A highly selective and sensitive turn-on catalytic chemodosimeter for Cu2+ in aqueous solution

Article abstract of DOI:10.1016/j.tetlet.2008.10.050

We report herein the first diaminocyclopent-2-enone-based catalytic chemodosimeter (3) for naked-eye and turn-on fluorescent detections of Cu²⁺ in pure aqueous solution. Compound 3 easily made available from furan-2-carbaldehyde and 2-aminobenz

Full text of DOI:10.1016/j.tetlet.2008.10.050

Tetrahedron Letters 50 (2009) 29–31
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Tetrahedron Letters
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A highly selective and sensitive turn-on catalytic chemodosimeter
for Cu2+ in aqueous solution
*
Qiang-Li Wang, Han Zhang, Yun-Bao Jiang
Department of Chemistry, College of Chemistry and Chemical Engineering, The MOE Key Laboratory of Analytical Sciences, Xiamen University, Xiamen 361005, China
a r t i c l e i n f o
a b s t r a c t
Article history:
We report herein the first diaminocyclopent-2-enone-based catalytic chemodosimeter (3) for naked-eye
and turn-on fluorescent detections of Cu2+ in pure aqueous solution. Compound 3 easily made available
from furan-2-carbaldehyde and 2-aminobenzoic acid was found to show a highly selective and sensitive
response toward Cu2+ by way of Cu2+-coordination promoted formation of Stenhouse salt and subsequent
decomposition to highly fluorescent 2-aminobenzoate.
Received 3 September 2008
Revised 29 September 2008
Accepted 11 October 2008
Available online 17 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Cu2+ as the third abundant heavy metal ion in human body has
recently attracted much attention due to its obvious biological
importance and increasing environmental concerns.1 Detection of
Cu2+ with high selectivity and sensitivity represents hence a chal-
lenging subject. Fluorescence signaling is advantageous in many
respects such as high sensitivity and easy operation. Cu2+ as a para-
magnetic species, however, shows an inherent fluorescence
quenching nature. As a consequence, most of the reported fluores-
cent chemosensors for Cu2+ operate under fluorescence quenching
mode.2,3 Fluorescence signaling showing an enhancement is for
sensitivity reason prior to those exhibiting quenching,4 especially
in aqueous solutions in which fluorescence could be weak because
of efficient quenching of highly polar water molecules. Fluorescent
chemosensors for detection of Cu2+ in aqueous solutions with a
fluorescence enhancement output have indeed been a subject of
many recent investigations;5 however, those successful in pure
aqueous solutions remain rare.6 We report herein a highly selective
yet simple chemosensor for Cu2+ with an enhanced fluorescence
output in pure aqueous solution.
2-Aminobenzoic acid (1, Scheme 1) has been widely employed
as a highly fluorescent label.7 Indeed, 1 has a high fluorescence
quantum yield7b,8 of 0.56 in aqueous HEPES buffer solution (pH
7.4, 10 mM). Obviously, there is only 2-fold fluorescence enhance-
ment remaining for 1 upon metal binding, if any. It is known that
substitution of the amino group to form a secondary amine would
lead to the loss of fluorescence.7b,9 This provides a new entry for
controlling its fluorescence of 1. Reaction of 1 with aldehyde seems
suitable in this regard and would yield a good fluorescent sensing
Scheme 1. Chemical structure of 1–3.
* Corresponding author. Tel./fax: +86 592 2185662.
E-mail address: ybjiang@xmu.edu.cn (Y.-B. Jiang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.050

30
Q.-L. Wang et al. / Tetrahedron Letters 50 (2009) 29–31
system if the product could undergo transformations into 1 in the
presence of an analyte.10,11 3 reported herein was therefore ob-
tained,11 which indeed has a low fluorescence quantum yield of
0.012 in aqueous 10 mM HEPES buffer solution of pH 7.4. Inspired
by the regioselective Cu2+-catalyzed amination of only 2-bromo-
benzoic acid rather than its 3- and 4-isomers, due probably to a
similar Cu2+-aminoacid coordination motif in the transition sta-
te,6e,12 we expected that 3 might show a high selectivity toward
Cu2+ by a fluorescence enhancement response with moiety 1 being
both the binding site and fluorophore.
A criterion for designing a chemodosimeter was considered that
it should be not only weakly fluorescent but also conditionally
stable (Fig. S1, Supplementary data). After screening a variety of
aldehydes, 3 was made available from a convenient one-pot
condensation of furan-2-carbaldehyde with 1 in ethanol (yield
85%).11,13 Absorption spectrum of 3 in 10 mM aqueous HEPES buf-
fer solution of pH 7.4 showed three bands at 210, 252, and 330 nm,
respectively (Fig. 1a). In the presence of Cu2+, the band at 330 nm
was attenuated, while absorbance at shorter wavelength was in-
creased with an isosbestic point observed at 320 nm. It is worthy
to note that a new band appeared at 512 nm that increases at
low Cu2+ concentration, whereas it undergoes a decrease at higher
Cu2+ concentration (Fig. 1a and inset). Other transition metal ions
such as Hg2+, Pb2+, Zn2+, Cd2+, Ni2+, Ag+, Co2+, and Fe3+, and some
alkali and alkaline earth metal ions were also tested (Fig. S2), but
showed no significant influence on the absorption spectrum of 3.
Selective interaction of 3 with Cu2+ was therefore made obvious.
The new band at 512 nm in the presence of Cu2+ affording a purple
color makes it feasible for naked-eye detection of Cu2+ (Fig. 2).
Fluorescence of 3 in the presence of metal ions in aqueous
HEPES buffer solution was monitored after assay condition optimi-
zations (Figs. S1 and S3). An enhanced emission was observed at
394 nm with increasing Cu2+ concentration (Fig. 1b), whereas the
tested other transition and alkali and alkaline earth metal ions pro-
duced no significant variations. This indicates a high selectivity in
its fluorescence enhancement response of 3 toward Cu2+ against
other metal ions (Fig. 3). The excellent selectivity was further dem-
onstrated in that the fluorescence enhancement by Cu2+ was not
affected by the co-existence of other metal ions (Fig. 3 inset).
Optimization established that fluorescence enhancement of 3
showed a good linearity (r = 0.998) over Cu2+ concentration of
0.5–2.25 lM in aqueous buffer solution (Fig. S4). The detection
limit of Cu2+ calculated on the basis of 3 /k14 is 15 nM or 1 ppb,
r
pointing to the high detection sensitivity. Counter anion of Cu2+
was found to exert no obvious influÀence on the fluorescence
À
À
response, with anions being ClO4À, Cl , AcO , SO42À, and NO3
(Fig. S5).
On the basis of the reversibility shown in the synthetic mecha-
nism (Scheme 1),11 and the known selective strong binding of
aminoacid with Cu2+ 6e,12
carbonyl oxygen in cyclopent-2-enone
,
should also take part in Cu2+ binding,11a in addition to chelating
to the aminoacid moiety so that Cu2+ acted as a Lewis acid to coop-
eratively promote decomposition of 3 to 1. Indeed, color changes
were observed for 3 in the presence of Cu2+ as that observed in
the case of H+ with the formation of purple Stenhouse salts 2
(Scheme 1).11a It should be pointed out that the purple color
decreases with standing time or further increase in Cu2+ concentra-
tion (Fig. 1a and inset). Decomposition of Stenhouse salts 2 to
colorless 1 was therefore suggested and the formation of 1 was
confirmed by TLC pattern, NMR, and ESI-MS data of the isolated
product. It has been proved that a catalytic chemodosimeter shows
a higher affinity toward an analyte than its decomposed product so
that the analyte could further re-interact with the chemodosime-
ter, affording a turnover number higher than 1.6h Although binding
constant of Cu2+ to 1 was determined as 1.3 Â 104 MÀ1, that of Cu2+
to 3 is unavailable, it is not straightforward to judge if 3 is a cata-
lytic or stoichiometric chemodosimeter.6h We therefore deter-
mined the reaction order of Cu2+ to be 1.6 (Fig. S6). It was hence
expected that, if 1 and 3 have the same binding constant toward
Cu2+, the actual concentration of Cu2+ that interacts with 3 will
be reduced by a half in the presence of 1 equiv of 1 in a 3-Cu2+
(1:1) solution, assuming a 1:1 stoichiometry both of 1 and 3
Figure 1. Absorption (a) and fluorescence (b) spectra of 3 in the presence of Cu2+
over 0–2.0 Â 10À5 M in aqueous 10 mM HEPES buffer solution of pH 7.4. Excitation
wavelength was 320 nm, an isosbestic point observed in the absorption titrations.
[3] = 1.0 Â 10À4 M (a) and 1.0 Â 10À6 M (b).
Figure 3. Fluorescent response of 3 toward metal ion at 2.5 Â 10À5 M in 10 mM
aqueous HEPES buffer solution of pH 7.4. Inset shows the response toward Cu2+ of
5 Â 10À6 M plus co-existing metal ion at 2.5 Â 10À5 M. ‘All’ means all the tested
interference metal ions are present but at a concentration of 5 Â 10À6 M each.
[3] = 1.0 Â 10À6 M.
Figure 2. Naked-eye detection of metal ions (1.0 Â 10À5 M) in aqueous 10 mM
HEPES buffer solution of pH 7.4. [3] = 1.0 Â 10À4 M. Note that 1
l
M Cu2+ is easily
detected by naked eyes.

Q.-L. Wang et al. / Tetrahedron Letters 50 (2009) 29–31
31
toward Cu2+. As a consequence, the fluorescent response rate
would decrease by a factor of ca. 0.33 when Cu2+ concentration de-
creased from 1.0 Â 10À6 M to 0.5 Â 10À6 M (cf. Fig. S6). In compe-
tition experiments, however, it was found that the fluorescent
response rate of 3 toward 1 equiv of Cu2+ was not affected by
2 equiv of 1 (Fig. S7). These observations indicated that 3 bound
more strongly toward Cu2+ than 1, likely due to more binding sites
in 3. This means that indeed Cu2+ could re-interact with 3 after
decomposition of a previous molecule of 3, hence less than stoichi-
ometric amount of Cu2+ being able to decompose 3 into 1. Although
it is still unable to get the real stoichiometry of 3 toward Cu2+, 20
turnovers of hydrolysis were observed assuming a 1:1 stoichiome-
try of 3-Cu2+ complex (Fig. S8). Compound 3 was therefore con-
cluded a catalytic chemodosimeter, capable of accumulating and
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amplifying the signal in response to Cu .
2+ 6h We noted that the fluo-
rescence of 1 was not quenched by Cu2+ under the tested Cu2+ con-
centration (Fig. S9), which explained the observed fluorescence
enhancement of 3 even at high Cu2+ concentration.
In summary, 3 was developed as a highly selective and sensitive
catalytic chemodosimeter for naked-eye and turn-on fluorescent
detections of Cu2+ in pure aqueous solution with a detection limit
of 1 ppb. Fluorescence of aqueous solution of 3 was found substan-
tially enhanced by Cu2+, which was shown to result from a metal-
coordination promoted decomposition of 3 into highly fluorescent
1. Compound 3 therefore represents a new kind of ‘turn-on’ fluo-
rescent chemodosimeter for Cu2+ 6a
Other structural motifs on
.
amine substitution are in general possible to allow for extended
applications of the reported strategy in constructing chemodosi-
meters for supramolecular analytical chemistry.15
Acknowledgments
This work was supported by NSFC through Grants Nos.
20425518, 20675069, and 20835005.
Supplementary data
13. Compound 3 was synthesized by stirring furan-2-carbaldehyde (0.173 mL,
0.18 mmol) and 1 (0.5 g, 0.36 mmol) in 15 mL ethanol at room temperature for
24 h. After filtration and washing with diethyl ether, 3 was obtained as a
yellow solid (0.63 g, yield 85%). 1H NMR (400 MHz, DMSO-d6), d (ppm): 4.51–
4.54 (ddd, J = 3.5, 3.7 and 3.5 Hz, 1H), 4.94–4.96 (m, 1H), 6.49 (dd, J = 1.7 and
J = 4.4 Hz, 1H), 6.56–6.63 (m, 2H), 6.73 (d, J = 8.5 Hz, 1H), 6.92 (d, J = 8.4 Hz,
1H), 7.17–7.21 (m, 1H), 7.26–7.31 (m, 1H), 7.74 (dd, J = 1.8 and J = 4.3 Hz, 1H),
7.78–7.84 (m, 2H), 8.31–8.34 (m, 2H), 12.76 (s, 2H); 13C NMR (100 MHz,
DMSO-d6), d (ppm): 59.46, 65.26, 111.32, 111.41, 112.55, 112.82, 115.79,
115.96, 132.12, 132.28, 132.84, 134.63, 134.96, 150.08, 150.66, 161.21, 170.30,
170.42, 203.47. HRMS, calcd. for (M+H)+ m/z 353.1132, found 353.1137.
Supplementary data (synthesis of 3, absorption spectra of 3 in
the presence of metal ions, and optimal conditions for fluorescence
assays) associated with this article can be found, in the online ver-
sion, at doi:10.1016/j.tetlet.2008.10.050.
References and notes
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