Terphenyl based 'Turn On' fluorescent sensor for mercury

Article abstract of DOI:10.1016/j.tetlet.2009.03.110

New terphenyl-based derivative 4 with pyrene as a fluorophore has been synthesized and examined for its cation recognition abilities toward various cations by NMR and fluorescence spectroscopy. The results show that it has very high binding affinity (log

Full text of DOI:10.1016/j.tetlet.2009.03.110

Tetrahedron Letters 50 (2009) 2649–2652
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Terphenyl based ‘Turn On’ fluorescent sensor for mercury
*
Vandana Bhalla , Ruchi Tejpal, Manoj Kumar, Rajiv Kumar Puri, Rakesh K. Mahajan
Department of Chemistry, UGC-Centre for Advanced Studies, 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:
New terphenyl-based derivative 4 with pyrene as a fluorophore has been synthesized and examined for
its cation recognition abilities toward various cations by NMR and fluorescence spectroscopy. The results
show that it has very high binding affinity (log b = 5.12) and selectivity for mercury. A fluorescence
enhancement of 375% was observed for the 4-Hg2+ system in THF. A Hg2+ selective electrode (ISE) was
also formed which showed excellent selectivity over all the other cations tested. The lower limit of detec-
tion is 2.1 ꢀ 10ꢁ6 M.
Received 26 January 2009
Revised 12 March 2009
Accepted 15 March 2009
Available online 20 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The development of selective sensors for heavy and soft metal
ions is very important because pollution due to them poses severe
risks for human health and environment.1 Among heavy and soft
metal ions, mercury contamination is widespread and occurs
through a variety of natural and soft metal anthropogenic sources2
including oceanic and volcanic emission,2,3 gold mining,4 solid
waste incineration, and combustion of fossil fuels.5 Even the low
dose exposure of mercury may lead to digestive, kidney and espe-
cially neurological diseases.6 Keeping in view the roles played by
mercury in day-to-day life, the development of techniques for mer-
cury hazard assessment and mercury pollution management is in
great demand. Fluorescence signaling is one of the first choices
due to its high detection sensitivity and simplicity which translates
molecular recognition into tangible fluorescence signals.7 Thus,
designing fluorescent sensors for mercury8 has drawn worldwide
attention. In most of the fluorescent sensors reported for mercury,
so far, the binding of the mercury with the ionophore results in
nonspecific fluorescence quenching via spin–orbit coupling8 asso-
ciated with the heavy atom effect, which will facilitate the inter-
system crossing process. Fluorescence quenching is not only
disadvantageous for a high signal output upon recognition but also
hampers temporal separation of spectrally similar complexes with
time-resolved fluorometry.9 Fluorescence enhancement on the
other hand is an ideal phenomenon for the metal ion recognition.
However, the designing of fluorescence ‘Turn On’ type sensors
upon mercury binding is a challenging issue and only a few fluo-
rescence ‘Turn On’ sensors for mercury have been reported.10
One of the approaches to this phenomenon would be the design
of receptor having an ’Off’ state of the fluorophore which upon
addition of an external analyte causes fluorescence enhancement
by turning ’On’ the fluorescence.
Our research involves the design, synthesis, and evaluation of
(thia)calix[4]arene-based receptors for selective soft metal ions
sensing. Recently, we reported a new ratiometric fluorescent sen-
sor for mercury based on calix[4]arene of partial cone conforma-
tion.11 The compound exhibited ratiometric sensing of Hg2+ and
the receptor behaves as a fluorescent molecular switch upon
chemical inputs of Hg2+ and Cu2+. Now, we have prepared a ‘Turn
On’ fluorescent sensor for Hg2+ ions based on terphenyl appended
with pyrene moieties. Terphenyls are the key intermediates for the
synthesis of symmetrically and unsymmetrically substituted tri-
phenylenes which play an important role in supramolecular and
material chemistry, as their liquid crystalline behavior can be mod-
ified by changing electronic properties of their substituents. Re-
cently Lehmann co-workers reported a [15] crown-5 appended
terphenyl which shows mesomorphic properties in the presence
of sodium ions.12 Thus, in the present letter, we report the synthe-
sis, characterization, and mercury sensing properties of terphenyl-
based compound 4 having pyrene moieties. We have chosen pyr-
ene as fluorophore because of its high detection sensitivity.13 In
the presence of Hg2+ ions, the receptor 4 undergoes 375% increase
in the emission band which is attributed to the receptor–Hg2+ com-
plex (Fig. 1). A mercury ion-selective electrode has also been
formed which showed excellent selectivity over all the other cat-
ions tested. To the best of our knowledge, this is the first report
where pyrene-substituted-terphenyl based compound has been
used for sensing of Hg2+ ions.
Compound 4 was synthesized in two steps (Scheme 1). Suzuki-
Miyaura cross coupling of 115 with 216 catalyzed by Pd(II) fur-
nished compound 3 (50%).17 The 1H NMR spectrum of compound
3 showed two singlets (18H, 12H) for tert-butyldimethylsilyl
(TBS) group, one broad signal for amino (NH2) group, one singlet,
and two doublets (2H, 4H, 4H) for aromatic protons of terphenyl
moiety. The FAB mass spectrum showed a parent ion peak at 520
(M+) corresponding to coupled product 3. Condensation of diamine
3 with 2.0 mol equiv. of 1-pyrene carboxaldehyde in ethanol gave
* Corresponding author. Tel.: +91 183 2258802 09x3202; fax: +91 183 2258820.
E-mail address: vanmanan@yahoo.co.in (V. Bhalla).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.110

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V. Bhalla et al. / Tetrahedron Letters 50 (2009) 2649–2652
Figure 2. Fluorescence enhancement ratio [(IꢁIo/Io) ꢀ 100] of receptor 4 (1.0
at 345 nm upon addition of different metal ions (30 equiv, 30 M) in THF–H2O
(9.5:0.5).
lM)
l
Figure 1. Fluorescence response of receptor 4 (1 l
M) on addition of Hg2+ (0.1–
30 equiv) in THF–H2O (9.5:0.5) kex = 345 nm. Inset: Job plot of receptor 4 with Hg2+
ions with a total concentration of ([L]+[Hg2+]) 2.5
lM in THF.
4. The addition of potassium iodide to the solution of 4-Hg2+ re-
sulted in quenching of fluorescence intensity which was revived
again on addition of Hg2+ ions indicating that the change in fluores-
cence on addition of mercury is reversible. The stoichiometry of the
complex formed between compound 4 and Hg2+ ion was evaluated
by the method of continuous variation (Job’s plot) and it was found
to be 1:1 (H:G) which indicated that one Hg2+ ion was interacting
with receptor 4. The association constant (log b) of compound 4
with Hg2+ ions was calculated from fluorescence titration experi-
ments by means of SPECFIT program (global analysis system V3.0
for 32-bit Window system), which uses singular value decomposi-
tion and non-linear regression modeling by the Lever berg–Marqu-
ardt method19 and was found to be 5.12. The global analysis
showed that the titration curves were consistent with the forma-
tion of 1:1 (H:G) complex.
target compound 418 in 50% yield (Scheme 1). The structure of
compound 4 was confirmed from its spectroscopic and analytical
data. The 1H NMR spectrum of compound 4 showed two singlets
(18H, 12H) for TBS group, two singlets and two doublets (2H, 4H,
2H, 2H) for aromatic protons of terphenyl moiety, one multiplet
(18H) for pyrene protons, and one singlet (2H) for imine proton
(N@C–H). A parent ion peak was observed at 945 (M+1)+ in the
FAB mass spectrum. These spectroscopic data corroborate with
structure 4 for this compound.
The binding behavior of compound 4 toward different cations
(Cu2+, Hg2+, Pb2+, Zn2+, Ni2+, Cd2+, Ag+, K+, Na+, and Li+) was investi-
gated by fluorescence and NMR spectroscopy. In the fluorescence
spectrum, compound 4 exhibits a weak monomer emission at
389 nm when excited at k = 345 nm. This weak emission from
compound 4 is due to photo-induced electron transfer (PET) from
the imino nitrogen to the photo-excited pyrene which leads to
poor emission. Upon addition of increasing amounts of Hg2+ from
0.1 to 30 lM to the solution of compound 4 in THF–H2O
(9.5:0.5), a significant increase (375%) in the emission band attrib-
uted to the receptor–Hg2+ complex is observed (Fig. 1). Such fluo-
rescence enhancement observed for 4 in the presence of Hg2+ is
attributed to the co-ordination of imino nitrogens of 4 with Hg2+
ions leading to the formation of co-ordination complex as a result
of which the PET from imino nitrogen to pyrene moiety is sup-
pressed which results in fluorescence enhancement. Under the
same conditions as used above for Hg2+, we also tested the fluores-
cence response of 4 to other metal ions such as Pb2+, Ag+, Cd2+, Zn2+
,
Cu2+, Ni2+, K+, and Li+ besides Hg2+, and as shown in Figure 2, no
significant fluorescence change of 4 occurred in the presence of
these metal ions which indicates that all these metal ions were
not coordinating with the imino nitrogen atoms of the compound
Figure 3. Partial 1H NMR spectrum (CDCl3–CD3CN, 8:2) of receptor 4 before (a) and
after (b) addition of Hg2+ ions.
NH2
N
OTBS
OTBS
ii
Br
Br
OTBS
OTBS
i
OTBS
O
B
OTBS
NH2
N
O
NH2
2
3
1
4
Scheme 1. Synthesis of receptor 4. Reagents and conditions: (i) [Pd(PPh3)2(Cl)2], dioxane, H2O, K2CO3, overnight refluxing17; (ii) 1-pyrene carboxaldehyde, absolute ethanol, rt.18

V. Bhalla et al. / Tetrahedron Letters 50 (2009) 2649–2652
2651
The detection limit of 4 as a fluorescent sensor for the analysis
of Hg2+ was found to be 2.1 ꢀ 10ꢁ6 mol Lꢁ1 which is sufficiently
low for the detection of submillimolar concentrations of Hg2+ ions
as found in many chemical systems.
The practical applicability of compound 4 as a Hg2+ selective
fluorescence sensor was tested by carrying out competitive exper-
iments in the presence of Hg2+ at 30 M mixed with Li+, K+, Ni+,
l
Cu2+, Zn2+, Cd2+, Ag+, and Pb2+ at 300
lM. As shown in Figure 4
To elucidate the binding mode of receptor 4 with Hg2+, the 1H
NMR spectrum of its complex with mercury perchlorate was also
recorded. A significant downfield shift of 1.26 ppm is observed
for the imino protons, which indicates that the imino nitrogens
are coordinating with Hg2+ ions through their lone pairs of elec-
trons (Fig. 3). Thus, from this NMR study, we may conclude that
mercury is interacting with receptor 4 as supported by fluores-
cence studies.
no significant variation in fluorescence intensity change (IꢁIo/
Io ꢀ 100) was found by comparison with or without the other me-
tal ions besides Hg2+ ions, except for Cu2+ ions which interfere with
the detection of Hg2+ ions.
Thus, from the fluorescence and NMR studies it may be con-
cluded that mercury ions selectively complex with 4 in compar-
ison to other cations. Based on the results of these binding
studies we envisaged that it should be possible to construct mer-
cury ion selective PVC membranes based on 4. Thus, a sensor
membrane for 4 was prepared and assembled as previously re-
ported from our laboratory for mercury ions.14 The composition
of this membrane is listed in Table 1. The PVC membrane of the
cation receptor generated a stable potential when placed in con-
tact with mercury nitrate solution. The emf response of the
membrane in the presence of a wide range of mercury ion solu-
tions is shown in Figure 5. The electrodes demonstrate a linear
response for Hg2+ ions in the concentration range from
1.0 ꢀ 10ꢁ1 to 5.0 ꢀ 10ꢁ5 mol dmꢁ3
.
The slope of the plot was approx. 28.86 mV per decade of con-
centration which indicates the near Nernstian nature of the elec-
trode. The response time of the membrane was measured at
different concentrations and was found to be less than 10 s and
no change was observed up to 5 min. Potentials were measured
periodically at a fixed concentration and the standard deviation
of ten identical measurements was 1 mV. The dependence of
the membrane potentials on pH was studied at 1.0 ꢀ 10ꢁ3
mol dmꢁ3 Hg2+ ion concentration. The potential remained con-
stant from pH 1.3 to 4.3 which may be taken as the operational
pH range of the sensor. The most important feature of an ion-
selective electrode is its response to its primary ion in the pres-
ence of various other cations. This is measured in terms of the
Figure 4. Competitive selectivity of receptor 4 (1.0
30 lM) in the presence of other metal ions (300 equiv, 300
l
M) toward Hg2+ (30 equiv,
M).
l
Table 1
Composition and potential response characteristics of mercury ion-selective electrode
potentiometric selectivity coefficient (Kpot
, B) which was evalu-
A
PVC
(mg)
DOS
(mg)
NaTPB
(mg)
Ionophore
(mg)
Linear range
(M)
Slope
(mV/decade)
ated by the fixed interference method at 1.0 ꢀ 10ꢁ2 mol dmꢁ3
concentrations of various interfering ions. Table 2 shows the
potentiometric selectivity coefficient data of the imine derivatized
terphenyl-based PVC membrane electrode for the interfering cat-
101.2
201.1
1.3
5.4
1.0 ꢀ 10ꢁ1ꢁ5.0 ꢀ 10ꢁ6
28.86
NaTPB: Sodium tetraphenylborate.
DOS = Dioctyl sebacate as plasticizer.
ions relative to Hg2+. Kpot
was fairly low for all the cations
A,
B
tested which indicates that there is no interference present with
the determinant ion (Hg2+).
56
28
0
The electrode assembly was tested as an indicator electrode to
determine the end point in the potentiometric titration of Hg2+ with
a standard solution of sodium iodide. A 20 ml solution of 1.0 ꢀ 10ꢁ2
mol dmꢁ3 mercury nitrate was titrated against 1.0 ꢀ 10ꢁ2 mol dmꢁ3
sodium iodide solution. The sharp rise in the potential indicates the
end point (Fig. 6).
Thus, we have prepared a new pyrene-substituted terphenyl-
based sensor 4 in high yield and its binding behavior toward differ-
ent metal ions was investigated by 1H NMR and fluorescence
spectroscopy. Minimization of PET mechanism on addition of
Hg2+ ions resulted in pronounced Off-On-type fluorescent signaling
behavior. The receptor can be used to form a mercury selective PVC
membrane. The mercury selectivity is due to the formation of coor-
dination between the imino moieties and the mercury ions. The
prepared compound may be utilized as a sensor for the analysis
of Hg2+ ions in the submillimolar concentration range.
-28
-56
-10
-8
-6
-4
-2
0
Log[Hg2+]
Figure 5. Potentiometric response curve of ISE based on receptor 4: Hg2+ selective
electrode.
Table 2
Selectivity coefficient values of mercury ion-selective electrode 4
Na+
K+
NH4
Ag+
Co2+
Ca2+
Mg2+
Cd2+
Cu2+
Pb2+
Ni2+
Zn2+
Fe3+
+
Secondary ions
Pot
LogK
ꢁ1.05
ꢁ1.08
ꢁ0.95
ꢁ0.15
ꢁ2.85
ꢁ3.10
ꢁ2.80
ꢁ3.02
ꢁ2.75
ꢁ2.78
ꢁ2.75
ꢁ2.95
ꢁ4.34
Hg2þ ;B

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16. Synthesis of 2: To
a suspension of [PdCl2(PPh3)2] (5.08 g, 39.73 mmol) in
Volume of sodium iodide solution added (in mL)
dioxane (15 ml) were added 4-bromoaniline (2.5 g, 14.45 mmol), 4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (5.087 g, 39.74 mmol), and triethylamine
(5.83 g, 57.8 mmol) under argon. After stirring for 5 h at 80 °C, the dioxane
was removed under vacuum and the residue so obtained was treated with
water, extracted with dichloromethane, and dried over anhydrous Na2SO4. The
organic layer was evaporated and the compound was purified by column
chromatography using dichloromethane as an eluent to give 2.3 g (75%) of
compound 3 as brown solid. Mp: 160 °C; 1H NMR (300 MHz, CDCl3, ppm): d
1.32 (s, 12H), 3.83 (s, 2H), 6.61 (d, J = 6 Hz, 2H), 7.62 (d, J = 6 Hz, 2H); 13C NMR
(300 MHz, CDCl3): d 24.82, 83.28, 114.06, 136.39, 149.26; FAB-MS m/z: 219
(M+).
Figure 6. Derivative curve for the titration of 1.0 ꢀ 10ꢁ2 M Hg2+ solution with
1 ꢀ 10ꢁ2 M NaI solution.
Acknowledgments
V.B. is thankful to DST (New Delhi) for financial support (Ref.
No. SR/FT/CS/10-2006). We are also thankful to the Central Drug
Research Institute (CDRI), Lucknow, for FAB mass spectra, UGC
for SAP program.
17. Synthesis of 3: To a solution of compound 2 (1.1 g, 5.03 mmol) and compound 1
(1.0 g, 2.20 mmol) in dioxane were added K2CO3 (1.10 g, 8.02 mmol), distilled
H2O (10 ml), and [Pd(Cl)2(PPh3)2] (0.21 g, 0.302 mmol) under argon and the
reaction mixture was then refluxed overnight. The dioxane was then removed
under vacuum and the residue so obtained was treated with water, extracted
with dichloromethane, and dried over anhydrous Na2SO4. The organic layer
was evaporated and the compound was purified by column chromatography
using dichloromethane–ethyl acetate mixture (10:1, v/v) as an eluent to give
0.627 g (60%) of compound 3 as light yellow solid. Mp = 150 °C; 1H NMR
(300 MHz, CDCl3, ppm): d 0.23 (s, 12H), 1.00 (s, 18H), 3.57 (s, 4H), 6.53 (d,
J = 9 Hz, 4H), 6.80 (s, 2H), 6.87 (d, J = 9 Hz, 4H); 13C NMR (300 MHz, CDCl3): d
ꢁ4.02, 18.42, 25.96, 114.66, 122.84, 130.69, 132.20, 133.41, 144.30, 145.37;
FAB-MS m/z: 520 (M+), 522 (M+2)+; Anal. Calcd for C30H44N2O2Si2: C, 69.18; H,
8.51; N, 5.38. Found: C, 68.98; H, 8.23; N, 5.09.
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1.06 (18H, s), 6.99 (2H, s), 7.27 (4H, s), 7.60–8.36 (18H, m), 8.91 (2H, d), 9.05
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