1-(4-Nitrophenyl)-benzimidazolium-based ratiometric chromogenic probes for cyanide ion

Article abstract of DOI:10.1016/j.tetlet.2009.05.047

1,3- and 1,4-bis-[1-(4-nitrophenyl)-benzimidazolium-3-methylene]benzene-based molecular probes interact selectively with cyanide ion to switch the absorbance from 270 nm to 376 nm and elaborate ratiometric chromogenic probes for the estimation of 1-270 μM

Full text of DOI:10.1016/j.tetlet.2009.05.047

Tetrahedron Letters 50 (2009) 4463–4466
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
1-(4-Nitrophenyl)-benzimidazolium-based ratiometric
chromogenic probes for cyanide ion
*
Subodh Kumar , Sandeep Kumar
Department of Chemistry, Guru Nanak Dev University, Amritsar, Punjab 143 005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
1,3- and 1,4-bis-[1-(4-nitrophenyl)-benzimidazolium-3-methylene]benzene-based molecular probes
interact selectively with cyanide ion to switch the absorbance from 270 nm to 376 nm and elaborate
Received 7 April 2009
Revised 11 May 2009
Accepted 16 May 2009
Available online 22 May 2009
ratiometric chromogenic probes for the estimation of 1–270
range for practical applications.
l
M cyanide ion—the desirable concentration
Ó 2009 Elsevier Ltd. All rights reserved.
Anion sensing is an area of immense contemporary investiga-
tions due to their significant role in many biological processes
and in biological structures such as amino acids, neurotransmit-
ters, enzyme substrates, co-factors, and nucleic acids.1 Amongst
anions, the cyanide is one of the most toxic anions and is lethal
to humans at concentrations of 0.5–3.5 mg/Kg body weight.2 In
the blood of fire victims, the lethal cyanide ion concentration is
trophotometer. The switching of absorbance from 270 nm to
376 nm on addition of the cyanide ions provides opportunities
for ratiometric estimation—which is useful for signal rationing
and the estimation of concentration of an analyte independent of
the concentration of the receptor. These molecular probes behave
as chemodosimeters where the cyanide ion adds at the C-2 of
benzimidazolium carbon to form adduct and thus releases the lone
pair of electrons on the nitroaniline unit to regenerate its color. The
benzimidazolium salt 5 has been used as a control compound
which on addition of the cyanide ion did not show any discernible
color change or the addition of the cyanide ion at its C-2 (1H NMR)
and points to the significance of 4-nitrophenyl unit.
1-(4-Nitrophenyl)-benzimidazole (1) on dry heating with dod-
ecylbromide (10 equiv) at 80–90 °C gave 2a (white solid, 60%).
The methanolic solution of 2a on treatment with NH4PF6 gave
2b.12 Similarly, 1 on heating with 1,4-bis-(bromomethyl)benzene
(6) and 1,3-bis-(bromomethyl)-2,4,6-trimethylbenzene (7) in
DMF at 110 °C gave 3a (light yellow solid, 69%) and 4a (light yellow
solid, 75%), respectively. The methanolic solution of 3a/4a on treat-
ment with NH4PF6 gave the respective compounds 3b and 4b. Con-
trol compound 5 was synthesized by alkylation followed by the
salt formation reaction of benzimidazole with dodecylbromide
(Scheme 1).
23–26 l
M.3 However, due to its wide applications in the produc-
tion of organic chemicals and polymers4 and its critical role in gold
extraction process,5 the effluents from these processes and affected
soil and water samples always need to be tested for >1 lM concen-
trations of cyanide ion. This scenario has necessitated the develop-
ment of the cyanide ion probes. The nucleophilic addition of the
cyanide ion to oxazine,6 pyrylium,7 squarine,8 and trifluoroace-
tophenone9 derivatives that possess suitable signaling moieties
has been used for developing such probes. These molecular probes
act as chemodosimeters and in general, the strong affinity of cya-
nide ion toward the polarized sp2-hybridized carbon plays key
role.10
1,3-Dialkyl imidazolium and benzimidazolium salts due to their
participation in both electrostatic and [C–H]+Á Á ÁXÀ interactions find
generous applications as anion probes.11 In all these molecular
probes used for optical signaling, the fluorescent group is linked
through sp3 carbon spacer and has eluded the development of
benzimidazolium-based ratiometric probes. Now we have de-
signed new molecular probes, in which chromogenic nitrophenyl
group is directly attached at one nitrogen of the benzimidazolium
moiety and on interaction with an anion would result in the
switching of absorbance wavelength through internal charge
transfer, thus providing opportunities for ratiometric sensing.
The molecular probes 2b, 3b, and 4b derived from 1-(4-nitro-
phenyl)benzimidazole (1) have been used for selective estimation
of the cyanide ion in MeOH through the naked eye or UV–vis spec-
Probe 2b (20
l
M, CH3CN) exhibits the absorption band at kmax
270 nm. On addition of AcOÀ, FÀ, CNÀ, and H2PO4 ions (10 equiv)
À
to the solution of 2b (20 lM, CH3CN), a new absorption band at
376 nm with varied intensities was observed (Fig. 1). During this
addition of anions, the colorless solutioÀn changed to yellow one.
However, the addition of NO3À, ClÀ, I , BrÀ, ClO4À, SCNÀ, and
HSO4À anions (10 equiv) did not give any apparent color or spectral
change. Similarly, the addition of AcOÀ, FÀ, CNÀ, and H2PO4À anions
to the solution of 3b and 4b (20 lM, CH3CN) gave a new absorption
band at 376 nm but in MeOH, the color/spectral change was ob-
served with the cyanide ion only. The control compound 5 did not
show any spectral or color change with these anions. Therefore,
probes 2b, 3b, and 4b in MeOH showed highly selective color and
* Corresponding author. Tel.: +91 0183 2258802; fax: +91 0183 2258820.
E-mail address: subodh_gndu@yahoo.co.in (S. Kumar).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.047

4464
S. Kumar, S. Kumar / Tetrahedron Letters 50 (2009) 4463–4466
N
N
N
N
(i)
+
+
N
N
.2X-
Br
Br
6
(ii) MeOH-NH4PF
6
1
NO2
NO2
NO2
Me
(i)
Me
Br
3a X = Br-
3b X = PF6-
Me
Br
(i) dodecyl bromide
(ii) MeOH-NH4PF6
7
(ii) MeOH-NH4PF6
Me
Me
(CH2)10CH3
X-
Me
N
N
+
N
+
+
(CH2)10CH3
.2X-
N
N
N
N
+
N
Br-
(CH2)10CH3
NO2
NO2
2aX = Br-
NO2
5
4a X = Br-
-
4b X = PF6-
2b X = PF6
Scheme 1.
cmÀ1) (Fig. 2). Therefore, 2b can be used as a probe for selective
estimation of the CNÀ ions using MeOH as solvent. In order to
study the effect of water, the estimation of cyanide ions was stud-
ied using MeOH–H2O (1:1) as the solvent. The analysis of spectral
data obtained by titration of 2b with TBA CN in MeOH–H2O (1:1)
revealed similar sensitivity to cyanide ions as observed in pure
MeOH. The presence of water did not affect the estimation of cya-
nide ion.
a0.45
b0.45
CN-
AcO-
2b+Anions
2b+Anions
-
F
0.3
0.15
0
CN-
450
0.3
0.15
0
H2PO4-
250
350
250
350
450
The switching ‘OFF–ON’ behavior at 270 nm and 376 nm on
addition of CNÀ ions to the solution of 2b provides a dual absorp-
tion channel for elaborating a ratiometric approach (Fig. 3). The ra-
Wavelength (nm)
Wavelength (nm)
Figure 1. Effect of anions on UV–vis spectrum of 2b (20 lM) (a) in CH3CN and (b) in
MeOH.
tio of the absorption of 2b (20
on gradual addition of cyanide ions and can be used to estimate
CNÀ ions between 60
M and 500 M.
lM, MeOH) varies from 0.02 to 2.44
l
l
spectral changes with the cyanide ion and so can be developed as
molecular probes for selective estimation of cyanide anion. This
selectivity toward CNÀ in MeOH could be attributed to the larger
Further to evaluate the cooperative effect of two benzimidazo-
lium units linked through 1,4-bis-(methylene)benzene or 1,3-bis-
(methylene)-2,4,6-trimethylbenzene as spacer, the probes 3b and
4b were studied. The presence of two benzimidazolium units in
solvation of FÀ, AcOÀ, and H2PO4 anions and higher nucleophilic-
À
ity of cyanide ion under protic conditions. On gradual addition of
probes 3b (kmax 270 nm,
e
34,600 l molÀ1 cmÀ1) and 4b (kmax
TBA CN to the solution of 2b (20
270 nm (
lM, MeOH), the absorbance at
270 nm,
e
30,400 l molÀ1 cmÀ1) did not have any effect on kmax val-
e
19,300 l molÀ1 cmÀ1) underwent gradual decrease in
intensity with a concomitant increase at 376 nm (
e
22,400 l molÀ1
2.5
0.45
0.4
2
0.2
0.3
0.15
0
0.2
0
1.5
1
0.1
0
0
400
800
0
50 100 150
0.5
0
[CN-] µM
-
[CN ] µM
250
400
550
700
0
400
800
1200
-
[CN ] µM
Wavelength (nm)
Figure 2. Changes in UV–vis spectrum of 2b (20
lM, MeOH) on gradual addition of
Figure 3. Plot of A376nm/A270nm versus [CNÀ] on titration of 2b (20
l
M, MeOH) with
TBA CN.
TBA CN.

S. Kumar, S. Kumar / Tetrahedron Letters 50 (2009) 4463–4466
4465
ues. Thus, any interaction between two benzimidazolium units
placed at 1,3 or 1,4 positions in 3b/4b is ruled out.
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0.03
0.02
0.01
0.00
The gradual addition of TBA CN to a solution of 3b (10 lM,
MeOH) caused the gradual decrease in absorbance intensity at
270 nm with concomitant increase in absorbance intensity at
376 nm (Fig. 4). The evaluation of these spectral data obtained by
titration of 3b with TBA CN in MeOH shows the formation of 1:1
and 1:2 (3b:CN) complexes. The presence of two slopes in the titra-
tion curve shows that cyanide ion and 3b interact in a stepwise
manner. The larger slope for the addition of the first cyanide ion
than that for the addition of the second cyanide ion points that
the presence of two benzimidazolium units though not conjugated
to each other, facilitates the interaction with cyanide ion which is
reflected in the increased sensitivity of 3b toward the first cyanide
0
5
10
15
[CN-] µM
0
200
400
600
[CN-] µM
Figure 6. Plot of A376nm/A270nm versus [CNÀ] on titration of 3b (10
lM, MeOH–H2O:
1:1) with NaCN.
ion (lower limit 1
(lower limit 60
l
M) in comparison to that observed in case of 2b
l
M). Probe 4b on titration with TBA CN showed
similar enhanced sensitivity toward cyanide ion.
In case of 3b and 4b, the plot of ratio of absorbances at 270 nm
and 376 nm shows an increase in the ratio from 0.01 to 3.49 imply-
ing nearly 350 times increase in ratio while varying the cyanide
amounts from 1 lM to 270 lM (Fig. 5). Therefore, probes 3b and
4b are significantly more sensitive to cyanide ions than probe 2b.
In order to evaluate the probe sensitivity toward inorganic cya-
nide ions, the titration of 3b against NaCN in MeOH–H2O (1:1) was
performed. Under these conditions, 3b is most sensitive to cyanide
ions between 50
lM and 240 lM concentration. However, even
10 M cyanide ions could be determined easily using ratiometric
l
approach (Fig. 6). However, due to poor solubility of 3b, its sensi-
tivity toward the cyanide ion in water could not be determined.
The mode of interaction of 3b with cyanide anion could be
determined by using 1H NMR titrations. 1H NMR spectrum of 3b
(2 mM, CD3OD–CDCl3) on addition of TBA CN showed the appear-
ance of new signals upfield in comparison to that of 3b. The inten-
sity of these signals increased with gradual addition of TBA CN and
was completed at 6.0 equiv of TBA CN. 1H NMR spectrum of 3a–CN
complex, isolated by addition of 10 equiv of NaCN to solution of 3a,
Figure 7. 1H NMR spectra of (a) 3a (free ligand) and (b) 3a–CN adduct in DMSO-d6.
shows a similar upfield shift of N–CH2 signal from d 5.89 to d 4.58
and C-2H and nitro aryl signals from d 10.54, 8.61, 8.16 to d 8.89/
8.44, 8.03, 6.80, respectively. These observations confirm that the
addition of cyanide ions at C-2 of benzimidazolium moieties in
3a leads to the formation of a neutral complex (Fig. 7). Therefore,
the conversion of benzimidazolium to 1,2-dihydrobenzimidazole
moiety releases internal charge transfer from the nitrogen lone
pair to nitro unit and is responsible for color change from colorless
to yellow.
0.4
0.2
0
0.45
0.3
0.15
0
0
200
400
The interference of other anions in the estimation of CNÀ ions
evaluated by measuring the UV–vis absorption changes in a series
of solutions containing 3b with different aÀmounts of CNÀ ions and
other anions (AcOÀ, HSO4À, H2PO4À, FÀ, Cl , BrÀ, NO3À, ClO4À, and
SCNÀ) in concentrations that were 100 times greater than that of
CNÀ ion in MeOH was found to be minimal.
[CN-] µM
250
350
450
Wavelength (nm)
550
650
Figure 4. Changes in UV–vis spectrum of 3b (10
lM, MeOH) on gradual addition of
TBA CN.
Thus, 1,4- and 1,3-bis-[1-(4-nitrophenyl)-benzimidazolium-3-
methylene]benzene derivatives 3b and 4b based on nucleophilic
addition of cyanide ion at C-2 elaborate ratiometric chromogenic
probes for the cyanide ion in the concentration range 1–
4b
3b
4.0
270 lM—the desirable concentration range for practical
3.0
2.0
1.0
applications.
0.8
0.4
0.0
Acknowledgments
We thank CSIR and DST, New Delhi for financial assistance and
UGC for Center of Advanced Studies.
0
20 40 60
[CN-] µM
0.0
References and notes
0
200
400
[CN-] µM
600
800
1. (a) Gale, P. A. Coord. Chem. Rev. 2003, 240, 191–221; (b) Beer, P. D.; Gale, P. A.
Angew. Chem., Int. Ed. 2001, 40, 486–516; (c) Gale, P. A. Coord. Chem. Rev. 2001,
213, 79–128; (d) Gale, P. A. Coord. Chem. Rev. 2000, 199, 181–233.
Figure 5. Plots of A376nm/A270nm versus [CNÀ] on titration of 3b and 4b (10
lM,
MeOH) with TBA CN.

4466
S. Kumar, S. Kumar / Tetrahedron Letters 50 (2009) 4463–4466
2. Muir, G. D. Hazarads in Chemical Laboratory, The Royal Chemical Society:
London, 1977.
3. Ishii, A.; Seno, H.; Watanabe-Suzuki, K.; Suzuki, O.; Kumazawa, T. Anal. Chem.
1998, 70, 4873–4876.
4. Ullmann’s Encyclopedia of Industrial Chemistry, 6th ed.; Wiley-VCH, New York,
1999.
5. Cyanide: Soc., Ind., Econ. Aspects, Proc. Symp. Annu. Meet., Miller, G. C.; Pritsos,
C. A. 2001, 73.
Kang, J. Tetrahedron Lett. 2005, 46, 7165–7167; (j) Yuan, Y.; Gao, G.; Jiang, Z.-L.;
You, J.-S.; Zhou, Z.-Y.; Yuan, D.-Q.; Xie, R.-G. Tetrahedron 2002, 58, 8993–8999.
12. General procedure: 1-(4-nitrophenyl)-benzimidazole (1 mmol, 239 mg) and
dodecylbromide (2 mmol, 500 mg) were heated overnight at 80–90 °C, the
reaction mixture was cooled to room temperature and diethyl ether was added
to remove excess of dodecylbromide and then the separated white-colored
solid was filtered to get pure compound 2a (60% yield, 290 mg). The solution of
NH4PF6 (244 mg, 1.5 mmol) in water was added dropwise to the solution 2a
(119 mg, 0.5 mmol) in methanol and the separated white solid was filtered off
to get pure 2b.
6. (a) Tomasulo, M.; Raymo, F. M. Org. Lett. 2005, 7, 4633–4636; (b) Tomasulo, M.;
Sortino, S.; White, A. J. P.; Raymo, F. M. J. Org. Chem. 2006, 71, 744–753.
7. García, F.; García, J. M.; García-Acosta, B.; Martínez-Máñez, R.; Sancenón, F.;
Soto, J. Chem. Commun. 2005, 2790–2792.
8. Ros-Lis, J. V.; Martínez-Máñez, R.; Soto, J. Chem. Commun. 2002, 2248–2249.
9. Chung, Y. M.; Raman, B.; Kim, D.-S.; Ahn, K. H. Chem. Commun. 2006, 186–188.
10. (a) Kim, Y. K.; Lee, Y.-H.; Kim, M. K.; Cha, G. S.; Ahn, K. H. Org. Lett. 2003, 5,
4003–4006; (b) Yang, Y.-K.; Tae, J. Org. Lett. 2006, 8, 5721–5723; (c) Chen, C.-L.;
Chen, Y.-H.; Chen, C.-Y.; Sun, S.-S. Org. Lett. 2006, 8, 5053–5056; (d) Sessler, J.
L.; Cho, D.-G. Org. Lett. 2008, 10, 73–75; (e) Lee, K. S.; Kim, H.-J.; Kim, G.-H.;
Shin, I.; Hong, J.-I. Org. Lett. 2008, 10, 49–51; (f) Ekmekci, Z.; Yilmaz, D.; Akkya,
E. U. Org. Lett. 2008, 10, 461–464; (g) Miyaji, H.; Kim, D.-S.; Chang, B.-Y.; Park,
E.; Park, S.-M.; Ahn, K. H. Chem. Commun. 2008, 753–755.
11. (a) Sato, K.; Arai, S.; Yamagishi, T. Tetrahedron Lett. 1999, 40, 5219–5222; (b)
Yun, S.; Ihm, H.; Kim, H. G.; Lee, C.-W.; Indrajit, B.; Oh, K. S.; Gong, Y. J.; Lee, J.
W.; Yoon, J.; Lee, H. C.; Kim, K. S. J. Org. Chem. 2003, 68, 2467–2470; (c)
Chellappan, K.; Singh, N. J.; Hwang, I.-C.; Lee, J. W.; Kim, K. S. Angew. Chem.
2005, 44, 2899–2903; (d) Kim, S. K.; Kang, B.-G.; Koh, H. S.; Yoon, Y. J.; Jung, S.
J.; Jeong, B.; Lee, K.-D.; Yoon, J. Org. Lett. 2004, 6, 4655–4658; (e) Kim, S. K.;
Singh, N. J.; Kim, S. J.; Kim, H. G.; Kim, J. K.; Lee, J. W.; Kwang, S.; Yoon, J. Org.
Lett. 2003, 5, 2083–2086; (f) Kim, K. S.; Kim, H.-S. Tetrahedron 2005, 61, 12366–
12370; (g) Kim, H.; Kang, J. Tetrahedron Lett. 2005, 46, 5443–5445; (h) Ihm, H.;
Yun, S.; Kim, H. G.; Kim, J. K.; Kim, K. S. Org. Lett. 2002, 4, 2897–2900; (i) In, S.;
Probe 2b: (100 mg, 66% yield). Mp 75 °C; FAB mass M+ m/z 409 [M + H]+; 1H
NMR (CD3CN): d 0.88 (t, 3H, J = 6.8 Hz, CH3), 1.27 (br s, 14H, 7 Â CH2), 1.37–
1.48 (m, 4H, 2 Â CH2), 2.05 (q, 2H, J = 7.5 Hz, CH2), 4.53 (t, 2H, J = 7.5 Hz, CH2),
7.75–7.83 (m, 3H, 3 Â ArH), 7.95 (d, 2H, J = 6.9 Hz, 2 Â ArH), 8.00–8.03 (m, 1H,
ArH), 8.54 (d, 2H, J = 6.9 Hz, 2 Â ArH), 9.29 (s, 1H, ArH); 13C NMR (CD3CN): d
14.3, 23.7, 26.9, 29.5, 29.6, 29.9, 30.0, 30.1, 30.2, 32.5, 48.8, 114.5, 114.9, 126.7,
127.5, 128.7, 129.1, 132.4, 132.6, 138.9, 141.7, 149.9. (C25H34N3O2 PF6 requires
C, 54.25; H, 6.15; N, 7.59. Found C, 54.47; H, 6.02; N, 7.82).
Probe 3b: 75% yield. Mp 252 °C; FAB mass M+ m/z 727 [M2+ + PF6À]; 1H NMR
(CD3CN): d 5.78 (s, 4H, 2 Â CH2), 7.60 (d, 4H, J = 7.5 Hz, ArH), 7.75–7.84 (m, 8H,
8 Â ArH), 7.95 (d, 4H, J = 9.3 Hz, 4 Â ArH), 8.54 (d, 4H, J = 9.3 Hz, 4 Â ArH), 9.39
(s, 2H, 2 Â ArH); 13C NMR (CD3CN): d 50.6, 113.5, 113.8, 125.5, 126.4, 127.6,
128.1 129.2, 131.0, 131.5, 133.3, 137.5, 141.1, 148.7. (C34H26N6O4 P2F12
requires C, 46.79; H, 2.98; N, 9.63. Found C, 46.57; H, 2.88; N, 9.54).
Probe 4b: 74% yield. Mp 265 °C; FAB mass M+ m/z 769 [M2+ + PF6À]; 1H NMR
(CD3CN): d 2.30 (s, 3H, CH3), 2.44 (s, 6H, 2 Â CH3), 5.74 (s, 4H, 2 Â CH2), 7.35 (s,
1H, ArH), 7.79–7.87 (m, 10H, 10 Â ArH), 8.15 (d, 2H, J = 6.6 Hz, 2 Â ArH), 8.42
(d, H, J = 6.9 Hz, 4 Â ArH), 8.60 (s, 2H, 2 Â ArH); 13C NMR (CD3CN): d 16.4, 20.1,
47.3, 114.5, 114.9, 126.3, 127.4, 127.7, 128.8, 129.5, 132.7, 132.9, 133.1, 138.6,
140.4, 141.2, 142.7, 149.7. (C37H32N6O4 P2F12 requires C, 48.58; H, 3.50; N, 9.19.
Found C, 48.52; H, 3.42; N, 9.32).