Preferential recognition of zinc ions through a new anthraquinonoidal calix[4]arene

Article abstract of DOI:10.1016/j.tetlet.2012.03.096

A novel anthraquinonoidal calix[4]arene derivative was designed and synthesized for the preferential recognition of biologically important zinc in preference to prominently similar cadmium ions and other metal ions via quenching of fluorescence intensity.

Full text of DOI:10.1016/j.tetlet.2012.03.096

Tetrahedron Letters 53 (2012) 2996–2999
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Preferential recognition of zinc ions through a new anthraquinonoidal
calix[4]arene
⇑
Har Mohindra Chawla , Richa Shukla, Shubha Pandey
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel anthraquinonoidal calix[4]arene derivative was designed and synthesized for the preferential
recognition of biologically important zinc in preference to prominently similar cadmium ions and other
metal ions via quenching of fluorescence intensity. The stoichiometry of host guest complexation has
been determined to be 1:1. The fluorescence changes associated with the recognition event may be
attributed to the interaction of zinc ions with the nitrogenous functionality attached at the lower rim
of calix[4]arene cavity which allows spatial disposition of the anthraquinonoid segments.
Ó 2012 Published by Elsevier Ltd.
Received 2 January 2012
Revised 22 March 2012
Accepted 23 March 2012
Available online 30 March 2012
Keywords:
Calix[4]arene
Anthraquinonoidal
Preferential recognition
Zinc ions
Calix[n]arenes are known to provide useful sigma framework
also interact with other biologically significant ions such as cal-
cium, magnesium, copper, nickel lead, mercury, manganese, iron,
and cobalt ions. The latter ions frequently quench fluorescence
and cause predominant analytical interference leading to low sig-
nal to noise ratios. Paucity of suitable sensor materials which do
not require elaborate analytical sample preparation protocols but
promise selective recognition of zinc ions without interference
from toxic cadmium and other ions present in the biological broth
is thus pivotal to further our knowledge on exploring the role of
for the design of molecular receptors for recognition of ionic and
1
molecular species. Their versatility is usually attributed to the
presence of a preorganized cavity and many potentially useful
2
functionalization sites. Macromolecules appended with fluores-
cent probes have also received considerable attention due to sensi-
tivity and high specificity associated with the fluorescence based
3
,4
technique.
The selection of a suitable fluorophore appended
calixarenes is thus extremely important to translate the recogni-
tion event into a measurable optical signal.5
,6
zinc in biological systems.
10
1
0b–d
Our interest in the development of suitable receptors for recog-
nition of zinc ions through non covalent interactions originates
both from academic and application challenges involved in such
a design. Zinc is the second most abundant transition metal ion
in the living organisms located mainly in brain, muscle, prostate,
bone, liver, and parts of the eye. It is believed to play a significant
role in the regulation of many cellular and enzymatic processes as
well. To expatiate the biological role of Zn2+, there is an urgent
need to develop a direct recognition method which could effi-
ciently differentiate it from closely resembling but toxic cadmium
Previous work on zinc ion complexation
helped us to de-
sign a new molecular receptor based upon calix[4]arene scaffold
in the cone conformation with imidazole as the binding unit and
anthraquinone as the signaling unit. The designed receptor was
11
synthesized through a series of steps as shown in Scheme 1. Its
1
13
molecular structure was confirmed by H NMR and C spectra as
well as ESI-MS analysis (Supplementary data, Fig. S1). The advan-
tage of designed and synthesized probe is that it emits and excites
in the visible region of the spectrum and thus promises reduced
1
2
scattering and low background emissions. In this Letter we de-
scribe our results on the evaluation of recognition capability of
the synthesized molecular receptor toward different metal ions
7
,8
ions.
It has been observed that though several fluorescent
2
+
chemosensors for Zn have been reported in the literature, exam-
ples of preferential recognition of Zn2 over Cd are rare. Amongst
known zinc probes are included zinc chelators like picolyamine,
iminodiacid, or cyclin based molecular probes which not only ush-
er covalent bonds and strict analytical protocols but unfortunately
+
2+
9
using UV–vis absorbance, fluorescence, and H NMR spectroscopic
1
techniques.
A reference compound (5) having similar binding motifs as well
as the signaling unit was also synthesized for comparison purposes.
2
+
The Zn recognition ability of 4 was first examined in CHCl
3
:
CH
3
CN (1:4, v/v) by determining the changes, if any, in its UV–
⇑
Corresponding author. Tel.: +91 11 26591517; fax: +91 11 26581 102.
E-mail addresses: hmchawla@chemistry.iitd.ernet.in, hmchawla@chemistry.iitd.
vis spectra in the presence of different metal ions (0.13 mM). It is
interesting to note that a significant change in the absorption
ac.in (H.M. Chawla).
0
040-4039/$ - see front matter Ó 2012 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2012.03.096

H. M. Chawla et al. / Tetrahedron Letters 53 (2012) 2996–2999
2997
(
i)
O
O HO H
O
OH
OHOH
OH
(1)
(2)
Br
Br
(
ii)
O
CH2)3
O O
O
(
H
H
(CH )
2 3
O
O
O
O
OHOH
O
(
iii)
O HN
NH O
N
O
N
(4)
(3)
O
CHO
O
CHO
OH
OH
O
O
NH2
O
HN
NH2
N
(
iii)
CHO
O
(
5)
Scheme 1. Synthesis of anthraquinonoidal calix[4]arene. Reagents and conditions: (i) 1,3 dibromo propane, K
2
CO
3
, reflux, (ii) p-hydroxy benzaldehyde, K
2
CO
3
, reflux, (iii) 1,2
diamino anthraquinone, acetic acid, lead tetra acetate, reflux.
spectrum of 4 was observed upon addition of Zn2+, while negligible
changes were observed in the presence of other cations investi-
gated (Fig. 1). The absorption maximum of 4 appeared at 422 nm
which is a characteristic absorption of anthraquinone functional-
ity. Upon addition of 3 equiv of Zn2 , a hypsochromic shift of
quenching of the fluorescence emission intensity observed in the
2
+
presence of Zn . Fluorescence intensity decreases by 75% in the
2
+
presence of 0.13 mM Zn
.
In order to evaluate the role of calix[4]arene scaffold for recog-
+
nition ability of 4, fluorescent properties of the reference com-
2
+
1
5 nm from 422 nm to 404 nm in the UV–vis spectra of 4 was ob-
pound 5 in the presence of Zn were investigated. Figure 3
presents a relative decrease in fluorescence intensity of 4 and ref-
erence compound 5, respectively, in the presence of Zn2+. It is quite
evident that the fluorescence quenching, while prominent for com-
pound 4, is insignificant for reference compound 5. This implies
that calixarene framework is exercising an important control on
2
+
served. This blue shift could be attributed to the interaction of Zn
with the nitrogen atoms of the imidazole rings.
The recognition of Zn2 by 4 was further studied by fluorescence
+
3 3
spectroscopy. A dilute solution of 4 (40 lM) in CHCl :CH CN (1:4, v/
v) was prepared and the fluorescence emission spectrum of the com-
pound was recorded by fixing the excitation wavelength at 420 nm
which exhibited a characteristic emission band at 565 nm, whereas
the maximum for anthraquinone unit alone was determined to ap-
pear at 555 nm (Supplementary data, Fig. S2).13
2
+
Zn recognition process by providing appropriate rigidity to the
molecule.
Selectivity is extremely important for ion sensing; especially for
zinc ion recognition (vide supra). To assess the selectivity of 4 to-
2
+
The fluorescence intensity of the compound 4 was measured in
the presence of varying concentrations of different metal ions.
Interestingly, the results obtained for Zn2 were in contrast to its
anticipated behavior as zinc is usually termed spectroscopically si-
lent metal ion which does not alter the properties of fluorescence
signal of many probes. Figure 2 clearly indicates a significant
ward Zn , titration experiments were performed with other metal
ions with perchlorate as the counter ion. Figure 4 depicts relative
decrease in the fluorescence intensity of 4 upon interaction with
+
2
+
2+
2+
various metal ions. It was found that Pb , Co , and Fe partly
quench the fluorescence intensity of 4. This might be due to the
collisional quenching of molecular fluorescence as are well-known

2
998
H. M. Chawla et al. / Tetrahedron Letters 53 (2012) 2996–2999
1
.50
1
.4
.3
.2
.1
.0
.9
.8
.7
.6
.5
.4
.3
.2
1
1
1
1
0
0
0
0
0
0
0
0
A
0.1
0
.00
3
00.0 320
340
360
380
400
420
440
460
480
500
520
540
560
580
6
Wavelength (nm)
Figure 1. Change in UV–vis absorption spectra of ligand (4) [60
lM] upon addition of various metal ions . Receptor alone.
Receptor + excess of different metal ions.
Receptor + 3 equiv of Zn2
+
.
1
1
0
0
0
0
0
.2
.0
.8
.6
.4
.2
.0
8
2+
Increasing Zn
6
4
2
0
4
5
500
525
550
575
600
625
650
0
.02 0.04 0.06 0.08 0.10 0.12 0.14
Zn2+ ] mM
Wavelength (nm)
[
Figure 2. Quenching of fluorescence intensity of (4) in the presence of Zn2+ in
CHCl :CH CN = (1:4, v/v) [(4) = 40 M, kexcitation = 420 nm].
3
3
l
Figure 3. Relative decrease in the fluorescence intensity of
compound 5 upon addition of Zn in CHCl :CH CN (1:4, v/v) (kexcitation = 420 nm).
4
and reference
2+
3 3
heavy metal ion quenchers which decrease the fluorescence inten-
sity by promoting intersystem crossing. This was further substan-
tiated by conducting similar experiments with the reference 5.
between the host and the guest. A plot of Fo/F versus [Zn2+] was
found to be linear indicating that between ligand [4] and was of
the 1:1 type (Supplementary data, Fig. S5).
Fluorescence quenching was observed with Pb2 , Co , and Fe
+
2+
2+
Selectivity coefficients were computed for many metal ions
upon titration with the reference compound 5. No change in the
n+ 2+
n+
2+
n+
2+
2
+
2+
using KM
=
D
mM
/D
mZn
=
D
FM
/D
FZn
where K is the
emission spectra was observed upon addition of Cd while Hg
,
,Zn
Ni , Li , Mn , and Na+ had marginal effect on the fluorescence
2
+
+
2+
selectivity coefficient,
D
m is the calibration sensitivity and F is
D
the decrease in fluorescence intensity in the presence of constant
concentration of metal ions. Selectivity coefficient for Cd2+ was
found to be zero indicating the absence of any interference from
it. Selectivity coefficients for all other metal ions were also found
to be much lower to pose any significant hindrance in the recogni-
emission signal of the compound (Fig. 4). Small enhancement in
the fluorescence intensity of 4 was observed in the presence of
2
+
+
+
Mn , Ag , and Li . This might be due to the poor complexation
1
4
of these ions with 4.
Fluorescence data of ligand [4] with increasing concentrations
of Zn were further studied to determine the mode of interaction
2
+
2
+
tion of Zn (Supplementary data, Fig. S3).

H. M. Chawla et al. / Tetrahedron Letters 53 (2012) 2996–2999
2999
9
7
6
4
3
1
0
5
0
5
0
5
0
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/
j.tetlet.2012.03.096.
References and notes
1.
2.
3.
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-
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15
30
(
e) Kim, J. S.; Quang, D. T. Chem. Rev. 2007, 107, 3780–3799.
Li+
4. (a)Applied Fluorescence in Chemistry, Biology, and Medicine; Rettig, W., Strehmel,
Na+
Ag+ Ni2+
Zn2+ Pb2+ Fe2+ Hg2+ Co2+
Mn2+
Cd2+
B., Schrader, S., Seifert, H., Eds.; Springer: Berlin, Heidelberg, New York, 1999;
(
b)Practical Fluorescence; Guilbault, G. G., Ed.; Marcel Dekker: New York, 1990.
Figure 4. Percentage decrease in the fluorescence intensity of the compound
5.
Pandey, S.; Azam, A.; Pandey, S.; Chawla, H. M. Org. Biomol. Chem. 2009, 7, 269–
279.
(
40
lM) upon addition of various metal ions in CHCl
3
:
CH
3
CN (1:4, v/v)
(k
excitation = 420 nm).
6. (a) Me’tivier, R.; Leray, I.; Valeur, B. Chem. Eur. J. 2004, 10, 4480–4490; (b) de
Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C. P.;
Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97, 1515–1566.
7
.
(a) Tamanini, E.; Katewa, A.; Sedger, L. M.; Todd, M. H.; Watkinson, M. Inorg.
Chem. 2009, 48, 319–324; (b) Pathak, R. K.; Ibrahim, S. M.; Rao, C. P. Tetrahedron
Lett. 2009, 50, 2730–2734.
To further analyze the selectivity of the synthesized receptor to
transition metal ions, competitive experiments with transition
metals in conjunction with Zn2 were performed (Supplementary
+
8. (a) Weng, Y.; Chen, Z.; Wang, F.; Xue, L.; Jiang, H. Anal. Chim. Acta 2009, 647,
215–218; (b) Du, J.; Fan, J.; Peng, X.; Li, H.; Sun, S. Sens. Actuators, B 2010, 144,
2
+
2+
2+
data, Fig. S4). The data clearly showed that Ni , Hg , Pb , and
337–341; (c) Ghosh, K.; Saha, I. Tetrahedron Lett. 2010, 51, 4995–4999; (d)
2
+
Fe have marginal effect; the fluorescence quenching observed
was slightly lower than that observed for the solution containing
Galceran, J.; Huidobro, C.; Companys, E.; Alberti, G. Talanta 2007, 71, 1795–
1803.
2
+
2+
2+
9. (a) Zhang, Y.; Guo, X.; Si, W.; Jia, L.; Qian, X. Org. Lett. 2008, 10, 473–476; (b)
Zhang, X.; Hayes, D.; Smith, S. J.; Friedle, S.; Lippard, S. J. J. Am. Chem. Soc. 2008,
Zn only. The presence of Mn with Zn resulted in reduction
in fluorescence intensity to an appreciable amount. However, the
extent of recognition through fluorescence quenching remains
1
30, 15788–15789; (c) Wang, H. H.; Gan, Q.; Wang, X. J.; Xue, L.; Liu, S. H.; Jiang,
H. Org. Lett. 2007, 9, 4995–4998.
unaltered in the presence of Co2 and Cd . These results highlight
+
2+
10. (a) Ngwendson, J. N.; Banerjee, A. Tetrahedron Lett. 2007, 48, 7316–7319; (b)
Zhu, L. N.; Gong, S. L.; Yang, C. L.; Qin, J. G. Chin. J. Chem. 2008, 26, 1424–1430;
2+
2+
2+
the much better selectivity for Zn over Cd and Co by 4.
(
c) Dessingou, J.; Joseph, R.; Rao, C. P. Tetrahedron Lett. 2005, 46, 7967–7971;
(d) Kim, J. S.; Shon, O. J.; Yang, S. H.; Kim, J. Y.; Kim, M. J. J. Org. Chem. 2002, 67,
514–6518; (e) Mashraqui, S. H.; Chandiramani, M. A.; Ghorpade, S. S.;
To elucidate the binding mode of Zn2 with compound 4, 1H
+
6
NMR titrations in CDCl
in the presence of increasing equivalents of Zn(ClO )
3
were performed. The NMR spectra of 4
resulted in
Estarellas, C.; Frontera, A. Chem. Lett. 2011, 40, 1163–1164; (f) Zapata, F.;
Caballero, A.; Espinosa, A.; Tarraga, A.; Molina, P. Org. Lett. 2007, 9, 2385–2388.
11. (a) Gutsche, C. D.; Iqbal, M. Org. Synth. 1990, 68, 234–237; (b) Gutsche, C. D.;
Iqbal, M.; Stewart, D. J. Org. Chem. 1986, 51, 742–745; (c) Chawla, H. M.; Sahu,
S. N.; Shrivastava, R. Tetrahedron Lett. 2007, 48, 6054–6058.
4 2
desheilding and broadening of the signals of the protons of anthra-
quinone unit as compared to those of free receptor. The addition of
2
+
5
equiv of Zn leads to the deshielding of anthraqunione protons
1
1
2. Kumar, S.; Luxami, V.; Kumar, A. Org. Lett. 2008, 10, 5549–5552.
3. Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.; Kluwer
Academics/Plenum: New York, 2006.
by 0.05–0.15 ppm, respectively. The effect becomes much more
prominent when excess of Zn2 is present in solution. In the aro-
matic region, peaks corresponding to anthraquinone unit became
broad but the positions of protons corresponding to the calixarene
ring remained unaffected. A small shift in the UV–vis spectra upon
+
14. Fan, J.; Peng, X.; Wu, Y.; Lu, E.; Hou, J.; Zhang, H.; Zhang, R.; Fu, X. J. Lumin.
2005, 114, 125–130.
15. Ngwendson, J. N.; Amiot, C. L.; Srivastava, D. K.; Banerjee, A. Tetrahedron Lett.
2006, 47, 2327–2330.
2
+
16. Batista, R. M. F.; Oliveira, E.; Costa, S. P. G.; Lodeiro, C.; Raposo, M. M. M. Org.
Lett. 2007, 9, 3201–3204.
addition of Zn ruled out the involvement of NH proton of imidaz-
ole ring in binding Zn2 . These results suggest that the interaction
of the zinc ions takes place with the other donor nitrogen atoms of
+
17. Procedure for the synthesis of 4: To a solution of calix[4]arene (3) (0.102 mmol)
in CH CN:EtOH(7:3, v/v) was added 1,2 diaminoanthraquinone (0.22 mmol).
3
15,16
The reaction mixture was refluxed for 24 h. The solvent was evaporated to
dryness under reduced pressure and the residue was stirred with lead
tetraacetate (0.11 mmol) in acetic acid (10 ml) for overnight. After
completion of the reaction, product was filtered which was further purified
the imidazole ring as observed earlier.
2+
It has been known that Zn can adopt various geometries with
the coordination numbers ranging from two to six.1 Thus it can be
stipulated that it can adopt this geometry by interacting with the
nitrogen atom of imidazole ring.
6
3
by column chromatography and recrystallized from CHCl /MeOH.
18. Analytical data for 4: 68%; mp 286–288 °C (decomposed); UV (kmax, CHCl
3
):
À1
4
23 nm. IR (KBr pellet, cm ): 3438, 2960, 1664, 1292, 1259.HRMS (ESI-MS) m/
z: calcd 1409.6517, found 1409.6573; H NMR (300 MHz, CDCl , d in ppm):
3
1
In conclusion, we have developed anthraquinonoidal calix[4]ar-
ene based compound (41 ), which is capable of recognizing Zn
effectively with high selectivity without interference from Cd
and a host of other toxic metal ions studied.
7,18
2+
2
10.62 (s, 2H, NH, D O exchangeable), 8.11 (m, 4H), 7.94 (m, 4H), 7.82 (m, 6H),
2
+
7.65 (m, 4H), 7.08 (s, 4H), 6.99 (d, 4H), 6.92 (s, 4H), 4.35 (m, 8H), 4.13 (t, 4H),
13
3
.41 (d, 4H), 2.47 (m, 4H), 1.29 (s, 18H), 1.04 (s, 18H); C NMR (75 MHz, CDCl
d in ppm): 184.46, 161.24, 150.56, 141.68, 133.94, 128.3, 127.17, 114.88, 33.78,
1.62, 29.8.
3
,
3
Acknowledgement
R.S. and S.P. thank CSIR, India for fellowships.