Dipyrrole carboxamide derived selective ratiometric probes for cyanide ion

Article abstract of DOI:10.1021/ol061969g

(Chemical Equation Presented) Two anion probes 1 and 2 featuring the dipyrrole carboxamide moiety for anion recognition have been prepared. These structurally simple anion probes display great selectivity for the cyanide anion over other common inorganic

Full text of DOI:10.1021/ol061969g

ORGANIC
LETTERS
2
006
Vol. 8, No. 22
053-5056
Dipyrrole Carboxamide Derived Selective
Ratiometric Probes for Cyanide Ion
5
Chun-Lin Chen,†,‡ Yen-Hsiu Chen, Chan-Yu Chen, and Shih-Sheng Sun*,†
†
†,§
Institute of Chemistry, Academia Sinica, 115 Nankang, Taipei, Taiwan, Republic of
China, Department of Chemistry and Biochemistry, National Chung Cheng UniVersity,
168 UniVersity Road, Min-Hsiung, Chia-Yi, 621, Taiwan, Republic of China, and
Department of Chemistry, National Central UniVersity, 320 Chungli, Taiwan,
Republic of China
sssun@chem.sinica.edu.tw
Received August 8, 2006
ABSTRACT
Two anion probes 1 and 2 featuring the dipyrrole carboxamide moiety for anion recognition have been prepared. These structurally simple
anion probes display great selectivity for the cyanide anion over other common inorganic anions in semiaqueous environment via the formation
of cyanohydrin derivatives.
The recognition and sensing of anions have received
considerable attention for their important roles in biological,
industrial, and environmental processes.1 In particular,
cyanide is a detrimental anion causing poisoning in biology
contaminant sources. While a number of synthetic receptors
for anions have been designed, relatively few have been
developed for the selective sensing of cyanide.
4
A colorimetric and ratiometric fluorescent chemosensor
2
1,5
and the environment. Despite its toxic nature, its application
is of particular interest due to its simplicity. In particular,
in various areas as raw materials for synthetic fibers, resins,
herbicides, and the gold-extraction process is inevitable,
which releases cyanide into the environment as a toxic
contaminant. Thus, there exists a need for an efficient sensing
system for cyanide to monitor cyanide concentration from
ratiometric sensing provides a way of avoiding any misin-
terpretation of analyte-induced fluorescence quenching or
enhancement due to photobleaching, sensor concentration,
and medium effects. Although the design of colorimetric
and fluorescent anion chemosensors has recently attracted
3
6
*
To whom correspondence should be addressed. Fax: +011-886-2-
(4) (a) Chung, Y. M.; Raman, B.; Kim, D.-S.; Ahn, K. H. Chem.
Commun. 2006, 186-188. (b) Tomasulo, M.; Sortino, S.; White, A. J. P.;
Raymo, F. M. J. Org. Chem. 2006, 71, 744-753. (c) Tomasolu, M.; Raymo,
F. M. Org. Lett. 2005, 7, 4633-4636. (d) Chow, C.-F.; Lam, M. H. W.;
Wong, W.-Y. Inorg. Chem. 2004, 43, 8387-8393. (e) Felscher, D.;
Wulfmeyer, M. J. Anal. Toxicol. 1998, 22, 363-366. (f) Ros-Lis, J. V.;
Mart ´ı nez-M a´ n˜ ez, R.; Soto, J. Chem. Commun. 2002, 2248-2249. (g)
Ajayaghosh, A. Acc. Chem. Res. 2005, 38, 449-459.
(5) (a) Martinez-Manez, R.; Sancenon, F. Chem. ReV. 2003, 103, 4419-
4476 and references therein. (b) Brooks, S. J.; Gale, P. A.; Light, M. E.
Chem. Commun. 2005, 4696-4698. (c) Brooks, S. J.; Edwards, P. R.; Gale,
P. A.; Light, M. E. New J. Chem. 2006, 30, 65-70. (d) Wu, C.-Y.; Chen,
M.-S.; Lin, C.-A.; Lin, S.-C.; Sun, S.-S. Chem. Eur. J. 2006, 12, 2263-
2269.
2
7831237. Phone: +011-886-2-27898596.
†
Academia Sinica.
National Chung Cheng University.
National Central University.
‡
§
(
1) (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486-
5
16. (b) Amendola, V.; Esteban-G o´ mez, D.; Fabbrizzi, L.; Licchelli, M.
Acc. Chem. Res. 2006, 39, 343-353.
2) (a) Kulig, K. W. Cyanide Toxicity; U.S. Department of Health and
(
Human Services: Atlanta, GA, 1991. (b) Baskin, S. I.; Brewer, T. G. In
Medical Aspects of Chemical and Biological Warfare; Sidell, F. R., Takafuji,
E. T., Franz, D. R., Eds.; TMM Publications: Washington, DC, 1997; pp
71-286. (c) Baird, C.; Cann, M. EnVironmental Chemistry; Freeman: New
York, 2005.
2
(
3) Miller, G. C.; Pritsos, C. A. Cyanide: Soc., Ind. Econ. Aspects, Proc.
(6) Ajayaghosh, A.; Carol, P.; Sreejith, S. J. Am. Chem. Soc. 2005, 127,
14962-14963.
Symp. Annu. Meet. TMS 2001, 73-81.
1
0.1021/ol061969g CCC: $33.50
© 2006 American Chemical Society
Published on Web 10/06/2006

attention, there are only a few examples of ratiometric
fluorescent chemosensors for anions.7
Amide and pyrrole groups represent the two most common
-
anion recognition moieties, which usually form N-H‚‚‚A
hydrogen bonds with selective anions.1,5 In our search for
selective and sensitive sensors of biologically important
anions, we recently developed a structurally simple chemical
sensing system integrating both pyrrole and amide function-
ality, which are expected to act as hydrogen bond donors
8
collectively. Herein we report the design and synthesis of
these anion probes and their unique interaction mode with
cyanide.
The structures and synthesis of 1 and 2 are shown in
Scheme 1. They are synthesized by condensation of 1-pyr-
Scheme 1. Synthesis of Chemosensors 1 and 2
Figure 1. Changes observed in the absorption (top) and fluores-
-
cence (bottom) spectra of 1 (10 µM) upon addition of CN (0-
-
4
5
.17 × 10 M) in CH
3 2
CN/H O (9:1, v/v) solution. Excitation is
at 363 nm.
blue to green. Figure 1 illustrates the absorption and emission
-
spectral changes for 1 on addition of CN . The absorption
bands at 291 and 378 nm decreased while three new bands
at 299, 372, and 428 nm appeared. The three isosbestic points
at 293, 360, and 391 nm indicated a clean conversion
throughout the titration process. Concomitantly, the fluores-
cence maximum of 1 at 425 nm showed a bathochromic shift
role-2-carbonyl chloride with corresponding aryldiamine in
the presence of triethylamine to afford 1 and 2 in low to
moderate yields. Compound 1 shows absorption at 290 and
3
79 nm and an emission at 427 nm (Φ ) 0.26) with a
f
-
1
to 554 nm (∆Eem ) 5479 cm ) with an isoemissive point
at 476 nm. The resultant Job plot indicated a 1:2 receptor-
lifetime of 0.89 ns. Compound 2 shows an absorption band
at 282 nm and a shoulder at 355 nm but showed no detectable
fluorescence in solution possibly due to the oxidative electron
transfer from excited 2 to the LUMO of the nitro groups
upon photoexcitation.
The ability of 1 and 2 to complex with anions was explored
with UV-vis absorption and fluorescence spectrometry.
9
cyanide binding stoichiometry. The binding constant cal-
culated from a 1:2 stoichiometry with global multivariate
10
factor analysis, based on absorption spectral changes, yields
-
2
log K ) 5.91 ( 0.07 M .
The absorption spectral changes of 2 on addition of
cyanide in CH CN/H O (9/1, v/v) solution are illustrated in
3 2
Among the 12 anions tested in solution (CH
3
CN:H
2
O, 90:
-
-
-
-
-
-
-
Figure 2. A new absorption band appeared at 465 nm. The
resultant Job plot also indicated a 1:2 binding stoichiometry
for 2. The calculated binding constant gives log K ) 9.20
1
0, v/v), namely, CN , F , Cl , Br , I , NO
3
, OAc ,
-
3-
-
-
-
PhCO
2
, HP O
2 7
2 4 4 4
, H PO , HSO , and ClO , both 1 and
-
2
responded to only CN resulting in a color change from
-
2
(
0.05 M . The colorimetric response of 2 to cyanide
colorless to yellow and the fluorescence change for 1 from
1
1
-
persists up to 50% water content. The selectivity of CN
(
7) (a) Peng, X.; Wu, Y.; Fan, J.; Tian, M.; Han, K. J. Org. Chem. 2005,
over other anions, in particular fluoride, is important because
most of the chemosensors reported for cyanide sensing suffer
7
2
(
0, 10524-10531. (b) Liu, B.; Tian, H. J. Mater. Chem. 2005, 15, 2681-
686. (c) Wen, Z. C.; Jiang, Y. B. Tetrahedron 2004, 60, 11109-11115.
d) Kubo, Y.; Yamamoto, M.; Ikeda, M.; Takeuchi, M.; Shinkai, S.;
Yamaguchi, S.; Tamao, K. Angew. Chem., Int. Ed. 2003, 42, 2036-2040.
(9) Connors, K. A. Binding Constants; John Wiley and Sons: New York,
1987.
(
e) Yann, B.; Martin, J. C.; David, P.; Rachel, S. Chem. Commun. 2002,
1
930-1931. (f) Nishizawa, S.; Kato, Y.; Teramae, N. J. Am. Chem. Soc.
(10) (a) SPECFIT, version 3.0; Spectra Software Associates. (b) Gampp,
H.; Maeder, M.; Meyer, C. J.; Zuberb u¨ hler, A. D. Talanta 1985, 32, 95-
101. (c) Gampp, H.; Maeder, M.; Meyer, C. J.; Zuberb u¨ hler, A. D. Talanta
1986, 33, 943-951.
(11) Compound 2 started to precipitate when water content was over
50%.
1
999, 121, 9463-9464.
(8) Cheng and coworkers reported a dipyrrole-2-carboxamide-phenylene
compound that exhibited weak binding affinity to fluoride in DMSO
solution. Yin, Z.; Li, Z.; Yu, A.; He, J.; Cheng, J.-P. Tetrahedron Lett.
2
004, 45, 6803-6806.
5054
Org. Lett., Vol. 8, No. 22, 2006

1
-
Figure 4. Plots of H NMR spectra of 2 on addition of CN in
DMSO-d
6
.
Figure 2. Absorption spectra changes of 2 (20 µM) upon addition
-
-3
of CN (0-1.67 × 10 M) in CH
3 2
CN/H O (9/1, v/v) solution.
mechanism for the formation of cyanohydrin derivative. The
potential hydrogen-bonding pocket, defined by the two amide
protons and two pyrrole protons, tends to bring the cyanide
the deleterious interference of other anions.12 The superior
selectivity of 2 for cyanide in H O/CH CN (1/1, v/v) solution
is evident from the absorbance response of the anions, as
2
3
13
illustrated in Figure 3. Such a selectivity in the semiaqueous
Scheme 2. Proposed Cyanohydrin Formation from Reaction
of Receptor 2 and Cyanide
to the vicinity of amide carbonyl groups, and this along with
the strong electron-withdrawing nature of NO groups renders
2
the amide groups highly electron deficient and susceptible
to the nucleophilic addition of cyanide to carbonyl groups.
The addition of cyanide resulted in a slow disappearance of
amide proton signal while the pyrrole protons shifted upfield.
The phenyl protons also exhibited a downfield shift due to
Figure 3. Absorbance response at 454 nm (A/A
the presence of 10 equiv of selected anions in CH
v/v) solution.
0
) of 2 (18 µM) in
CN/H O (1/1,
3
2
1
5
the electrostatic through-space effect. The spectral shift is
virtually stopped after addition of 2 equiv of cyanide. The
solution became colorless again on addition of excess acid.
The formation of cyanide adduct was further confirmed by
environment is promising for aqueous samples.
Further insights into the nature of chemosensor-cyanide
1
3
mass spectrometry and the C NMR spectrum (see the
Supporting Information). The electrospray ionization mass
spectrum of the precipitated orange solid showed a molecular
mass of 948.60, which corresponds to the formula of
1
interactions were investigated by H NMR titration experi-
1
ments. Figure 4 shows the H NMR spectra of 2 upon
6
addition of tetrabutylammonium cyanide in DMSO-d solu-
1
tion. To account for the H NMR spectral changes on
+
- +
[
5+2Bu
4
N +CN ] (calculated m/z 948.68, see the Sup-
addition of cyanide, we propose the formation of a cyanide
1
6
porting Information).
adduct (cyanohydrin).4
a,14
Scheme 2 outlines the possible
On the other hand, addition of cyanide anion into DMSO-
1
d
6
solution of 1 resulted in slightly different H NMR spectral
(12) (a) Badugu, R.; Lakowicz, J. R.; Geddes, C. D. J. Am. Chem. Soc.
2
005, 127, 3635-3641. (b) Sun, S.-S.; Lees, A. J.; Zavalij, P. Y. Inorg.
changes compared to 2 (see Figure 5) although the final
Chem. 2003, 42, 3445-3453. (c) Anzenbacher, P., Jr.; Tyson, D. S.;
Jursikov a´ , K.; Castellano, F. N. J. Am. Chem. Soc. 2002, 124, 6232-6233.
(d) Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40, 154-157.
(14) Kim, Y. K.; Lee, Y.-H.; Lee, H-Y.; Kim, M. K.; Cha, G. S.; Ahn,
K. H. Org. Lett. 2003, 5, 4003-4006.
(15) Boiocchi, M.; Del Boca, L.; Esteban-G o´ mez, D.; Fabbrizzi, L.;
Lucchelli, M.; Monzani, E. Chem. Eur. J. 2005, 11, 3097-3104.
(13) Compound 1 also displays high selectivity of cyanide over other
common inorganic anions. See the Supporting Information for the fluores-
cence response of 1 in the presence of 10 equiv of selected anions.
Org. Lett., Vol. 8, No. 22, 2006
5055

of pyrrole moieties with the cyanide anion in the receptor-
cyanide complex. The amide protons in 1 are expected to
be less acidic compared to those in 2. Thus, the proton
exchange is expected to involve not only the amide protons
but also possibly the pyrrole NH protons as well.
In summary, we have successfully developed a highly
selective receptor for the sensing of cyanide in a semiaqueous
environment. A unique colorimetric and ratiometric fluores-
cent response to cyanide is realized through the new mode
of receptor-cyanide interaction by formation of the cyano-
hydrin derivative via a highly electron-deficient amide moiety
in a semiaqueous environment. Although these two anion
probes are not soluble in water, the facile synthesis and
modification of the structural framework of these pyrrole
carboxamide compounds reveal the potential development
of a family of ratiometric chemosensors for detecting cyanide
in aqueous solution.
1
Figure 5. Plots of H NMR spectra of 1 on addition of CN- in
DMSO-d
6
.
product is also confirmed by mass spectrometry to be the
cyanide adduct (see Figure S2 in the Supporting Informa-
tion).17 The most significant differences come from the
gradual disappearance of the pyrrole NH proton signal and
downfield shift of the â proton signal of pyrrole on addition
of cyanide anion. This observation confirms the interaction
Acknowledgment. We are grateful to the National
Science Council of Taiwan (Grant Nos. 93-2113-M-001-029
and 94-2113-M-001-014) and Academia Sinica for support
of this research.
(
16) The formation of cyanide adduct is also indirectly supported by
anion competition experiments. The yellow color of cyanide-chemosensor
complex persists in the presence of a 50 equiv excess of other anions
Supporting Information Available: Synthesis, charac-
terization data, experimental procedures, and mass spectra
of cyanide adducts. This material is available free of charge
via the Internet at http://pubs.acs.org.
2
3
-
-
-
except for HP2O7 , H2PO4 , and HSO4 . The ability to protonate the
cyanide adduct by these three anions and turn the solution back to colorless
is consistent with the final process depicted in Scheme 2.
1
3
(
17) The attempt to acquire C NMR spectrum of the cyanide adduct
was unsuccessful due to the very low solubility of 1.
OL061969G
5056
Org. Lett., Vol. 8, No. 22, 2006