Regulation of metal ion recognition by allosteric effects in thiacalix[4]crown based receptors

Article abstract of DOI:10.1016/j.tet.2009.07.014

Three new ditopic receptors 3a-c based on thiacalix[4]arene of 1,3 alternate conformation possessing two different complexation sites have been designed and synthesized for both soft and hard metal ions. The imino nitrogens bind soft metal ion (Ag⁺

Full text of DOI:10.1016/j.tet.2009.07.014

Tetrahedron 65 (2009) 7510–7515
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Regulation of metal ion recognition by allosteric effects in thiacalix[4]-
crown based receptors
*
Manoj Kumar , Abhimanew Dhir, Vandana Bhalla
Department of Chemistry, UGC Center for Advanced Studies, Guru Nanak Dev University, Amritsar 143005, Punjab, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Three new ditopic receptors 3a–c based on thiacalix[4]arene of 1,3 alternate conformation possessing
two different complexation sites have been designed and synthesized for both soft and hard metal ions.
The imino nitrogens bind soft metal ion (Agþ/Pb2þ/Cu2þ) and the crown moiety binds Kþ ion. The
preliminary investigations show that 3a–c behave as ditopic receptors for Agþ/Kþ, Pb2þ/Kþ, and Cu2þ/Kþ
Received 27 April 2009
Received in revised form 27 June 2009
Accepted 1 July 2009
Available online 8 July 2009
ions, respectively. In all the three receptors it was observed that the formation of 3a$Agþ/3b$Pb2þ
/
3c$Cu2þ complex triggers the decomplexation of Kþ ion from crown moiety and acts as a gateway, which
regulates the binding of alkali metal to crown moiety. Thus, allosteric binding between metal ions ‘switch
off’ the recognition ability of crown ether ring.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Our research involves the design, synthesis, and evaluation of
calix[4]arene and thiacalix[4]arene based receptors, which are se-
The present day activity in designing new functional molecules
having sensing ability for cations stems from the role these ions play
in chemistry, biology and environment.1 Calixarenes with appro-
priate appended groups are good candidates for cation recognition2
because they have been shown to be highly specific ligands and their
potential as sensing agents has received increasing interest.3 Among
the different calix[4]arene derivatives, calix[4]crowns are very in-
teresting because it is possible to have different number and nature
of donor atoms in the crown ring thus making it possible to ac-
commodate a variety of guests.4 Thiacalix[4]arene5 reported as the
second generation of the calixarene chemistry is good receptor for
soft and transition metal ions.6 A 1,3 alternate thiacalix[4]crown
platform provides a crown ether ring for metal ion complexation
lective for soft metal ions9 and anions.10 We recently reported
a ratiometric11 fluorescent sensor for mercury ions based on partial
cone conformation of calix[4]arene, which behaves as NOR logic
gate with YES logic function and a ratiometric12 fluorescent sensor
for copper ions based on a thiacalix[4]arene of 1,3 alternate con-
formation, which behaves as an INHIBIT logic gate with NOT and
YES logic functions but no allosteric behavior was observed in
above reported receptors. In present manuscript, we have designed
and synthesized receptors 3a–c based on thiacalix[4]crown of 1,3
alternate conformation, which show allosteric behavior between
two different metal ions. The three receptors 3a–c contain two
binding sites, imine units for binding soft metal ions, and crown
ether moiety for binding alkali metal ions. The Agþ, Pb2þ, and Cu2þ
ions bind imino nitrogens and Kþ ions bind to the crown ether ring
in receptors 3a–c, respectively. The complexation of ligand with
soft metal ion ‘switch off’ the recognition of crown ether ring and
act as a gateway, which regulates the binding of Kþ ion to crown
moiety. Thus, the formation of 3a$Agþ/3b$Pb2þ/3c$Cu2þ complex
triggers the decomplexation of Kþ ion and shows allosteric be-
havior between Agþ/Kþ, Pb2þ/Kþ, and Cu2þ/Kþ in receptors 3a–c,
respectively. Earlier Nabeshima et al. and Yamato et al. reported
such behaviors in calix[4]arene13 and thiacalix[4] arene14 between
Agþ/Naþ/Kþ and Agþ/Liþ, respectively, but such behaviors between
Agþ/Kþ, Pb2þ/Kþ and Cu2þ/Kþ on thiacalixarene are still un-
precedented. Allosteric behavior of Kþ ions is significant as mem-
brane transport of Kþ ions in living systems is allosterically
controlled and changes in their concentration affect the biological
process such as opening of ion channels.
with a potential for additional binding by cation–p interactions
between the two rotated benzene rings.7 Such systems can also be
used for mimicking allosteric regulation that play a major role in
biological systems.8 Allosteric binding can be defined as binding of
regulatory molecule or an ion to a specific allosteric site of a protein,
structurally distinct from the active site brings about the alteration
in the conformation of the protein that indirectly modifies the
properties of biologically active site. The guest can either enhance or
decrease the binding or catalytic efficiency of the protein. Ulti-
mately, the activity is switched ‘ON’ or ‘OFF’.
* Corresponding author. Tel.: þ91 183 2258802–09x3205; fax: þ91 183 2258820.
E-mail addresses: mksharmaa@yahoo.co.in, mksharma.chem@gndu.ac.in
(M. Kumar).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.014

M. Kumar et al. / Tetrahedron 65 (2009) 7510–7515
7511
2. Results and discussion
60
50
Condensation of thiacalix[4]crown diamine 115 with aromatic
monoaldehydes 2a–c in 20 ml of CHCl3/MeOH (1:1) yielded com-
pounds 3a–c. The products were virtually insoluble in the mixed
solvent to separate out as pure solid. The structures of thiacalix[4]-
arene receptors 3a–c were confirmed from their spectroscopic and
analytical data. The IR spectra of receptors 3a–c showed C]N
stretching bands at 1630, 1630, and 1635 cmꢀ1, respectively. There is
no absorption band corresponding to free aldehyde and amino
groups, which indicates that the condensation has taken place. This
was confirmed by the FAB mass spectra, which showed parent ion
peaks corresponding to the 1:2 condensation products at m/z 1143
(MþHþ), 1205 (MþHþ), and 1173 (MþHþ) for receptors 3a–c, re-
spectively. The 1HNMR spectra ofreceptors3a–c showedtwosinglets
(18H each) at 1.27–1.28 and 1.36 ppm corresponding to the tert-butyl
protons, multiplet (8H) at 2.98–3.0 to 3.03–3.13 ppm corresponding
to NCH2 and OCH2 protons, two broad signals (4H each) corre-
sponding to OCH2 protons at 3.38–3.39 and 3.59–3.60 ppm, two
triplets (4H each) corresponding to OCH2 protons at 3.94–3.96 and
4.08–4.12 ppm, two singlets (4H each) at 7.36–7.39 and 7.40–
7.43 ppm corresponding to aromatic protons of thiacalix[4]arene and
a singlet for imino protons (2H) at 8.24, 8.12, and 8.19 ppm, re-
spectively. These spectroscopic data corroborate the structures 3a–c
for these compounds (see Supplementary data S9–S14) (Scheme 1).
The binding abilities of these receptors were studied toward
different metal ions by two-phase solvent extraction, UV–vis, and
fluorescence methods. To evaluate the binding ability of receptor 3a
toward different metal ions, two-phase solvent extraction of metal
picrates (Pb2þ, Hg2þ, Zn2þ, Ni2þ, Agþ, Naþ, Kþ, Ca2þ, Ba2þ) was car-
ried out. A chloroform solution of receptor (0.1 mM) was equilibrated
with an aqueous solution of a metal picrate (0.1 mM) under neutral
conditions. The ion extractability (E) was calculated from the picrate
concentration in the organic phase, which was determined by UV–
vis spectroscopy. The % age extraction of different metal ions is
shown in Figure 1. It is clear from Figure 1 that maximum extraction
was observed in case of Agþ ions, however, significant extraction of
40
30
20
10
0
Na+ K+ Ca2+ Ba2+ Pb2+ Hg2+ Zn2+ Ag+ Ni2+
Metal ions
Figure 1. Solvent extraction results for 3a upon addition of different metal ions. Source
phase (aqueous solution of metal picrate, 2 mL), [MPic¼0.1 mM]; organic phase (CHCl3,
2 mL), carrier¼0.1 mM. Extractability¼(concentration of the extracted metal)/(con-
centration of the organic ligand)ꢁ100%. The data are the average value of three in-
dependent determinations.
The binding constant log b1 for Agþ and Kþ ions was calculated to be
4.50 and 2.28 from UV–vis spectroscopy.16 The stoichiometry of the
3a–Agþ complex was determined by a two-phase extraction exper-
iment (H2O/CHCl3), using the continuous variation method (Job’s
plot).17 Thepercent extraction for Agþ reach maximum at 0.5 mole
K
þ ions was also observed. Multi-ion recognition of Agþ and Kþ ions
by 3a can be attributed to the presence of imino and pyridyl nitro-
gens, which bind to Agþ ions and polyether ring that bind to the Kþ
ions. These binding modes were confirmed by 1H NMR spectroscopy.
On addition of 1.0 equiv of Agþ ions to 3a, the signals of imino pro-
tons were shifted downfield by 0.25 ppm, which indicates that imino
nitrogens were interacting with Agþ ions (Fig. 2B). Similarly, on
addition of 1.0 equiv of Kþ ions to 3a there was a shift and co-
alescence of protons of crown moiety, which indicates that Kþ ions
were interacting with oxygens of crown ring of receptor 3a (Fig. 2C).
Figure 2. 1H NMR spectra of 3a in CDCl3/CD3CN (8:2). (A) Free ligand; (B) in presence
of 1.0 equiv of silver perchlorate; (C) in presence of 1.0 equiv of potassium perchlorate;
(D) addition of 1.0 equiv of silver perchlorate to ligand/potassium complex. NMR fre-
quency is 300 MHz.
O
O
O
But
But
O
O
But
But
O
O
O
O
O
O
S
S
S
S
S
S
S
2
S
O
O
O
N
O
N
But But
But But
MeOH /CHCl3
reflux
NH2
NH2
1
OH
OH
3a-c
N
=
OH
a
b
c
Scheme 1.

7512
M. Kumar et al. / Tetrahedron 65 (2009) 7510–7515
fraction, indicating the formation of 1:1 complex (see Supplemen-
tary data S2). The possible ‘switch on-switch off’ of the recognition
behavior of 3a was studied by a set of 1H NMR experiments. On
adding 1.0 equiv of Agþ ions to 3a–Kþ complex, 1H NMR spectrum of
compound completely changed to that of to 3–Agþ complex (Fig. 2D)
When Kþ ions were added to 3–Agþ complex no spectral changes
were observed, which indicate that the complexation of 3a with Agþ
ion suppresses the recognition of Kþ ion in crown moiety. Thus, the
formations of Agþ complex ‘switch off’ the recognition ability of
crown ether ring.
70
60
50
40
30
20
10
0
0
Pb2+
500 µM
In receptor 3b, the pyridine unit of 3a was replaced by catechol
moiety. UV–vis spectroscopy was used to evaluate the binding
behavior of 3b toward different metal ions. Receptor 3b shows an
absorption band at
l¼267 nm in THF/H2O (9.5:0.5). On addition of
Pb2þ ions (1.0– 15.0 equiv), two new bands were formed at 320 nm
and 450 nm with an isosbestic point at 345 nm (Fig. 3). The mod-
ulation in the electron-donating capabilities of the nitrogen atom of
imine nitrogen in the presence and in the absence of Pb2þ ions
directly influences the intramolecular charge transfer (ICT) from
imine nitrogen to catechol moiety. Pb2þ ions bind with the imino
nitrogens and phenolic oxygen with simultaneous deprotonation of
phenolic OH, which reduces extent of ICT from nitrogen to catechol
moiety. Kim et al. had reported similar binding of Pb2þ ions with
nitrogen and oxygen of phenol with simultaneous deprotonation of
phenolic OH.18 Under the same conditions as used for the Pb2þ ions,
we also tested the UV–vis response of receptor 3b toward various
metal ions (Cu2þ, Hg2þ, Zn2þ, Cd2þ, Ni2þ, Agþ, Kþ, Naþ, and Liþ), no
significant variation was observed with any other metal ion (see
Supplementary data S3). Thus, 3b is selective for Pb2þ ions.
290
340
390
440
Wavelength
Figure 4. Fluorescence response of 3b (10
THF/H2O (9.5:0.5,v/v) buffered with HEPES, pH¼7.0; lex¼267 nm.
m mM) in
M) on addition of Pb2þ ions (500
0.5
0.4
Pb2+
0.3
1.0 equiv.
0.2
to
15.0 equiv.
0.1
Figure 5. 1H NMR spectra of 3b in CDCl3/CD3CN (8:2). (A) Free ligand; (B) in presence
of 1.0 equiv of lead perchlorate; (C) in presence of 1.0 equiv of potassium perchlorate;
(D) addition of 1.0 equiv of lead perchlorate to ligand/potassium complex. NMR fre-
quency is 300 MHz.
0
250
350
Wavelength
450
Figure 3. UV–vis spectrum of 3b (1ꢁ10ꢀ5 M) in the presence of Pb2þ ions
(1.0–15.0 equiv) in THF/H2O (9.5:0.5, v/v) buffered with HEPES, pH¼7.0.
similar change in the chemical shift as was observed in case of 3a in
presence of Kþ ions (Fig. 5C). Fitting the changes in the fluorescence
spectrum of compound 3b with Pb2þ and Kþ ions using the non-
linear regression analysis program SPECFIT20 gave a good fit and
demonstrated that 1:1 stoichiometry (host/guest) was the most
stable species in the solution with a binding constant log b1¼3.52
and log b1¼2.22 for Pb2þ and Kþ ions, respectively (for SPECFIT data
of 3b$Pb2þ complex see Supplementary data S15). The method of
continuous variation (Job’s plot)17 was also used to prove the 1:1
stoichiometry (host/guest) (see Supplementary data S4). To test the
practical applicability of compound 3b as a Pb2þ selective sensor,
competitive experiments were carried out using UV–vis spectros-
In the fluorescence spectrum, receptor 3b exhibits an emission
band at 330 nm in THF/H2O (9.5:0.5, v/v). Upon addition of Pb2þ
ions (500 mM) quenching in the emission band was observed
(Fig. 4), whereas in the presence of Kþ ions an enhancement of the
emission band was observed (see Supplementary data S5). The
quenching with Pb2þ ions can be attributed to the reverse photo
induced electron transfer process (PET)19 and the enhancement
with Kþ ions can be ascribed to the fact that the Kþ ions binds to the
polyether chain and as a result of which the photo induced electron
transfer to the photo excited catechol moiety is suppressed. Earlier,
we12 and Kim et al. have reported similar fluorescence enhance-
ment in the presence of Kþ ions where the Kþ ions bound to crown
ether ring of calixarene of 1,3 alternate conformation bearing pyr-
ene moieties.19 The binding of Pb2þ and Kþ ions was also confirmed
by NMR spectroscopy. Imino protons of 3b show downfield shift of
0.15 ppm on addition of 1.0 equiv of Pb2þ ions, which indicates the
formation of 3b$Pb2þ complex (Fig. 5B). Protons of crown ring show
copy in the presence of Pb2þ ions at 15.0 equiv mixed with Cu2þ
,
Hg2þ, Zn2þ, Ni2þ, Cd2þ, Agþ, Kþ, Naþ, and Liþ at 15.0 equiv, no sig-
nificant variation in the absorption was found by comparison with
and without the other metal ions. The allosteric behavior was ob-
served between Pb2þ and Kþ ions with 1H NMR and fluorescence
spectroscopy. On adding 1.0 equiv of Pb2þ ions to 3b–Kþ complex,
the 1H NMR spectrum of compound completely changed to that of
3b–Pb2þ complex (Fig. 5D). In contrast, when 3b–Pb2þ complex

M. Kumar et al. / Tetrahedron 65 (2009) 7510–7515
7513
was titrated to Kþ ions, no spectral changes were observed. These
90
80
70
60
50
40
30
20
10
0
findings suggest that the complexation of 3b with Pb2þ ion act as
a gateway, which regulates the binding of Kþ ion in crown moiety.
The allosteric behavior between Pb2þ and Kþ ions was also in-
vestigated by fluorescence spectroscopy. Thus, addition of Pb2þ
0
ions (850 m mM) complex results in
M vs 3b) to 3b$Kþ (1.66
quenching of fluorescence (Fig. 6). However, no change in fluores-
cence was observed when Kþ ions were added to 3b–Pb2þ complex
Thus, the formations of Pb2þ complex ‘switch off’ the recognition
ability of crown ether ring.
Cu2+
450 µM
0 µM
3b. K+
90
80
70
290
310
330
350
Wavelength
370
390
410
Pb2+
60
Figure 8. Fluorescence response of 3c (10
(450
M) in THF/H2O (9.5:0.5,v/v) buffered with HEPES, pH¼7.0; lex¼264 nm.
m
M) in response to addition of Cu2þ ions
50
40
30
m
The fluorescence spectrum of 3c (10
at 322 nm in THF/H2O (9.5:0.5, v/v). The addition of Cu2þ ions
(450 M) to the solution of 3c quenches the fluorescence emission
mM) gave an emission band
850 µM
m
20
(Fig. 8), while on adding Kþ ions, enhancement in the emission
spectrum was observed (see Supplementary data S7). Binding
constant (log b1) of 3c with Cu2þ and Kþ ions was found to be 4.18
and 2.44, respectively, using nonlinear regression analysis program
SPECFIT,20 which gave a good fit for 1:1 species. Job’s plot also
proved 1:1 stoichiometry (host/guest) (see Supplementary data
S8). Fluorescence spectroscopy was used to observe switching be-
10
0
300
350
Wavelength
400
Figure 6. Fluorescence response of 3b$Kþ (1.66
m
M) in presence of Pb2þ(850
mM) ions
in THF/H2O (9.5:0.5, v/v) buffered with HEPES, pH¼7.0; lex¼267 nm.
havior of receptor 3c. When Cu2þ ions (640
ually added to the solution of 3c$Kþ (2.75
m
M vs 3c) were grad-
mM) complex
Receptor 3c, which has a phenolic moiety was found to have
preference for Cu2þ ions. In the UV spectrum receptor 3c shows an
fluorescence was quenched by the Cu2þ ions (Fig. 9) showing that
the Cu2þ moves in and the Kþ moves out from 3c. In the reverse of
this metal ion exchange process, when Kþ ions were added to so-
lution of 3c$Cu2þ complex, no change in emission spectrum was
observed. Thus, the formation of 3c$Cu2þ complex, triggers the
decomplexation of Kþ ion and ‘switch off’ the recognition ability of
crown ether ring. Thus, in all the three receptors 3a–c formation
of soft metal ion (Agþ/Pb2þ/Cu2þ) complex inhibits the binding of
receptor with Kþ ions. The binding constant data reveals that in all
the three cases binding of receptors through imine units with soft
metal ion (Agþ/Pb2þ/Cu2þ) is stronger than binding with Kþ ion in
crown ether ring. When soft metal ion (Agþ/Pb2þ/Cu2þ) is added to
the 3a$Kþ/3b$Kþ/3c$Kþ complex, respectively, imine units having
absorption band at
l
¼264 nm in THF/H2O (9.5:0.5, v/v). On addition
of Cu2þ ions (1.0–10.0 equiv), new band was formed at 367 nm with
an isosbestic point at 333 nm (Fig. 7), which can be attributed to the
deprotonation of hydroxyl group with simultaneous complexation
of Cu2þ ions.21 Under the same conditions as used above for the
Cu2þ ions, we also tested the UV–vis response of receptor 3c toward
various metal ions (Pb2þ Hg2þ, Zn2þ, Cd2þ, Ni2þ, Agþ, Kþ, Naþ, and
Liþ), no significant variation was observed with any other metal ion
(see Supplementary data S6). To test the practical applicability of
compound 3c as a Cu2þ selective sensor, competitive experiments
were carried out using UV–vis spectroscopy in the presence of Cu2þ
ions at 10.0 equiv mixed with Pb2þ, Hg2þ, Zn2þ, Niþ, Cd2þ, Agþ, Kþ,
Naþ, and Liþ at 10.0 equiv, no significant variation in the absorption
was found by comparison with and without the other metal ions.
120
3c. K+
0 µM
100
0.8
0.7
0.6
0.5
80
Cu2+
60
Cu2+
0.4
1.0 equiv.
40
0.3
0.2
0.1
0
to
640 µM
10.0 equiv
20
0
250
300
350
Wavelength
400
290
340
390
Wavelength
Figure 7. UV–vis spectrum of 3c (1ꢁ10ꢀ5 M) in the presence of Cu2þ ions
(1.0–10.0 equiv) in THF/H2O (9.5:0. 5, v/v) buffered with HEPES, pH¼7.0.
Figure 9. Fluorescence response of 3c$Kþ (2.75
m
M) in presence of Cu2þ ions (640
mM)
in THF/H2O (9.5:0.5, v/v) buffered with HEPES, pH¼7.0; lex¼264 nm.

7514
M. Kumar et al. / Tetrahedron 65 (2009) 7510–7515
K+
O
O
O
O
But
But
But
O
But
O
K+O
O
O
But
But
t
O
O
But
Bu
S
O
O
O
O
O
O
O
O
O
K+
S
S
S
S
S
S
S
S
S
S
S
S
Pb2+
S
Cu2+
Ag+
S
S
K+
O
O
O
O
O
O
O
O
ButBut
t
BuBut
ButBut
ButBut
N
N
N
N
N
N
N
N
Ag+
2+Cu2+
Ag+
Pb2+
Pb
Cu2+
3a-3c
3a-3c
3a-3c
3a-3c
OH
OH
OH
N
a
b
c
=
Pb2+
Cu2+
Ag+
b
c
a
Figure 10. Schematic scheme representing allosteric behavior between metal ions.
stronger affinity for soft metal ion forms complex with simulta-
neous decomplexation of Kþ ion due to the conformational changes
induced during formation of 3a$Agþ/3b$Pb2þ/3c$Cu2þ complex.
When Kþ ions were added to 3a$Agþ/3b$Pb2þ/3c$Cu2þ complex, no
change was observed, due to weak binding of Kþ ion with receptor
it is unable to decomplex soft metal ion (Agþ/ Pb2þ / Cu2þ). The
behavior can be summarized in schematic representation (Fig. 10).
(s¼singlet, d¼doublet, br s¼broad singlet, m¼multiplet), coupling
constants (Hz), integration, and interpretation. Silica Gel 60 (60–120
mesh) was used for column chromatography.
4.2. General procedure for synthesis of 3a–3c
To a solution of thiacalix[4]crown diamine 1 (0.10 g, 0.10 mmol)
in 1:1 mixture of chloroform and methanol (20 ml) was added
a solution of aldehyde 2a–c (0.21 mmol) in methanol (5 ml). The
mixtures were refluxed for 24 h to separate a solid, which was fil-
tered, washed, and recrystallized from CHCl3/MeOH (1:9) to obtain
compounds 3a–3c.
3. Conclusion
To conclude, three new ditopic receptors based on thiaca-
lix[4]arene of 1,3 alternate conformation have been designed and
synthesized possessing two complexation sites. The complexations
of the receptors with soft metal ion ‘switch off’ the recognition
ability of hard metal ion binding site. Thus, the binding of soft metal
ion acts as a gate, which regulates the binding of hard metal ion.
Such type of gate systems utilizing the co-ordination of metal ions
provides an insight to regulate molecular systems by external ef-
fector. The regulatory process in living systems is complicated since
conformational changes induced by an allosteric effector binding to
one subunit can be transmitted to the other subunits. Allosteric
modulation of activity is fundamental for cellular function and is
a common feature of biological receptors and enzymes, in partic-
ular those involved in metabolic pathways. Moreover, this type of
work has been inspired in part by role played by metal ions in the
transduction of nerve signals. Thus, designing more synthetic re-
ceptors to mimic biological systems will help in understanding
biological processes in more simplified way.
4.2.1. Compound 3a
Yield 85% (0.10 g); mp 252 ꢂC; nmax (KBr pellet) 1630 cmꢀ1
;
1H
NMR (CDCl3, 300 MHz):
d
¼1.28 [s, 18H, C(CH3)3], 1.36 [s, 18H,
C(CH3)3], 3.0–3.13 [m, 8H, (OCH2, NCH2)], 3.39 [br s, 4H, OCH2], 3.60
[br s, 4H, OCH2], 3.96 [t, J¼7.95, 4H, OCH2], 4.12 [t, J¼8.25, 4H,
OCH2], 7.27–7.31 [m, 2H, ArH], 7.36 [s, 4H, ArH], 7.43 [s, 4H, ArH],
7.71 [t, J¼7.35, 2H, ArH], 7.91 [d, J¼7.8, 2H, ArH], 8.60 [d, J¼4.2, 2H,
ArH], 8.24 [s, 2H, HC]N]; 13C NMR (CDCl3, 75 MHz):
d¼31.42 [CH3],
31.47 [CH3], 34.35 [C], 34.40 [C], 58.39 [NCH2], 65.61 [OCH2], 66.68
[OCH2], 70.26 [OCH2], 73.48 [OCH2], 103.16 [ArC], 121.15 [ArC],
124.60 [ArC], 126.14 [ArC], 127.40 [ArC], 127.67 [ArC], 127.99 [ArC],
136.38 [ArC], 146.34 [ArC], 146.41 [ArC], 149.26 [ArC], 154.54 [ArC],
155.55 [ArC], 156.50 [ArC]N], 162.63[ArC]; FABMS m/z 1143
(MþHþ). Anal. Calcd for C64H78N4O7S4: C, 67.25%; H, 6.83%; N,
4.90%. Found: C, 67.20%; H, 6.35%; N, 4.87%.
4. Experimental
4.1. General
4.2.2. Compound 3b
Yield 80% (0.10 g); mp 245 ꢂC; nmax (KBr pellet) 1630 cmꢀ1
;
1H
NMR (CDCl3, 300 MHz):
d
¼1.27 [s, 18H, C(CH3)3], 1.36 [s, 18H,
C(CH3)3], 2.98–3.04 [m, 8H, (OCH2, NCH2)], 3.39 [br s, 4H, OCH2],
3.60 [br s, 4H, OCH2], 3.94 [t, J¼8.1, 4H, OCH2], 4.08 [t, J¼7.95, 4H,
OCH2], 6.69–6.71 [m, 4H, ArH], 6.95 [t, J¼4.65, 2H, ArH], 7.37 [s, 4H,
ArH], 7.40 [s, 4H, ArH], 8.12 [s, 2H, HC]N]; 13C NMR (CDCl3,
75 MHz): 31.12 [CH3], 31.47 [CH3], 34.25 [C], 34.33 [C], 56.98 [NCH2],
65.57 [OCH2], 70.39 [OCH2], 71.50 [OCH2], 73.52 [OCH2], 115.25
[ArC], 117.15 [ArC], 118.50 [ArC], 127.75 [ArC], 128.13 [ArC], 128.33
[ArC], 145.89 [ArC], 146.24 [ArC], 155.74 [ArC], 157.41 [ArC]N],
164.70 [ArC],167.65 [ArC]; FABMS m/z 1205 (MþHþ). Anal. Calcd for
C66H80N2O11S4: C, 65.78%; H, 6.64%; N, 2.33%. Found: C, 65.73%; H,
6.35%; N, 2.09%.
All reagents were purchased from Aldrich and were used with-
out further purification before use. UV Spectra were recorded on
SHIMADZU UV-2450 spectrophotometer, with a quartz cuvette
(path length: 1 cm). All the fluorescence spectra were recorded on
SHIMADZU RF 5301 PC spectrofluorometer. Binding studies were
performed in THF AR grade and deionized distilled water was used
to prepare THF/H2O mixture.1H and 13C NMR spectra were recorded
on JEOL-FT NMR-AL 300 MHz spectrophotometer using CDCl3 and
CD3CN as solvent and TMS as internal standards. Data are reported
as follows: chemical shifts in parts per million (d), multiplicity

M. Kumar et al. / Tetrahedron 65 (2009) 7510–7515
7515
4.2.3. Compound 3c
programme, UGC for SAP programme, Guru Nanak Dev University
for laboratory facilities and CDRI, Lucknow for FAB mass spectra.
Yield 82% (0.10 g); mp 247 ꢂC; nmax (KBr pellet) 1635 cmꢀ1 1H
;
NMR (CDCl3, 300 MHz):
d
¼1.28 [s, 18H, C(CH3)3], 1.36 [s, 18H,
C(CH3)3], 2.99–3.03 [m, 8H, (OCH2, NCH2)], 3.38 [br s, 4H, OCH2],
3.59 [br s, 4H, OCH2], 3.95 [t, J¼8.25, 4H, OCH2], 4.08 [t, J¼8.1, 4H,
OCH2], 6.82–6.95 [m, 4H, ArH], 7.12–7.15 [m, 2H, ArH], 7.29–7.32 [m,
2H, ArH], 7.36 [s, 4H, ArH], 7.40 [s, 4H, ArH], 8.19 [s, 2H, HC]N]; 13C
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.07.014.
NMR (CDCl3, 75 MHz):
d
¼31.43[CH3], 31.47 [CH3], 34.37 [C], 55.97
[NCH2], 66.36 [OCH2], 70.13 [OCH2], 71.41 [OCH2], 73.54 [OCH2],
116.73 [ArC], 117.17 [ArC], 118.10 [ArC], 121.88 [ArC], 126.36 [ArC],
126.88 [ArC], 127.69 [ArC], 127.94 [ArC], 145.39 [ArC], 146.91 [ArC],
151.12 [ArC]N], 165.65 [ArC]; FABMS m/z 1173 (MþHþ). Anal. Calcd
for C66H80N2O9S4: C, 67.58%; H, 6.83%; N, 2.39%. Found: C, 67.33%;
H, 6.55%; N, 2.29%.
References and notes
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Stock solutions (10 mM) of receptors 2a and 2b were prepared
in CDCl3/CD3CN (8:2). Similarly, stock solutions (20 mM) of cations
(Kþ, Agþ, Pb2þ) perchlorate salts were prepared in CDCl3/CD3CN
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4.5. Extraction measurements
For the extraction experiments, metal picrate solutions
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of receptor 2a (0.1 mM) were prepared in chloroform (AR grade).
An aqueous solution (2 mL) of metal picrate (0.1 mM) and a chlo-
roform solution (2 mL) of the 2a (0.1 mM) were shaken in a glass
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5 h. An aliquot of the chloroform layer (1 mL) was withdrawn with
a syringe and diluted with acetonitrile to 10 mL. The UV absorp-
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374 nm. Extraction of the metal picrate was calculated as the per-
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We are thankful to UGC (New Delhi, India) for the financial as-
sistance (research project No. 33-276/2007(SR)). V.B. is also
thankful to DST (New Delhi) for financial support (Ref. No. SR/FT/
CS/10-2006). We are also thankful to DST (New Delhi, India) for FIST