An efficient route to pyridine and 2,2'-bipyridine macrocycles incorporating a triethylenetetraminetetraacetic acid core as ligand for lanthanide ions

Article abstract of DOI:10.1016/j.tetlet.2009.09.030

Two novel macrocyclic chelators L₁ and L₂ incorporating an intracyclic pyridine or 2,2'-bipyridine unit and a triethylenetetraminetetraacetic acid core (TTTA) were synthesized with the aim of forming lanthanide complexes suitable as

Full text of DOI:10.1016/j.tetlet.2009.09.030

Tetrahedron Letters 50 (2009) 6522–6525
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient route to pyridine and 2,20-bipyridine macrocycles incorporating a
triethylenetetraminetetraacetic acid core as ligand for lanthanide ions
*
Ghassan Bechara, Nadine Leygue, Chantal Galaup, Béatrice Mestre, Claude Picard
CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, UMR-5068, 118 Route de Narbonne, F-31062 Toulouse cedex 9, France
Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 118 route de Narbonne, F-31062 Toulouse cedex 9, France
a r t i c l e i n f o
a b s t r a c t
Two novel macrocyclic chelators L1 and L2 incorporating an intracyclic pyridine or 2,20-bipyridine unit
and a triethylenetetraminetetraacetic acid core (TTTA) were synthesized with the aim of forming lantha-
nide complexes suitable as efficient long-lived luminophores. For this goal, an efficient methodology for
the preparation of TTTA derivatives using prealkylated precursors is described. Starting from commer-
cially available compounds, the target ligands were obtained in seven (L1) and nine (L2) steps in 40%
and 20% overall yields, respectively. Stable Tb(III) complexes were prepared and displayed interesting
luminescence properties.
Article history:
Received 26 June 2009
Revised 1 September 2009
Accepted 4 September 2009
Available online 9 September 2009
Keywords:
Polyazapolycarboxylic acid
Functionalized polyamine
Macrocyclic ligand
Pyridine
Ó 2009 Elsevier Ltd. All rights reserved.
Terbium
Luminescence
Some of the most widely used ligands in chemistry for the con-
struction of metal complexes in aqueous solutions are ligands that
possess both amino and carboxylate groups as metal-binding sites.
From fundamental studies in coordination chemistry to the present
day, this family of chelating agents has played a central role. In par-
ticular, they have found broad applications in pharmaceutical
industry for diagnostic and therapeutic purposes. Thus, complexes
combining lanthanide(III) and related ions with these ligands have
been widely employed in magnetic resonance imaging (contrast
agents based on Gd3+),1 in radiodiagnosis and radiotherapy (radio-
pharmaceuticals using metal radionuclides such as 86,90Y, 111In,
153Sm, 177Lu, etc.),2 or more recently, in fluorescence imaging
(luminophores based on Eu3+ and Tb3+).3 A general advantage of
these luminophores based on Ln3+ over conventional dyes is that
ising chemical and photophysical properties.5 The macrocyclic
structure provides high chelate stability and the chromophore-
to-cation sensitization step (antenna effect)6 occurs between part-
ners in a rigid conformation that can improve the energy-transfer
DTPA
HO2C
HO2C
DOTA
HO2C
CO2H
CO2H
CO2H
N
N
N
N
CO2H
CO2H
N
N
N
HO2C
TTTA
PCTA
N
N
CO2H
their long-emission lifetimes (ls–ms range) permit easier distinc-
H
N
N
N
H
tion from the shorter-lived (ns range) endogenous fluorescence
present in most biological matrices.4 For these numerous applica-
tions in the biomedical domains, open-chain and macrocyclic poly-
azapolycarboxylate ligands DTPA, DOTA, and PCTA [12] are the
main representative examples (Scheme 1).
In the domain of time-resolved fluorescence Ln(III) bioprobes,
we and others have shown that macrocyclic lanthanide chelates
comprising an intracyclic chromophoric unit and a diethylenetri-
aminetriacetic acid (DTTA) core (such as PCAT [12]) exhibit prom-
N
N
N
HO2C
CO2H
CO2H
CO2H
HO2C
HO2C
L2
L1
HO2C
N
N
N
CO2H
CO2H
HO2C
N
N
N
N
N
N
N
N
HO2C
CO2H
CO2H
HO2C
* Corresponding author. Tel.: +33 5 61 55 62 96; fax: +33 5 61 55 60 11.
E-mail address: picard@chimie.ups-tlse.fr (C. Picard).
Scheme 1. Ligands for lanthanide ions based on polyazapolycarboxylate cores.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.030

G. Bechara et al. / Tetrahedron Letters 50 (2009) 6522–6525
6523
rates. However, as a coordination number of 9 is very common for
lanthanide complexes in aqueous solutions, the introduction of a
monodentate (pyridine) or bidentate (2,20-bipyridine, N,C-pyrazol-
ylpyridine) chromophoric unit in such macrocyclic DTTA systems
allows two or one water molecules to coordinate the metal center,
respectively. When solvents containing OH groups are coordinated
to Eu(III) and Tb(III) ions, efficient nonradiative deactivation of the
metal emissive states takes place via weak vibronic coupling be-
tween f electronic states of the central ion and vibrational states
of high-frequency O–H oscillators.7 The result is a partial quench-
ing of the metal fluorescence.
In order to overcome this drawback and in the course of our
previous work on the synthesis of macrocyclic 2,20-bipyridine-
DTTA derivatives,8 we have planned to introduce an octadentate
host, a triethylenetetraminetetraacetic acid (TTTA) core in the
macrocyclic framework. The use of a TTTA core in the field of che-
lating agents is less extensive than one might expect. To the best of
our knowledge, there are no reports in the academic literature
involving TTTA ligand (Scheme 1). On the other hand, four patents
claimed its potential use but no data were reported.9
We report here a convergent synthetic route to two novel mac-
rocycles (L1, L2, Scheme 1) based on pyridine and 2,20-bipyridine
chromophores and a TTTA backbone. In this synthetic pathway,
the macrocyclization step involves tetra-N-alkylated tetramine
block incorporating masked acetate arms (compound 3, Scheme
2). This functionalized polyamine is a useful building block for
the construction of macrocyclic structures, since it contains two
secondary amine functions at the ends which can be connected
by various heterocyclic cross-linkers. In addition, some preliminary
luminescence properties of the L1Tb and L2Tb complexes are
presented.
The preparation of the key compound 3 was firstly carried out
following our previously reported procedure for the preparation
of the corresponding diethylenetriamine skeleton.10 This route is
depicted in Scheme 2 and involves a three-step sequence: (i)
reductive amination of commercially available triethylenetetr-
amine with benzaldehyde, according to literature procedures,11
(ii) tetra-alkylation on the resulting secondary tetramine with
tert-butyl bromoacetate, (iii) removal of the benzyl-protecting
groups by catalytic hydrogenation with Pd/C. This strategy allowed
us to obtain the target compound (9% overall yield),12 but, clearly,
was hampered by the poor yield resulting from the per-alkylation
reaction in the 2nd steps. As a matter of fact, when the four second-
ary amine groups of 1 were alkylated with tert-butyl bromoacetate,
the tertiary compound 2 was isolated in 19% yield, at best, after
extensive column chromatography. In fact, chromatographic puri-
fication of 2 was complicated due to the formation of polyalkylated
by-products which are very difficult to differentiate from the de-
sired product by TLC. Attempts to direct the reaction towards
exclusive formation of 2, mainly by varying mole ratios of the re-
agents and reaction time always yielded complex mixtures of
alkylation products. This brings us to consider another way to have
access to the key synthon 3.
In order to minimize the formation of overalkylated by-prod-
ucts, an alternative method for the synthesis of 2 consists in the
use of prealkylated precursor molecules. In this direction, the cou-
pling reaction of N,N0-dialkylated ethylenediamine derivative 9 and
two equivalents of N-Bn-protected monoalkylated bromide 6 was
expected to provide the target compound 2 while simplifying the
purification process (Scheme 3). These two precursor molecules
were prepared in two steps from commercially available com-
pounds 4 and 7. Alkylation at the amine group of N-benzyl ethanol-
amine was performed with tert-butyl bromoacetate in the
presence of N,N-diisopropylethyl amine (DIPEA) as a base, provid-
ing 5 in a quantitative yield. Note that the use of this hindered or-
ganic base, instead of K2CO3,13 prevents a lactonization side
reaction forming 4-benzyl-morpholin-2-one. Under these condi-
tions, methyl ester and benzyl ester analogs of the tert-butyl ester
compound 5 can be obtained in excellent yields (90–100%). The hy-
droxyl group of 5 was then replaced by bromine group by reaction
with NBS/PPh3 using standard methodology, yielding 6 in 82%
yield. Starting from N,N0-benzyl ethylenediamine, a combination
of alkylation with tert-butyl bromoacetate followed by a deprotec-
tion step under mild hydrogenolysis conditions produced the sec-
ond precursor molecule 9 in 100% yield for the two steps.14 Finally,
the K2CO3-promoted coupling reaction of 9 and 6 (2 equiv) in
CH3CN successfully provided the tetra-tert butyl ester 2 in high
yield (92%) after a simple column chromatography. The total yield
of this reaction sequence was 75% in compound 2.
We investigated the synthetic flexibility of this approach, study-
ing the possibility (i) to mix the nature of carboxyl-protective
groups of the four acid groups in the TTTA core, a feature which
H
NH2
NH
N
N
H
H2N
a
b
H
OH
H
N
N
7
8
N
4
5
N
H
H
N
H
N
H
1
a
c
CO2tBu
CO2tBu
N
N
OH
N
N
N
N
CO2tBu
CO2tBu
N
CO2tBu
tBuO2C
b
tBuO2C
d
2
CO2tBu
NH
c
Br
6
N
9
HN
+
CO2tBu
N
CO2tBu
H
CO2tBu
H
e
N
N
N
CO2tBu
tBuO2C
tBuO2C
2
3
Scheme 3. Improved synthesis of compound 2. Reagents and conditions: (a)
BrCH2COOtBu, iPr2NEt, DMF, rt, 24 h, 100%; (b) NBS/PPh3, CH2Cl2, rt, 82%; (c)
BrCH2CO2tBu (2 equiv), K2CO3, CH3CN, reflux, 24 h, 100%; (d) Pd/C (10%), H2 (2 bar),
MeOH, rt, 12 h, 100%; and (e) 6 (2 equiv), K2CO3, CH3CN, reflux, 24 h, 92%.
Scheme 2. Conventional synthesis of key compounds
conditions. (a) PhCHO, NaBH4, CHCl3, 48%; (b) BrCH2COOtBu (5 equiv), iPr2NEt,
DMF, rt, 48 h, 19%; and (c) Pd/C (10%), H2 (2 bar), MeOH, rt, 12 h, 100%.
2 and 3. Reagents and

6524
G. Bechara et al. / Tetrahedron Letters 50 (2009) 6522–6525
opens the way to further selective modifications and (ii) to prepare
a precursor of an acyclic analog of DOTA (12 and 13, Scheme 4).
Starting from N-benzyl ethanolamine and N-methyl ethanolamine,
the bromo compounds 10 and 11 were prepared in two steps
according to the procedure described above (70% and 65% overall
yield, respectively). Subjecting the dialkylated material 9 to further
dialkylation with bromo derivative 10 affords mixed tetraester 12
in 50% isolated yield in which the terminal and central carboxyl
groups are differentiated as methyl and tert-butyl esters.12 Simi-
larly, proceeding with secondary diamine 9 and bromo derivative
11, tetraester 13 was obtained in 65% yield after chromatographic
purification.12
Having established a reliable synthetic route to 3, we next
investigated the use of this building block for the assembly of mac-
rocyclic structures. Actually, reaction of 3 with 2,6-bis-(bromo-
methyl)-pyridine and 6,60-bis (bromomethyl)-2,20-bipyridine15
gave the 15-membered and 18-membered macrocycles 14 and
15, respectively (Scheme 5). The synthesis was carried out in
refluxing CH3CN for 24 h, in the presence of Na2CO3 as the base
and without the use of high dilution techniques. 1H, 13C NMR
and MS analyses of the crude mixtures evidenced the presence of
a major species, characterized as the sodium monomeric complex.
In both cases, attempted purification of the sodium complex by
chromatography led to isolation of the mixtures of sodium com-
plex and free ligand, as a result of alumina-mediated decomplex-
ation. However, when the crude mixture was treated with a
saturated EDTA solution (to remove sodium species) the free mac-
rocycles 14 and 15 were readily obtained after chromatography on
alumina in 54% and 58% yield, respectively. Finally, desired chela-
tors L1 and L2 were obtained quantitatively by the treatment of the
corresponding tetra-tert-butyl esters in a mixture of dichlorometh-
ane and trifluoroacetic acid (1:1) at room temperature.12
The Tb3+ complexes of ligands L1 and L2 were prepared by the
addition of TbCl3ꢀ6H2O to the aqueous solutions of ligands.16 Pho-
toexcitation of the complexes (1 ꢁ 10ꢂ5 M in Tris buffer, pH 7.4)
from the lowest energy absorption band of the pyridine or bipyri-
dine moiety (268 and 310 nm, respectively) gave rise to a bright
and long-lived green luminescence, indicating that these chromo-
phoric moieties are able to transfer the excitation light to the lumi-
nescent f–f excited states of the metal ion. The measured excited
state lifetimes are respectively of 1.54 and 2.18 ms for L1Tb and
L2Tb in water with quantum yields of 11% and 26%,17 respectively,
improving the data previously observed for open chain and macro-
cyclic analogs.5a,d,18 Comparison of the lifetimes obtained in H2O
and D2O at 298 K allowed an assessment of the hydration state
of these terbium complexes. By using the well-established method
of Parker and co-workers,19 these analyses indicate that there is
one metal-bound water molecule in L1Tb and no bound water mol-
ecule in L2Tb. Thus, the introduction of a TTTA moiety (vs DTTA) in
these macrocyclic systems displaces one water molecule from the
first coordination sphere of the lanthanide ion. A full study of the
photophysical properties of terbium and other lanthanide com-
plexes derived from these ligands is currently in progress.
Br
H3C
Br
10
11
N
N
As a conclusion, an efficient synthetic approach to macrocylic li-
gands for lanthanide complexation based on a triethylenetetr-
aminetetraacetic acid (TTTA) backbone and pyridine or bipyridine
heterocycles is described. The key steps were (i) the formation of
functionalized polyamine 2 which was achieved in high yield and
in high purity by the use of prealkylated precursors, (ii) the macro-
cyclization reaction which gave azamacrocycles 14 and 15 in satis-
fying yields as a result of a sodium template-mediated cyclization.
Presumably, the present procedures are quite useful for convenient
synthesis of numerous open-chain and macrocyclic derivatives of
TTTA. The terbium complexes derived from these ligands are stable
in aqueous solutions and display attractive luminescence proper-
ties, as a result of a high degree of shielding of the metal.
CO2Me
CO2tBu
CO2tBu
N
N
N
12
13
N
CO2Me
MeO2C
tBuO2C
CO2tBu
CH3
H3C
N
N
N
N
CO2tBu
tBuO2C
tBuO2C
Scheme 4. TTTA derivatives 12, 13 and their precursors 10, 11.
References and notes
1. (a) Chan, K. W.-Y.; Wong, W.-T. Coord. Chem. Rev. 2007, 251, 2428–2451; (b)
Hermann, P.; Kotek, J.; Kubícek, V.; Luke, I. Dalton Trans. 2008, 3027–3047; (c)
Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Chem. Rev. 1999, 99, 2293–
2352.
2. (a) Fichna, J.; Janecka, A. Bioconjugate Chem. 2003, 14, 3–17; (b) Liu, S.; Edwards,
D. S. Bioconjugate Chem. 2001, 12, 7–34; (c) Anderson, C. J.; Welch, M. J. Chem.
Rev. 1999, 99, 2219–2234.
n
N
N
N
n
tBuO2C
CO2tBu
a
N
N
3
N
N
+
Br
Br
N
n = 0, 1
3. (a) Yuan, J.; Wang, G. Trends Anal. Chem. 2006, 25, 490–500; (b) Beeby, A.;
Botchway, S. W.; Clarkson, I. M.; Faulkner, S.; Parker, A. W.; Parker, D.;
Williams, J. A. J. Photochem. Photobiol., B: Biol. 2000, 57, 83–89; (c) Marriott, G.;
Heidecker, M.; Diamandis, E. P.; Yan-Marriott, Y. Biophys. J. 1994, 67, 957–965.
4. Yuan, J.; Wang, G. J. Fluoresc. 2005, 15, 559–568.
CO2tBu
14 n = 0
tBuO2C
b
15 n = 1
5. (a) Kim, W. D.; Kiefer, G. E.; Maton, F.; McMillan, K.; Muller, R. N.; Sherry, A. D.
Inorg. Chem. 1995, 34, 2233–2243; (b) Siaugue, J.-M.; Segat-Dioury, F.; Favre-
Réguillon, A.; Wintgens, V.; Madic, C.; Foos, J.; Guy, A. J. Photochem. Photobiol., A
2003, 156, 23–29; (c) Galaup, C.; Couchet, J.-M.; Bedel, S.; Tisnès, P.; Picard, C. J.
Org. Chem. 2005, 70, 2274–2284; (d) Nasso, I.; Galaup, C.; Havas, F.; Tisnès, P.;
Picard, C.; Laurent, S.; Vander Elst, L.; Muller, R. N. Inorg. Chem. 2005, 44, 8293–
8305; (e) Tircsó, G.; Kovács, Z.; Sherry, A. D. Inorg. Chem. 2006, 45, 9269–9280;
(f) Nasso, I.; Bedel, S.; Galaup, C.; Picard, C. Eur. J. Inorg. Chem. 2008, 2064–2074.
6. Weissman, S. I. J. Chem. Phys. 1942, 10, 214–217; Sabbatini, N.; Guardigli, M.;
Lehn, J.-M. Coord. Chem. Rev. 1993, 123, 201–228.
n
n
N
N
N
N
N
N
c
-O2C
Na+.
-
CO2
CO2H
HO2C
Tb3+
N
N
N
N
N
N
-O2C
CO2
-
HO2C
CO2H
L1Tb n = 0
L2Tb n = 1
L1 n = 0
L2 n = 1
7. Sammes, P. G.; Yahioglu, G. Nat. Prod. Rep. 1996, 13, 1–28.
8. (a) Couchet, J. M.; Galaup, C.; Tisnès, P.; Picard, C. Tetrahedron Lett. 2003, 44,
4869–4872; (b) Havas, F.; Danel, M.; Galaup, C.; Tisnès, P.; Picard, C.
Tetrahedron Lett. 2007, 48, 999–1002.
9. (a) Maruyama, T.; Miho, T. Jpn. Patent 63,128,017, 1988; Chem. Abstr. 1988, 109,
191057.; (b) Gibby, W. A. U.S. Patent 4,822,594, 1989; Chem. Abstr. 1989, 111,
Scheme 5. Synthesis of new macrocyclic ligands L1, L2 and their corresponding
Tb(III) complexes. Reagents and conditions: (a) Na2CO3, CH3CN, reflux, 24 h,
[reactants] = 2.7 ꢁ 10ꢂ3 M, 54% (14) and 58% (15); (b) HCOOH, 60 °C, 24 h, 100%
(L1 and L2); and (c) TbCl3.6H2O, rt, H2O, pH 7.4.

G. Bechara et al. / Tetrahedron Letters 50 (2009) 6522–6525
6525
228130.; (c) Nakabayashi, M.; Okabe, K.; Mishima, T.; Mano, H.; Haraya, K. Eur.
Patent 638,353, 1995; Chem. Abstr. 1995, 122, 191535.; (d) Mori, T.; Ogawa, M.;
Amano, Y. Eur. Patent 708,335, 1996; Chem. Abstr. 1996, 125, 29567.
(CH2), 51.9 (CH2), 54.5 (CH2), 55.6 (CH2), 57.1 (CH2), 123.7 (CH), 128.0 (CH),
147.9 (Cq), 151.4 (Cq), 172.6 (Cq). HRMS (ES+) calcd for C26H34N6O8+K+,
597.2075, found, 597.2070 (100%).
10. Galaup, C.; Couchet, J. M.; Picard, C.; Tisnès, P. Tetrahedron Lett. 2001, 42, 6275–
6278.
13. Chong, H.-S.; Ma, X.; Lee, H.; Bui, P.; Song, H. A.; Birch, N. J. Med. Chem. 2008, 51,
2208–2215.
11. Denat, F.; Tripier, R.; Boschetti, F.; Espinosa, E.; Guilard, R. Arkivoc 2006, 212–233.
12. Compound 2: 1H NMR (300 Mz, CDCl3): d = 1.43 (s,18H), 1.45 (s, 18H), 2.68 (m,
4H), 2.75 (m, 8H), 3.23 (s, 4H), 3.29 (s, 4H), 3.78 (s, 4H), 7.28–7.31 (m, 10H). 13C
NMR (75.4 MHz, CDCl3): d = 28.20 (CH3), 28.23 (CH3), 52.1 (CH2), 52.6 (CH2),
52.9 (CH2), 55.2 (CH2), 56.1 (CH2), 58.4 (CH2), 80.62 (Cq), 80.67 (Cq), 127.0
(CH), 128.3 (CH), 128.9 (CH), 139.2 (Cq), 170.87 (Cq), 170.98 (Cq). LRMS (ES+)
calcd for C44H70N4O8+H+, 783.5; found, 783.7 (100%); calcd for
C44H70N4O8+2H+, 392.3; found, 392.6 (97%). Compound 3: 1H NMR (300 Mz,
CDCl3): d = 1.44 (s,18H), 1.46 (s, 18H), 2.81 (m, 4H), 3.01 (m, 8H), 3.40 (s, 4H),
3.59 (s, 4H). 13C NMR (75.4 MHz, DMSO-d6): d = 28.2 (CH3), 28.3 (CH3), 45.5
(CH2), 49.0 (CH2), 50.2 (CH2), 51.3 (CH2), 55.3 (CH2), 81.0 (Cq), 82.5 (Cq), 168.5
(Cq), 171.2 (Cq). LRMS (ES+) calcd for C30H58N4O8+H+, 603.4; found, 603.5
(100%). Compound 12: 1H NMR (300 Mz, CDCl3): d = 1.42 (s, 18H), 2.70–2.95 (m,
12H), 3.37 (s, 4H), 3.42 (s, 4H), 3.66 (s, 6H), 3.79 (s, 4H), 7.20–7.35 (m, 10H). 13C
NMR (75.4 MHz, CDCl3): d = 28.06 (CH3), 28.14 (CH3), 47.0 (CH2), 50.1 (CH2),
51.3 (CH3), 51.6 (CH2), 52.4 (CH2), 52.5 (CH2), 54.1 (CH2), 55.8 (CH2), 58.5 (CH2),
81.3 (Cq), 82.7 (Cq), 127.2 (CH), 128.3 (CH), 129.1 (CH), 138.4 (Cq), 169.8 (Cq),
170.4 (Cq), 171.9 (Cq). LRMS (ES+) calcd for C38H59N4O8+H+, 699.4; found, 699.7
(100%). Compound 13: 1H NMR (300 Mz, CDCl3): d = 1.42 (s, 18H), 1.43 (18H),
2.34 (s, 6H), 2.57–2.62 (m, 4H), 2.72 (s, 4H), 2.72–2.77 (m, 4H), 3.15 (s, 4H),
3.30 (s, 4H). 13C NMR (75.4 MHz, CDCl3): d = 28.17 (CH3), 28.20 (CH3), 42.4
(CH3), 52.3 (CH2), 53.0 (CH2), 55.0 (CH2), 56.2 (CH2), 59.5 (CH2), 80.7 (Cq), 80.8
(Cq), 170.3 (Cq), 170.9 (Cq). LRMS (ES+) calcd for C32H62N4O8+H+, 631.5; found
631.7 (100%). Compound L1: 1H NMR (300 Mz, D2O): d = 3.42 (m, 4H), 3.55–3.66
(m, 8H), 3.71 (s, 4H), 3.87 (s, 4H), 4.67 (s, 4H), 7.59 (d, J = 7.8 Hz, 2H), 8.05(t,
J = 7.8 Hz, 1H). 13C NMR (75.4 MHz, D2O): d = 51.0 (CH2), 51.6 (CH2), 53.0 (CH2),
54.8 (CH2), 56.7 (CH2), 58.1 (CH2), 124.7 (CH), 140.6 (CH), 150.4 (Cq), 170.3
(Cq), 172.3 (Cq). HRMS (ES+) calcd for C21H31N5O8+H+, 482.2251, found,
482.2244 (100%); calcd for C21H31N5O8+Na+, 504.2070, found, 504.2075 (96%).
Compound L2: 1H NMR (300 Mz, D2O): d = 3.20–3.40 (m, 8H), 3.49–3.60 (m, 4H),
3.63 (s, 4H), 3.67 (s, 4H), 4.63 (s, 4H), 7.88 (d, J = 7.4 Hz, 2H), 8.41(t, J = 7.4 Hz,
2H), 8.49 (d, J = 7.8 Hz, 2H). 13C NMR (75.4 MHz, D2O): d = 51.0 (CH2), 51.2
14. The preparation of compound 9 was reported very recently, using a similar
procedure and with an overall yield of 53% starting from 7. Burdinski, D.;
Pikkemaat, J. A.; Lub, J.; de Peinder, P.; Nieto Garrido, L.; Weyhermuller, T.
Inorg. Chem. 2009, 48, 6692–6712.
15. 6,60-Bis (bromomethyl)-2,20-bipyridine was obtained in two steps starting
from 6,60-dimethyl–2,20-bipyridine. The latter compound was treated with
mCPBA to form the corresponding di (N-oxide) derivative in 90% yield.
Subsequent treatment in acetic anhydride, then in hydrobromic acid, and 40%
in acetic acid, gave the desired compound in 52% isolated yield.
16. A water solution of TbCl3 (1 equiv) was added dropwise while maintaining the
pH at 7.4. The resulting mixture was then stirred during 24 h at room
temperature and passed through chelex-100 to trap the eventual free Tb3+, and
the Tb3+-loaded complex was recovered. The solvent was removed, the
resulting solid was dissolved in a minimum of MeOH, and Et2O was added to
precipitate the desired complex, which was isolated by centrifugation and
dried under vacuum. The absence of free Tb3+ ions was verified using the
Arsenazo test and no peak ascribable to the free ligand was observed in the
mass spectra of the isolated complexes. L1Tb: 80% yield. LRMS (ESꢂ) calcd for
C21H28N5O8TbꢂHꢂ, 636.1, found, 636.1 (100%). Luminescence (Tris buffer pH
7.4, kexc = 268 nm): kem (relative intensity, corrected spectrum), 488 (41), 544
(100), 584 (32), 620 (26) nm. L2Tb: 86% yield. LRMS (ESꢂ) calcd for
C26H31N6O8TbꢂH+, 713.1, found, 713.1 (100%). Luminescence (Tris buffer pH
7.4, kexc = 310 nm): kem (relative intensity, corrected spectrum), 490 (40), 545
(100), 585 (33), 621 (24) nm.
17. Absolute quantum yields were determined relatively to Quinine sulfate in 1 N
sulfuric acid (/ = 0.546). Meech, S. R.; Phillips, D. J. Photochem. 1983, 23, 193–
217.
18. Latva, M.; Takalo, H.; Mukkala, V.-M.; Matachescu, C.; Rodriguez-Ubis, J.-C.;
Kankare, J. J. Lumin. 1997, 75, 149–169.
19. Beeby, A.; Clarkson, I. M.; Dickins, R. S.; Faulkner, S.; Parker, D.; Royle, L.; de
Sousa, A. S.; Williams, J. A. G.; Woods, M. J. Chem. Soc., Perkin Trans. 2 1999,
493–503.