Fluoride triggered fluorescence turn on sensor for Zn 2+ ions based on pentaquinone scaffold that works as a molecular keypad lock

Article abstract of DOI:10.1021/ol301030z

A pentaquinone based compound 3a has been synthesized which exhibits pronounced fluorescence enhancement in the presence of Zn²⁺ ions under a F^- triggered synergistic effect. Derivative 3a also behaves as a molecular keypad lock with sequential chemical inputs of Zn²⁺ and F^- ions.

Full text of DOI:10.1021/ol301030z

ORGANIC
LETTERS
2012
Vol. 14, No. 11
2802–2805
Fluoride Triggered Fluorescence “Turn On”
Sensor for Zn2þ Ions Based on
Pentaquinone Scaffold That Works
as a Molecular Keypad Lock
Vandana Bhalla,* Roopa, and Manoj Kumar
Department of Chemistry, UGC Sponsored-Centre for Advanced Studies-I, Guru Nanak
Dev University, Amritsar-143005, Punjab, India
vanmanan@yahoo.co.in
Received April 19, 2012
ABSTRACT
A pentaquinone based compound 3a has been synthesized which exhibits pronounced fluorescence enhancement in the presence of Zn2þ ions
under a Fꢀ triggered synergistic effect. Derivative 3a also behaves as a molecular keypad lock with sequential chemical inputs of Zn2þ and Fꢀ ions.
Recently, fluorescent chemosensors for zinc ions have
received wide attention because of vital roles played by
zinc in numerous biological processes, including catalytic
activity,1 brain activity, gene transcription, immune func-
tion, and cellular transport,2 and the lack of an adequate
zinc level in the body may lead to a number of severe
neurological diseases, developmental defects, and mal-
functions.3 Further, detection of zinc is also important
for environmental safety as zinc is a harmful metal pollu-
tant to the environment.4 Thus, intensive efforts have been
devoted to develop sensitive fluorescent sensors for detec-
tion of trace amounts of zinc ions in both biological and
environmental systems5 and a variety of chemosensors for
zinc have been reported in the past.6 However, most
of them suffer from a turn off response, low detection
limit, and cross sensitivity toward other heavy metal ions.
Therefore, it remains a challenge to develop a sensitive
chemosensor for Zn2þ ions with fluorescenceenhancement
exhibiting a high selectivity for Zn2þ ions over other metal
ions.
Our research work involves the development of chemo-
sensors for soft metal ions and evaluation of their logic
behaviors for the construction of molecular switches and
molecular level devices.7 Recently, we reported a hexaphe-
nylbenzene based derivative which showed fluorescence
enhancement in the presence of Zn2þ ions and works as
a multichannel keypad system by using Zn2þ, phosphate,
and AMP as chemical inputs.8 In continuation of this
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2004, 104, 769. (d) Mikata, Y.; Yamanaka, A.; Yamashita, A.; Yano, S.
Inorg. Chem. 2008, 47, 7295. (e) Tamanini, E.; Flavin, K.; Motevalli, M.;
Piperno, S.; Gheber, L. A.; Todd, M. H.; Watkinson, M. Inorg. Chem.
2010, 49, 3789. (f) Hirano, T.; Kikuchi, K.; Urano, Y.; Higuchi, T.;
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Chem.ꢀEur. J. 2012, 18, 3765.
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10.1021/ol301030z
Published on Web 05/11/2012
2012 American Chemical Society

work, we have now designed and synthesized a new
fluorescent chemosensor 3a for Zn2þ ions based on a
pentaquinone scaffold. Pentaquinone derivatives are a
key precursor for the synthesis of solution processable
acenes derivatives. However, their utility as a fluorescent
sensor has not been explored yet, despite the fact that these
derivatives emit at a higher wavelength. Derivative 3a
exhibits high sensitivity and selectivity toward Zn2þ ions
as compared to other reported chemosensors for Zn2þ
ions.9 Derivative 3a undergoes fluorescence enhancement
(Φ = 0.23) in the presence of zinc ions and, interestingly,
exhibits more pronounced fluorescence enhancement
(Φ = 0.80) under a fluoride triggered synergistic effect.
Such a pronounced response of a chemosensor toward
Zn2þ ions under the Fꢀ triggered effect has no precedent.
Moreover, derivative 3a mimics the functions of a security
keypad lock on sequential addition of Zn2þ and Fꢀ ions.
To the best of our knowledge, this is the first report where a
pentaquinone derivative senses zinc ions under the fluoride
triggered synergistic effect and behaves as a molecular
keypad lock with sequential chemical inputs of Zn2þ and
Fꢀ ions.
Figure 1. Fluorescence response of receptor 3a (5 μM) on
addition of Zn2þ ions (0ꢀ2.0 equiv) in THF; λex = 350 nm.
Inset: (A) fluorescence before and after the addition of Zn2þ
ions; (B) change in the fluorescence intensity of receptor 3a as a
function of Zn2þ ion concentration.
530 nm, when excited at 350 nm which is attributed to the
very fast enol-imine to keto-amine tautomerism involving
the phenomenon of excited state intramolecular proton
transfer (ESIPT). To confirm the phenomenon of tauto-
merism, we also prepared compound 3b in which the
phenolic hydroxyl groups of compound 3a were protected
by methyl groups (SI, Figure S7). On excitation at 350 nm,
the compound 3b did not exhibit any band at 530 nm (SI,
Figure S8). This result confirms the presence of an ESIPT
phenomenon in compound 3a. Upon addition of Zn2þ
ions (0ꢀ2.0 equiv) to the solution of 3a, a new emission
band appeared at 496 nm which undergoes significant
fluorescence enhancement (7.6-fold) along with the ap-
pearance of a green colored fluorescence (inset A Figure 1).
This blue shift (34 nm) in fluorescence emission is attrib-
uted to the interaction between compound 3a and the Zn2þ
ion, which inhibits the enol-imine to keto-amine tautomer-
ism and results in the appearance of a fluorescence emis-
sion at a shorter wavelength (496 nm). The emission
intensity of compound 3a increased linearly as a function
of Zn2þ ion concentration as shown in inset B Figure 1.
The fluorescence quantum yield (Φfs) of compound 3a in
the free state was found to be 0.03 and in the Zn2þ-bound
state to be 0.23. Fitting the changes in the fluorescence
spectraofcompound 3awithZn2þ ions using the nonlinear
regression analysis program SPECFIT11 gave a good fit
and demonstrated that 1:1 stiochiometry (host/guest) was
the most stable species in the solution with the binding
constant (log β) = 4.81 ( 0.25. The method of continuous
variation (Job’s plot)12 was also used to prove the 1:1
stiochiometry (SI, Figure S9). The binding of Zn2þ ions
with receptor 3a is also proved by mass spectroscopy (SI,
Figure S10). The mass spectrum showed a peak at m/z
763.31 corresponding to the [3aꢀZn2þ] complex which not
only confirms the binding of Zn2þ ions with receptor 3a
but also proves the 1:1 stoichiometry of host and guest
species. We also carried out 1H NMR studies to prove the
Scheme 1. Synthesis of Compound 3a
The condensation of pentaquinone diamine 110 with
2-hydoxybenzaldehyde 2a in THFꢀethanol furnished
compound 3a in 70% yield (Scheme 1). The structure of
compound 3a was confirmed by its spectroscopic and
analytical data (Supporting Information (SI), Figures
S1ꢀS4).
The binding behavior of compound 3a toward different
cations (Zn2þ, Cu2þ, Hg2þ, Fe2þ, Fe3þ, Co2þ, Pb2þ, Ni2þ
,
Cd2þ, Agþ, Ba2þ, Mg2þ, Kþ, Naþ, and Liþ) as their
perchlorate salts was investigated by UVꢀvis and fluores-
cence spectroscopy. The UVꢀvis spectrum of compound
3a(5 μM) exhibits absorptionbands at298 and350 nm and
a shoulder at 414 nm ascribed to a pentaquinone moiety
(SI, Figure S5). Upon addition of Zn2þ ions (0ꢀ10 equiv),
the absorption band at 350 nm decreases slightly and the
band at 414 nm increases slightly along with the formation
of an isosbestic point at 390 nm. However, no significant
variation in the absorption spectra was observed in pre-
sence of other metal ions (SI, Figure S6). The fluorescence
spectrum of compound 3a exhibits a very weak emission at
(8) Bhalla, V.; Vij, V.; Kumar, M.; Sharma, P. R.; Kaur, T. Org. Lett.
2012, 14, 1012.
(9) (a) Das, P.; Bhattacharya, S.; Mishra, S.; Das, A. Chem. Commun.
2011, 47, 8118. (b) Ravikumar, I.; Ghosh, P. Inorg. Chem. 2011, 50, 4229.
(10) Bhalla, V.; Roopa; Gupta, A.; Dhir, A.; Kumar, M. Dalton
Trans. 2011, 40, 5176.
(11) Gampp, H.; Maeder, M.; Meyer, C. J.; Zuberbulher, A. D.
Talanta 1985, 32, 95.
(12) Job, P. Ann. Chim. 1928, 9, 113.
Org. Lett., Vol. 14, No. 11, 2012
2803

binding of compound 3a with Zn2þ ions. On addition of
Zn2þ ions to the receptor 3a, broadening of the signal of
the hydroxyl protons was observed which indicates inter-
action between Zn2þ and the oxygen atom of the hydroxyl
group (SI, Figure S18). Under the same conditions as used
above for the Zn2þ ions, we also tested the fluorescence
response of receptor 3a for other metal ions (SI, Figures
S11ꢀS12). No significant change in emission spectra was
observed in the presence of other metal ions. To check out
the practical applicability of receptor 3a as a Zn2þ selective
fluorescent sensor, we carried out competitive experiments
in the presence of Zn2þ mixed with various metal ions (SI,
Figure S12), no significant variation in the fluores-
cence intensity change was found by comparison with or
without the other metal ions. Yet, compound 3b which
lacks phenolic hydroxyl groups did not exhibit any fluor-
escence enhancement in the presence of Zn2þ ions (SI,
Figure S19).
In addition to cation binding properties, we also inves-
tigated the fluorescence behavior of compound 3a toward
different anions and biomolecules (CNꢀ, AcOꢀ, Clꢀ, Brꢀ,
Iꢀ, NO3ꢀ, H2PO4ꢀ, HSO4ꢀ, PPiꢀ, AMP, ADP, and ATP).
Among the various anions and biomolecules tested, only
the addition of Fꢀ ions (0ꢀ20 equiv) slightly quenches the
fluorescence emission of 3a, indicating that the presence
of Fꢀ inhibits the ESIPT phenomenon (SI, Figure S13).
This inhibition of the ESIPT phenomenon is ascribed to
the intermolecular proton transfer from phenolic oxygen
to Fꢀ ions.
sequence, the gradual addition of just 0.8 equiv of Zn2þ
ions to the solution of 3aꢀFꢀ led to the 31-fold fluores-
cence enhancement at 496 nm (Figure 2) in comparison to
the 7.6-fold emission enhancement upon direct addition of
Zn2þ ions to the solution of 3a. This fluorescence enhance-
ment is due to the fact that the initial addition of Fꢀ ions
results in the formation of a deprotonated species (SI,
Figure S17). The deprotonated species then forms a strong
complex with zinc ions leading to an increase in the rigidity
of the system; as a result the nonradiative decay from the
excited state becomes less possible, and consequently the
emission intensity increases. The formation of deproto-
nated species is also confirmed by 1H NMR studies where-
in the hydroxyl protons completely disappeared on
addition of Fꢀ ions to the solution of compound 3a.
Subsequent addition of Zn2þ ions leads to broadening of
the spectrum with a small shift in the imino protons. These
1H NMR studies indicate that the binding is mainly
through the oxygen atoms of the phenolic hydroxyl groups
(SI, Figure S15). The fluorescence quantum yield of the Fꢀ
triggered 3aꢀZn2þ complex was found to be 0.80, which
indicates the formation of highly fluorescent species. The
detection limit of the Fꢀ triggered 3aꢀZn2þ complex as a
fluorescent chemosensor for the analysis of Zn2þ ions was
found to be 30 ꢁ 10ꢀ9 mol Lꢀ1 which suggests high sen-
sitivity as well as selectivity for Zn2þ recognition in the
presence of Fꢀ as a coexisting anion. We also tested the
fluorescence response of receptor 3a toward Zn2þ ions in
the presence of other anions. No significant change in
the fluorescence was observed in the presence of other
anions except the CNꢀ ion which slightly triggers the
fluorescence enhancement (Figure 3a; SI, Figure S16).
To investigate the practical applicability of receptor 3a as
a Zn2þ selective fluorescent sensor in the presence of Fꢀ
ions, we studied the fluorescene behavior of derivative
3a toward Zn2þ ions in the presence of 20 equiv of Fꢀ ions
mixed with 20 equiv of various anions (Figure 3b). These
results show the chemosensing behavior of derivative
Figure 2. Fluorescence response of receptor 3a (5 μM) þ 20
equiv of Fꢀ in THF with increasing amount of Zn2þ ions (0ꢀ0.8
equiv) in THF; λex = 350 nm.
Since compound 3a shows optical sensing toward Zn2þ
and Fꢀ ions in contrasting modes, we further investigated
the “OnꢀOff” switching process and sequence dependent
emission output of 3a using Zn2þ and Fꢀ as chemical
inputs. In the first sequence, when Fꢀ ions were added to
the solution of the 3aꢀZn2þ complex, the emission band at
496 nm undergoes fluorescence quenching (SI, Figure S14).
This fluorescence quenching is due to the removal of Zn2þ
from the 3aꢀZn2þ complex by Fꢀ ions as the interaction
between Zn2þ and Fꢀ ions is stronger in comparison to
Zn2þ and compound 3a. However, in the reverse input
Figure 3. (a) Selectivity of receptor 3a (5 μM) toward Zn2þ ions
in the presence of various anions and biomolecules. (b) Compe-
titive selectivity of receptor 3a (5 μM) toward Zn2þ ions in the
presence of 20 equiv of Fꢀ ions mixed with 20 equiv of various
anions and biomolecules in THF, λex = 350 nm.
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Org. Lett., Vol. 14, No. 11, 2012

3a toward Zn2þ ions under Fꢀ triggered conditions is not
influenced by the presence or absence of other anions. We
also carried out the fluorescence studies of compound 3a
toward various cations and anions in a mixed aqueous
medium, but no significant change in the emission beha-
vior was observed.
Recently, there has been a lot of interest in the develop-
ment of molecular logic systems for the construction of
molecular devices.13 Different types of molecular devices
such as moleculators, multiplexers, and demultiplexers
have been reported in literature.14 Most of the devices
reported in literature were based on combinatorial logic
circuits. However, present sophisticated digital electronic
devices are based on sequential logic circuits i.e. circuits
whose output depends upon both the inputs of the circuit
and its previous state. In other words, we need circuits that
have memory elements. The memory elements are devices
capable of storing binary information. The binary infor-
mation stored in the memory elements at any given time
defines the state of the sequential circuit. The input and the
present state of the memory element determine the output.
All digital microprocessors are designed on such sequential
systems. Thus, to meet the recent demands of digital
electronics we need molecular systems which can store
information. We recently reported two sequential molecu-
lar devices, molecular traffic lights and a molecular keypad
lock which provide a way of protecting information at the
molecular level.15 In continuation of our research program
to construct electronic devices at the molecular level, we
examined our system as a molecular keypad lock.
Figure 4. Molecular keypad lock to access a secret code at
496 nm.
the emission at 496 nm was in the “On” state and it created
secret password “ATM” (M defines the On state); see
Figure 4. Reversal of the input sequence, i.e. the first input
is T and the second input is A, gave fluorescence quenching
(Off, designated as letter B). Thus, the wrong password
“TAB” fails to open the lock (Figure 4). Therefore, only
the exact password “ATM” can open the lock, and such
types of chemical systems may be applicable to protect
information at the molecular level as it requires the correct
order of inputs.
In conclusion, we designed and synthesized a pentaqui-
none based fluorogenic receptor 3a for Zn2þ ions. Deriva-
tive 3a exhibits significant fluorescence enhancement in
the presence of Zn2þ ions with a detection limit up to a
nanomolar range under the F-triggered synergistic effect.
In addition, derivative 3a behaves as a molecular keypad
with sequential chemical inputs of Zn2þ and Fꢀ ions.
To acquire a molecular keypad lock system based on
Boolean arithmetic from the fluorescence behavior of 3a,
we envisaged Zn2þ and Fꢀ as inputs. To simplify the input
sequence as a password of the molecular keypad lock,
inputs Fꢀ and Zn2þ were designated as “A” and “T”.
When the input “A” was added first and followed by “T”,
Acknowledgment. We are thankful to DST [Reference
No. SR/S1/OC-63/2010] for financial support. Roopa is
thankful to CSIR (New Delhi) for a senior research fellowship.
Supporting Information Available. Experimental data
and synthetic detail of compound 3aꢀb. This materials is
available free of charge via the Internet at http://pubs.acs.
org.
(13) de silva, A. P.; McClenaghan, N. D.; McCoy, C. P. Molecular
Level Electronics, Imaging and Information, Energy and Environment, in
Electron Transfer Chemistry; Balzani, V., Ed.; Wiley-VCH: Weinheim,
2001; Vol. 5.
(14) Szacilowski, K. Chem. Rev. 2008, 108, 3481.
(15) (a) Kumar, M.; Dhir, A.; Bhalla, V. Org. Lett. 2009, 11, 2567.
(b) Kumar, M.; Dhir, A.; Bhalla, V. Chem. Commun. 2010, 46, 6744.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 11, 2012
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