Fluoride-driven 'turn on' ESPT in the binding with a novel benzimidazole-based sensor

Article abstract of DOI:10.3762/bjoc.11.61

A novel fluorescence sensor (BIP) bearing NH and OH subunits displayed a highly selective and sensitive recognition property for fluoride over other anions. Fluoride-driven ESPT, poorly used in anion recognition and sensing, was suggested to be responsible for the fluorescence enhancement with a blue shift of 35 nm in the emission spectrum.

Full text of DOI:10.3762/bjoc.11.61

Fluoride-driven ‘turn on’ ESPT in the binding with a novel
benzimidazole-based sensor
Kai Liu*1,2, Xiaojun Zhao1, Qingxiang Liu2, Jianzhong Huo2, Bolin Zhu2 and Shihua Diao2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 563–567.
1Key Laboratory of Inorganic-Organic hybrid Functional Material
Chemistry, Ministry of Education, Tianjin Normal University, Tianjin,
300387, China and 2Tianjin Key Laboratory of Structure and
Performance for Functional Molecules, College of Chemistry, Tianjin
Normal University, Tianjin, 300387, China
doi:10.3762/bjoc.11.61
Received: 14 January 2015
Accepted: 08 April 2015
Published: 24 April 2015
Email:
Associate Editor: S. C. Zimmerman
Kai Liu* - hxxylk@mail.tjnu.edu.cn
© 2015 Liu et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
anion recognition; deprotonation; ESPT; fluoride; ‘turn on’
fluorescence
Abstract
A novel fluorescence sensor (BIP) bearing NH and OH subunits displayed a highly selective and sensitive recognition property for
fluoride over other anions. Fluoride-driven ESPT, poorly used in anion recognition and sensing, was suggested to be responsible for
the fluorescence enhancement with a blue shift of 35 nm in the emission spectrum.
Introduction
Design and synthesis of selective and efficient sensors for and sensing [2,11-16]. In the ESPT molecules, a five or six-
various anions involved in biological, industrial and environ- membered intramolecular hydrogen-bonded ring formed, and a
mental processes have drawn a lot of attention [1-3]. In recent proton/hydrogen atom is transferred to an electronegative atom
years, much effort has been devoted to the development of at the excited state [2,17,18]. By regulating the proton acidity of
anion fluorescent sensors [4]. Of particular interest concerning the H-bond donor which plays a vital role in the ESPT process,
anion recognition and sensing was fluoride [5-7], as it is impor- the biologically and chemically important anion would be
tant to human health (for example, dental care, osteoporosis and distinguished by the different optical outputs for the interaction
osteosarcoma). To realize the high selectivity and sensitivity to between sensor and anion [2,14,15,19].
fluoride, many anion fluorescent sensors have been designed
based upon numerous signal mechanisms [4,8-10]. However, During the last few years, various types of artificial sensors
excited-state intra/intermolecular proton transfer (ESPT), as an have been developed for anion recognition and sensing
extensively exploited mechanism in many biological and chem- [1,4,14,15,19,20]. Among these, the hydrogen bond, especially
ical processes, has been employed poorly in anion recognition NH [21-24], was particularly useful and effective
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Beilstein J. Org. Chem. 2015, 11, 563–567.
[1,3,14,15,19,20]. However, to OH-based anion sensors it has
been paid less attention [25,26]. In fact, we have succeeded in
designing and synthesizing the anion fluorescent probes, based
on ESPT [15,16], containing phenolic OH as H-bond donor. In
these systems, the probe displayed a narrower linear range for
fluoride. Furthermore, to the best of our knowledge, there were
few reports on the anion sensors containing both NH and OH
binding sites [14,25,27]. On the foundation of the above-
mentioned background, herein we report the synthesis and
H-bond donor ability of the novel anion sensor (E)-2-(((1H-
benzo[d]imidazol-2-yl)imino)methyl)-5-(dimethylamino)phenol
(BIP) made up of benzimidazole and phenol units with a C=N
linker. Although BIP is weakly fluorescent, its anion-binding
adduct is expected to be highly fluorescent by opening up ESPT
channel [2,14,15,19]. In this paper, we demonstrated that BIP
displayed selectively fluorescence enhancement for fluoride by
ESPT. Importantly, BIP displayed a fluoride-selective fluores-
cence response with a wider linear range from 0.04 to 1.2 μM.
Figure 1: Spectral changes of BIP (4 × 10−5 M) in CH3CN after the ad-
dition of 50 equiv of anions (as their tetrabutylammonium salts).
The interaction of BIP with fluoride was further investigated by
UV–vis spectroscopic titration. As seen from Figure 2, the spec-
Results and Discussion
BIP was synthesized by the condensation of 2-aminobenzimida- tral changes with two well-defined isosbestic points (344,
zole and 4-(dimethylamino)salicylaldehyde according to the 270 nm) indicated the formation of a single complex between
literature [28,29] with little modification, as displayed in BIP and fluoride [2]. Evidence for 1:1 complex formation was
Scheme 1. It was well characterized by 1H NMR, mass spec- also validated by non-linear least-square analysis [31] for BIP
trometry and elemental analysis before its practical application. with F−. The association constant, calculated from the UV−vis
plot at 410 nm as the function of anion concentration [15], was
The anion binding and sensing properties of BIP were first eval- 1.25 × 104 (R = 0.9926) for F− (see Figure S1 in Supporting
uated by UV–vis studies. There were three characteristic bands Information File 1). Due to the little spectral changes of BIP
centered at 410, 276 and 228 nm in CH3CN. Among these, the upon other anions (Cl−, Br−, I−, NO3−, H2PO4−, AcO−, added as
band in the region around 276 and 228 nm is attributed to the TBA salts), as displayed in Figure 1, the binding constants
excitation of π electrons localized at the C=N bond and at the cannot be determined. Furthermore, the similar absorption was
aromatic system [30], and the peak at 410 nm was ascribed to found for BIP with F− and OH− (see Figure S4 in Supporting
the intramolecular charge transition between the phenol and Information File 1), which suggested the occurrence of deproto-
benzimidazole [2,30]. Upon addition of F− (as tetrabutylammo- nation during the titration process.
nium salts, TBA salts), as shown in Figure 1, the intensity of the
band at 410 nm decreased and broadened, and a new shoulder The mechanism of the UV–vis response for F− was further
around 466 nm formed, meanwhile, the shoulder peak at assessed by 1H NMR studies, which were conducted in DMSO-
228 nm increased. However, no noticeable spectral changes d6. The characteristic peak of BIP at 12.85 ppm suggested the
were found for other anions (Cl−, Br−, I−, H2PO4−, NO3−, formation of an intramolecular hydrogen bond in BIP itself
AcO−, added as their TBA salts). This indicated the poor inter- between the imine nitrogen and the phenolic OH proton [32-
action between BIP and these anions.
34], that progressively disappeared with the successive addition
Scheme 1: Synthesis of sensor BIP.
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Beilstein J. Org. Chem. 2015, 11, 563–567.
Figure 2: UV−vis absorption spectra of BIP (4 × 10−5 M) in CH3CN
after the addition of 0–50 equiv of TBAF. Insert: Non-linear curve fit of
absorbance changes at 410 nm as a function of fluoride concentration.
Figure 3: Emission spectral changes of BIP (4 × 10−7 M) in CH3CN
upon addition of 0–20 equiv TBAF. Insert: Linear plot of emission
intensity at 376 nm against fluoride concentration.
of F− (see Figure S5 and Figure S6 in Supporting Information
File 1). This indicated that the proton transfer from BIP to F−
[1]. Meanwhile, the NH signal of BIP at 12.41 ppm was shifted
downfield, broadened and weakened, which was ascribed to the
formation of an intermolecular hydrogen bond between F− and
the above-mentioned proton in BIP.
To further explore the photophysical sensing properties of BIP
with various anions (F−, Cl−, Br−, I−, H2PO4−, NO3−, AcO−,
added as TBA salts), fluorescence measurements were carried
out. The weak fluorescence emission at 411 nm, corresponding
to the enol form of a Schiff base [32-34], suggested the forma-
tion of the geometrically restricted six-membered intramolec-
ular hydrogen bond ring in the BIP at transition state [32-34].
As displayed in Figure 3, with gradual addition of F− to the
CH3CN solution of BIP, the fluorescence intensity at 411 nm
increased slowly. This indicated the occurrence of hydrogen-
Figure 4: Emission spectral changes of BIP (4 × 10−7 M) in CH3CN
after the addition of 20 equiv of anions (added as their TBA salts).
bonding interaction between BIP and F−. Moreover, the acidity The binding constant of BIP with F− was also determined by
of the OH group of BIP was expected to be enhanced by anion nonlinear regression based on spectrofluorometric titration.
binding, and the ESPT channel would be open [8-10,15]. The Good nonlinear curve fits (R = 0.9907) also indicated the for-
subsequent spectral behavior proved our assumption. The new mation of an 1:1 stoichiometric complex of BIP with F− (see
peak at 376 nm occurred and reached a limiting value after the Figure S2 in Supporting Information File 1). The association
addition of 20 equiv F−. The fluoride-driven ESPT displayed a constant was 8.79 × 105 M−1, which was bigger than that
fluorescence enhancement and a dramatically blue-shift with obtained from UV–vis spectroscopy. This suggested the
35 nm in the emission spectrum.
enhancement of the phenolic OH acidity by the photoexcitation
[2,11-15]. Moreover, fluoride-dependent fluorescent intensity at
Analogous investigations were carried out with Cl−, Br−, I−, 376 nm displayed an excellent linearity (R = 0.9880) in the
NO3−, H2PO4− and AcO−. As shown in Figure 4, the fluores- concentration range of 0.04–1.2 μM (insert Figure 3 and Figure
cence emission hardly experienced any perturbation on adding a S3 in Supporting Information File 1). The limit of detection for
similar amount of anions as done with F−. Also, the detection of F− was found to be 0.021 μM, which is lower than 0.10 μM set
F− displayed no interference in presence of other competitive by the US Environmental Protection Agency. This suggested
anions (See Figure S7 in Supporting Information File 1). This that BIP had a good sensitivity for fluoride and has the poten-
demonstrated BIP has a high selectivity for F−.
tial utility to detect fluoride.
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Beilstein J. Org. Chem. 2015, 11, 563–567.
Based on the aforementioned UV–vis, spectrofluorimetric and yield 3.30 g of 1. 1H NMR (400 MHz, CDCl3) δ 3.09 (s, 6H,
1H NMR studies, the possible mechanism of F− recognition by CH3), 6.10–7.29 (m, 3H, Ar-H), 9.53 (s, 1H, OH), 11.61 (s, 1H,
BIP was proposed and illustrated in Scheme 2. On binding of CHO). This was consistent with the literature.
F−, the isomerization of BIP was restricted, which enhanced the
intramolecular charge transfer interaction between the assembly Synthesis of compound BIP: 2-Aminobenzimidazole (0.80 g,
of binding sites with F− to the chromophore [1]. With further 6 mmol) and compound 1 (0.99 g, 6 mmol) were dissolved in
addition of F−, intermolecular hydrogen bond formation 25 mL ethanol. The resulting solution was heated at reflux for
disturbed the intramolecular hydrogen bonding and destroyed 4 h. The solvent was removed by a rotary evaporator at reduced
the geometrically restricted conformation [2], at the same time, pressure. The crude product was purified by silica gel column
the new geometrically restricted intermolecular H-bonding ring chromatography (ethyl acetate/n-hexane 1:3) and recrystallized
formed. Subsequent the fluoride-triggered ESPT occurred, with ethanol to yield yellow solid. Yield: 1.03 g (61.2%);
which displayed ‘turn-on’ fluorescence.
1H NMR (400 MHz, DMSO-d6) δ 3.05 (s, 6H, CH3), 6.16–7.53
(m, 7H, Ar-H), 9.34 (s, 1H, CH=N), 12.41 (s, 1H, NH), 12.85
(s, 1H, OH); ESIMS: 280.1408 (M + H+).
Conclusion
In conclusion, a new benzimidazole-based BIP has been devel-
oped which is selective for the recognition of F− also in the
presence of anions with similar basicity and surface charge
density such as AcO− and H2PO4−. Fluorescence spectral
changes were driven by original hydrogen bonding interaction
between BIP and F−, and the subsequent ESPT which resulted
in the ‘turn-on’ of fluorescence. The strategy for the design of
simple sensors to detect the important neutral and anionic guest
may contribute to design more efficient anion chemosensors.
Supporting Information
Supporting Information File 1
Data analysis of QP after the addition of fluoride.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-11-61-S1.pdf]
Acknowledgements
Experimental
Authors thank the Tianjin Science & Technology Development
Fund Planning Project for Colleges and Universities (No.
20120507), Tianjin Nature Science Foundation (Nos.
13JCQNJC06000 and 14JCYBJC20300).
Synthesis of compound 1: 4-(Dimethylamino)salicylaldehyde
was synthesized according to the literature [15,16] with little
modification. POCl3 (4.0 mL, 43.2 mmol) was added dropwise
to dry DMF (21.0 mL, 271.8 mmol) containing 3-(dimethyl-
amino)phenol (3.10 g, 22.6 mmol) at 0 °C, and the mixture was
stirred for 10 min, slowly warmed to room temperature and
stirred for another 30 min. The reaction mixture was heated at
80 °C overnight. After cooling to room temperature, the mix-
ture was poured into ice cold water. The solution was neutral-
ized with saturated Na2CO3. The precipitate was washed
several times with distilled water, and dried under vacuum to
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