Hg2+-selective fluorogenic chemodosimeter based on naphthoflavone

Article abstract of DOI:10.1016/j.tetlet.2009.10.111

A new Hg²⁺-selective chemodosimeter based on α-naphthoflavone was investigated. The chemodosimetric behavior is based on the Hg²⁺-triggered desulfurization of flavothione into its oxygen analogue flavone. The signaling was effective in aqueous environment and the selective signaling was not affected in the presence of common physiologically and environmentally important metal ions.

Full text of DOI:10.1016/j.tetlet.2009.10.111

Tetrahedron Letters 51 (2010) 167–169
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Hg2+-selective fluorogenic chemodosimeter based on naphthoflavone
*
Ji Eun Namgoong, Hye Lim Jeon, Youn Hwan Kim, Myung Gil Choi, Suk-Kyu Chang
Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
A new Hg2+-selective chemodosimeter based on
a-naphthoflavone was investigated. The chemodosimet-
Article history:
ric behavior is based on the Hg2+-triggered desulfurization of flavothione into its oxygen analogue fla-
vone. The signaling was effective in aqueous environment and the selective signaling was not affected
in the presence of common physiologically and environmentally important metal ions.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 28 August 2009
Revised 20 October 2009
Accepted 23 October 2009
Available online 30 October 2009
The development of selective signaling systems for Hg2+ ions
has attracted interest in the chemosensing field because of the
toxic nature of Hg2+ and the substantial impact of mercurials on
the environment.1 The human body is continually exposed to an
increasing number of mercury sources, and the toxic impact of
mercurials has been well documented. A number of sophisticated
signaling systems have been developed to accommodate varying
sample concentrations and origins of Hg2+-containing com-
pounds.2 A chemodosimetric approach frequently yields successful
results in the selective and sensitive signaling of Hg2+ ions. Several
Hg2+-selective systems based on versatile fluorophores such as
rhodamine, fluorescein, anthracene, 1,8-naphthalimide, squaraine
dye, and organopalladiums have been devised,3 beginning with
the classical anthracene-based dosimeter4 developed by Czarnik
et al. Other sophisticated chemodosimeter systems are based on
sulfur-containing derivatives5 and employ desulfurization or sub-
sequent transformation reactions of thioamide,6 thiourea,7 and thi-
one.8 We have recently reported that the simple transformation of
thio-coumarin to its desulfurized derivative can be used for effi-
cient Hg2+-selective chemodosimeter system.9
Conversion of thiocarbonyl compounds into their carbonyl ana-
logues has attracted the interest of synthetic organic chemists.10
These conversions include oxidative procedures that involve inor-
ganic and organic reagents, as well as hydrolytic reactions.11 For
the hydrolysis of thiocarbonyl compounds, processes catalyzed
by metal ions result in clean reactions because the metal ion acts
as an electrophile for thiocarbonyl group sulfur, thus weakening
the C@S bond.10 Among the frequently employed metal ions, Ag+,
Au3+, Fe3+, Cu+, and Hg2+ are especially effective. For example, the
desulfurization of thioesters proceeds rapidly using solutions of
Hg2+ carboxylates in chloroform or pyridine.12
flavones have been widely investigated and crowned flavone has
À
À
been utilized as a fluorescent chemosensor for HSO4 or H2PO4
ions.13 Naphthoflavothione showed a sensitive, Hg2+-selective sig-
naling behavior in an aqueous environment.
Naphthoflavothione 1 was prepared from
a-naphthoflavone 2
by reaction with Lawesson’s reagent in good yield (Scheme 1).14
Thiocarbonyl derivatives 3–5 of other representative flavones,
including b-naphthoflavone, were similarly prepared from their
flavone precursors.
The UV–vis spectroscopic behavior of 1 toward representative
metal ions was investigated by treating it with physiologically
important alkali, alkaline earth, and transition metal perchlorates
in aqueous 50% methanol solution. Flavothione 1 exhibited strong
absorption bands at 370 and 400 nm. Upon interaction with vari-
ous metal ions, significant changes in absorption spectra were ob-
served particularly with Hg2+ and Cu2+ (Fig. S1). A concomitant
chromogenic change from yellow to colorless was observed. Other
metal ions caused relatively minor changes in the absorption spec-
tra of 1.
Fluorescence signaling of 1 was investigated in the presence of
100 equiv of representative metal perchlorates in the same solvent
system. Generally, flavothiones are known to exhibit very weak
S
O
Lawesson's reagent
Toluene
O
O
2
1
S
S
S
HO
In this Letter we report a simple chemodosimeter system for
selective Hg2+ signaling that is based on the Hg2+-induced transfor-
mation of flavothione into flavone. The photophysical properties of
O
3
O
5
O
4
* Corresponding author. Tel.: +82 2 820 5199; fax: +82 2 825 4736.
E-mail address: skchang@cau.ac.kr (S.-K. Chang).
Scheme 1. Preparation of flavothione chemodosimeters.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.111

168
J. E. Namgoong et al. / Tetrahedron Letters 51 (2010) 167–169
emission compared to their flavone analogues,15 and in fact, flavo-
S
O
thione 1 exhibited a weak fluorescence centered around 440 nm,
and
Hg(II)
a
pronounced ‘off–on’ type signaling toward Hg2+ ions
+
HgS
Tris buffer
(pH 8)
O
O
(Fig. 1). Upon interaction with various metal ions, the fluorescence
intensity at 438 nm was markedly enhanced (45-fold) with Hg2+
ions, while other metal ions did not cause any noticeable responses
(I/Io varied between 0.57 for Na+ and 1.79 for Cd2+) (Fig. S2).
The signaling mechanism is based on Hg2+-induced desulfuriza-
tion of the thio derivative (Scheme 2). The thioketone group of 1 is
readily transformed to its ketone function by reaction with Hg2+
ions16 and the liberated sulfur atom forms a stable species of
HgS with Hg2+ ions.17 As a result of this transformation, the weakly
1
2
Strongly fluorescent
Weakly fluorescent
Scheme 2. Off–on type Hg2+ signaling by desulfurization of 1.
fluorescent flavothione 1 (
transformed into strongly emitting naphthoflavone
= 0.107).18
The proposed transformation was confirmed by 1H NMR mea-
U = 0.003 in 50% aqueous methanol) is
a
2
(U
surements. Upon treatment with 2 equiv of Hg2+ ions, the 1H
NMR spectrum of 1 was converted to that of 2 (Fig. 2). Among
the changes, particularly, the significant shift for the resonance of
3-H proton from 8.06 to 7.21 ppm was noticeable. Fluorescence
measurements also supported the conversion from flavothione to
flavone (Fig. S3). The chemodosimetric nature of the signaling
was further verified by testing reversibility of the 1–Hg2+ system
with EDTA treatment. The enhanced fluorescence of the 1–Hg2+
system was not affected by treatment with EDTA, but in the pres-
ence of EDTA, the fluorescence of 1 was not enhanced upon addi-
tion of Hg2+ ions (Fig. S4). These observations demonstrated that
the 1–Hg2+ signaling system operates based on an irreversible
chemodosimetric process.
Figure 2. Partial 1H NMR spectra of 1 in the absence and presence of Hg2+ ions in
DMSO-d6. [1] = 5.0 Â 10À3 M, [Hg2+] = 1.0 Â 10À2 M.
18
15
12
9
Based on these results, the potential for general Hg2+ signaling
by representative flavones was assessed. Neither the fluorescence
of flavone nor that of 6-hydroxyflavone was sufficiently strong
for an effective ‘off–on’-type Hg2+-signaling system, using the same
experimental conditions as used for 1. In addition, b-naphthoflav-
one, which has a slightly different structure than the
exhibited similar Hg2+-selective signaling behavior, also failed to
exhibit sufficiently strong fluorescence compared to the -isomer.
Under the testing conditions, only -naphthoflavone out of several
a-isomer and
6
a
3
a
typical flavones surveyed exhibited fluorescence strong enough for
the construction of an efficient ‘off–on’ signaling of Hg2+ ions
through transformation from the flavothione into the desulfurized
flavone analogue (Fig. S5).
0
The effects of other common metal ions on the Hg2+ signaling of
1 were assessed under competitive conditions. The fluorescence in-
crease was not significantly affected by the presence of other metal
ions at 100 equiv, except for Cu2+ (Fig. 3). In the presence of Cu2+
Figure 3. Fluorescence intensity ratio (I/I0) at 438 nm of 1-Hg2+ system in the
presence of various metal ions. [1] = 5.0 Â 10À6 M, [Hg2+] = 5.0 Â 10À5 M.
[Mn+] = 5.0 Â 10À4 M. kex = 350 nm.
8
ions, the fluorescence increase was somewhat less effective, reach-
ing 83% of the 1–Hg2+ system. The decreased fluorescence might be
due to the quenching nature of paramagnetic Cu2+ ions (Fig. S6).
The observation indicated that Hg2+-selective signaling is retained
in the presence of common physiologically and environmentally
important metal ions, except for Cu2+ ions.
Hg(II)
6
4
Fluorescence titration was carried out to gain quantitative in-
sight into the signaling behavior of 1 toward Hg2+ ions. As the con-
centration of Hg2+ ions increased, the fluorescence intensity
increased steadily without any shifts in emission maximum
(Fig. 4). From the Hg2+ concentration dependency of the signaling
behavior, the detection limit of 1 for the analysis of Hg2+ ions
was estimated to be 1.6 Â 10À6 M.
2
1 only, Na(I), K(I), Mg(II),
Ca(II), Fe(II), Co(II), Ni(II),
Cu(II), Zn(II), Cd(II)
0
The Hg2+ signaling of 1 was relatively slow compared with that
of other chemodosimeters based on sulfur derivatives. A time trace
revealed that signaling was complete within about 30 min at 20 °C
(Fig. 5). Although the signaling could be moderately hastened
within 20 min at elevated temperature of 37 °C, these observations
370
420
470
520
570
620
670
Wavelength (nm)
Figure 1. Changes in fluorescence spectra of 1 in the presence of various metal ions.
In H2O/CH3OH (1:1) at pH 8.09 (10 mM tris buffer). [1] = 5.0 Â 10À6 M, [Mn+] =
5.0 Â 10À4 M. kex = 350 nm.

J. E. Namgoong et al. / Tetrahedron Letters 51 (2010) 167–169
169
8
6
4
2
In summary, a simple Hg2+-selective chemodosimetric system
based on naphthoflavothione was investigated. The signaling is
due to the Hg2+-induced desulfurization of flavothione. The trans-
formation induced Hg2+-selective chromogenic and fluorogenic
signaling behaviors of 1. The Hg2+-induced transformation from
thioketone to ketone might be used for the construction of novel
switching or signaling systems for Hg2+ ions.
8
4
0
Hg(II)
0
1
2
Equiv of Hg(II)
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.111.
0
References and notes
370
420
470
520
Wavelength (nm)
570
620
670
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decomposed; however, spontaneous decomposition of 1 itself un-
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from preparation. These observations suggest that the selective
determination of Hg2+ ions by fluorescence enhancement could
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