Design of a dual sensing highly selective cyanide chemodosimeter based on pyridinium ring chemistry

Article abstract of DOI:10.1039/c0nj00715c

A new chemodosimeter, Quino-P, recognizes the strongly nucleophilic cyanide by dual colorimetric and fluorescence 'off-on' signalling responses. Noteworthily, several other anions, even in significantly higher concentrations, induce no detectable photophysical perturbations. The chemodosimeter mechanism involves formation of a C4-cyano adduct, which exhibits an uncommon phenomenon of enhanced internal charge transfer interaction. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011.

Full text of DOI:10.1039/c0nj00715c

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LETTER
Design of a dual sensing highly selective cyanide chemodosimeter based
on pyridinium ring chemistryw
Sabir H. Mashraqui,*a Rupesh Betkar,a Mukesh Chandiramani,a
Carolina Estarellasb and Antonio Fronterab
Received (in Montpellier, France) 18th September 2010, Accepted 2nd November 2010
DOI: 10.1039/c0nj00715c
trifluoroacetophenone,11 dicyano-vinyl calix[4]pyrrole12 and
analogs.13 Typically, these chromophores are specifically
A new chemodosimeter, Quino-P, recognizes the strongly
nucleophilic cyanide by dual colorimetric and fluorescence
‘off–on’ signalling responses. Noteworthily, several other anions,
even in significantly higher concentrations, induce no detectable
photophysical perturbations. The chemodosimeter mechanism
involves formation of a C4–cyano adduct, which exhibits an
uncommon phenomenon of enhanced internal charge transfer
interaction.
designed so as to undergo disruption in their p-conjugations
upon irreversible addition of cyanide, offering color bleaching
responses. However, ICT-based chemodosimeters capable of
executing absorbance red shifts upon exposure to cyanide are
indeed rare.6,14
Herein, we present a new chemodosimeter design that
carries the requisite structural elements to convert the CNÀ
binding event into an enhanced ICT process, delivering
absorbance red shift and a high fluorescence turn-on response.
The p-deficient pyridinium ring is well-known to react readily
with a variety of carbon and hetero-atom nucleophiles to form
the p-rich, 1,4-dihydropyridine (DHP) adducts, often with
good regioselectivity.15 Mimicking this aspect of the
pyridinium ring chemistry, we have designed a novel CNÀ
selective probe, Quino-P, incorporating a pyridinium ring as a
CNÀ receptor, while a quinoline moiety is appended to serve
as an electron withdrawing chromogenic unit.
The development of optical chemosensors for anions of
biological, environmental, and clinical concerns is currently
under active investigation.1 Among anions of interest, the
trace detection of cyanide is of prime importance because of
its lethal effects on livestock, mammals, humans and the
environment.2 Cyanide contamination in the environment is
possible due to its widespread uses in synthetic fibres, resins,
herbicides, gold-extraction and various metallurgy processes.3
Moreover, incidences of cyanide poisoning in human and
animals can also occur through ingestion of cyanogenic glyco-
sides found in certain vegetables and dietary foodstuffs.4
Cyanide exposure through accidental or intentional release
in drinking water or food-chains can culminate in environ-
mental damages and in humans, cyanide poisoning can result
in convulsion, loss of consciousness, and even death.
The synthesis of Quino-P was readily accomplished by
implementing Scheme 1. Base catalyzed condensation of isatin
1 with 3-acetylpyridine 2 afforded quinoline–pyridyl conjugate
3, which upon esterification yielded 4. Quaternization of 4 with
CH3I in dry CH3CN afforded iodide salt 5, which upon
perchlorate anion exchange with Mg(ClO4)2 gave the target,
Quino-P as a pale yellow solid in good overall yield. A
proposed CNÀ sensing mechanism is illustrated in Scheme 2.
A recent review by Yoon et al. summarizes the hitherto
reported optical cyanide sensing strategy,5 which includes
H-bonding interaction, metal ion displacements, cyano-
borane adduct formations, rearrangements and quantum dots.
Besides, the strong nucleophilic character of CNÀ has also
been harnessed to design internal charge transfer (ICT) based
chemodosimeters carrying receptors, such as oxazine,6 pyry-
lium salts,7 squarane,8 acridinium salt,9 cyanine dye,10
a Department of Chemistry, University of Mumbai, Vidyanagari,
Santacruz(E), Mumbai-400098, India.
E-mail: sh_mashraqui@yahoo.com; Fax: +91 022-6528547;
Tel: +91 022-26526091
b Department of Quimica, Universitat de les Illes Balears, Spain.
E-mail: toni.frontera@uib.es
w Electronic supplementary information (ESI) available: Spectra of
compound 4 and Quino-P, competitive fluorescence binding, Job’s
plot, detection limit, D2O exchange, 1H NMR interpretation of
Quino-P and its cyanide adduct, 13C NMR of Quino-P with added
KCN and molecular modelling studies. See DOI: 10.1039/c0nj00715c
Scheme 1 Synthesis of Quino-P.
c
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Scheme 2 Proposed cyanide sensing mechanism.
Fig.
1
Absorption spectra of Quino-P (2.8
Â
10À5 M) in
DMSO–H2O (7 : 3, v/v) in tris-HClÀin the presence of TBA salts of
BrÀ, ClÀ, IÀ, H2PO4 at
À
, NO3 ,
FÀ, AcOÀ, SCNÀ, HSO4
À
7.5 Â 10À2 M each, whereas CNÀ is 7.6 Â 10À3 M.
Fig. 2 (a) Spectrophotometric response of Quino-P (2.8 Â 10À5 M) in
DMSO–H2O (7 : 3, v/v) in tris-HCl at pH 7.0 with increasing TBACN
(0–7.6 Â 10À3 M). (b) Ratiometric response (406 nm/330 nm) of
Quino-P (2.8 Â 10À5 M) towards anions.
Presuming regioselective reaction, the nucleophilic attack of
cyanide on the C4 position of the pyridinium ring would form
the corresponding cyano–1,4-DHP adduct. Being p-electron
rich, the 1,4-DHP moiety in the resulting cyano-adduct is
expected to engage in a push–pull interaction with the
conjugated, p-deficient, quinoline ring. This phenomenon
would provoke enhanced ICT interaction, thereby forming
the basis of a potentially novel cyanide signalling protocol.
The sensitivity of Quino-P towards various anions, as their
tetra-n-butylammonium (TBA) salts, was evaluated by optical
spectral analysis. The absorption spectrum of Quino-P
displayed maxima at 330 and 267 nm, attributable to the local
excitations of pyridinium and quinoline rings, respectively. As
shown in Fig. 1, the UV-vis profile of the probe (2.8 Â 10À5 M)
blue shifts due to the p-conjugation break-down. By contrast,
Quino-P delivers a rare phenomenon of absorbance red shift
because of the inducement of a dominant ICT transition, as
proposed in Scheme 2.
The emission spectrum of Quino-P (lex = 345 nm)
displayed a broad band with a maximum at 435 nm, and the
quantum yield, calculated with respect to anthracene
(F = 0.27), was found to be 0.0041. The weak emission
efficiency of Quino-P may be attributable to photoinduced
electron transfer (PET) from the excited quinoline fluorophore
to the redox active, pyridinium ion.16 This proposition finds
support in the fact that quinoline–pyridyl conjugate 4, a
neutral analog of the ionic Quino-P, fluoresces 12 times more
intensely (F = 0.054) than Quino-P.
in DMSO–H2O (7 : 3, v/v) in tris-HCl buffer pH 7.0 was
essentially insensitive to each of FÀ, AcOÀ, SCNÀ, HSO4
,
À
NO3À, BrÀ, ClÀ, IÀ and H2PO4À, up to 7.5 Â 10À2 M,
implying the absence of any detectable ground state inter-
actions of these anions with the probe. In contrast, cyanide, at
10-fold lower concentration (7.6 Â 10À3 M), induced a
significant interaction, as evidenced by an instant color change
from the initial colorless to deep yellow, an event that allows
selective visual detection of cyanide by the naked eye.
Evaluation of the fluorescence profile of the probe (1 mM)
with 2.5 Â 10À3 M each of FÀ, AcOÀ, SCNÀ, HSO4À, NO3
,
À
BrÀ, ClÀ, IÀ and H2PO4 revealed no evidence of interaction
under the excited sate condition as well. Noteworthily, a
significant fluorescence ‘on–off’ response was induced by
CNÀ at a significantly lower concentration. Fluorimetric
titration (Fig. 3) revealed a linear increase in the emission
intensity, until saturating at 2.5 Â 10À4 M of CNÀ, the
emission enhancement reached ca. 10 fold (F = 0.046)
compared to that of the native probe (inset in Fig. 3).
À
Fig. 2a depicts the concentration dependent absorbance
profile of Quino-P with the added CNÀ (0–7.6 Â 10À3 M).
The spectral response occurred instantly, and the probe’s
maximum at 330 nm was progressively red shifted to generate
a new, more intense absorbance at 406 nm with incremental
addition of cyanide. In addition, the higher energy band at
267 nm was also markedly diminished in its absorbance.
Absorbance ratiometric analysis of CNÀ is possible using the
ratio, 406 nm/330 nm (Fig. 2b). It may be noted that many
known ICT based CNÀ chemodosimeters exhibit absorbance
The emission off–on response could be attributable to the
transformation of a PET-capable pyridinium ring of the free
receptor into one of the PET-disabled, electron rich DHP ring
within the cyano–Quino-P adduct. The PET nature of
the probe is also evident from the observation that the
c
58 New J. Chem., 2011, 35, 57–60
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causes pronounced upfield shifts (d 1.34 to 4.05) of the N–CH3
and the pyridinium ring protons because of the charge
neutralization.
Though not directly involved in the cyanide reaction, some
of the quinoline ring as well as –CO2CH3 protons also
experience discernible upfield shifts in the range of d 0.12 to
0.55. These upfield shifts obviously reflect an increase in
charge density on the quinoline ring, and thus provide a
further confirmation of the presence of the ICT interaction
in the Quino-P + CNÀ adduct. Consistent with the 1H NMR
results, the 13C NMR of the probe also displayed prominent
upfield shifts of the N–CH3 signal as well as those of the
pyridyl ring carbons after adding KCN (ESIw).
Fig. 3 Fluorimetric titration of Quino-P (1 mM) in buffer DMSO
with increasing CNÀ cyanide (0–2.5 Â 10À4 M). Inset: emission
enhancement as a function of CNÀ concentration.
In conclusion, we have disclosed a new and efficient
chemodosimeter design, which has the in-built structural
features to deliver absorbance red shift by undergoing a
unique ICT process, and the fluorescence turn-on signalling
by cancellation of the PET, post-cyanide addition. The unique
selectivity of cyanide is evident since many potentially
competing anions pose no detectable optical interferences even
in excess concentrations. The NMR analysis confirms the
regioselective C4 addition of cyanide, and in agreement with
the experimental findings, the theoretical studies (ESIw)
support a strong tendency towards p-conjugation in the
fluorescence amplification is not accompanied by any emission
wavelength shift.17 A competitive fluorescence experiment was
used to verify the unique chemodosimeter action of Quino-P
towards CNÀ only. Addition of 2.5 Â 10À3 M each oÀf FÀ,
AcOÀ, SCNÀ, HSO4À, NO3À, BrÀ, ClÀ, IÀ and H2PO4 did
not detectably alter the fluorescence profile of Quino-P
recorded in the presence of 2.5 Â 10À4 M of CNÀ. Thus, a
potential clearly exists in the probe to selectively discriminate
cyanide even when other anions may be present in higher
concentrations (ESIw).
Quino-P–CNÀ adduct. The detection limit of 1.6 Â 10À6
M
is satisfactory for cyanide monitoring up to the toxic threshold
of 1.9 mg in drinking water recommended by WHO.
The strong nucleophilicity of cyanide and the aqueous
measurement capability of the probe ensure that the optical
interferences, frequently encountered from the strongly
hydrated, weakly nucleophilic or acidic anions, are not
Experimental
observed.18 The Job’s plot showed
a
1 : 1 binding
Reagents and instrumentation
stoichiometry and the apparent association constant, log K,
was found to be 3.95. The detection limit of CNÀ, derived
from the emission data, was found to be 1.6 mM (ESIw).
Though we presumed a regioselective 1,4-cyanide addition,
competitive reactions on the other reactive C2 and C6 of the
pyridinium ring cannot be entirely ruled out. To establish the
Reagents and solvents used were purchased from S.D. Fine
Chemicals, India, or Sigma–Aldrich. IR spectra were recorded
using a Perkin-Elmer FT-IR spectrometer and pellets were
made by using KBr. 1H NMR and 13C NMR spectra were
recorded on BRUKER model Avance II 300 of 300 MHz.
UV–vis spectra were recorded using
a
Shimadzu
1
actual binding mode, we carried out H NMR analysis of the
UV–vis recording spectrophotometer, model no. UV-2401PC.
Fluorescence studies were carried out using a Shimadzu
spectrofluorimeter, model no. RF-5301PC. The slit-width
was set at 3 nm for both excitation and emission and the
PMT detector voltage was 700 V.
probe without and with added five equiv. of KCN in
DMSO–d6-D2O. The proton assignments for Quino-P and
its cyano-adduct are shown in Fig. 4a and b, respectively (for
NMR interpretation, see ESIw). The NMR data indicated
the formation of C4–Quino-P–CNÀ adduct with complete
regioselectivity. As shown in Fig. 4b, the cyanide addition
Synthesis
Compound 3 was prepared by modifying the literature
procedure as follows. Isatin 1 (1 mmol, 147 mg) and
3-acetylpyridine 2 (1.5 mmol, 182 mg) were refluxed in 30%
aqueous KOH (20 mL) for 10 h. Then, the reaction mixture
was cooled in ice-bath and acidified with acetic acid to
precipitate acid 3 as a buff-white solid. After filtration, the
solid was washed with cold water, then methanol, and
air-dried to afford compound 3 in 80% yield (200 mg). mp
315–317 1C [Lit.19 mp 316–318 1C].
To a stirred solution of compound 3 (2.5 mmol, 625 mg) in
dry MeOH (20 mL) was added an excess of thionyl chloride
(3.75 mmol, 0.5 mL) drop-wise at 0 1C. The reaction was
allowed to warm to room temperature for 30 min and then
refluxed for 5 h. Methanol was distilled out and the residual
Fig. 4 300 MHz 1H NMR of (a) Quino-P. (b) 1H NMR Quino-P + 5
equiv. of KCN in 70 : 30 (v/v) DMSO–d6-D2O.
c
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New J. Chem., 2011, 35, 57–60 59

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solid recrystallised from CHCl3 : pet. ether (1 : 1 v/v) to afford
compound 4 in 76% yield (500 mg), mp 95–96 1C, IR
(KBr; cmÀ1): 3057, 2956, 1728, 1590, 1508, 1482, 1459, 1345,
Soc., Ind. Econ. Aspects, Proc. Symp. Annu. Meet. TMS
2001, 73.
4 K. W. Kulig, Cyanide Toxicity, U.S. Department of Health and
Human Services, Atlanta, GA, 1991.
5 Z. Xu, X. Chen, H. N. Kim and J. Yoon, Chem. Soc. Rev., 2010,
39, 127.
6 (a) M. Tomasulo and F. M. Raymo, Org. Lett., 2005, 7, 4633;
(b) M. Tomasulo, S. Sortino, A. J. P. White and F. M. Raymo,
J. Org. Chem., 2006, 71, 744; (c) J. Ren, W. Zhu and H. Tian,
Talanta, 2008, 75, 760.
1
1257, 1203, 1016, 794, 774. H NMR (CDCl3): d 4.1 (s, 3H),
7.57 (m, 2H), 7.69 (t, 1H, J = 8.4), 7.83 (t, 1H, J = 9.3), 8.25
(d, 1H, J = 9.3), 8.42 (s, 1H), 8.67 (d, 1H, J = 9.9), 8.7 (d, 1H,
J = 12.9), 9.46 (s,1H). 13C NMR (CDCl3): d 52.83, 119.70,
123.79, 124.20, 125.49, 128.34, 130.22, 130.32, 134.35, 134.99,
135.922, 148.42, 149.28, 150.23, 153.81, 166.44. Mass m/z
value = 265. Anal. Calcd for C16H12N2O2: C, 72.72; H,
4.54; N, 7.69%. Found: C,72.99; H, 4.39; N, 7.48%.
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Compound 4 (1 mmol, 264 mg) was dissolved in dry
acetonitrile (5 mL) and CH3I (5 mmol, 0.31 mL) was added.
The reaction was left at room temperature for 2 days to afford
the quaternized salt 5 as a yellow solid in nearly quantitative
yield. The obtained iodide 5 was redissolved in warm
acetonitrile (5 mL) and Mg(ClO4)2Á2H2O (250 mg) dissoved
in 2 mL was added. The reaction mixture was vigorously
stirred at room temperature for 24 h and then refrigerated
overnight. The desired product, Quino-P was obtained as a
light yellow solid in 80% yield (291 mg), mp 256–257 1C, IR
(KBr; cmÀ1): 3038, 2951, 1718, 1584, 1503, 1472, 1418, 1258,
1204, 1153, 1017, 777, 666.
1H NMR (DMSO–d6-D2O): d 4.06 (s, 3H), 4.49 (s, 3H), 7.84
(t, 1H, J = 7.7), 7.97 (t, 1H, J = 7.5), 8.29 (m, 2H), 8.62
(d, 1H, J = 8.7), 8.7 (s, 1H), 9.1 (d, 1H, J = 6), 9.4 (d, 1H,
J = 8.1), 9.87 (s, 1H). 13C NMR (DMSO–d6-D2O): d 48.77,
53.66, 119.96, 124.37, 125.86, 128.26, 130.046, 130.41, 131.76,
137.45, 137.81, 143.08, 145.19, 146.29, 148.60, 150.54, 166.41.
Mass m/z = 279 [minus perchlorate ion]. Anal. Calcd for
C17H15N2O5Cl: C, 53.89; H, 3.96; N, 7.39; Cl, 9.37%. Found:
C, 53.83; H, 3.68; N, 7.62; Cl, 9.13%.
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Acknowledgements
Thanks are due to the BRNS, Government of India, and
the MICINN, Spain (project CTQ2008-00841/BQU), for
generous financial support. C.E. thanks the MEC, Spain, for a
fellowship. We also thank the CESCA for computational facilities.
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