Highly activated Michael acceptor by an intramolecular hydrogen bond as a fluorescence turn-on probe for cyanide

Article abstract of DOI:10.1039/c0cc03910a

An activated Michael acceptor type of probe by an intramolecular hydrogen bond has shown a selective fluorescence turn-on response to cyanide through a conjugated addition of the nucleophilic anion to the enone probe with a 1300-fold increase in its fluor

Full text of DOI:10.1039/c0cc03910a

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Highly activated Michael acceptor by an intramolecular hydrogen
bond as a fluorescence turn-on probe for cyanidew
Seokan Park and Hae-Jo Kim*
Received 16th September 2010, Accepted 11th October 2010
DOI: 10.1039/c0cc03910a
An activated Michael acceptor type of probe by an intramole-
cular hydrogen bond has shown a selective fluorescence turn-on
response to cyanide through a conjugated addition of the nucleo-
philic anion to the enone probe with a 1300-fold increase in its
fluorescence intensity.
The extreme toxicity of cyanide ions in physiological1 as well as
environmental2 systems has led many researchers to develop
optical probes3 for the sensitive and selective detection of
cyanide. Recently, fluorescent probes have attracted
considerable interest owing to their simple and fast
implementation as well as their high sensitivity.4 Although a lot
of fluorescence turn-on probes have been introduced by applying
chemosensor,5 displacement6 or dosimeter approaches,7 most of
Fig. 1 Partial 1H NMR spectra of 1 (20 mM) upon addition of NaCN
them have shown, however, a less than several tenths increase in
(1 equiv.) in DMSO-d6/D2O (v/v, 100 : 1). (A) 1; (B) 1+ NaCN, 0.5 h;
their fluorescence intensity in the presence of cyanide and this
(C) 1+ NaCN, 10 h.
therefore limits their resolution in the presence of other anions.
Herein we report a fluorescent probe for the cyanide anions,
To investigate the reaction pathway of 1 with cyanide, we
monitored 1H NMR spectra upon the addition of cyanide
anions to 1 in D2O/DMSO solvent (Fig. 1). A new peak at 4.4
ppm appeared while vinylic protons (8.3 and 7.5 ppm)
disappeared and finally, a simple set of 1H NMR spectra
were obtained at rt after 10 h. The transformation was the
Michael addition of the cyanide anions to the enone of 1 and
corroboratively evidenced also by 13C NMR and HRMS
spectra. 13C NMR spectrum showed two additional aliphatic
peaks at around 44 and 31 ppm (Fig. S2, ESIw), and high
resolution MS spectral analysis (Fig. S8, ESIw) indicated the
presence of the Michael product at m/z 294.1363 ([M]+, cal’d
294.1368).
which is activated by an intramolecular hydrogen bond and
therefore easily reacts with cyanide to exhibit a fluorescence
intensity increase of over one thousand-fold.
Recently, we have prepared optical probes with an o-hydroxy
carbonyl group for effective intramolecular hydrogen bonding.8
The hydrogen bonds activate the neighboring carbonyl oxygen
for the fast sensing of cyanide anions. In this line of
our research, we prepared a chalcone derivative having an
o-hydroxy carbonyl group according to the literature
procedure (Scheme 1).9 The carbonyl group of 1 is plausibly
being activated by the intramolecular hydrogen bond of the
o-hydroxy group in order for the fast Michael addition of the
cyanide ion. Probe 2 without a hydroxyl group was also
prepared as a control compound.
Time-dependent UV-vis spectra of
1
showed the
hypsochromic shift upon addition of cyanide in acetonitrile
(Fig. 2). As the reaction proceeds, a new peak at lmax 260 nm
(e = 2.8 Â 104 MÀ1 cmÀ1) increases whereas the original
maximum peak at lmax 430 nm (e = 3.9 Â 104 MÀ1 cmÀ1
)
decreases with an isosbestic point at 272 nm. The kinetic
analysis gave the rate constant k = 8.2 Â 10À5 sÀ1 under the
pseudo first-order reaction conditions.
The fluorescence of 1 is completely quenched due to the
possible donor-excited photoinduced electron transfer from
diethylamino-phenyl to the hydrogen bonded carbonyl group.
However, the fluorescence intensity of 1 (10 mM in CH3CN)
becomes stronger upon addition of cyanide ions (100 equiv.)
with a ca. 1300-fold intensity enhancement, the highest value
ever known.10 In contrast, other anions such as FÀ, ClÀ, BrÀ,
IÀ, N3À, H2PO4À, HSO4À, and AcOÀ have induced negligible
fluorescence changes, therefore the solutions exhibited almost
the same fluorescence intensities as that of 1 itself (Fig. 3). In
addition, compound 2 without an intramolecular hydrogen
Scheme 1 Synthesis of 1 and 2.
Department of Chemistry, Hankuk University of Foreign Studies,
Yongin 449-791, Korea. E-mail: haejkim@hufs.ac.kr;
Fax: +82 31-330-4566; Tel: +82 31-330-4703
w Electronic supplementary information (ESI) available: Experimental
details, NMR spectra, fluorescence and UV data. See DOI: 10.1039/
c0cc03910a
c
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Chem. Commun., 2010, 46, 9197–9199 9197

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Fig. 2 Time-dependent UV-vis spectral changes upon addition of
100 equiv. of CNÀ to 1 (10 mM in CH3CN). Inset: its kinetics.
Fig. 4 Visible (A) and fluorescence (B, lex 365 nm) images of 1 (10 mM)
in the presence of 100 equiv. of anions (tetrabutylammonium salts) in
CH3CN.
Fig. 5 Proposed reaction mechanism.
Fig. 3 Relative fluorescence intensities of 1 (10 mM in CH3CN) in the
presence of various anions (100 equiv.), where F0 is the fluorescence
intensity exerted by 1 only. lex 272 nm, lem 469 nm.
crucial role of the Michael acceptor and reacts fast with the
cyanide anion to afford an intermediate enol, which will
tautomerize to the stable keto form to furnish the fluorescent
phenolate 3.13
bond, however, did not induce any significant chromophoric
changes under the same condition as 1 (Fig. S4, ESIw). The
higher selectivity of 1 for cyanide over other various anions
may come from the hydrogen bonded enone of 1 as an
activated electrophile as well as the nucleophilicity of cyanide.
The competition reaction of 1 with the cyanide ion in the
presence of other anions showed corroborative evidence for the
selectivity of 1 toward cyanide (Fig. S5, ESIw).
The prominent changes of 1 were also observable by the
naked eye (Fig. 4). Upon addition of cyanide anions, the
solution color of 1 changed from yellow to colorless whereas
other anions did not induce any color changes. The solution of
1–cyanide adduct also displayed a strong blue fluorescence
under a hand-gun UV spectroscopy.
In summary, we have developed a simple chalcone derivative
(1) having an o-hydroxy carbonyl group, which is highly
activated by an intramolecular hydrogen bond. The Michael
addition of cyanide to 1 showed a highly selective fluorescence
turn-on response for the cyanide anion with a 1300-fold
increase in the fluorescence intensity.
A study of the
fluorescence turn-on mechanism with a series of chalcone
derivatives is on the way.
This research was supported by the National Research
Foundation of Korea (2010-0008165) and Hankuk
University of Foreign Studies.
To evaluate the detection limit of cyanide in solution, we
measured the fluorescence changes by increasing the amount of
cyanide. The lower limit of detection was ca. 1.7 mM with a
signal-to-noise ratio of 3 in CH3CN (Fig. S6, ESIw), meaning
that probe 1 is operable well below the WHO cyanide standard
in drinking water (1.9 mM)11 and it is also useful for monitoring
the lethal level of cyanide in fire victims (20 mM).12 A Job’s plot
was carried out and the binding stoichiometry between 1 and
CNÀ was observed to be 1 : 1 (Fig. S7, ESIw).
From the spectroscopic evidence, we propose a plausible
mechanism for the reaction of 1 with cyanide (Fig. 5).
The activated a,b-unsaturated carbonyl group by the
intramolecular hydrogen bond of o-hydroxyl group plays a
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