A selective and sensitive chemosensor for Cu2+ based on 8-hydroxyquinoline

Article abstract of DOI:10.1016/j.tetlet.2006.01.091

A novel 8-hydroxyquinoline derivative 3 was synthesized. Significant fluorescent quenching was found in the presence of Cu²⁺ and Hg²⁺ with notably higher selectivity for Cu²⁺ than Hg²⁺.

Full text of DOI:10.1016/j.tetlet.2006.01.091

Tetrahedron Letters 47 (2006) 2447–2449
A selective and sensitive chemosensor for Cu2+ based on
8-hydroxyquinoline
Yujiang Mei, Paul A. Bentley* and Wei Wang
Department of Chemistry, MSC03 2060, University of New Mexico, Albuquerque, NM 87131-0001, USA
Received 28 November 2005; revised 18 January 2006; accepted 18 January 2006
Available online 21 February 2006
Abstract—A novel 8-hydroxyquinoline derivative 3 was synthesized. Significant fluorescent quenching was found in the presence of
Cu2+ and Hg2+ with notably higher selectivity for Cu2+ than Hg2+
.
ꢀ 2006 Published by Elsevier Ltd.
The detection of Cu2+ has important implications in the
areas of environmental and biological analysis. Copper
has been shown to be a biochemically essential metal,
for example, copper–zinc superoxide dismutase’s role
in the enzymatic defense against oxygen toxicity.1 Fur-
thermore, copper has been identified as an environmen-
tal pollutant.2
Chemosensors that have displayed selectivity for Hg2+
have also shown a much more limited fluorescent change
in the presence of Cu2+ 8–10 Hg2+ has a larger atomic ra-
.
dius than Cu2+, thus by increasing the steric hindrance
around the binding site (8-HQ) it was anticipated that
a significant enhancement in the selectivity for Cu2+
compared to Hg2+ would be achieved.
The 8-hydroxyquinoline (8-HQ) moiety has been one of
the most useful ionophores, used in a variety of investi-
gations involving metal ion recognition.3 In recent years,
many chemosensors based on 8-HQ have been devel-
Based on the above observations, the sensor, 3, which
consisted of 8-HQ moiety as a binding site and BODIPY
as a reporting group was designed. Compound 3 was
efficiently synthesized from styrene. Compound 1 was
prepared from styrene by following known proce-
dures.17 Reaction of 1 with methoxytetralone in the
presence of NaH gave rise to 2 in 91% yield.18 Chemo-
sensor 3 was obtained by a one-pot three-step conver-
sion. Condensation of 8-HQ-carbaldehyde with pyrrole
2 afforded the dipyrromethane, which was subsequently
oxidized to the dipyrromethene. Subsequent treatment
with BF3–OEt2 gave 3 (Scheme 1).19
oped for sensing Zn2+
,
Cd2+,6 Pb2+,7 and Hg2+
.
4,5
8–10
However, use of 8-HQ derivatized chemosensors for
the detection of Cu2+ has not been developed. This letter
reports a highly sensitive and selective fluorescence sen-
sor for Cu2+
.
The dipyrrometheneboron difluoride (difluoroboradi-
aza-s-indacene, BODIPY) fluorescent dyes have been
widely used,11 since they have relatively high fluores-
cence quantum yields, good photo-stabilities, and
absorption coefficients.12–14 Long-wavelength absorp-
tion and emission have been shown to significantly re-
duce background absorption, background fluorescence,
and light scattering. Moreover, maximal fluorescence
emission was tunable to longer wavelength by extending
the conjugation and rigidity of the BODIPY core.15,16
Fully elaborated chemosensor 3 constitutes a flouro-
phore with absorption (660 nm) and emission (680 nm)
in the visible region, the 8-HQ also behaves as an iono-
phore. Chemosensor 3 had a more intense, sharper
absorption band compared with a more flexible BODI-
PY structure.20
Initially, metal ion selectivity was examined in aqueous
dioxane (1:1, v/v) solution. Changes of the fluorescence
properties of 3 caused by various metal ions including
Cu2+, Hg2+, K+, Mg2+, Zn2+, Fe3+, Ni2+, Co2+, and
Cd2+ (10 equiv used) were measured once emission
intensity was constant. Only Cu2+ and Hg2+ produced
Keywords: 8-Hydroxyquinoline; BODIPY; Cu2+ ion; Chemosensor.
*
Corresponding author. Tel.: +1 505 243 8073; fax: +1 505 277
2609; e-mail: pbentley@unm.edu
0040-4039/$ - see front matter ꢀ 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2006.01.091

2448
Y. Mei et al. / Tetrahedron Letters 47 (2006) 2447–2449
O
O
N
N
B
F
i.
ii., iii., iv.
F
O
OH
+
N
1
N
O
H
N
2
3
O
Scheme 1. Synthesis of chemosensor 3. Reagents and conditions: (i) NaH, DMSO, 25 ꢁC, N2 (g), 91%; (ii) 8-hydroxyquinoline-2-carbaldehyde,TFA,
DCM, 25 ꢁC, N2 (g); (iii) p-chloranil, DCM, 25 ꢁC, N2 (g); (iv) TEA, BF3–OEt2, 25 ꢁC, N2 (g), 25% (for ii, iii, iv).
5000000
4000000
3000000
2000000
1000000
0
100
free metal
Hg2+
90
10 equiv. Hg2+
10 equiv. Cu2+
Cu2+
80
600
650
700
750
800
70
0
10
20
30
40
Wavelength (nm)
Time (min)
Figure 1. Fluorescence emission spectra of 3 (5.0 · 10À6 M) in an
aqueous dioxane (1:1, v/v) solution in the presence of different metal
ions (5.0 · 10À5 M). Excitation wavelength is 550 nm. Emission
wavelength is 680 nm.
Figure 2. Fluorescence intensity of 3 (5.0 · 10À6 M) in an aqueous
dioxane (1:1, v/v) solution in the presence of Cu2+ and Hg2+
(5.0 · 10À5 M). Excitation wavelength is 550 nm. Emission wavelength
is 680 nm.
significant changes in the fluorescent spectra of 3
(Fig. 1). More significantly, as expected, the fluorescent
quenching induced by Cu2+ (quenched 97% by 10 equiv)
was more pronounced in the fluorescent quenching
induced by Hg2+ (quenched 77% by 10 equiv).
5000000
free metal
0.25 equiv. Cu2+
4000000
0.5 equiv. Cu2+
0.75 equiv. Cu2+
Interestingly, the fluorescence emission intensity of 3 in
the presence of Hg2+ increased over 45 min whilst in the
presence of Cu2+ fluorescence emission intensity de-
creased over 15 min (Fig. 2). This suggests that the com-
plex of compound 3 with Hg2+ is not very stable,
possibly due to the steric hindrance of Hg2+ with the
phenyl functionality of 3.
3000000
2000000
1000000
0
1 equiv. Cu2+
2 equiv. Cu2+
10 equiv. Cu2+
The sensitivity of the fluorescence emission response of 3
toward Cu2+ was subsequently examined under the
same conditions with various Cu2+ concentrations
(Fig. 3). The sensor exhibited high sensitivity as low as
sub-millimolar concentration. The association constant
of 3 with Cu2+ was determined as 3.11 · 105 (assuming
the formation of 1:1 complex8,21).
600
650
700
750
800
Wavelength (nm)
Figure 3. Fluorescence emission spectra (excitation at 550 nm) of 3
(5.0 · 10À6 M) in an aqueous dioxane (dioxane:water = 1:1, v/v)
solution in the presence of different concentrations of Cu2+
.
In summary, a novel chemosensor (3) based on 8-HQ
was designed and synthesized. Compound 3 showed
played higher sensitivity for Cu2+ than Hg2+ in an aque-
ous dioxane solution, which has taken advantage of the
conformationally restricted and sterically hindered
BODIPY core.
no sensitivity to numerous metal ions (K+, Mg2+
,
Zn2+, Fe3+, Ni2+, Co2+, and Cd2+). However, 3 has dis-

Y. Mei et al. / Tetrahedron Letters 47 (2006) 2447–2449
2449
8. Moon, S. Y.; Cha, N. R.; Kim, Y. H.; Chang, S.-K. J.
Org. Chem. 2004, 69, 181–183.
Acknowledgments
9. Youk, J.-S.; Kim, Y. H.; Kim, E.-J.; Youn, N. J.; Chang,
S.-K. Bull. Korean Chem. Soc. 2004, 25, 869–872.
10. Zhang, H.; Han, L.-F.; Zachariasse, K. A.; Jiang, Y.-B.
Org. Lett. 2005, 7, 4217–4220.
Financial support from the Department of Chemistry
and the Research Allocation Committee, University of
New Mexico, is gratefully acknowledged.
11. Haugland, R. P. Handbook of Fluorescent Probes and
Research Products, 9th ed.; Molecular Probes: Eugene,
2002.
Supplementary data
12. Vos de Wael, E.; Pardoen, J. A.; van Koeveringe, J. A.;
Lugtenburg, J. Recl. Trav. Chim. Pays-Bas 1977, 96, 306–
309.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.01.091.
13. Johnson, I. D.; Kang, H. C.; Haugland, R. P. Anal.
Biochem. 1991, 198, 228–237.
˚
14. Karolin, J.; Johansson, L. B.-A.; Strandberg, L.; Ny, T. J.
References and notes
Am. Chem. Soc. 1994, 116, 7801–7806.
15. Rurack, K.; Kollmannsberger, M.; Daub, J. New J. Chem.
2001, 25, 289–292.
16. Rurack, K.; Kollmannsberger, M.; Daub, J. Angew.
Chem., Int. Ed. 2001, 40, 385–387.
1. McCord, J.; Fridovich, I. J. Biol. Chem. 1969, 244, 6049–
6055.
2. Kra¨mer, R. Angew. Chem., Int. Ed. 1998, 37, 772–773.
3. Zhang, L.; Meggers, E. J. Am. Chem. Soc. 2005, 127, 74–
75.
17. Hortmann, A. G.; Robertson, D. A.; Gillard, B. K. J. Org.
Chem. 1972, 37, 322–324.
4. Pearce, D. A.; Jotterand, N.; Carrico, I. S.; Imperiali, B. J.
Am. Chem. Soc. 2001, 123, 5160–5161.
18. Sato, S.; Kato, H.; Ohta, M. Bull. Chem. Soc. Jpn. 1967,
40, 2936–2938.
5. Kawakami, J.; Ohta, M.; Yamauchi, Y.; Ohzeki, K. Anal.
Sci. 2003, 19, 1353–1354.
6. Prodi, L.; Montalti, M.; Zaccheroni, N.; Bradshaw, J. S.;
Izatt, R. M.; Savage, P. B. Tetrahedron Lett. 2001, 42,
2941–2944.
19. Baruah, M.; Qin, W.; Basaric, N.; De Borggraeve, W. M.;
Boens, N. J. Org. Chem. 2005, 70, 4152–4157.
20. Zhao, W.; Carreria, E. M. Angew. Chem., Int. Ed. 2005,
44, 1677–1679.
21. Nishizawa, S.; Cui, Y.-Y.; Minagawa, M.; Morita, K.;
Kato, Y.; Taniguchi, S.; Kato, R.; Teramae, N. J. Chem.
Soc., Perkin Trans. 2 2002, 866–870.
7. Martins, A. O.; da Silva, E. L.; Laranjeira, M. C. M.; de
Favere, V. T. Microchim. Acta 2005, 150, 27–33.