln. After 48 h stirring at r.t., the
3
mixture was concentrated and the orange oil washed with portions of CH Cl (3 ꢂ 30 ml) and MeOH
2
2
(
3 ꢂ 30 ml). Finally, a white solid was precipitated from a conc. MeOH soln. with Et O, isolated by
2
filtration, and dried under reduced pressure: 0.455 g (97%) of H · 1 · 3 CF COOH · 4 H O. UV/VIS
6
3
2
(
(
H O): 201 (13900, p ! p*), 270 (4800, n ! p*). IR: 1638 (C¼O), 1681 (C¼O), 1540 (NO ), 1356
2
2
1
3
NO ). H-NMR (400 MHz, (D )DMSO, 1208): 2.93 (t, J ¼ 4.0, 4 CH ring); 3.04 (dt, 8 CH ring); 3.13 (t,
2
6
2
2
3
J ¼ 4.0, 4 CH ring); 3.55 (s, CH CO); 3.60 (s, 2 CH CO); 4.10 (s, 2 ArCH N); 7.92 (s, 1 arom. H); 8.20 (s,
2
2
2
2
13
2
1
arom. H). C-NMR (102 MHz, CD OD, 258): 55.2, 56.5, 57.4 (Me C); 66.9 (CH N); 113.9, 119.7, 122.6,
3 3 2
þ
þ
27.9 (arom. C); 160.3 (C¼O). ESI-MS (pos., H O): 840 (32, [M þ H] ), 863 (16, [M þ Na] ), 431
2
2þ
2þ
(
[M þ H þ Na] ), 420 ([M þ 2 H] ). Anal. calc. for C H N O · 3 CF COOH · 4 H O: C 40.23, H 5.47,
36
57
9
14
3
2
N 10.05; found: C 40.30, H 5.12, N 10.22.
1
0,10’-[(5-Amino-1,3-phenylene)bis(methylene)]bis[1,4,7,10-tetraazacyclododecane-1,3,7-triacetic
Acid] (H · 2). As described for H · 1, with hexaester 7 · 0.5 NaBr (0.350 g, 0.269 mmol), CH Cl (4 ml),
6
6
2
2
and CF COOH (4 ml, 54.04 mmol): 0.330 g (96%) of H · 2 · 3.5 CF COOH · 4 H O. UV/VIS (H O): 201
3
6
3
2
2
1
(
(
2
8
10000, p ! p*), 245 (4600, sh, p ! p*), 295 (5000, n ! p*). IR: 1675 (C¼O), 1184 (CꢀN). H-NMR
400 MHz, (D )DMSO, 1208): 2.95 (m, 8 CH ring); 3.11 (m, 8 CH ring); 3.45 (s, 4 CH CO); 3.59 (s,
6
2
2
2
þ
CH CO); 4.13 (s, 2 ArCH N); 6.70 – 6.74 (br., 3 arom. H). MALDI-MS (H O): 810 (38, [M þ H] ),
þ
2
2
2
32 (6, [M þ Na] ). Anal. calc. for C H N O · 3.5 CF COOH · 4 H O: C 40.32, H 5.55, N 9.84; found:
36
59
9
12
3
2
C 39.92, H 4.97, N 10.96.
{
m-{10,10’-[(5-Nitro-1,3-phenylene)bis(methylene)]bis[1,4,7,10-tetraazacyclododecane-1,4,7-tri-
1
4
7
10
1
4
7
acetato(3ꢀ)-kN ,kN ,kN ,kN ,kO ,kO ,kO ]}}dilanthanide Complex [Ln (1)]. The lanthanide triflate
2
(
0.191 mmol) and H · 1 · 3 CF COOH · 4 H O (0.100 g, 0.076 mmol) were dissolved in MeOH (2 ml) and
6 3 2
stirred for 48 h at 508. The excess lanthanide salts were removed by dialysis, and H O was evaporated. A
2
white solid was obtained by slow diffusion between MeOH and Et O. This was isolated by filtration and
2
dried under reduced pressure.

2
436
Helvetica Chimica Acta – Vol. 92 (2009)
[
Nd (1)]: Yield 0.042 g (63%). UV/VIS (H O): 205 (22000, p – p*), 270 (7100, n ! p*).
2
2
þ
Luminescence: l 337 nm, l 1055, 1330 nm. MALDI-MS (H O): 1103 (37, [M ꢀ O] ), 1119 (52,
ex
em
2
þ
[
M þ H] ).
[
Eu (1)]: Yield 0.099 g (66%). UV/VIS (H O): 204 (19000, p ! p*), 270 (6600, n ! p*). IR: 1592
2
2
þ
þ
(
C¼O), 1537 (NO
2
), 1351 (NO
2
). MALDI-MS (H
2
O): 1132 (9, [M ꢀ O] ), 1138 (16, [M þ H] ). Anal.
calc. for C H Eu N O · 5 CF SO H · 5 H O: C 24.96, H 3.12, Eu 15.40, N 6.03; found: C 24.28, H 3.37,
36
51
2
9
14
3
3
2
Eu 14.39, N 6.03.
Gd (1)]: Yield 0.087 g (62%). UV/VIS (H O): 203 (24000, p ! p*), 268 (8400, n ! p*). IR: 1591
[
2
2
þ
þ
(
C¼O), 1535 (NO ), 1353 (NO ). MALDI-MS (H O): 1130 (7, [M ꢀ O] ), 1149 (20, [M þ H] ). Anal.
2
2
2
calc. for C H Gd N O · 3.5 CF SO H · 10 H O: C 25.59, H 4.05, Gd 16.97, N 6.80, S 6.05; found: C
36
51
2
9
14
3
3
2
2
5.58, H 3.80, Gd 13.04, N 6.51, S 5.56.
[
Tb (1)]: Yield 0.138 g (98%). UV/VIS (H O): 205 (18000, p ! p*), 270 (6600, n ! p*).
2
2
Luminescence: l 268 nm, l 545 nm, t
1.60 ms, t
D2O
2.78 ms, q 1.0. IR: 1632 (C¼O), 1532
þ þ
ex
em
H2O
(
NO ), 1353 (NO ). MALDI-MS (H O): 1151 (98, [M þ H] ), 1173 (16, [M þ Na] ). Anal. calc. for
2
2
2
C H N O Tb · 3.5 CF SO H · 10 H O: C 24.50, H 3.41, N 6.27, Tb 15.81; found: C 24.08, H 3.42, N 6.26,
36
51
9
14
2
3
3
2
Tb 13.65.
[
Yb (1)]: Yield 0.076 g (54%). UV/VIS (H O): 206 (14000, p ! p*), 270 (5900, n ! p*). IR: 1598
2 2
2
2
(
C¼O), 1535 (NO ), 1353 (NO ). Luminescence: l 337 nm, l 980 nm, t
H O
1.60 ms, tD O 5.31 ms, q 0.3.
2
2
ex
em
1
H-NMR (500 MHz, D O): ꢀ 92.0; ꢀ 83.9; ꢀ 77.9; ꢀ 76.1; ꢀ 68.8; ꢀ 66.3; ꢀ 61.9; ꢀ 59.5; ꢀ 40.1; ꢀ
2
3
5.8; ꢀ 32.3; ꢀ 21.8; 20.7; 27.9; 32.5; 36.1; 46.3; 51.5; 72.7; 111.8; 127.9; 135.5; 141.0 (only major
þ
resolved peaks outside the range þ 20 to ꢀ 21 reported). MALDI-MS (H O): 1181 (12, [M þ H] ), 1203
2
þ
(
3, [M þ Na] ). Anal. calc. for C H N O Yb · 4 CF SO H · 5 H O: C 25.69, H 3.50, N 6.74, Yb 18.50;
36
51
9
14
2
3
3
2
found: C 25.24, H 3.70, N 6.37, Yb 14.94.
m-{10,10’-[(5-Amino-1,3-phenylene)bis(methylene)]bis[1,4,7,10-tetraazacyclododecane-1,4,7-tri-
{
1
4
7
10
1
4
7
acetato(3ꢀ)-kN ,kN ,kN ,kN ,kO ,kO ,kO ]}}dilanthanide Complex [Ln (2)]. Method A. To a soln. of
2
[
2
Ln (1)] (0.100 g, 0.054 – 0.096 mmol) in MeOH (3 ml), a catalytic amount of Pd/C (0.010 g) was added,
and the mixture was heated to reflux temp. Then NH NH · H O was added (2 ml, 68 mmol). After 1 h,
2
2
2
the mixture was allowed to cool and filtered through a slurry of Celite in MeOH to remove the catalyst.
The MeOH was evaporated and, through repeated washing with MeOH followed by evaporation, the
NH NH was removed. A white solid was precipitated from a conc. MeOH soln. by dropwise addition of
2
2
Et O. This was isolated by filtration and dried under reduced pressure.
2
Method B. As described for [Ln (1)], with lanthanide triflate (0.115 – 0.121 g, 0.195 mmol), H · 2
2
6
(
0.100 g, 0.078 mmol), and MeOH (2 ml).
[
Nd
2
(2)]: Yield 0.110 g (84%). UV/VIS (H
2
O): 205 (24000, p ! p*), 241 (5100, p ! p*), 294 (2400,
þ
þ
n ! p*). MALDI-MS (H O): 1087 (27, [M þ H] ), 1109 (21, [M þ Na] ). Anal. calc. for
2
C H N Nd O · 4 CF SO H · 4 H O: C 27.22, H 3.71, N 7.14, S 7.27, Nd 16.35; found: C 23.67, H 3.46,
36
53
9
2
12
3
3
2
N 7.67, S 7.13, Nd 15.25.
[
Eu (2)]: Yield 0.061 g (72%). UV/VIS (H O): 206 (p ! p*), 238 (p ! p*), 292 (n ! p*).
2
2
Luminescence: l 268 nm, l 617 nm, t
H
2
O
0.50 ms, tD O 0.98 ms, q 0.9. IR: 1581 (C¼O), 1241 (CꢀN).
ex
em
2
þ
þ
1
MALDI-MS (H O): 1108 (26, [M þ H] ), 1109 (11, [M þ Na] ). H-NMR (500 MHz, D O): ꢀ 19.3;
2
2
ꢀ
17.1; ꢀ 15.9; ꢀ 12.2; ꢀ 11.6; ꢀ 9.6; ꢀ 7.1; 5.5; ꢀ 2.4; 10.0; 22.4 (only major resolved peaks outside the
range þ 9 to þ 1 reported).
[
Gd (2)]: Yield 0.140 g (84%). UV/VIS (H O): 205 (21000, p ! p*), 240 (3900, p ! p*), 294 (1300,
2
2
þ
n ! p*). IR: 1581 (C¼O), 1239 (CꢀN). MALDI-MS (H O): 1117 (26, [M þ H] ), 1109 (10, [M þ
2
þ
Na] ). Anal. calc. for C H Gd N O · 6 CF SO H · 10 H O: C 22.49, H 3.62, Gd 14.30, N 5.73, S 8.75;
36
51
2
9
14
3
3
2
found: C 22.29, H 3.21, Gd 15.54, N 5.72, S 7.99.
[
Tb (2)]: Yield 0.143 g (96%). UV/VIS (H O): 206 (22000, p ! p*), 240 (4200, p ! p*), 294 (1600,
2
2
n ! p*). Luminescence: l 242, 291 nm, l 545 nm, t
1.82 ms, t
2.98 ms, q 0.8. IR: 1582 (C¼O),
ex
em
H2O
D2O
þ
þ
1
240 (CꢀN). MALDI-MS (H O): 1122 (75, [M þ H] ), 1109 (40, [M þ Na] ). Anal. calc. for
2
C H N O Tb · 5 CF SO H · 5 H O: C 25.11, H 3.44, N 6.43, S 8.17, Tb 16.21; found: C 20.47, H 3.04, N
36
51
9
14
2
3
3
2
6
.49, S 8.05, Tb 14.60.
Yb (2)]: Yield 0.101 g (72%). UV/VIS (H O): 207 (27000, p ! p*), 240 (5300, p ! p*), 294 (2100,
[
2
2
n ! p*). Luminescence: l 337 nm, l 980 nm, t
0.99 ms, t
D2O
5.83 ms, q 0.1. IR: 1583 (C¼O), 1239
ex
em
H2O

Helvetica Chimica Acta – Vol. 92 (2009)
2437
1
(
CꢀN). H-NMR (500 MHz, D O): ꢀ 98.5; ꢀ 82.7; ꢀ 72.2; ꢀ 69.5; ꢀ 643; ꢀ 59.7; 58.5; ꢀ 13.8; 10.2;
2
1
1
4
1
1.9; 18.3; 21.5; 26.8; 33.1; 35.7; 38.4; 110.3; 124.3; 128.1; 132.9 (only resolved peaks outside the range þ
þ
0 to ꢀ 13 reported). MALDI-MS (H O): 1151 (41, [M þ H] ). Anal. calc. for C H N O Yb ·
2
36 51
9
14
2
CF SO H · 5 H O: C 26.11, H 3.67, N 6.85, S 6.97, Yb 18.81; found: C 22.40, H 3.39, N 7.34, S 7.17, Yb
3
3
2
6.14.
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Received April 24, 2009