Highly selective ratiometric fluorescent sensing for Hg2+ and Au3+, respectively, in aqueous media

Article abstract of DOI:10.1021/ol1024585

A nonsulfur probe based on a 1,8-naphthalimide and alkyne conjugate for the ratiometric fluorescent sensing for Hg²⁺ and Au³⁺ through the tuning of pH in different aqueous solutions is described. This work provides a novel reaction-based approach for selective recognition of these two ions with significant change of fluorescence color and constitutes the first ratiometric case for Au³⁺.

Full text of DOI:10.1021/ol1024585

ORGANIC
LETTERS
2010
Vol. 12, No. 22
5310-5313
Highly Selective Ratiometric Fluorescent
Sensing for Hg2+ and Au3+,
Respectively, in Aqueous Media
Ming Dong, Ya-Wen Wang,* and Yu Peng*
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous
Metals Chemistry and Resources Utilization of Gansu ProVince and College of
Chemistry and Chemical Engineering, Lanzhou UniVersity, Lanzhou 730000, China
ywwang@lzu.edu.cn; pengyu@lzu.edu.cn
Received October 11, 2010
ABSTRACT
A nonsulfur probe based on a 1,8-naphthalimide and alkyne conjugate for the ratiometric fluorescent sensing for Hg2+ and Au3+ through the
tuning of pH in different aqueous solutions is described. This work provides a novel reaction-based approach for selective recognition of
these two ions with significant change of fluorescence color and constitutes the first ratiometric case for Au3+
.
As one of the most toxic heavy metal elements, mercury
can lead to the dysfunction of the brain, kidney, stomach,
and central nervous system because of the thiophilic nature
in proteins and enzymes.1 Thus, mercury pollution has
sparked interest in the design of new tactics to monitor Hg2+
in biological and environmental samples. Especially, various
fluorescent chemosensors for Hg2+ have been described
recently2 owing to their high sensitivity, selectivity, versatil-
ity, and relatively simple handling. Also, since Czarnik
pioneeringly described the first synthetic chemodosimeter for
the selective determination of Hg2+,3 this new approach based
on an irreversible chemical reaction has emerged as an active
research area of significant importance.4
However, most chemodosimeters contain an “S” group just
like traditional reversible chemosensors based on coordina-
tion of Hg2+ to the S atom.5 The corresponding mechanisms
stem from irreversible organic reactions triggered by ex-
tremely strong Hg-S affinity, including: (1) ring opening
of spirocyclic systems (rhodamine and fluorescein, etc.),6 (2)
intramolecular cyclic guanylation of thiourea derivatives,7
(4) For a very recent review, see: Quang, D. T.; Kim, J. S. Chem. ReV.
2010, 110, 6280–6301.
(5) For selected recent examples, see: (a) Yoon, S.; Albers, A. E.; Wong,
A. P.; Chang, C. J. J. Am. Chem. Soc. 2005, 127, 16030–16031. (b) Nolan,
E. M.; Lippard, S. J. J. Am. Chem. Soc. 2007, 129, 5910–5918. (c) Zhu,
M.; Yuan, M.; Liu, X.; Xu, J.; Lv, J.; Huang, C.; Liu, H.; Li, Y.; Wang, S.;
Zhu, D. Org. Lett. 2008, 10, 1481–1484. (d) Chen, X.; Nam, S.-W.; Jou,
M. J.; Kim, Y.; Kim, S.-J.; Park, S.; Yoon, J. Org. Lett. 2008, 10, 5235–
5238. (e) Suresh, M.; Mishra, S.; Mishra, S. K.; Suresh, E.; Mandal, A. K.;
Shrivastav, A.; Das, A. Org. Lett. 2009, 11, 2740–2743. (f) Tian, M.; Ihmels,
H. Chem. Commun. 2009, 3175–3177.
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Pickering, I. J.; George, G. N. Science 2003, 301, 1203. (c) Onyido, I.;
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(2) For a recent review, see: Nolan, E. M.; Lippard, S. J. Chem. ReV.
2008, 108, 3443–3480.
(3) Chae, M.-Y.; Czarnik, A. W. J. Am. Chem. Soc. 1992, 114, 9704–
9705.
10.1021/ol1024585  2010 American Chemical Society
Published on Web 10/29/2010

and (3) conversion of thiocarbonyl compounds into their
carbonyl analogues8 (Scheme 1) and a sequential desulfuriza-
herein we report a highly selective ratiometric fluorescent
probe for Hg2+ in water at neutral pH based on the 1,8-
naphthalimide fluorophore tethered via an alkyne moiety.
Switch of selectivity to Au3+ was also observed after the
tuning of pH, which constituted the first ratiometric case.
As shown in Scheme 2, the probe 1 was easily prepared from
Scheme 1.
Reaction-Based Tactics for the Sensing of Hg2+
Scheme 2. Synthesis of Probe 1
tion-lactonization reaction.9 This thiophilic approach cannot
avoid potential interference in sulfur-rich environments where
mercury is abundant,10 and undesired oxidation of the probes
containing a sulfur atom by air or oxidizing reagents always
takes place. Other drawbacks may be utilization of elevated
temperature or excess quantities of Hg2+ to drive these
desulfurization reactions to completion. Thus, investigation
of a nonsulfur strategy11 except a direct mercuration reac-
tion12 is highly desirable. Although hydration of alkynes
catalyzed by Hg2+ (Kucherov reaction)13 has been known
for a century, curiously, the great potential of this classic
reaction has not been recognized until recently, and only two
examples that are limited in the coumarin and fluorescein
fluorophores, both of which are not ratiometric, can be found
to date.14 Extension of this methodology to other fluoro-
phores for the development of more effective (especially
ratiometric) sensors is still in high demand.
5-nitroacenaphthene by modifying the reported procedure16
(see Supporting Information).
Next, Hg2+, Ag+, Au3+, Au+, Al3+, Ba2+, Ca2+, Cd2+,
Co2+, Cu2+, Fe2+, Fe3+, K+, Li+, Mg2+, Mn2+, Na+, Ni2+,
Pb2+, Sr2+, and Zn2+ ions were used to measure the
selectivity of probe 1 (5 µM) in HEPES buffer (0.01 M, pH
) 7.4) (0.05% DMSO, v/v), and fluorescence spectra were
recorded after 5 min upon the addition of 2.0 equiv of each
of these metal ions. Compared to other metal ions examined,
only Hg2+ caused the change of the maximum fluorescence
emission band of probe 1 from 543 to 486 nm (Figure 1a).
To validate the selectivity of 1 in practice, the competition
experiments were also measured by addition of 0.12 equiv
of Hg2+ to the aqueous solutions in the presence of 1.0 equiv
of other metal ions as shown in Figure 1b. All competitive
metal ions had no obvious interference with the detection
of the Hg2+ ion, which indicated that the system of 1-Hg2+
was hardly affected by these coexistent ions. These results
suggested that probe 1 displayed an excellent selectivity
toward Hg2+ in water at neutral pH.
In connection with our continuing research of sensors for
biologically and environmentally important metal ions,15
(6) (a) Yang, Y.-K.; Yook, K.-J.; Tae, J. J. Am. Chem. Soc. 2005, 127,
16760–16761. (b) Yang, Y.-K.; Ko, S.-K.; Shin, I.; Tae, J. Nat. Protoc.
2007, 2, 1740–1745. (c) Shi, W.; Ma, H. Chem. Commun. 2008, 1856–
1858. (d) Lin, W.; Cao, X.; Ding, Y.; Yuan, L.; Long, L. Chem. Commun.
2010, 46, 3529–3531.
The fluorescence titration of Hg2+ was conducted using a
5 µM solution of 1 in HEPES buffer (0.01 M, pH ) 7.4)
(0.05% DMSO, v/v). Upon the addition of Hg2+ to the
solution, a significant decrease of the fluorescence intensity
at 543 nm and an increase of fluorescence emission band
centered at 486 nm were observed with an isoemission point
at 509 nm, which indicated a clear ratiometric fluorescence
change (Figure 1c).17 The ratio of fluorescence intensity at
(7) (a) Wu, J.-S.; Hwang, I.-C.; Kim, K. S.; Kim, J. S. Org. Lett. 2007,
9, 907–910. (b) Lee, M. H.; Lee, S. W.; Kim, S. H.; Kang, C.; Kim, J. S.
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Namgoong, J. E.; Chang, S.-K. Chem. Commun. 2009, 3560–3562. (c)
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Tetrahedron Lett. 2010, 51, 167–169.
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K. H. Chem. Commun. 2009, 2115–2117. (b) Cho, Y.-S.; Ahn, K. H.
Tetrahedron Lett. 2010, 51, 3852–3854. (c) Du, J.; Fan, J.; Peng, X.; Sun,
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A.-J.; Dong, Y.-M.; Wang, Y.-W.; Peng, Y. Dyes Pigm. 2010, 87, 164–
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Y.-W. J. Lumin. 2010, 130, 888–892.
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Ann. N.Y. Acad. Sci. 2008, 1130, 218–223. (b) Kele, P.; Li, X.; Link, M.;
Nagy, K.; Herner, A.; L’orincz, K.; Be´ni, S.; Wolfbeis, O. S. Org. Biomol.
Chem. 2009, 7, 3486–3490.
(13) (a) Kucherov, M. G. Chem. Ber. 1909, 42, 2759–2762. For a recent
review, see (b) Hintermann, L.; Labonne, A. Synthesis 2007, 1121–1150.
(14) (a) Lee, D.-N.; Kim, G.-J.; Kim, H.-J. Tetrahedron Lett. 2009, 50,
4766–4768. (b) Koide developed a chemodosimeter based on tandem
hydration of the alkyne and ꢀ-elimination; however, indispensable high
temperature (90 °C) could not be compatible in the thermosensitive systems.
See: Song, F.; Watanabe, S.; Floreancig, P. E.; Koide, K. J. J. Am. Chem.
Soc. 2008, 130, 16460-16461.
(17) To date, all known ratiometric chemodosimeters utilized “S”
approach and work in mixed organic/aqueous media. See: (a) Liu, B.; Tian,
H. Chem. Commun. 2005, 3156–3158. (b) Zhang, X.; Xiao, Y.; Qian, X.
Angew. Chem., Int. Ed. 2008, 47, 8025–8029. (c) Shang, G.-Q.; Gao, X.;
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Org. Lett., Vol. 12, No. 22, 2010
5311

Figure 2
and 543 nm of 1 (5 µM) in HEPES (0.01 M) in the absence and
presence of 0.5 µM Hg2+
. Effect of pH on the ratio of fluorescence intensity at 486
.
gold ions are underdeveloped.21 We surmised that the switch
of selectivity is feasible owing to strong alkynophilicity of
gold ions just like that of mercury.22,23 To our delight,
ratiometric sensing of Au3+ is observed through careful
adjustment of test conditions.24
Upon the addition of various metal ions to the MeOH-H2O
(95:5 v/v, pH ) 9.0) solution of probe 1, only Au3+ caused the
change of the maximum fluorescence emission band of 1 from
509 to 473 nm (Figure 3a). All competitive metal ions had no
obvious interference (Figure 3b). The ratio of fluorescence
intensity between 509 and 473 nm increased linearly with
increasing Au3+ concentration (100-150 µM) (Figure 3c), and
a change from green to blue in fluorescence color was also
observed (Figure 3d). These results indicated that 1 could be a
fluorescent ratiometric probe for the Au3+ ion.
Figure 1. (a) Fluorescence responses of 1 (5 µM) with various
metal ions (10 µM) in HEPES buffer (0.01 M, pH )7.4) (0.05%
DMSO, v/v) (λex ) 420 nm). (b) Metal-ion selectivity of 1 (5 µM).
The black bars represent the emission intensity of 1 in the presence
of other cations (5 µM). The gray bars represent the emission
intensity that occurs upon the subsequent addition of 0.6 µM Hg2+
to the above solution. From 1 to 21: none, Ag+, Au3+, Au+, Al3+
Ba2+, Ca2+, Cd2+, Co2+, Cu2+, Fe2+, Fe3+, K+, Li+, Mg2+, Mn2+
,
,
Na+, Ni2+, Pb2+, Sr2+, Zn2+, and Pd2+. (c) Fluorescent spectra of 1
(5 µM) upon addition of Hg2+ (λex ) 420 nm). Inset: Ratiometric
fluorescence intensity [I486/I543] as a function of [Hg2+]. (d)
Fluorescence change of 1. Left to right: 1 only, Hg2+, Zn2+, Cd2+
,
Cu2+, Ag+, Au3+, Pb2+
.
The rational analysis of selective recognition of Hg2+ and
Au3+ is accommodated in the well-established Kucherov
reaction mechanism13b (Scheme 3). In this case, the initial
formation of the short-lived π-complex25 is attacked by water
with Markovnikov regioselectivity and anti stereoselectivity.
The resulting oxymercuration intermediate 2 will be con-
verted to methyl ketone 3 eventually through tautomerization
and hydrode-mercuration. It is noteworthy that vinylmercury
2 (Figures S6-S8, Supporting Information) instead of 3
(Figure S9, Supporting Information) is responsible for
ratiometric sensing and the blue shift of fluorescence. As
486-543 nm increased linearly with the concentration of
Hg2+ (0.01-10 µM). The corresponding detection limit18
was determined to be 0.05 µM (10 ppb) (Figure S1,
Supporting Information). In addition, only the aqueous
solution containing Hg2+ showed a change of fluorescence
color from yellowish green to teal (Figure 1d). These results
indicated that 1 can function as a fluorescent ratiometric
probe for the Hg2+ ion in aqueous solution.
The pH dependence of the fluorescence intensity of 1 and
the 1-Hg2+ system is shown in Figures 2 and S2 and S3
(Supporting Information).19 Free 1 was insensitive against
H+ and OH-. However, as pH value of the solution
decreased, the fluorescence intensity at 486 nm was enhanced
more significantly. These results promoted us to explore the
function of 1 at an acidic pH value similar to gastric juice.
As shown in Figures S4 and S5 (Supporting Information), 1
functions well at very low pH (1.0) and could serve as a
potential probe for recognition of the Hg2+ under gastric juice
condition, although it could not provide a ratiometric
response.
(20) (a) Fu¨rstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46,
3410–3449. (b) Li, Z.; Brouwer, C.; He, C. Chem. ReV. 2008, 108, 3239–
3265. (c) Arcadi, A. Chem. ReV. 2008, 108, 3266–3325. (d) Jime´nez-Nu´nez,
E.; Echavarren, A. M. Chem. ReV. 2008, 108, 3326–3350. (e) Gorin, D. J.;
Sherry, B. D.; Toste, F. D. Chem. ReV. 2008, 108, 3351–3378. (f) Hashmi,
A. S. K.; Rudolph, M. Chem. Soc. ReV. 2008, 37, 1766–1755
.
(21) Only 4 examples were reported so far, and three of them are based
on ring opening of rhodamine derivatves. see: (a) Jou, M. J.; Chen, X.;
Swamy, K. M. K.; Kim, H. N.; Kim, H.-J.; Lee, S.-g.; Yoon, J. Chem.
Commun. 2009, 7218–7220. (b) Yang, Y.-K.; Lee, S.; Tae, J. Org. Lett.
2009, 11, 5610–5613. (c) Egorova, O. A.; Seo, H.; Chatterjee, A.; Ahn,
K. H. Org. Lett. 2010, 12, 401–403. (d) Do, J. H.; Kim, H. N.; Yoon, J.;
Kim, J. S.; Kim, H.-J. Org. Lett. 2010, 12, 932–934. All of them are not
ratiometric cases.
(22) This similar behavior has been attributed to the common electronic
properties for these two elements in the valence shell, in part due to
relativistic effects. See: Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–
Despite considerable recent interest and advances in gold-
catalyzed organic transformations,20 fluorescent sensors for
403
(23) Use of gold for the hydration of alkyne: Leyva, A.; Corma, A. J.
Org. Chem. 2009, 74, 2067–2074, and references cited therein
.
(18) For the details, see: Chatterjee, A.; Santra, M.; Won, N.; Kim, S.;
Kim, J. K.; Kim, S. B.; Ahn, K. H. J. Am. Chem. Soc. 2009, 131, 2040–
2041.
.
(24) For an example in which subtle change of condition resulted the
dramatic switch of selectivity, see: Kim, K. N.; Choi, M. G.; Noh, J. H.;
Ahn, S.; Chang, S.-K. Bull. Korean Chem. Soc. 2008, 29, 571–574.
(25) For the related coinage metal π-complexes, see: Shapiro, N. D.;
Toste, F. D. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 2779–2782.
(19) For a fluorescent probe for Hg2+ with a broad pH range, see:
Shiraishi, Y.; Sumiya, S.; Hirai, T. Org. Biomol. Chem. 2010, 8, 1310–
1314, and references cited therein.
5312
Org. Lett., Vol. 12, No. 22, 2010

Scheme 3. Mechanistic Analysis
and MS (Figures S19-S21, Supporting Information). The
ratiometric sensing of Au3+ also followed a similar pathway
through the analogus vinylgold intermediate.26,27
In summary, we have developed a highly selective
ratiometric fluorescent probe for Hg2+ or Au3+ in aqueous
media depending on reaction conditions. This work provides
a novel nonsufur approach for selective recognition of these
two ions and constitutes the first ratiometric case for Au3+.
Figure 3
. (a) Fluorescence responses of 1 (5 µM) with various
metal ions (180 µM) in MeOH-H2O (95:5 v/v, pH ) 9.0) (λex
)
420 nm). (b) Metal-ion selectivity of 1 (5 µM). The black bars
represent the emission intensity of 1 in the presence of other cations
(500 µM). The gray bars represent the emission intensity that occurs
upon the subsequent addition of 180 µM Au3+ to the above solution.
From 1 to 21: none, Ag+, Au+, Al3+, Ba2+, Ca2+, Cd2+, Co2+, Cu2+
,
,
Fe2+, Fe3+, Hg2+, K+, Li+, Mg2+, Mn2+, Na+, Ni2+, Pb2+, Sr2+
Zn2+, and Pd2+. (c) Fluorescent spectra of 1 (5 µM, MeOH-H2O,
95:5 v/v, pH ) 9.0) upon addition of Au3+ (0-36.0 equiv) (λex
)
Acknowledgment. This work was supported by NSFC
(No. 20802029 and 21001058) and MOE (lzujbky-2009-72
and lzujbky-2010-38). We thank Prof. Liming Zhang of
UCSB as a mentor in Gold Chemistry.
420 nm). Inset: Ratiometric fluorescence intensity [I473/I509] as a
function of [Au3+]. (d) Fluorescence change of 1. Left to right: 1
only, Au3+, Hg2+, Zn2+, Cd2+, Cu2+, Ag+, Pb2+
.
Supporting Information Available: Experimental pro-
1
cedures, spectral data, and copies of H/13C NMR and MS.
shown in Figure S10 (Supporting Information), a new peak
(δ ) 6.01 ppm) assigned as the double bond proton of 2
was observed, and other corresponding signals were all
downfield shifted upon the addition of Hg2+ to 1. Mass
spectrometry analysis (m/z 505.1) also supported the exist-
ence of 2 (Figure S11, Supporting Information). In the test
conditions, it needed about 5 h for Hg2+ and 12 h for Au3+
to obtain 3, respectively. After increasing the concentration
of Hg2+ or Au3+ (∼33 mM), 3 was observed immediately,
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL1024585
(26) For the selected studies involving characterization of vinylgold
species, see: (a) Liu, L.-P.; Xu, B.; Mashuta, M. S.; Hammond, G. B. J. Am.
Chem. Soc. 2008, 130, 17642–17643. (b) Hashmi, A. S. K. Angew. Chem.,
Int. Ed. 2010, 49, 5232–5241, andreferences cited therein
.
(27) The mass spectrum of 1 + AuCl3 displayed two main peaks at m/z
1
which was then isolated and characterized by H/13C NMR
534.9 [M + H] and 268.1 [M-AuCl2]. See Figure S12 (SI) for details.
Org. Lett., Vol. 12, No. 22, 2010
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