Fluorescent carbazolyldithiane as a highly selective chemodosimeter via protection/deprotection functional groups: A ratiometric fluorescent probe for Cd(II)

Article abstract of DOI:10.1016/j.tetlet.2011.03.109

A carbazole-based bis-dithiane (1) was rationally constructed in a straightforward manner for the selective and ratiometric fluorescent detection of Cd²⁺ with the concept of aldehyde group protection/deprotection. The probe showed a ratiometric fluorescent response to Cd²⁺ with a large emission wavelength shift (>50 nm) and displayed high selectivity for Cd²⁺ over other metal ions due to distinct deprotection conditions. In addition, a Cd²⁺-promoted dethioacetalization mechanism was proposed.

Full text of DOI:10.1016/j.tetlet.2011.03.109

Tetrahedron Letters 52 (2011) 2965–2968
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Fluorescent carbazolyldithiane as a highly selective chemodosimeter via
protection/deprotection functional groups: a ratiometric fluorescent probe
for Cd(II)
⇑
Ajit Kumar Mahapatra , Jagannath Roy, Prithidipa Sahoo
Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711 103, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A carbazole-based bis-dithiane (1) was rationally constructed in a straightforward manner for the selec-
Received 31 December 2010
Revised 17 March 2011
Accepted 24 March 2011
Available online 3 April 2011
2+
tive and ratiometric fluorescent detection of Cd with the concept of aldehyde group protection/depro-
2+
tection. The probe showed a ratiometric fluorescent response to Cd with a large emission wavelength
2+
shift (>50 nm) and displayed high selectivity for Cd over other metal ions due to distinct deprotection
conditions. In addition, a Cd2 -promoted dethioacetalization mechanism was proposed.
+
Ó 2011 Elsevier Ltd. All rights reserved.
The development of fluorescent chemosensors for sensing and
reporting heavy transition metal ions has been receiving consider-
able attention in recent years.1 Cadmium (Cd), an inessential ele-
ment for life, has been recognized as a highly toxic heavy metal
and is listed by the U.S. Environmental Protection Agency as one
of 126 priority pollutants. As a result of its wide use in industry
and agriculture, such as special alloys, nickel–cadmium batteries,
a chemical sensor through a specific chemical reaction between a
dosimeter molecule and target species, leading to the formation
of a fluorescent product. It is possible that when a functional
,2
11
group is in close proximity to a fluorophore, the change in elec-
tronic properties of the functional group due to protection/depro-
tection may influence the photophysical states of the sensor, and
it should lead to an observable change in the emission profile of
the fluorescent probe. This serves as the basis for the design
of fluorescent probes by the concept of protection/deprotection
of functional groups. The cyclic or acyclic thioacetals derivatives
of aldehydes are used as protective groups in multistep synthesis,
3
and phosphate fertilizers, etc., the resulting high level of cadmium
4
contamination in soil and crops has raised great concern. It causes
serious environmental and health problems, including lung, pros-
tate, and renal cancers.5 In particular, cadmium ion detection by
optical probes is a rapidly growing area owing to its strong toxicity
within the human body.6 Since cadmium can be accumulated in
organisms, there is a great need for analytical methods of detecting
and monitoring cadmium levels in an environmental sample.
In multistep synthesis, if a chemical reaction is to be carried out
selectively at one reactive site in a multifunctional compound,
other reactive sites must be temporarily blocked by using func-
12
as they are stable under both acidic and basic conditions. As an
2+
approach of the chemodosimeters toward the Cd ion, desulfur-
ization of a thioacetal can be taken into account. To date, a variety
of desulfurization methods have been devised using heavy or tran-
+
13
3
sition-metal salts with additives, such as Ag /NBS or NCS, AgNO /
1
3d
14
15
15a
I
2
,
Hg (ClO
4
)
2
/CaCO
3
,
HgO/Et
2
OÁBF
3
,
HgCl
2
/HgO/LiBF
4
and
1
6
CuCl
2
/CuO. However, to the best of our knowledge, this is the
first case of Cd -promoted dethioacetalization reaction exploited
7
2+
tional group protection/deprotection strategy. In general, protec-
2
+
tive group must be selectively removed in good yield by readily
available chemical reagents that do not attack the regenerated
functional group or under illumination with light. Photolabile pro-
in the design of Cd fluorescent probes under mild conditions.
Thus in this work, we tuned the reaction conditions to successfully
construct a ratiometric fluorescent probe (1) for Cd based on the
protection/deprotection of an aldehyde group (2), which was con-
nected to a fluorophore.
2
+
8
tecting groups, originally developed for use in organic synthesis,
9
has been employed in the ‘caging’ of biological cell imaging by
using fluorescent dyes. More recently, a number of cadmium ion
chemical sensors were developed as potent luminescent probes.
A particularly attractive alternate is the use of chemodosimeter as
As part of our ongoing research toward the development of flu-
1
0
17
oroionophores, we were interested in the construction of a ratio-
2
+
metric fluorescent probe for Cd with a large emission wavelength
shift (>50 nm). Generally the ICT (Intramolecular Charge Transfer)
1
8
is effective for an emission wavelength shift, and we decided to
⇑
Corresponding author. Tel.: +91 33 2668 4561; fax: +91 33 26684564.
E-mail addresses: akmahapatra@rediffmail.com, mahapatra574@gmail.com (A.K.
employ this signaling mechanism in our probe design. Probe 1 is
composed of
a N-butylcarbazole fluorophore unit and two
Mahapatra).
Present address: Chemistry and Chemical Biology Department, Rutgers Univer-
sity, 610 Taylor Road, Piscataway, NJ 08854, USA
1
,3-dithiane protective groups. We hypothesized that the elec-
2+
tron-rich 1,3-dithiane protective group could be removed by Cd
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.03.109

2
966
A. K. Mahapatra et al. / Tetrahedron Letters 52 (2011) 2965–2968
The selectivity of probe 1 for the Cd2+ ion was also observed by
n-Butylbromide
CO /CH CN/heat
2
+
fluorescence measurements. When the Cd concentration was in-
creased in aqueous acetonitrile (30:70 CH CN/H O (v/v), 50 mM
HEPES at pH 7.4), the intensity of the emission maximum at
83 nm progressively decreased with the concomitant formation
K
2
3
3
N
N
3
2
H
R
R = n-butyl
4
3
3
of an intense new peak around 437 nm (Fig. 2a). This large shift,
up to 55 nm, in the emission spectra allows the significant separa-
POCl
DMF
3
S
S
OHC
CHO
2+
tion of the emission peaks before and after treatment with Cd , so
S
S
18
SH SH
BF -ether
that useful ratiometric measurement could be made, which
N
3
N
should provide a dynamic range of fluorescent measurements. Fur-
thermore, a well-defined isoemissive point at 393 nm was ob-
served, which suggested that only a new species was formed.
The 1:2 stoichiometry of the complexes was proved by Job plots
R
R
1
2
Scheme 1. Synthetic scheme of 1.
(
Fig. S7). Probe 1 displayed a remarkable enhancement of emission
2
+
intensity about 5 times upon Cd solution treatment.
ions due to thiophilic affinity of Cd2+ to reveal the electron-defi-
cient dialdehyde groups. Thus, thioacetal 1 is converted into
dialdehyde 2. The ICT process within compound 2 from the elec-
tron-donating N-butylcarbazole moiety19 to the electron with-
drawing aldehyde group should lead to a bathochromic shift in
both the absorption and emission spectra. Therefore, modulation
of the electronic features of the aldehyde functional group on the
probe in the context of protection/deprotection could manipulate
ICT to afford a large wavelength shift in the spectra of the probe be-
fore and after treatment with Cd2 ions.
+
Compound 2 was synthesized from N-butylcarbazole in two
steps according to a literature procedure.20 Subsequently, 1 could
be prepared from the reaction of 2 with 1,3-ethanedithiol in the
presence of Et
2
OÁBF
3
in diethyl ether (Scheme 1).
1
The molecular structure of 1 was clearly characterized by its H
and 1 C NMR, and mass spectra analysis21 (see the Supplementary
data Figs. S1–S3).
3
The cation binding and sensing properties of 1 have been stud-
ied by using UV/vis spectroscopic technique. Figure 1 shows that
an intense absorption band of 1 in the UV–vis spectrum appears
around 273–303 nm in a solution of 30:70 CH
attributed to p–p transitions. However, the absorption spectrum
3
CN/H
2
O, which is
⁄
22
of compound 2 at 342 nm (Fig. 1) has a marked bathochromic shift
when compared to probe 1. This red shift is apparently attributed
to ICT. In addition, the red shift in absorption (Dk = 39 nm)
indicates that, indeed, the aldehyde group acts as an electron-with-
drawing group in the ICT process.
2
+
When the Cd ion was added at room temperature, the absorp-
tion maximum of 1 did not cause any significant change thus pro-
viding little useful information (Fig. S5). Therefore, we examined
the optical response of the probe 1 toward Cd2 by fluorescence
emission and excitation spectroscopy.
+
À5
Figure 2. (a) Emission spectra of 1 (1.0 Â 10 M) at different concentrations of
2+
3 2
Cd in CH CN–H O solution (30:70, v/v, 50 mM HEPES at pH 7.4), kex = 273 nm;
2
+
Figure 1. Absorption spectra of 1 and 2 in CH
3
CN-water solution (30:70, v/v)
(b) normalized emission spectra of 1(red), 2(black), 1+ 30 equiv. of Cd (green);
À4
2+
(
c = 1.0 Â 10 M.).
(c) ratiometric calibration curve I437 nm/I383 nm as a function of Cd concentration.

A. K. Mahapatra et al. / Tetrahedron Letters 52 (2011) 2965–2968
2967
2
+
More importantly, the emission spectra of 2 and 1+Cd are
2
+
nearly identical, indicating that desulfurization of 1 by Cd ions af-
fords 2 (Fig. 2b). In other words, the emission spectrum of com-
pound
2 displays a more than 50 nm bathochromic shift
compared with that of compound 1. This red shift in emission is
consistent with the bathochromic shift in absorption, and has been
ascribed to the ICT from the electron rich N-butylcarbazole moiety
to electron-deficit aldehyde group. This large emission red shift
indicates that ‘protected’ 1 and ‘deprotected’ 2 could be exploited
2
+
for the development of ratiometric fluorescent Cd
probes
(
Fig. 2c), provided that 1 could be selectively deprotected by
2
+
Cd ions to afford 2. The probe was treated with various metal ions
to investigate the selectivity. The selectivity and sensitivity of 1 to-
ward Cd were not influenced by biologically active metal ions
such as highly concentrated Na , K , Ca , and Mg (100 equiv)
as well as transition metal and other ions also Co , Pb , Cu
Hg , Fe , Cr , Ni , Mn , Sr , Ba , Zn only induced minimum
perturbation in the fluorescence spectra of probe 1 (Fig. 3a and Fig.
S6). Compound 1 retained a high Cd2 -selective chemodosimetric
response, even under polluted conditions containing heavy and
transition metal cations. Thus, probe 1 shows high selectivity for
2
+
+
+
2+
2+
2+
2+
2+
,
2
+
3+
3+
2+
2+
2+
2+
2+
Figure 4. Time dependent emission intensity change when 1 (10.0
l
M) was treated
with Cd2 (30 equiv) in 30:70 CH CN/H O.
+
3
2
+
that the nature of Cd2+-promoted desulfurization reaction is hydro-
2
3
lysis and that cadmium ions have good affinity for sulfur. The
coordination of Cd(ClO or CdCl with the sulfur atom, due to
2
+
Cd over other metal ions examined.
4
)
2
2
Furthermore, the emission color of probe 1 is metal-ion depen-
dent and displays blue fluorescence with Cd2 (Fig. 3b), demon-
strating that the probe could be employed for a convenient
the thiophilicity of the cadmium ion, activates the carbon atom
of the thioacetal, which is then hydrolyzed by water to afford the
corresponding aldehyde unit (Scheme S1).
+
2
+
visual sensing of Cd
.
To gain insight into the proposed deprotection mechanism, we
2+
2+
To examine the sensitivity of 1 for Cd ion sensing, its kinetic
study was monitored for the reaction of Cd2 -promoted deprotec-
tion of compound 1. In the literature, the dethioacetalization is of-
ten performed under drastic reaction conditions, by treating
further investigated the effect of chelating chemicals for the Cd
+
2+
ion-mediated desulfurization of 1, EDTA was added to the 1+Cd
1
0k
solution.
The resulting red-shifted emission bands of 1 caused
by Cd showed no apparent fluorescence changes upon addition
of highly concentrated EDTA solution (100 equiv) (Fig. S8).
The changes in H NMR spectroscopy during Cd -ion induced
transformation of protected 1 into the deprotected 2 at room tem-
perature was confirmed (Fig. 5). Upon gradual addition of
2
+
2 4 2 3
thioacetals with CuCl /CuO or Hg (ClO ) /CaCO in refluxing ace-
1
6
1
2+
tone for 1–2 h. However, we found that the dethioacetalization
could proceed under much milder conditions at pH 7.4, by treating
4 2 2
cyclic thioacetals with Cd(ClO ) or CdCl in aqueous acetonitrile
(
30:70 CH CN/H O (v/v), 50 mM HEPES at pH 7.4) at room temper-
3
2
4 2 3 2
Cd(ClO ) into 1 in a 50:50 CDCl :D O, the 1,3-dithiane methine
proton at d 5.38 ppm disappeared with a concomitant appearance
of a new peak at d 10.07 ppm, assignable to the corresponding
2+
ature 25 °C. Upon addition of Cd at room temperature, a pro-
nounced enhancement of fluorescent intensity (Fig. 4) was noted
even after 3–5 mins, indicative of a rapid deprotection of protected
1
2+
aldehyde proton of 2. The H NMR spectrum of 1+ Cd was iden-
tical to that of the standard, 2 (Fig. S4). In addition, the absorption,
1
to give deprotected 2.
2
+
From the results observed, we propose a reaction mechanism
excitation, and emission spectra of 1+Cd are identical with those
of the standard compound 2, suggesting that, indeed, probe 1 was
transformed into compound 2 by Cd ions. This clearly demon-
2
+
for Cd -promoted desulfurization mechanism. It is well accepted
2
+
2
+
strates that the coordination of Cd ion on the sulfur atom is req-
Figure 3. (a) Fluorescence emission spectra of probe 1 (10.0
of various metals (50 equiv) in 30:70 CH CN:H (kex = 273 nm); (b) visual
fluorescence emission of probe 1 to metal ions (50 equiv except 10 equiv Cd ) in
0:70 CH CN:H O (50 mM HEPES at pH 7.4).
lM) upon the addition
Figure 5. Partial 1H NMR (300 MHz) spectra of (a) probe 1, (b) 1 and 0.5 equiv of
Cd2+, (c) 1 and 1.0 equiv of Cd2+ and (d) 1 and 2.0 equiv of Cd (identical with
standard compound 2) in 50:50 CDCl /D O.
3 2
3
2
O
2+
2+
3
3
2

2
968
A. K. Mahapatra et al. / Tetrahedron Letters 52 (2011) 2965–2968
2
+ 14
uisite for hydrolysis of the probe. Other metal ions, such as Hg
,
8. Pillai, V. N. R. Synthesis 1980, 1; (a) Barltrop, J. A.; Schofield, P. Tetrahedron Lett.
1962, 3, 697.
2
+ 16
and Cu
,
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elicit the ratiometric fluorescence response of probe 1 (Fig. S6b),
which allows the probe to exhibit high selectivity for Cd2 . We rec-
ognized this high selectivity to distinct reaction conditions re-
quired for the hydrolysis of cyclic thioacetals by different metal
ions.
In conclusion, a carbazole-based cyclic thioacetals derivative (1)
capable of chemodosimetric Cd ion detection was synthesized.
The ratiometric fluorescent Cd2 probe was rationally constructed
in a straightforward manner under the concept of aldehyde group
protection/deprotection. The probe showed ratiometric fluorescent
+
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Acknowledgments
1
We thank the DST [W.B. Government, project no. 694(sanc.)/ST/
P/S&T/6G-6/2007] for financial support. J.R. thanks the CSIR, New
Delhi for a fellowship. We also acknowledge DST, AICTE, UGC-
SAP and MHRD for funding instrumental facilities in our
department.
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2
3
, 300 MHz): d 8.22 (s, 2H, ArH),
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–
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,
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,
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13
3
1
1
C
6
3 6
H, –CH , J = 7.30 Hz). C NMR (DMSO-d , 75 MHz): 141.01, 130.04, 125.54,
22.95, 120.07, 109.15, 52.44, 44.37, 32.44, 31.24, 30.05, 25.47, 21.06,
+
4.24 ppm. FAB MS m/z (M À1): Calcd 458.739. Found 458.80. Anal.Calcd for
24 4
H29NS (459.739): C, 62.70; H, 6.36; N, 3.05; S, 27.89. Found: C, 62.58; H,
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6
7
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