Single-electron transfer driven cyanide sensing: A new multimodal approach

Article abstract of DOI:10.1021/ol1008558

A new SET-driven reaction-based strategy is reported for sensing of cyanide with indicators having low LUMO levels. The cyanide-specific reaction produces an air-stable radical anion marker and by virtue of its spin, charge, and the SOMO-LUMO-based electronic transition generates multimodal signal outputs. High selectivity and sensitivity (0.2-16 μM) were observed when compared to other reducing anions. This new indicator system exhibits regenerability and dip-stick sensing, and fabrication of an electronic sensing device for cyanide is demonstrated.

Full text of DOI:10.1021/ol1008558

ORGANIC
LETTERS
2010
Vol. 12, No. 11
2646-2649
Single-Electron Transfer Driven Cyanide
Sensing: A New Multimodal Approach
M. R. Ajayakumar and Pritam Mukhopadhyay*
Supramolecular and Material Chemistry Lab, School of Physical Sciences, Jawaharlal
Nehru UniVersity, New Delhi 110067, India
Sarita Yadav and Subhasis Ghosh
School of Physical Sciences, Jawaharlal Nehru UniVersity, New Delhi 110067, India
m_pritam@mail.jnu.ac.in
Received April 15, 2010
ABSTRACT
A new SET-driven reaction-based strategy is reported for sensing of cyanide with indicators having low LUMO levels. The cyanide-specific reaction
produces an air-stable radical anion marker and by virtue of its spin, charge, and the SOMO-LUMO-based electronic transition generates multimodal
signal outputs. High selectivity and sensitivity (0.2-16 µM) were observed when compared to other reducing anions. This new indicator system
exhibits regenerability and dip-stick sensing, and fabrication of an electronic sensing device for cyanide is demonstrated.
There is continuous effort toward the design of anion sensors
based on small molecules and their ensembles.1 Among the
anions, cyanide has evinced maximum interest due to its
severe toxicity. Recently, reaction-based indicators/chemo-
dosimeters have evolved as an attractive platform for sensing
cyanide anions2 and other analytes.3 Cyanide sensors are also
based on H-bonding, time-gated fluorescence, metal ion
complexes, conformational changes, quantum dots, and thin-
film sensing.4a-h
Cyanide sensing with reaction-based indicators utilizes the
nucleophilic nature of the cyanide, and the design comprises
a substrate and a reporter unit. Functional groups such as
carbonyl/ene/imine5 or Lewis acidic boranes6 are used as
substrates, while π-conjugated chromophores are used as the
reporter units (Scheme 1a).
(1) (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–
516. (b) Lavigne, J. J.; Anslyn, E. V. Angew. Chem., Int. Ed. 2001, 40,
3118–3130. (c) Mart´ınez-Ma´ñez, R.; Sanceno´n, F. Chem. ReV. 2003, 103,
4419–4476. (d) Sessler, J. L.; Seidel, D. Angew. Chem., Int. Ed. 2003, 42,
5134–5175. (e) Best, M. D.; Tobey, S. L.; Anslyn, E. V. Coord. Chem.
ReV. 2003, 240, 3–15. (f) Mart´ınez-Ma´ñez, R.; Sanceno´n, F. Coord. Chem.
ReV. 2006, 250, 3081–3093.
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Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40, 154–157. (c)
Anzenbacher, P., Jr.; Tyson, D. S.; Jursikova´, K.; Castellano, F. N. J. Am.
Chem. Soc. 2002, 124, 6232–6233. (d) Badugu, R.; Lakowicz, J. R.; Geddes,
C. D. J. Am. Chem. Soc. 2005, 127, 3635–3641. (e) Palomares, E.; Mart´ınez-
D´ıaz, M. V.; Torres, T.; Coronado, E. AdV. Funct. Mater. 2006, 16, 1166–
1170. (f) Jo, J.; Lee, D. J. Am. Chem. Soc. 2009, 131, 16283–16291. (g)
Shang, L.; Jin, L.; Dong, S. Chem. Commun. 2009, 3077–3079. (h) Gimeno,
N.; Li, X.; Durrant, J. R.; Vilar, R. Chem.sEur. J. 2008, 14, 3006–3012.
(2) (a) Mohr, G. J. Chem.sEur. J. 2004, 10, 1082–1090. (b) Sessler,
J. L.; Cho, D.-G. Chem. Soc. ReV. 2009, 38, 1647–1662.
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4806. (b) Zhang, S.-W.; Swager, T. M. J. Am. Chem. Soc. 2003, 125, 3420–
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10.1021/ol1008558  2010 American Chemical Society
Published on Web 05/10/2010

significantly larger in substrates having LL than for substrates
having HL (Scheme 1b).9
Scheme 1
.
CN- Sensing by Nucleophilic or New SET-Based
Reaction and Its STPs
This reaction-based system produces an air-stable radical
anion marker, which is selective and sensitive (0.2-16 µM)
to cyanide. This STP is based on a SOMO-LUMO based
eT, a complete shift from the conventional HOMO-LUMO
eT (Scheme 1b). The formation of spin and charge in the
marker leads to multiple modes of sensing. The indicator
exhibits regenerability and dip-stick sensing. Importantly, the
high conductivity of the radical anion let us fabricate an
electronic device for sensing cyanide.
We synthesized molecular indicators belonging to three
classes: naphthalene-bis-hydrazimide (NBHI)10 (1a-c), NDI
(2a,b), and PDI derivatives (3a) with varying functionalities
X, Y, Z and extent of core conjugation, n, and characterized
by NMR, IR, and mass spectrometry.
Next, to confirm that the Y/Z groups and the linker X can
indeed affect electron-withdrawing (EW) ability of the
carbonyl groups and lower the LUMO levels, we carried out
theoretical calculations and verified the results with IR and
cyclic voltammetry (CV) (Supporting Information, Page No.
S8 and S9). Figure 1 clearly depicts substantial lowering of
These indicators harness high-lying LUMO (HL), and thus,
nucleophilic addition is preferred. They utilize internal
charge-transfer (ICT)-based signal transduction pathway
(STP) involving HOMO-LUMO-based electronic transition
(eT). As a result, signal readability relies on a particular
analytical technique, and instrumentation errors due to limited
signal outputs become inevitable (Scheme 1a). In addition,
some of them require elevated reaction temperature, biphasic
conditions, and lag-time in sensing. This necessitates search
for new indicators having new STPs which can circumvent
the above problems.
In this context, single-electron transfer (SET) based
biological sensors, e.g., redox-active cofactors in bacteria,
1e- oxidation of cyanide, and its complex formation with
cytochrome c oxidase (CcO), etc.,7 motivated us to design
molecules with new STP for anions which are anticipated
to have easy and multiple signal readability.
Figure 1. LUMO levels, IR frequencies, and reduction potentials
for indicators 1a-3a.
the LUMO levels going from 1c f 1a or 2b f 2a (effect
of Y/Z groups) and also nicely discern the pivotal role of
the linker X (NH/CH2) in controlling the electron acceptor
properties in NBHI (1a-c) versus NDI/PDI (2a,b, 3).
The first electron reduction potential (E1) also shows a
significant lowering with substitution of the Y, Z and by
the NH group. IR studies further substantiated that the EW
ability of the carbonyl groups can be enhanced by substitution
effects, e.g., stretching frequency of carbonyl groups in 1a
increases by 18 and 22 cm-1 compared to 2a.
As a proof-of-concept, herein we report the first SET-based
cyanide indicator which is based on a low-LUMO (LL)
design. We chose naphthalenediimide (NDI)8a and perylene-
diimide (PDI)8b moiety as the core unit since (a) the NDI/
PDI moieties have LL levels and provide synthetic scope to
further lower them and (b) they contain carbonyl groups ideal
for electron acceptance. This design aspect is crucial since
for a given anion the electron-transfer component would be
We then explored the colorimetric sensing ability of 1a
and 3a in the presence of anions 1-14. Only in the presence
of cyanide do 1a and 3a with an extended core show an
instantaneous change from colorless to dark brown and from
an initial orange to a turquoise-blue solution, respectively
(Figure 2). The other anions remained nonresponsive. These
color changes are specific to the 1e- transfer to the NDI/
(5) (a) Garc´ıa, F.; Garc´ıa, J. M.; Garc´ıa-Acosta, B.; Mart´ınez-Ma´ñez,
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(10) Compounds 1a and 1b were reported recently; see: Ajayakumar,
M. R.; Mukhopadhyay, P. Chem. Commun. 2009, 3702–3704.
Org. Lett., Vol. 12, No. 11, 2010
2647

3a with cyanide and their relative intensity ratios perfectly match
with the signature peaks due to D0fDn eTs for the radical
anions of the NDI and PDI moiety, respectively.12 This validates
formation of 1a•-/3a•- and also the SET-driven reaction.
The multioptical outputs for 1a•- (Inset of Figure 3) and
the facile NIR absorption provides reliability in sensing
cyanide and would also aid in reducing interference from
biological chromophores.
We confirmed the air stability of the radical anion marker
by UV-vis-NIR spectroscopy. The presence of clear
isosbestic points and clean spectral plots for 1a-3a in
presence of cyanide point to an uncluttered SET process.
Thus, 1a•- could be kept in open vials up to 3 h without
decomposition, while in closed vials it could be stored at
ambient temperature for a few weeks (Supporting Informa-
tion, S11). Further, the radical anions of 1a•- upon oxygen
purging were stable up to 35 min after which it shows slow
decomposition. This confirms the high stability and ap-
plicability of this marker for sensing.
Figure 2. Photographs of 1a in (a) DMF/H2O (97:3); (b) DMF
and 3a in (c) THF/H2O (97:3); (d) THF with anions 1-14; [1a;
1.2 × 10-4 M, 1-14 in DMF/H2O (97:3); 4.3 × 10-4 M and in
DMF; 2.2 × 10-4 M, 3a; 6 × 10-5 M, 1-14 in THF/H2O (97:3);
9 × 10-4 M and in THF; 2.2 × 10-4 M].
This stability of the radical anion originates from the
number of low-energy charge delocalized resonating struc-
tures, which is dependent on the LUMO levels of the
indicators (Supporting Information, S12). In order to ex-
perimentally confirm this, we compared the response of
indicators 1a-2b toward cyanide and hence its propensity
to form the radical anion marker. Indeed, in line with the
LUMO levels, the optical response and propensity to form
the radical anion follows the order: 1a > 1c > 2a > 2b
(Supporting Information, S12-S14).
We then explored the multiple signal outputs emanating
from the radical anion as a consequence of cyanide sensing
(Supporting Information, S15-S17). We chose 3a due to
its strong fluorescence. The SET-driven formation of 3a•-
induces complete quenching of the 531-620 nm fluorescent
bands within an extremely narrow concentration window of
0.2-3.5 µM of cyanide (Figure 3b).13 The other strong
evidence for the SET driven reaction comes from the
diagnostic EPR signal unique to the imide radicals (g )
2.0056) of 1a•-, formed in the presence of cyanide.11 Square-
wave voltammetry (SWV) also exhibited a cyanide specific
3-fold reduction in current and cathodic shifts of reduction
waves of up to 20 mV. This is due to the fact that cyanide
induced electron transfer makes it difficult to reduce 1a.
Similarly, the frequencies of carbonyl groups in 1a at 1725
and 1690 cm-1 show a decrease in the intensity and new
peaks arise at 1663 and 1625 cm-1 with cyanide as a result
of greater degree of single bond character in the radical anion.
Compound 1a was found to be highly selective toward
cyanide in mixed-aqueous, polar aprotic, and nonpolar
solvents; e.g., 1a in DMF/H2O (97:3) was found to be 2.1
× 102, 1 × 102, and 42 times more selective toward CN-
PDI moiety11 and indicates formation of the radical anion
marker 1a•-/3a•-. Importantly, the sensing could be per-
formed under ambient conditions in mixed aqueous, polar
aprotic, as well as nonpolar solvents. Because of the high
air stability of the radical anion, no special precautions like
glovebox were required during the sensing process.
The formation of the radical-anion marker during this
sensing process would make it amenable to various spec-
troscopic techniques and provide diagnostic spectral signa-
tures. Thus, to confirm our proposed SET-based reaction
mechanism and to explore the multimodal signal readability,
we verified the marker with UV-vis-NIR, fluorescence,
EPR, IR, and electrochemical techniques.
UV-vis-NIR spectroscopy of 1a show peaks at 358 and
377 nm. In the presence of cyanide, a new set of highly red-
shifted peaks at 470, 603, 701, 786, and 1100 nm appeared
(Figure 3a), while 3a with cyanide shows a new set of peaks at
Figure 3. (a) UV-vis-NIR spectra showing the response of 1a (1.2
× 10-4 M) upon incremental addition of CN-, 1 in DMF. Inset
shows the response of the optical channels as a function of CN-.
(b) Fluorescence spectra showing the response of 3a (1.5 × 10-7
M) upon addition of CN- in THF (excited at 485 nm). Inset show
the plot of fluorescence intensity (I, integrated fluorescence from
500-700 nm) as a function of CN-.
(11) Andric, G.; Boas, J. F.; Bond, A. M.; Fallon, G. D.; Ghiggino,
K. P.; Hogan, C. F.; Hutchison, J. A.; Lee, M. A.-P.; Langford, S. J.;
Pilbrow, J. R.; Troup, G. J.; Woodward, C. P. Aust. J. Chem. 2004, 57,
1011–1019.
(12) Gosztola, D.; Niemczyk, M. P.; Svec, W.; Lukas, A. S.; Wasielews-
ki, M. R. J. Phys. Chem. A 2000, 104, 6545–6551.
(13) Baggerman, J.; Jagesar, D.-C.; Valle´e, R. A. L.; Hofkens, J.; De
Schryver, F. C.; Schelhase, F.; Vo¨gtle, F.; Brouwer, A. M. Chem.sEur. J.
2007, 13, 1291–1299.
699, 761, 794, 952, and 1100 nm (Supporting Information, S10).
These new peaks at 470-786 nm for 1a and 699-952 nm for
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Org. Lett., Vol. 12, No. 11, 2010

-
over F-, H2PO4 , and OH-/OAc-, respectively, while being
completely nonresponsive toward other anions (Figure 4a).14
Figure 5.
(a) Photograph depicting sensing of CN-, 1 with thin
films of 3a: (i) 0 mM of 1, (ii) 0.1 mM of 1 in petroleum ether,
(iii) 0.2 mM of 1 in Pet. ether, (iv) 4 mM of 1 in water, (v) 8 mM
of 1 in water. Photographs were taken after 90 min of soaking with
1 in water. (b) Regenerability experiments of 1a/3a with CN- and
NOBF4. (c) I-V curves of 1a and with different amounts of 1 or
5. Inset shows the two terminal electronic devices.
Figure 4. Selectivity profile of 1a with anions 1-14 evaluated in
terms of four optical channels: (a) DMF/H2O (97:3) (1a, 1.2 ×
10-4 M; 1-14, 4.3 × 10-4 M) and (b) DMF (1a, 1.2 × 10-4 M;
1-14, 2.2 × 10-4 M). ∆A refers to A - A0, where A and A0 stand
for the absorbance in the presence and absence of anions,
respectively.
dark brown (1a•-) and the turquoise-blue (3a•-) solution
formed in the presence of cyanide could be instantaneously
switched to the original sensors 1a/3a (Figure 5b).
Finally, we could successfully fabricate a cyanide sensing
two-terminal device applying this SET-based reaction. The
device consisted of two Au electrodes deposited on a glass
plate with a gap of 80 µm (Figure 5c). Compound 1a shows
negligible current, however, with increasing amounts of
cyanide; e.g., with 0.4 mM of cyanide, the current is more
than 4 orders of magnitude higher than 1a. No major increase
in current was observed with excess of other anions (Sup-
porting Information, S6).16
In conclusion, we have demonstrated a new SET-driven
reaction which is highly selective and sensitive to cyanide.
This new STP is completely different from the conventional
HOMO-LUMO-based STPs known to date. The multiple
signal outputs emanating from the radical anion marker and
its spectroscopic signatures were duly characterized. The
effect of the LUMO levels of the indicators on the cyanide
response was evaluated. Air-stability and high conductivity
of the marker allowed us to fabricate an electronic device
for cyanide sensing.
When compared with other reducing anions, 1a was ∼4 and
10 times more selective for cyanide over thiosulfate and
dithionite, respectively, while ferrocyanide, nitrite, and sulfite
remained completely nonresponsive (Supporting Information,
S18 and S19). In DMF, 1a was selective toward cyanide
-
with respect to OH-, OAc-, H2PO4 , and F- by 38, 25, 22,
and 8 times, respectively (Figure 4b). The other anions
remained completely silent. No interference from reducing
amine like hydrazine and from nucleophile/base like iodide
and OH- were observed. This specificity for cyanide was
also confirmed with multiple signal outputs (Supporting
Information, S20). The high specificity toward cyanide is
supported by the well-known R-effect. The stability of
radicals R to a lone pair is available only to cyanide in
contrast to other anions studied here.15
Compound 1a exhibited a highly attractive sensitivity
toward cyanide in a diverse range of solvents. Sensitivity of
0.67 and 1.3 µM was achieved in THF and DMF. In DMF/
H2O (97:3), a sensitivity of 16 µM could be determined
(Supporting Information, S20 and S21). An attractive
sensitivity of 0.2 µM (∼ 5 ppb) in THF could be achieved
by monitoring the fluorescence intensity of 3a.
Since only a handful of sensors are known to sense cyanide
on the solid surface,4h we analyzed the dip-stick sensing
ability of 3a. Interestingly, thin films of 3a fabricated by
vapor deposition technique onto glass substrates could detect
cyanide in nonpolar solvents like petroleum-ether as well as
in pure water (Figure 5a). Furthermore, the indicator systems
show regenerability with an oxidizing agent like NOBF4. The
Acknowledgment. We thank CSIR, DST and FIST-II for
the financial support and Prof. P. K. Bharadwaj and Mr. R. K.
Das (IIT Kanpur) for the EPR experiments. We thank the
500 MHz NMR facility at AIRF, JNU, and MALDI-TOF
facility at CIF, SLS, JNU, New Delhi.
Supporting Information Available: Experimental pro-
cedures, synthesis, various spectroscopic data, and supple-
mentary spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(14) We were unable to use buffer solution for the DMF/H2O experiment
as the buffers interfered with the radical anion sensor.
(15) Edwards, J. O.; Pearson, R. G. J. Am. Chem. Soc. 1962, 84, 16–
24. This extra stabilization of the radical has been explained on the basis
of the MO diagram of a three-electron system, and this effect is predominant
at carbonyl or other unsaturated carbons.
OL1008558
(16) Penneau, J.-F.; Stallman, B. J.; Kasai, P. H.; Miller, L. L. Chem.
Mater. 1991, 3, 791–796.
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