A Molecular keypad lock based on the thiacalix[4]arene of 1,3-alternate conformation

Article abstract of DOI:10.1021/ol900845g

A chemosensor based on the thiacalix[4]arene of 1,3-a/temate conformation has been designed and synthesized. The binding behavior of this chemosensor has been studied toward different metal ions by fluorescence spectroscopy, and it was observed that the c

Full text of DOI:10.1021/ol900845g

ORGANIC
LETTERS
2009
Vol. 11, No. 12
2567-2570
A Molecular Keypad Lock Based on the
Thiacalix[4]arene of 1,3-Alternate
Conformation
Manoj Kumar,* Abhimanew Dhir, and Vandana Bhalla*
Department of Chemistry, Guru Nanak DeV UniVersity,
Amritsar, Punjab-143005, India
mksharmaa@yahoo.co.in; Vanmanan@yahoo.co.in
Received April 17, 2009
ABSTRACT
A chemosensor based on the thiacalix[4]arene of 1,3-alternate conformation has been designed and synthesized. The binding behavior of this
chemosensor has been studied toward different metal ions by fluorescence spectroscopy, and it was observed that the chemosensor selectively
senses Cu2+ ions. The chemical inputs of Cu2+ and F- in a sequential manner generate an output which mimics the functions of a security
keypad lock.
Fluorescent sensors that change their fluorescence behavior
upon binding with heavy transition metal ions and anions
are one of the most widely used analytical tools on the basis
of which various molecular switches and logic gates have
been proposed.1 These molecular logic gates and circuits play
an important role in electronic devices from digital comput-
ers, calculators, video games, and store automation to music
equipment.2
Recently, the combination of molecular logic gates and
logic circuits has also been used for developing a keypad
lock3 at the molecular level. This is an electronic device
which is capable of processing password entries, hence access
to an object or data can be restricted to a limited number of
people. In other words, one needs to know the password
which opens the lock. Such molecular devices which can
distinguish between the sequences of different chemical
inputs are expected to be better than simple logic gates. The
development of such a molecular scale keypad lock is a
particularly attractive goal as it represents a new approach
for protecting information at the molecular scale. Such
sequential logic circuits can also be used to design molecular
keyboards capable of crossword puzzles.4 Thus, keeping in
view the role played by soft transition metal ions and
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Switches; B. Feringa, L., Ed.; Wiley-VCH: Weinheim, 2000. (b) Raymo,
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ChemphysChem. 2003, 4, 49. (d) Guo, X.; Zhang, D.; Wang, T.; Zhu
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Chem.-Eur. J. 2004, 10, 574. (f) Qu, D. H.; Wang, Q. C.; Tian, H. Angew.
Chem. 2005, 117, 5430. (g) Qu, D. H.; Ji, F. Y.; Wang, Q. C.; Tian, H.
AdV. Mater. 2006, 18, 2035. (h) Andreasson, J.; Straight, S. D.; Kodis, G.;
Park, C. D.; Hambourger, M.; Grevaldo, M.; Albinson, B.; Moore, T. A.;
Moore, A. L.; Gust, D. J. Am. Chem. Soc. 2006, 128, 16259.
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Chem. Soc. 2007, 129, 347. (b) Suresh, M.; Ghosh, A.; Das, A. Chem.
Commun. 2008, 3906.
(2) (a) Adamatzky, A.; De Lacy Costello, B.; Asai, T. Reaction-Diffusion
Computers; Elsevier Science: Amsterdam, The Netherlands, 2005. (b)
Teuscher, C.; Adamatzky, A., Eds. UnconVentional Computing 2005: From
Cellular Automata to Wetware; C. Luniver Press: Beckington, U.K. 2005.
(c) Dittrich, P. Lect. Notes Comput. Sci. 2005, 3566, 19. (d) Hjelmfelt, A.;
Ross, J. Physica D 1995, 84, 180. (e) Najmabadi, P.; La Clair, J. J.; Burkart,
M. D. Org. Biomol. Chem. 2007, 5, 2140. (f) Stojanovic, M. N.; Stefanovic,
D. Nat. Biotechnol. 2003, 21, 1069.
(4) Guo, Z. Q.; Zhu, W. H.; Shen, L. J.; Tian, H. Angew. Chem., Int.
Ed. 2007, 46, 5549.
(5) (a) Kumar, R.; Bhalla, V.; Kumar, M. Tetrahedron 2008, 64, 8095.
(b) Bhalla, V.; Kumar, R.; Kumar, M.; Dhir, A. Tetrahedron 2007, 63,
11153. (c) Dhir, A.; Bhalla, V.; Kumar, M. Tetrahedron Lett. 2008, 49,
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10.1021/ol900845g CCC: $40.75
Published on Web 05/18/2009
 2009 American Chemical Society

electronic devices in day to day life, the development of
fluorescent sensors for their applications in electronic devices
is very important.
A parent ion peak at m/z 1264 (M + 1)+ corresponding to
the 1:2 condensation product was observed in the FAB mass
spectrum. These spectroscopic data corroborate the structure
2 for this compound.
The binding behavior of compound 2 toward different
cations (Cu2+, Pb2+, Hg2+, Zn2+, Cd2+, Ni2+, Ag+, K+, Na+,
and Li+) was investigated by fluorescence spectroscopy. The
fluorescence spectrum of compound 2 (10 µM) shows an
emission band at 313 nm in THF:H2O (9.5:0.5,v/v). The
fluorescence is quenched upon addition of Cu2+ ions (100
µM) to the solution of compound 2 (Figure 1). The quenching
Our research work involves the development of fluorescent
sensors5 for soft metal ions, and we recently reported6 a
ratiometric fluorescent sensor for mercury ions based on the
partial cone conformation of calix[4]arene which behaves
as a NOR logic gate with YES logic function upon chemical
inputs of Hg2+ and Cu2+ ions. Now we have synthesized a
chemosensor based on a thiacalix[4]arene of 1,3-alternate
conformation which upon chemical inputs of Cu2+ and F-
in a sequential manner generates an output which mimics
the functions of a security keypad lock. Such a type of
security keypad lock based on thiacalix[4]arene is unprec-
edented.
Condensation of diamine 1 with 2.0 mol equiv of 2-hy-
droxy-5-nitrobenzaldehyde furnished target compound 2 in
84% yield (Scheme 1). The diamine 1 was synthesized from
Scheme 1
Figure 1. Fluorescence spectra of 2 (10 µM) in response to the
presence of Cu2+ ions (100 µM) in THF:H2O (9.5:0.5,v/v) buffered
with HEPES, pH ) 7.0; λex ) 269 nm.
of fluorescence could be attributed to a photoinduced charge
transfer mechanism (PCT).7 Under the same conditions as
used above for Cu2+, we also tested the fluorescence response
of 2 to other metal ions such as Pb2+, Hg2+, Zn2+, Cd2+,
Ni2+, Ag+ K+, Na+, and Li+ (Figure 2). No significant
,
a known precursor (for synthetic details, see Supporting
Information S3-S5 and S23-S25). The structure of com-
pound 2 was confirmed by its spectroscopic and analytical
data (see Supporting Information S5-S6 and S16-S18). The
1H NMR spectrum of compound 2 showed two singlets (18H
each) at 1.28 and 1.34 ppm corresponding to the tert-butyl
protons, four triplets (4H each) at 3.0 ppm for NCH2 protons
and at 3.14, 3.94, and 4.12 ppm for OCH2 protons, two broad
signals (4H each) at 3.39 and 3.59 ppm corresponding to
OCH2 protons, four singlets (4H and 2H each) corresponding
to the aromatic and imino protons at 7.36, 7.39, 8.17, and
8.26 ppm respectively, two doublets (2H each) at 6.99 and
8.20 ppm corresponding to the aromatic protons, and a broad
signal corresponding to the phenolic proton at 14.16 ppm
(see S16, Supporting Information). The IR spectrum of
compound 2 showed a CdN stretching band at 1630 cm-1.
Figure 2
.
Fluorescence intensity changes [(I - I0)/I0 × 100] of
receptor 2 (10 µM) in THF:H2O (9.5:0.5, v/v) upon addition of
100 µM of various metal perchlorates. The excitation wavelength
was 269 nm. I0 is the fluorescence intensity at 313 nm of each free
host, and I is the fluorescence intensity after adding metal ions.
variation was observed except in the case of K+ ions where
a 25% enhancement in the emission intensity was observed
(7) (a) Choi, J K.; Kim, S. H.; Yoon, J.; Lee, K. H.; Bartsch, R. A.;
Kim, J. S. J. Org. Chem. 2006, 71, 8011. (b) Lee, S. H.; Kim, H. J.; Lee,
Y. O.; Vicens, J.; Kim, J. S. Tetrahedron Lett. 2006, 47, 4373.
(6) Dhir, A.; Bhalla, V.; Kumar, M. Org. Lett. 2008, 10, 4891.
2568
Org. Lett., Vol. 11, No. 12, 2009

(see Supporting Information S11). The enhancement in the
case of K+ ions can be ascribed to the fact that the K+ ions
bind to the polyether ring, and as a result, photoinduced
electron transfer (PET) from the polyether ring to the
photoexcited nitro phenyl moiety is suppressed. Earlier, Kim
et al. have reported similar fluorescence enhancement in the
presence of K+ ions where the K+ ions bound to the crown
ether ring of a calix[4]arene of 1,3-alternate conformation
bearing pyrene moieties.8 We also synthesized a reference
compound 3 from a known precursor9 without incorporating
the crown ether moiety (for synthetic details, see Supporting
Information S6-S7 and S20-S22). No change in fluores-
cence was observed on addition of K+ ions to the receptor
3 (see Supporting Information S12) confirming that the
fluorescence enhancement observed in the case of 2 with
K+ ions is due to interaction of the crown ring with K+ ions.
Fitting the changes in the fluorescence spectra of com-
pound 2 with copper ions, using the nonlinear regression
analysis program SPECFIT,10 gave a good fit and demon-
strated that 1:1 stoichiometry (host:guest) was the most stable
species in the solution with a binding constant log ꢀ1 ) 4.16.
The method of continuous variation (Job’s plot) was also
used to prove the 1:1 stoichiometry (see Supporting Informa-
tion S9).
employed (see Supporting Information S14). To further
investigate the proposed deprotonation, we synthesized
compound 4 which contains relatively weakly acidic phenolic
protons (for synthetic details, see Supporting Information
S7-S8 and S26-S28). When binding studies of compound
4 were performed in the presence of different cations and
anions under the same conditions as used for the receptor 2,
the profound selectivity of compound 4 was observed for
Cu2+ ions (see Supporting Information S15); however, no
change in emission was observed in the presence of any
anion. Thus, we can conclude that the presence of the nitro
groups in receptor 2 makes the phenolic protons relatively
more acidic, deprotonation of which by F- ions results in
changes in the emission spectra being observed, whereas no
such phenomenon was observed in compound 4 which has
relatively less acidic phenolic protons due to the absence of
a nitro group.
Recently, there has been a lot of interest in the develop-
ment of materials which could protect information at the
molecular level. However, there are only a few reports of
such systems which can function as security or memory
devices. Das et al. have recently reported a chemosensor
which functions as a molecular keypad lock using Cu2+ and
F- as ionic inputs.3b Tian et al. recently reported a fluoro-
phore capable of crossword puzzles and logic memory.4
Since there has not been any report in which thiacalix[4]arene
was used for such applications, we examined our system as
a molecular keypad lock. For construction of such devices,
we performed fluorescence experiments in the simultaneous
presence of Cu2+ and F- ions in dry THF, and spectra were
taken immediately after the addition of analytes. The addition
of Cu2+ ions to solution of 2 containing F- ions results in
quenching of the fluorescence (Figure 3), whereas on addition
To test the practical applicability of compound 2 as a Cu2+-
selective fluorescence sensor, competitive experiments were
carried out in the presence of Cu2+ ions at 100 µM mixed
with Li+, Na+, K+, Ni+, Zn2+, Cd2+, Ag+, and Pb2+ at 100
µM. No significant variation in the intensity was found by
comparison with and without the other metal ions (see
Supporting Information S10).
In addition to cation binding properties, we also investi-
gated the sensing properties of 2 toward different anions (F-,
-
-
-
Cl-, Br-, I-, HSO4 , CH3COO-, H2PO4 , and NO3 ) using
tetrabutylammonium as a countercation. There was no change
in the fluorescence behavior of compound 2 on adding these
anions except in the case of fluoride ions where a 16%
enhancement in the fluorescence intensity was observed (see
Supporting Information S13). We propose that the fluores-
cence enhancement of 2 on addition of fluoride ions probably
occurs by the deprotonation of the phenolic hydroxyl group
by F- which results in the formation of an anion. This
promotes the delocalization of π electrons in the nitrophenyl
moiety which results in fluorescence enhancement. To
confirm this assumption and evaluate the intermolecular
interactions between the compound 2 and fluoride ions, we
carried out NMR studies in CDCl3. It was found that on
addition of small amounts of tetrabutylammonium fluoride
to a solution of compound 2 in CDCl3 the hydroxyl protons
completely disappeared indicating that the deprotonation of
the hydroxyl group is taking place in the presence of fluoride
ions (see Supporting Information S19). Similar results were
obtained when a relatively strong base such as Bu4NOH was
Figure 3. Fluorescence spectra of 2 (10 µM) in response to the
addition of F- ions (300 µM) and further addition of Cu2+ ions in
THF; λex ) 269 nm.
of F- ions to the 2·Cu2+ complex, a new red-shifted band is
formed at 370 nm (Figure 4). When Cu2+ ions are added to
a solution of 2 containing F- ions, Cu2+ ions bind to the
imino nitrogens and F- ions, and the PCT comes into
operation which quenches the fluorescence emission. On the
other hand, when F- ions are added to a solution of the
2·Cu2+ complex, presumably binding of F- to the Cu2+ center
(8) Kim, S. K.; Lee, S. H.; Lee, J. Y.; Lee, J. Y.; Bartsch, R. A.; Kim,
J. S. J. Am. Chem. Soc. 2004, 126, 16499.
(9) Bhalla, V.; Babu, J. N.; Kumar, M.; Hattori, T.; Miyano, S.
Tetrahedron Lett. 2007, 48, 1581.
(10) Gampp, H.; Maeder, M.; Meyer, C. J.; Zubberbulher, A. D. Talanta
1985, 32, 95.
Org. Lett., Vol. 11, No. 12, 2009
2569

Figure 4. Fluorescence spectra of 2 (10 µM) in response to the
addition of Cu2+ ions (100 µM) and further addition of F- ions in
THF; λex ) 269 nm.
Figure 5. Fluorescence keypad to access a secret code at 370 nm.
with each number or letter specifying each input. Thus, an
access code would be made possible by assigning the correct
starting (Cu2+) and ending (F-) ions to two specific letters
“A” and “R”, respectively, and different ions to all of the
other letters, to ensure that only one code would work.
However, there are many combinations to try which adds to
the complexity of opening the keypad lock. Thus, the
sequence dependence of inputs is mandatory for the con-
struction of the molecular keypad lock.
of the 2·Cu2+ complex causes redistribution in the energy
levels of the 2·Cu2+ complex, and as a result one of the two
degenerate orbitals of the Cu2+ ions dz2 and dx2-y gets
2
stabilized and the other gets destabilized. Due to this energy
difference in the d-orbitals of the Cu2+ ions, their participa-
tion in the emission quenching decreases which leads to the
revival of fluorescence intensity. Furthermore, the coordina-
tion of Cu2+ ions to the receptor 2 probably decreases the
energy of the LUMO of the nitrophenyl moiety which
reduces the HOMO-LUMO gap of the 2·Cu2+ complex. This
lowering of energy of the 2·Cu2+ complex accounts for the
emission at a longer wavelength upon the addition of fluoride
ions.3b With the above fluorescence outputs, we have used
our system for the construction of a security keypad lock.
To generate an input sequence as a password entry for a
keypad lock, inputs Cu2+ and F- were designated as “A”
and “R” (Figure 5). For the first input sequence, “A”
followed by “R” gave emission “ON” at 370 nm and created
a secret code “ARM” where “M” defines the “ON” state.
When the input sequence is reversed, i.e., the first input is
“R” and then “A”, fluorescence was in the “OFF” state at
370 nm. Thus, this sequence is a wrong entry “RAT” (T
defines the OFF state) which failed to open the keypad lock
(Figure 5). Numerical digits (0-9) or letters from (A-Z)
can be used as password entries. In total, 90 combinations
of numerals and 650 combinations of letters can be formed,
In conclusion, we have designed and synthesized a
chemosensor based on a thiacalix[4]arene of 1,3-alternate
conformation which behaves as a molecular keypad lock with
sequential chemical inputs of Cu2+ and F- ions.
Acknowledgment. We are thankful to UGC (research
project no. 33-276/2007(SR), DST (ref. No. SR/FT/CS/10-
2006), and CSIR (01(1934)/04/EMR-II) New Delhi, for
financial support, Guru Nanak Dev University Amritsar for
research facilities, and Central Drug Research Institute
(CDRI), Lucknow, India, for FAB mass spectra.
Supporting Information Available: Experimental details
and spectroscopic data of compounds 1, 2, 3, and 4. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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