A highly selective fluorescence turn-on probe for Zn2+ based on new diaryloxadiazole chelate

Article abstract of DOI:10.1246/cl.2011.1163

A new chelating diaryloxadiazole probe, oxazid displayed emission red shift and 16-fold emission enhancement upon binding with Zn²⁺ in buffered condition, while competing Cd²⁺, Ca²⁺, Mg²⁺, and several potentially quenching metal ions posed no significant optical interferences. Experimental evidences indicated 1:1 complexation, and the computational work revealed formation of a stable octahedral geometry.

Full text of DOI:10.1246/cl.2011.1163

doi:10.1246/cl.2011.1163
Published on the web September 28, 2011
1163
A Highly Selective Fluorescence Turn-on Probe for Zn2+ Based
on New Diaryloxadiazole Chelate
Sabir H. Mashraqui,*1 Mukesh A. Chandiramani,1 Sushil S. Ghorpade,1 Carolina Estarellas,2 and Antonio Frontera2
1Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai-400098, India
2Department of Quimica, Universitat de les Illes Balears, Crta. De Valldemossa km 7.5, 07122 Palma (Baleares), Spain
(Received July 8, 2011; CL-110585; E-mail: sh_mashraqui@mu.ac.in)
N
N
N
N
A new chelating diaryloxadiazole probe, oxazid displayed
emission red shift and 16-fold emission enhancement upon
BrCH COOC(CH )
3 3
i)
K2CO3/DMF
/
2
O
O
binding with Zn2+ in buffered condition, while competing Cd2+
,
ii) HCl/Dioxane
O
O
OH
HO
Ca2+, Mg2+, and several potentially quenching metal ions posed
no significant optical interferences. Experimental evidences
indicated 1:1 complexation, and the computational work
revealed formation of a stable octahedral geometry.
O
O
OR
OR
R =
1
-
C(CH3)3
2
Oxazid
R = H
Scheme 1. Synthetic sequence toward diaryloxadiazole recep-
tor, oxazid.
Metal-ion-triggered optical modulation of photoemittive
receptors constitutes one of the key approaches for the
recognition of chemically and biologically significant metal
ions.1 Zinc, an essential micronutrient, regulates many cellular
and enzymatic processes.2 However, Zn2+ metabolic disorder is
associated with many debilitating neurological conditions.3
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10
5
Consequently, a heightened interest persists in designing Zn2+
-
selective optical probes.4 Among the known Zn2+ luminophores,
some prominent examples include TSQ, RhodaZin-3, ZinPyr-1,
Rhodafluor-2, and ZnAF-1.5 These probes are constructed by
hosting nitrogenous zinc chelators, such as dipicolylamine,
iminodiacid or cyclen onto the photoemittive fluorescein,
rhodamine, or quinoline platforms.5 Despite continuing advan-
ces, the cross affinities, especially from biologically abundant
Ca2+ and Mg2+ and toxic Cd2+, frequent emission quenching
observed from Co2+, Ni2+, and Cu2+, and the need for
nonaqueous measurements forms limitations in many cases.
Thus, it was of interest to a explore new class of fluorescent
chelators which might exhibit selective discrimination of Zn2+
over competing metal ions, thereby enabling useful sensing
properties.
0
350
400
450
500
550
600
Wavelength/nm
Figure 1. Fluorimetric titration of oxazid (1 © 10¹6 M) with
incremental Zn2+ (0-10¹4 M) in MeCN-H2O (7:3 v/v, buffered
by 10 mM Tris-HCl).
measured with respect to anthracene. The low Φf may be
attributable in part to the nonradiative aryl-ring-rotation proc-
esses in free probe. The emission profile of oxazid (1 © 10¹6 M)
was not significantly perturbed when 500 equiv of Li+, Na+, K+,
Mg2+, Ca2+, Ba2+, Co2+, Ni2+, Cu2+, Cd2+, Hg2+, and Pb2+ as
their perchlorates were introduced.9 In contrast, addition of just
100 equiv of Zn2+ induced marked changes both in the intensity
and energy of the probe’s emission.
Diaryloxadiazole motif is a stable fluorophore, which
others6 and we7 have previously incorporated as a reporter
group to design certain luminescent metal-ion sensors. With
intent to extending the range of the reporter ligands for Zn2+, we
now describe a new diaryloxadiazole chemoreceptor, oxazid,
carrying oxyacetic acid chelates for the selective “off-on”
signaling for Zn2+ under semiaqueous buffer conditions.
Synthesis of oxazid involved O-alkylation of 2,5-di(2-
hydroxyphenyl)-1,3,4-oxadiazole (1) with t-butyl bromoacetate
in K2CO3/DMF to form diester 2, which upon acid-catalyzed
hydrolysis afforded the target, oxazid8 (Scheme 1). With regard
to the sensing mechanism, we presumed that metal-ion binding
might induce the chelation-enhanced fluorescence due to the
conversion of the conformationally flexible probe into the
conformationally restricted metal ion complex.9
Fluorimetric titration of oxazid (Figure 1) revealed linear
enhancement in emission intensity with incremental addition of
Zn2+. At saturating 10¹4 M of Zn2+, a high 16-fold emission
enhancement (Φf = 0.264), accompanied with 17 nm red shift
was observed. Figure 2a shows that relative to other metal ions
examined, only Zn2+ is capable of inducing high fluorescence
“off-on” signaling response. To further demonstrate the selec-
tive interaction with Zn2+, initially the fluorescence of the
probe (1 © 10¹6 M) in the presence of a matrix consisting of
5 © 10¹4 M each of Li+, Na+, K+, Mg2+, Ca2+, Ba2+, Co2+
,
Ni2+, Cu2+, Cd2+, Hg2+, and Pb2+ was recorded. As shown in
Figure 2b, the matrix barely impacted the fluorescence intensity
(<1.5-fold enhancement) of the probe. Subsequently, addition
of just 10¹4 M of Zn2+ induced emission enhancement by ca.
14-fold. This finding clearly validates the selective binding of
Zn2+ even though other metals may be present in excess
The fluorescence sensitivities of oxazid toward selected
metal ions of biological and/or environmental relevance were
evaluated in MeCN-H2O (7:3 v/v, buffered by 10 mM Tris-HCl,
pH 7.2)10 Excitation of oxazid at 314 nm resulted in a weak
emission band at 352 nm with quantum yield Φf of 0.017
Chem. Lett. 2011, 40, 1163-1164
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1164
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5
OXAZID + Matrix + Zn2+
OXAZID + Matrix
OXAZID
0
0
Lig Li Na
K
Mg Ca Ba Co Ni Cu Cd Hg Pb Zn
Ligand and Metal ions
350
400
450
500
550
600
Wavelength/nm
Figure 2. a) Relative emission intensity of oxazid (1 ©
10¹6 M) with metal ions (100 equiv), b) competitive matrix
experiment: emission spectra of oxazid alone (1 ¯g), oxa-
Figure 3. Optimized structures of oxazid-Zn2+ complex and
their difference in energies.
zid + 5 © 10¹4 M each of Li+, Na+, K+, Mg2+, Ca2+, Ba2+
,
Co2+, Ni2+, Cu2+, Cd2+, Pb2+, and Hg2+ and oxazid +
matrix + Zn2+ (10¹4 M).
system should be a welcome new addition to the repertoire of the
potentially useful zinc fluorescence sensors.
References and Notes
concentrations. The Job plot indicated 1:1 binding stoichiom-
etry, and the stability constant, log K for Zn2+, was determined to
be 3.72.8 For other metal ions tested, the emission changes were
relatively insignificant to allow a reliable measure of their
log KS. The detection limit of Zn2+ determined from the
fluorescence data was found to be 5.75 © 10¹7 M.8
1
a) A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M.
Huxley, C. P. McCoy, J. T. Rademacher, T. E. Rice, Chem. Rev.
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a) J. M. Berg, Y. Shi, Science 1996, 271, 1081. b) B. L. Vallee,
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The shift of the IR band from 1694 cm¹1 in the free receptor
¹1
to 1600 cm in the oxazid-zinc complex confirms the coordi-
nation of carboxylic acids with Zn2+.8 The 1H NMR spectrum of
the probe displayed a singlet for -OCH2CO2- at ¤ 4.76, but
in the Zn2+ complex, this signal, while retaining its singlet
character, was upfield shifted to ¤ 4.41. In addition, relative to
the free probe, the aryl ring protons in the zinc complex were
also upfield shifted in the range of ¤ 0.13 to 0.22.8 These NMR
data together with Job’s plot imply that both the -OCH2CO2H
groups are probably bound to a single, centrally located Zn2+ in
a 1:1 complexation mode.
3
4
5
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To theoretically study the energetic and geometric features
of the oxazid-Zn2+ complex, calculations were performed
using DFT (RI-BP86/def2-TZVP) within the program
TURBOMOLE11a version 5.10 taking into account solvent
effects (water) using the COSMO approximation.11b Depending
on the orientations of the oxadiazole ring, several possible
geometries of 1:1 complexation were analyzed. However, we
found only one computationally suitable conformation which
had the oxygen atom of the oxadiazole ring pointing to the Zn2+
(1¢ZnA, Figure 3). Inclusion of an explicit water molecule in
the inner coordination sphere of the Zn2+ (1¢ZnB) afforded extra
6
7
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¹1
5.4 kcal mol stabilization.12 The ability of the probe to form
stable octahedral complex could account for the selective zinc
coordination.
8
9
Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html,
and includes synthesis of oxazid, IR, NMR, and Mass data, UV-
vis, Job’s plot, stability constant, and detection limit.
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J. V. Mello, N. S. Finney, Angew. Chem., Int. Ed. 2001, 40, 1536. c)
K. R. A. S. Sandanayake, K. Nakashima, S. Shinkai, J. Chem. Soc.,
Chem. Commun. 1994, 1621.
Understandably, Cu2+, Co2+, and Ni2+, which predomi-
nately form either the square-planar or tetrahedral coordination,
fail to interact. Moreover, in the Zn2+ octahedral complex, the
rotations around aryl-oxadiazole bonds would be severely
restricted. This phenomena might contribute to emission
amplification by enhancing the radiative channels over thermal
quenching processes prevailing in the conformationally flexible
probe.8
10 UV-vis profile of the probe remained essentially invariant to
several metal ions, including Zn2+, implying none or at best weak
perturbation of the ground state of the probe.
11 a) R. Ahlrichs, M. Bär, M. Häser, H. Horn, C. Kölmel, Chem. Phys.
Lett. 1989, 162, 165. b) A. Klamt, G. Schüürmann, J. Chem. Soc.,
Perkin Trans. 2 1993, 799.
12 The interaction energy was computed as the difference between the
optimized complex (with water) and the sum of the monomers
(water and the complex without water).
In conclusion, we have reported a new, structurally simple
diaryloxadiazole chelate which affords high fluorescence turn-on
response for targeting Zn2+. Noteworthily, many potentially
interfering or quenching metal ions displayed no significant
optical perturbations even in relatively higher concentrations.
The present probe, carrying wholly “oxygen”-based ligand
Chem. Lett. 2011, 40, 1163-1164
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/