Synthesis, crystal structure and fluorescent properties of a novel benzothiazole-derived fluorescent probe for Zn2+

Article abstract of DOI:10.3184/174751915X14450160708347

A novel turn-on fluorescent probe containing a benzothiazole fluorophore has been synthesised and its structure confirmed by single crystal X-ray diffraction. The probe exhibited high selectivity to Zn2+ over other metal ions and demonstrated high sensiti

Full text of DOI:10.3184/174751915X14450160708347

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 NOVEMBER, 661–664
RESEARCH PAPER 661
Synthesis, crystal structure and fluorescent properties of a novel
2
+
benzothiazole-derived fluorescent probe for Zn
Fan Fang-Lu , Jing Jin-Qiu and Chen Xue-Mei
a
a*
a
b
School of Materials and Metallurgy and bSchool of Chemical and Materials Engineering, Hubei Polytechnic University, Huangshi 435003, P. R. China
A novel turn-on fluorescent probe containing a benzothiazole fluorophore has been synthesised and its structure confirmed by single
2
+
2+
crystal X-ray diffraction. The probe exhibited high selectivity to Zn over other metal ions and demonstrated high sensitivity for Zn with
2
+
2+
a 12-fold fluorescence enhancement. It also showed a fast response to Zn and a complexation ratio towards Zn of 1:1.
2
+
Keywords: benzothiazole, crystal structure, Zn , fluorescent probe, selectivity, sensitivity
Zinc is the second most abundant d-block metal after iron in
the human body. It plays an important role in various biological
processesincludingstructuralcofactors, geneexpression, catalytic
the chelating moiety of 3, the dihedral angle of the two pyridine
rings is 37.17 (2)°, and their centroid-to-centroid distance is 5.826
nm. The angle C(16)–N(3)–C(22) is 114.19(2)°, which leads to
the V-shape of the chelating moiety. The C–N bond distances
range from 1.294(2) to 1.463(2) Å, and the C–N (benzothiazolyl)
bonds are shorter than the C–N(amino) bonds. The bond length
of C(13)-N(2) is longer than that of C(14)-N(2), due to the fact
1-3
centres, regulators of enzymes and neural signal transmission.
In industry, zinc is thought to be an environmental contaminant,
2
+
an excess of Zn may reduce soil microbial activity and produce
4
,5
2+
phytotoxic effects. Therefore, the use of Zn chemosensors in
environmental and biological systems is of great interest. Many
2
that C(14) is sp hybridised, whereas C(13) is part of the aromatic
2
+
recent studies have reported the successful application of Zn
fluorescent probes based on quinoline, fluorescein, rhodamines,
coumarin, indole and naphthalimide. Although there are
several commercially available Zn probes to satisfy different
needs, the search for readily accessible Zn fluorescent probes
with high selectivity and sensitivity is still a challenge. We
now report a new fast-response, highly selective and sensitive
fluorescent probe for Zn .
ring. The C(7)–S(1) bond length [1.747 (2) Å] is also found to be
longer than the C(1)–S(1)bond length [1.722(2) Å] for the same
reason.
6
-12
2
+
The maximum excitation (λ ) and emission (λ ) wavelengths
ex
em
2
+
of 3 in EtOH/tris-HCl buffer (V/V = 1/4, pH 7.4) are 355 and
13
-1
470 nm, respectively. The selectivity of 3 (10 µmol L ) toward
+
2+
+
2+
2+
2+
3+
2+
2+
various cations (K , Ca , Na , Mg , Mn , Fe , Fe , Co , Ni ,
2
+
2+
2+
+
2+
2+
3+
2+
Cu , Zn , Ag , Pb , Cd , Cr and Hg ) was investigated using
fluorescent spectrometry. As illustrated in Fig. 2, significant
fluorescent enhancement of 3 was observed on addition of
Results and discussion
2
+
-1
Benzothiazole is often used as a fluorophore for designing
fluorescence probes to detect metal ions due to its good
Zn (30 µmol L ). Under identical conditions, the other tested
cations showed nearly negligible fluorescence changes, except
14,15
2+
2+
photophysical properties. We have designed a benzothiazole-
based fluorescent probe 3, in which the benzothiazole group
is linked to a chelating moiety 2-picolylamine (Scheme 1).
Compound 3 was synthesised by a nucleophilic substitution
reaction of a primary halogenoalkane and secondary amine, and
it was fully characterised by IR, NMR, MS, elemental analysis
and single crystal X-ray diffraction. Metal-binding properties
toward cations showed that 3 is highly selective and sensitive to
that Cu and Co responded with different extent of decrease in
the fluorescent intensity. Moreover, ion interference experiments
-1
further illustrated that 3 (10 µmol L ) was selective for the
2
+
recognition of Zn by the addition of 10 equiv. of competing
metal ions (Fig. 3). The fluorescence enhancement of 3 caused by
2
+
most of the mixtures of Zn with other cations was similar to that
2
+
caused by Zn alone. A fluorescence quenching effect was found
2
+
2+
2+
when Zn was mixed with Cu or Co , demonstrating that these
2
+
2+
Zn in a aqueous EtOH solution.
paramagnetic metal ions might compete with Zn for binding
with 3. These facts suggested that probe 3 could recognise Zn
2
+
Yellow crystals of 3 were obtained by slow evaporation of an
ethyl acetate solution at room temperature. In its crystal structure,
the benzothiazole ring system and neighbouring benzene ring
comprise the fluorescent moiety of 3; they are nearly coplanar,
and the dihedral angle between them is 13.85 (2)° (Fig. 1). In
with high selectivity.
2
+
To get an insight into the sensitivity of 3 to Zn , fluorescence
titration experiments were performed (Fig. 4). Probe 3
displayed a weak fluorescence with a quantum yield (Φ) of
COOH
S
NH2
SH
ClCH COCl
polyphosphoric acid
N , 220°C
2
+
NH
2
CH Cl , (Et) N
2
N
2
2
3
H N
2
(1)
Cl
O
N
N
HN
HN
N
S
S
N
H
N
N
N
N
CH CN, KI, K CO
3
3
2
O
(2)
(3)
Scheme 1 Synthesis of fluorescent probe 3.
*
Correspondent. E-mail: flfan2014@163.com

6
62 JOURNAL OF CHEMICAL RESEARCH 2015
-
1
Fig. 1 An ORTEP drawing of 3 with displacement ellipsoids shown at the
0% probability level.
Fig. 2 Fluorescence intensities of probe 3 (10 µmol L ) upon addition
-1
3
of various metal ions (30 µmol L ) in CH3CH2OH/Tris-HCl buffer (1/4,
V/V, pH 7.4).
Zn2
+
.
v
i
u
q
e
3
~
0
-1
2+
-1
Fig. 3 Fluorescence response of 3 (10 µmol L ) to Zn in the presence
Fig. 4 The fluorescence spectral changes of 3 (10 µmol L ) in the
-1
2+
-1
of different metal ions (100 µmol L ).
presence of increasing Zn concentrations (0–30 µmol L ), the inset
shows the linear relationship between the emission intensity of 3 and
2
+
-1
concentrations of Zn (0.2–3.2 µmol L ).
-1
Fig. 5 Effect of pH on the fluorescence intensity of 3 (10 µmol L )
-1
Fig. 6 Response of fluorescence intensity of 3 (10 µmol L ) in the
2
+
measured with and without Zn .
2+
presence of Zn as a function of time, the inset shows the visual
fluorescence colour of 3 before (left) and after (right) incubation with
2
+
Zn under UV light (365 nm).

JOURNAL OF CHEMICAL RESEARCH 2015 663
2
+
2+
-1
2+
Fig. 7 Job’s plot of probe 3 and Zn ([3]+ [Zn ] = 10 mmol L ).
Scheme 2 The proposed sensing mechanisms of probe 3 for Zn .
2
+
0
.05. On addition of Zn , the fluorescence intensity increased
Experimental
2
+
remarkably. When the concentration of Zn increased to 3
equiv., the fluorescence response reached a maximum point,
and an approximately 12-fold fluorescence enhancement
could be observed (Φ = 0.58). As depicted in the inset in Fig.
, the fluorescent intensity of 3 was nearly proportional to the
concentration of Zn in the range of 0.2–3.2 µmol L (linear
correlation coefficient R = 0.9913). The detection limit of 3
to Zn was determined to be 0.68 µmol L according to the
calculation method reported in the literature.
The influence of pH on the fluorescence of 3 was also
examined (Fig. 5). The fluorescence intensity of 3 was nearly
invariable over a wide pH value range of 2–12, however,
upon addition of Zn , it was enhanced between pH 6 and 10,
indicating that it could be applied to the detection of Zn in
pH values close to physiological conditions. Furthermore, the
response time of 3 (10 µmol L ) to Zn was explored (Fig. 6). It
was found that the fluorescence enhancement reached a plateau
after 30 s, indicating the quick response of 3 to Zn . This
fluorescence change was also observable by the naked eye (Fig.
All reagents were purchased from commercial companies and
directly used without further purification, unless otherwise noted.
Melting points were determined with an XT4A micro melting point
apparatus and were uncorrected. IR spectra were performed on a
PerkinElmer Spectrum BX FT-IR instrument in tablets with potassium
4
2
+
-1
1
bromide. The H NMR spectra were recorded on a Mercury Plus-400
2
spectrometer in CDCl . Electrospray ionisation mass spectra (ESI-
3
2
+
-1
MS) were acquired on an Applied Biosystems API 2000 LC/MS/MS
system. Elemental analyses were carried out on a PerkinElmer 2400
instrument. Fluorescence spectra were measured on a FluoroMax-P
spectrofluorimeter.
16
Synthesis
2
+
The intermediates 1 and 2 were synthesised according to reported
2
+
17,20
procedures. Fluorescent probe 3, 2-picolylamine (0.40 g, 2 mmol)
and the intermediate 2 (0.60 g, 2 mmol) were dissolved in acetonitrile
-1
2+
(100 mL), then K CO (0.28 g, 2 mmol) and a catalytic amount of
2 3
KI (0.05 g) were added to the resulting solution. After stirring and
refluxing for 24 h until the reaction was complete as detected by
TLC, the mixture was cooled to room temperature, and the solvent
was removed under reduced pressure. The residue was purified using
column chromatography (silica, AcOEt/CH Cl , 5/1, v/v) to give a
2
+
5
3
inset). Under irradiation at 365 nm, the fluorescence colour of
turned from pale blue to bright blue after the addition of Zn .
In order to determine the binding stoichiometry between
2
+
2
2
yellow solid. Yield 78%; m.p. 116–117 °C. IR (KBr): 3430, 3150, 2935,
1675, 1568, 1525, 1440 cm . H NMR (400 MHz, CDCl , ppm): 8.66
2
+
-1 1
3
and Zn , a Job’s plot experiment was employed. In Fig. 7,
3
the emission intensity at 470 nm is plotted as a function of the
(d, J = 7.8 Hz, 2H), 7.86–8.21 (m, 5H), 7.25–7.56 (m, 10H), 4.06(s,
2
+
13
molar fraction of Zn , and the total molar concentration of 3
4H), 3.44(s, 2H). C NMR (75 MHz, CDCl ): 170.8, 166.6, 158.1,
3
2
+
-1
and Zn was 10 µmol·L . Maximum fluorescence intensity was
154.6, 148.3, 139.5, 138.8, 134.7, 129.2, 128.8, 127.9, 127.6, 125.7,
125.6, 125.2, 124.9, 122.6, 121.8, 116.4, 63.2, 59.8. ESI-MS: m/z 465.2
2
+
reached when the mole fraction was 0.5, indicating that Zn
+
formed a 1:1 complex with 3.
(M ). Anal. calcd for C H N OS: C, 69.65; H, 4.98; N, 15.04; found:
2
7
23
5
C, 69.28; H, 5.18; N, 15.32%.
Based on above results and some recent reports, we propose a
2
+
17-19
possible sensing mechanisms of probe 3 for Zn (Scheme 2).
X-ray diffraction study of 3
The weak fluorescence emission of probe 3 can be attributed to
the emission of its normal excited state, and the photoinduced
electron transfer (PET) from aliphatic amine nitrogen to the
excited state of the phenylbenzothiazole moiety (fluorophore)
A yellow crystal of 3 having approximate dimensions of 0.12 mm
0.10 mm ×0.10 mm was mounted on a glass fibre in a random
×
orientation at 298(2) K. The determination of unit cell and the data
collection were performed using MoKα radiation (λ = 0.71073 Å) on
a Bruker APEX-II CCD diffactometer. A total of 22280 reflections
were collected in the range of 1.81 < θ < 30.00° at room temperature.
The structure was solved by direct methods and semi-empirical
absorption corrections were applied. The non-hydrogen atoms were
refined anisotropically and the hydrogen atoms were determined
by theoretical calculation. The final cycle of full matrix least-
squares refinement was based on 6689 independent reflections [I >
2
+
decreased its emission intensity. Zn binding to 3 could not
only induce a conformation restriction but also block PET
quenching of the singlet excited state of the fluorophore, thus a
drastic fluorescence enhancement was observed.
In conclusion, we have prepared a benzothiazole-based
2
+
fluorescent probe 3 for Zn , which has been characterised
by single crystal X-ray diffraction. Probe 3 was sensitive and
2
+
1
2
selective to Zn , even in presence of an excess of other metal
2σ(I)] and 308 variable parameters with R = 0.0477, wR = 0.1333.
2
+
ions. It also displayed rapid recognition of Zn and formed a
All calculations were carried out on a PC using SHELXS–97 and
2
+
21,22
1
:1 complex with Zn .
SHELXL–97 programs.
Crystal data: C H N OS, M = 465.56,
27 23 5

6
64 JOURNAL OF CHEMICAL RESEARCH 2015
Monolinic, space group P 2(1)/C, a = 9.4764(17) Å, b = 22.451(4) Å,
5
6
7
8
9
E. Callender and K. C. Rice, Environ. Sci. Technol., 2000, 34, 232.
P. Kaur, H. Kaur and K. Singh, RSC Adv., 2013, 3, 64.
3
c = 10.919(2) Å, α =90°, β =98.013(3)°, γ =90°, V = 2300.3(7) Å , Z = 4,
-3
-1
M. M. Henary, Y. G. Wu and C. J. Fahrni, Chem. Eur. J., 2004, 10, 3015.
C. C. Woodroofe and S. J. Lippard, J. Am. Chem. Soc., 2003, 125, 11458.
Z. C. Xu, X. Liu, J. Pan and D. R. Spring, Chem. Commun., 2012, 48, 4764.
Y.Y. Lv, M. D. Cao, J. K. Li and J. B. Wang, Sensors, 2013, 13, 3131.
D. Wang, X. Y. Xiang, X. L. Yang, X. D. Wang, Y. L. Guo, W. S. Liu and W.
W. Qin, Sensor. Actuat. B-Chem., 2014, 201, 246.
Dc = 1.344 Mg m , μ = 0.172 mm . The data have been deposited as
CCDC 1416988 which contains the supplementary crystallographic
information for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac. uk/conts/ retrieving.html or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; E-mail: deposit@ccdc.cam.ac.uk.
1
0
11
12 L. Dong, Y. Zang, D. Zhou, X. P. He, G. R. Chen, T. D. Jamesc and J. Li,
Chem. Commun., 2015, 51, 11852.
1
3
Z. Xu, J. Yoon and D. R. Spring, Chem. Soc. Rev., 2010, 39, 1996.
This work was supported by the National Natural Science
Foundation of China (Grant No. 51173060).
14 M. Santra, B. Roy and K. H. Ahn, Org. Lett., 2011, 13, 3422.
15
W. Sun, W. H. Li, J. Li, J. Zhang, L. P. Du and M. Y. Li, Tetrahedron Lett.,
2
012, 53, 2332.
16 M. Shortreed, R. Kopelman, M. Kuhn and B. Hoyland, Anal. Chem., 1996,
8, 1414.
L. J. Tang, X. Dai, K. L. Zhong, X. Wen and D. Wu, J. Fluoresc., 2014,
4, 1487.
Received 5 September 2015; accepted 6 October 2015
Paper 1503580 doi: 10.3184/174751915X14450160708347
Published online: 1 November 2015
6
17
2
18
Y. M. Liu, Q. Fei, H. Y. Shan, M. H. Cui, Q. Liu, G. D. Feng and Y. F. Huan,
Analyst, 2014, 139, 1868.
References
1
9
M. L. Chen, X. Lv, Y. L. Liu, Y. Zhao, J. Liu, P. Wang and W. Guo, Org.
Biomol. Chem., 2011, 9, 2345.
1
2
3
J. M. Berg and Y. Shi, Science, 1996, 271, 1081.
M. Lu and D. Fu, Science, 2007, 317, 1746.
S. C. Burdette and S. J. Lippard, Proc. Natl. Acad. Sci. USA, 2003, 100,
20 J. Zhang and W. Guo. Chem. Commun., 2014, 50, 4214.
21 G.M. Sheldrick, SHELXS-97, A Program for the Solution of Crystal
Structures, University of Göttingen, Germany, 1997.
3
605.
4
A. Voegelin, S. Pfister, A. C. Scheinost, M. A. Marcus and R. Kretzschmar,
Environ. Sci. Technol., 2005, 39, 6616.
22 G.M. Sheldrick, SHELXL-97, A Program for the Refinement of Crystal
Structures, University of Göttingen, Germany, 1997.