being particularly employed in the sensing of anions.9,10 We
have recently developed luminescent sensors for anions,11
such as for medium size aliphatic dicarboxylates, e.g., pimelic
and tartaric acids, or aromatic acids, e.g., salicylic or
terephthalic acid with Tb(III)-based complexes.12 While the
Tb(III) emission of this complex was modulated upon anion
recognition, the sensor lacked an appropriate antenna, the
emission occurred at relatively short wavelengths, and the
emission enhancement was minor for aliphatic acids. Con-
sequently, we set out to improve our design, and developed
1‚Eu2, a bismacrocyclic dinuclear Eu(III) complex13 designed
to achieve the luminescent sensing of small biologically
important dicarboxylates such as malonic, succinic, and
glutaric acids. Herein, the results from this investigation are
presented, which demonstrate that only for malonic acid was
the Eu(III) emission significantly modulated upon sensing
by 1‚Eu2.
Scheme 1. Synthesis of 1 and the Corresponding Eu(III)
Complex
In designing 1‚Eu2, several important objectives were kept
in mind: (i) a suitable antenna was needed for the population
of the lowest Eu(III) excited state (17,200 cm-1); (ii) a second
binding site for the Eu(III) ion was needed to enable the
binding of small biscarboxylates, and hence (iii) the coor-
dination environment of each lanthanide ion should include
two metal bound water molecules (e.g., q ) 2 at each), at
the same time as; and (iv) the resulting dinuclear complex
should be stable toward metal dissociation. The outcome of
this design is the bismacrocyclic ligand 1, the synthesis of
which is shown in Scheme 1. Here, a naphthalene fluoro-
phore was chosen as an antenna, which is known to
successfully populate the lanthanide excited state.14 Secondly,
hepta- or octadentate cyclen (1,4,7,10-tetraazacyclododecane)
ligands form stable complexes with lanthanide ions.15
Moreover, cyclen is easily functionalized. Therefore, we
decided to use cyclen as our central macrocyclic unit.16
However, a second coordination moiety was needed, and we
decided on using monoaza-18-crown-6. Such crown ethers
are known to bind lanthanide ions, at the same time as
enabling the ions to coordinate the necessary water mol-
ecules.17
The synthesis of the mixed cyclen-crown ether conjugate
ligand 1 involved the initial formation of the monoalkylated
cyclen derivative 2 in 69% yield, which was achieved by
reacting an excess of cyclen with the R-naphthalene chloro-
amide, in DMF in the presence of Cs2CO3. The second
alkylation of this product, using the 18-crown-6 based
R-chloroamide 3, Cs2CO3, and KI in DMF, gave the 1,7-
disubstituded cyclen-crown ether conjugate 4, in 67% yield
after heating at 80 °C for 3 days, following purification with
alumina column chromatography (CH2Cl2:MeOH 10:0.5).
Finally, the remaining two amines of the cyclen moiety were
alkylated, giving 1, in 80% yield, using the N,N-dimethyl-
accetamide 5 in the presence of diisopropylamine in MeOH
at room temperature for 12 h. The bis-Eu(III) complex of 1,
1‚Eu2, was formed by adding Eu(ClO4)3 to a stirring solution
of 1 (20 mg) in MeOH (2 mL). This led to the formation of
an off-white precipitate that was redissolved in 2 mL of
CH3CN. The solution was then left to evaporate at room
temperature overnight. This gave a solid that was washed
with MeOH and collected with suction filtration to give the
desired complex in 62% yield. Analysis of this complex
(9) (a) Pope, S. J. A.; Burton-Pye, B. P.; Berridge, R.; Khan, T.; Skabara,
P. J.; Faulkner, S. Dalton Trans. 2006, 2907. (b) Yu, J. H.; Parker, D. Eur.
J. Org. Chem. 2005, 4249. (c) Gunnlaugsson, T.; Harte, A. J.; Leonard, J.
P.; Nieuwenhuyzen, M. Supramol. Chem. 2003, 15, 505. (d) Gunnlaugsson,
T.; Harte, A. J.; Leonard, J. P.; Nieuwenhuyzen, M. Chem. Commun. 2002,
2134. (e) Dickins, R. S.; Aime, S.; Batsanov, A. S.; Beeby, A.; Botta, M.;
Bruce, J. I.; Howard, J. A. K.; Love, C. S.; Parker, D.; Peacock, R. D.;
Puschmann, H. J. Am. Chem. Soc. 2002, 124, 12697.
(10) (a) Poole, R. A.; Kielar, F.; Richardson, S. L.; Stenson, P. S.; Parker
D. Chem. Commun. 2006, 4084. (b) Parker, D.; Yu, J. Chem. Commun.
2005, 3141. (c) Parker, D. Coord. Chem. ReV. 2000, 205, 109.
(11) (a) Gunnlaugsson, T.; Glynn, M.; Tocci (ne´e Hussey), G. M.; Kruger,
P. E.; Pfeffer, F. M. Coord. Chem. ReV. 2006, 250, 3094. (b) Gunnlaugsson,
T.; Kruger, P. E.; Jensen, P.; Tierney, J.; Ali, H. D. P.; Hussey, G. M. J.
Org. Chem. 2005, 70, 10875.
(12) Harte, A. J.; Jensen, P.; Plush, S. E.; Kruger, P. E.; Gunnlaugsson,
T. Inorg. Chem. 2006, 45, 9465.
(13) Examples of other dinuclear Ln-complexes include: (a) Tremblay,
M. S.; Sames, D. Chem. Commun. 2006, 4116. (b) Gunnlaugsson, T.; Harte,
A. J. Org. Biomol. Chem. 2006, 4, 1572.
(14) (a) Parker, D. Chem. Soc. ReV. 2004, 33, 156. (b) Bruce, J. I.;
Dickens, R. S.; Govenlock, L. J.; Gunnlaugsson, T.; Lopinski, S.; Lowe,
M. P.; Parker, D.; Peacock, R. D.; Perry, J. J. B.; Aime, S.; Botta, M. J.
Am. Chem. Soc. 2000, 122, 9674. (c) Dickins, R. S.; Gunnlaugsson, T.;
Parker D.; Peacock, R. D. Chem. Commun. 1998, 1643.
(15) (a) Fanning, A.-M.; Plush, S. E.; Gunnlaugsson, T. Chem. Commun.
2006, 3791. (b) Gunnlaugsson, T.; Brougham, D. F.; Fanning, A.-M.;
Nieuwenhuyzen, M.; O’Brien, J. E.; Viguier, R. Org. Lett. 2004, 6, 4805.
(c) Gunnlaugsson, T. Tetrahedron Lett. 2001, 42, 8901.
1
clearly showed that two metal ions were present; the H
NMR (400 MHz, CDCl3) showed the characteristic shifting
(16) Examples of mixed macrocyclic complexes using a single lanthanide
ion include: (a) Li, C.; Law, G.-L.; Wong, W.-T. Org. Lett. 2004, 6, 4841.
(b) Li, C.; Wong, W.-T. Tetrahedron Lett. 2004, 45, 6055. (c) Li, C.; Wong,
W.-T. Chem. Commun. 2002, 2034.
(17) Magennis, S. W.; Craig, J.; Gardner, A.; Fucassi, F.; Cragg, P. J.;
Robertson, N.; Parson, S.; Pikramenou, Z. Polyhedron 2003, 22, 745.
1920
Org. Lett., Vol. 9, No. 10, 2007