A novel heteroacene, 2-(2,3,4,5-tetrafluorophenyl)-1H-imidazo[4,5-b] phenazine as a multi-response sensor for F- detection

Article abstract of DOI:10.1016/j.tetlet.2013.03.030

A novel heteroacene, 2-(2,3,4,5-tetrafluorophenyl)-1H-imidazo[4,5-b] phenazine has been successfully synthesized. The heteroacene can selectively detect F^- over Cl^-, Br^-, I^-, NO ₃^-, HSO₄^-, ClO₄ ^-, and BF₄^- in organic solvents through colorimetric and fluorescent responses. The interaction between the heteroacene and F^- was investigated through UV-Vis, fluorescence, and ¹H NMR titration experiments, which suggested that the effects might occur via a combined process including hydrogen bond, deprotonation, and anion-π interactions between the sensor and F^-.

Full text of DOI:10.1016/j.tetlet.2013.03.030

Tetrahedron Letters 54 (2013) 2633–2636
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel heteroacene, 2-(2,3,4,5-tetrafluorophenyl)-1H-imidazo[4,5-b]phenazine
as a multi-response sensor for FÀ detection
⇑
Chengyuan Wang, Gang Li, Qichun Zhang
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel heteroacene, 2-(2,3,4,5-tetrafluorophenyl)-1H-imidazo[4,5-b]phenazine has been successfully
À
synthesized. The heteroacene can selectively detect FÀ over ClÀ, BrÀ, IÀ, NO3À, HSO4À, ClO4À, and BF4
Received 1 January 2013
Revised 3 February 2013
Accepted 7 March 2013
Available online 16 March 2013
in organic solvents through colorimetric and fluorescent responses. The interaction between the heteroa-
cene and FÀ was investigated through UV–Vis, fluorescence, and 1H NMR titration experiments, which
suggested that the effects might occur via a combined process including hydrogen bond, deprotonation,
and anion–p
interactions between the sensor and FÀ.
Keywords:
Heteroacene
Synthesis
Ó 2013 Elsevier Ltd. All rights reserved.
Selective
Multi-response
Anion sensor
Combined process
Fluoride plays an important role in the physiology of human
beings. Sufficient fluoride is crucial for dental health, while
over-exposure of fluoride causes skeletal fluorosis.1 Thus, quick
and efficient analysis of fluoride (FÀ) in drinking water and other
environments is very important to provide information for fluoride
hazard assessment and pollution management. In recent years, the
development of colorimetric and luminescent sensors for FÀ recog-
nition and concentration monitoring has attracted significant atten-
tion.2 There are many series of sensors reported for detecting FÀ,
including boron-based Lewis acids,3 functionalized pyrroles and
benzopyrroles,4 and 1,8-naphthalimide derivatives.5 However, the
application of these sensor systems can be limited by drawbacks
such as low sensitivity and difficulties in their preparation. There-
fore, developing new, simple, and highly sensitive FÀ sensors
remains a challenge.
processes, and could have potential applications in medicine and
in the environment.7 Since N-substituted heteroacenes are elec-
tron-deficient compounds,8–10 we anticipate that they should be
good candidates for FÀ recognition through combined processes.
Herein, we report a new heteroacene based sensor, 2-(2,3,4,5-
tetrafluorophenyl)-1H-imidazo[4,5-b]phenazine (1), which can rec-
ognize selectively FÀ with multiple responses. As shown in
Scheme 1, compound 1 was obtained as an orange powder in 19%
yield through a one-pot, solid-state reaction between 2,3-phenazin-
ediamine, zinc acetate, and 3,4,5,6-tetrafluorophthalic anhydride at
F
O
N
N
NH2
NH2
F
F
+
O
O
Imidazole is a widely used functional group in FÀ detecting sen-
sor systems because it is able to behave as an excellent hydrogen
bond donor moiety, and the acidity of the NH group can be easily
tuned by adjusting the electronic properties of neighboring substit-
uents so that it can recognize FÀ through deprotonation.6
Currently, the interesting non-covalent binding motif between
F
2
3
Zn(OAc)2
220 °C
F
electron-deficient aromatic rings and anions, namely anion–
interactions, is generating much interest in theoretical and exper-
imental investigations, because anion– or anion–proton
p
F
H
N
N
N
F
p
N
interactions play a crucial role in many chemical and biological
F
1
⇑
Corresponding author. Tel.: +65 67904705; fax: +65 67909081.
E-mail address: qczhang@ntu.edu.sg (Q. Zhang).
Scheme 1. Synthesis of compound 1.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.03.030

2634
C. Wang et al. / Tetrahedron Letters 54 (2013) 2633–2636
Figure 1. (a) Single crystal structure and (b) molecular packing diagram of 1. Carbon, nitrogen, hydrogen, and fluoride are colored in gray, blue, white gray and green,
respectively.
the inset shows the corresponding fluorescence changes under a
UV lamp. On addition of FÀ to a CH3CN solution of 1, the original
emission at 512 nm was quenched, and a new emission centered
at 637 nm appeared, which resulted in a change in the fluorescence
from green to orange. In comparison, there was almost no fluores-
À
cence change on the addition of ClÀ, BrÀ, IÀ, NO3À, HSO4À, ClO4
,
and BF4À. Analysis of the Job plot revealed that the binding stoichi-
ometry between 1 and FÀ was 1:1 in CH3CN (Fig. S6, Supplemen-
tary data).5b,13 Based on the changes in the UV–Vis and
fluorescence spectra, compound 1 showed high sensitivity and
selectivity for FÀ over other anions, indicating that 1 represents a
robust multi-response sensor for detecting FÀ.
The interaction between 1 and FÀ was further investigated
through spectrophotometric titration methods by adding a stan-
dard solution of FÀ to a CH3CN solution of 1 (2 Â 10À5 M). Figure 4
shows the UV–Vis spectral changes of 1 on treatment with FÀ.
Upon addition of 0.5 equiv of FÀ, little change was observed. As
the amount of FÀ increased from 0.5 to 10 equiv, the initial maxi-
mum absorbance at 392 nm progressively decreased, and the band
at 422 nm gradually increased. At the same time, the broad band in
the range from 438 to 491 nm decreased and a new broad peak
centered at 540 nm appeared, which indicated stronger intermo-
lecular charge transfer between compound 1 and the FÀ anions.
The three well-defined isosbestic points demonstrated neat inter-
conversion in the equilibria.14 These results suggested that the
interaction between 1 and FÀ might be a combined process includ-
Figure 2. Changes in the UV–Vis spectra of 1 (2 Â 10À5 M) in CH3CN upon addition
of 2 equiv of different anions as TBA salts. Inset: the corresponding color changes.
220 °C under an argon atmosphere for 12 h.11 The novel compound
1 was fully characterized by MALDI-TOF and HR-TOF, and 1H NMR,
19F NMR and FT-IR spectroscopy (see Fig. S1–S5, Supplementary
data).
ing hydrogen bond, deprotonation of the NH group, and anion–
p
Needle-like single crystals of compound 1, which were suitable
for single-crystal X-ray diffraction, were obtained in DMSO. As
shown in Figure 1a, the single crystal structure (CCDC number:
922629, ORTEP plot see Fig. S10, Supplementary data) analysis
indicated that the 2,3,4,5-tetrafluorophenyl unit and 1H-imi-
dazo[4,5-b]phenazine moiety were in the same plane, which dem-
onstrates the existence of strong intramolecular hydrogen bonds.
Figure 1b presents a packing diagram for compound 1, which
shows that it adopts interlayer face-to-face stacking with a neigh-
boring interplanar distance of 3.38 Å, suggesting the existence of
interactions between 1 and FÀ.15 The inset to Figure 4 shows the
near-linear correlation curves of 1 at 422 and 392 nm (vs fluoride
equiv concentration in CH3CN), which indicates the potential
strong p–p
stacking.12
As shown in the UV–Vis spectrum (Fig. 2), compound 1 has
three UV–Vis absorption peaks at 392 nm (strongest), 438 nm,
and 465 nm. The last two broad peaks might result from intramo-
lecular charge transfer. The anion sensing properties of 1 were
investigated by addition of different anions [all as tetrabutylam-
monium (TBA) salts] in CH3CN. Figure 2 shows the changes in
the UV–Vis spectra of 1 (2 Â 10À5 M) in CH3CN after adding 2 equiv
of the anion. The inset shows the corresponding color response of
compound 1 with eight different anions (ClÀ, BrÀ, IÀ, NO3À, HSO4
,
À
ClO4À, BF4À, and FÀ). Clearly, compound 1 showed no response to
ClÀ, BrÀ, IÀ, NO3À, HSO4À, ClO4À, or BF4À. When FÀ was added to
the solution of 1, the absorbance was red shifted, leading to a color
change from yellow to red, which could be detected by the ‘naked-
eye’.
Figure 3. Changes in the fluorescence spectra of 1 (2 Â 10À5 M) in CH3CN upon
addition of 2 equiv of different anions as TBA salts excited at 392 nm. Inset: the
corresponding fluorescence changes under a UV lamp.
Figure 3 shows the fluorescence spectra of 1 (2 Â 10À5 M, ex-
cited at 392 nm) in CH3CN with 2 equiv of various anions, and

C. Wang et al. / Tetrahedron Letters 54 (2013) 2633–2636
2635
Next, we examined whether compound 1 could retain its sens-
ing properties for FÀ in the presence of potential competing an-
ions. Thus, 1 was treated with FÀ in the presence of ClÀ, BrÀ, IÀ,
NO3À, HSO4À, BF4À, ClO4À, and BF4À in CH3CN, respectively. As dis-
played in Figures S8 and S9 (Supplementary data), all the tested
competing anions had virtually no influence on the response of
1 to the detection of FÀ. Thus, compound 1 shows potential to
be useful for selectively sensing FÀ in the presence of competing
anions.
The mechanism of the interaction between compound 1 and FÀ
was further studied by 1H NMR titration experiments. Figure 6
shows the FÀ titration 1H NMR spectra of 1 in d6-DMSO. Clearly,
even on addition of only 0.1 equiv of FÀ, the proton of the NH group
disappeared immediately, which may suggest rapid binding be-
tween the NH groups and FÀ. With the addition of a further amount
of FÀ, the protons of the phenazine rings were shifted upfield sig-
nificantly, which indicates the increase of electron density on the
conjugated imidazo[4,5-b]phenazine unit, suggesting: (1) deproto-
nation of the NH group, and (2) FÀ–
p interactions. At the same
time, a downfield shift of H1 was observed, indicating that the
electron density of the tetrafluorophenyl group had changed. This
phenomenon can be explained by the fact that deprotonation of
the NH group prevented intramolecular hydrogen bonding be-
tween the tetrafluorophenyl group and the imidazo[4,5-b]phena-
zine unit, leading to the interruption of the coplanar structure.
These results corresponded with the spectrophotometric titration
results and further suggested that the mechanism of the FÀ sensing
process was a combination of hydrogen bond, deprotonation of the
Figure 4. UV–Vis titration of 1 (2 Â 10À5 M) with FÀ (as the TBAF salt from 0 to
10 equiv) in CH3CN. Inset: near-linear correlation curve of 1 monitored at 422 nm
(black) and 392 nm (red) versus fluoride equiv concentration in CH3CN.
utility of sensor 1 for calibrating and determining the FÀ concen-
tration in CH3CN. The detection limitation was determined to be
8.6298 Â 10À5 M under the experimental conditions using a re-
ported method (Fig. S7, Supplementary data).16 The overall associ-
ation constant cannot be calculated because of the small
absorbance changes upon addition of 0.5 equiv of FÀ.17
NH group, and anion–p interactions.
The results of the fluorescence titrations of 1 with FÀ are shown
in Figure 5. The fluorescence spectra changed little upon the addi-
tion of 0.5 equiv of FÀ. On further increasing the concentration of
FÀ (0.5–10 equiv), the original fluorescent emission peak at
512 nm decreased progressively and a new fluorescence emission
centered at 637 nm appeared, that is, the same trend to that found
for the UV–Vis changes. The inset shows the near-linear correlation
curves of 1 at 512 and 637 nm (vs fluoride equiv concentration in
CH3CN), which demonstrated the potential utility of compound 1
for quantitative determination of FÀ in CH3CN.
In summary, we have designed and synthesized novel heteroa-
cene 1 as a multi-response sensor for FÀ detection with high sensi-
tivity and selectivity. Upon addition of FÀ, 1 showed an obvious
color change from yellow to red and a change in fluorescence from
green to orange on excitation at 392 nm through combined hydro-
gen bonding, deprotonation, and anion–p interactions. Impor-
tantly, the obvious color and fluorescence change of 1 was also
observed in the presence of other competing anions. Our strategy
should be helpful to develop new multiple response sensors for
FÀ detection.
Figure 5. Fluorescence titration of 1 (2 Â 10À5 M) with FÀ (as the TBAF salt from 0
to 10 equiv) in CH3CN excited at 392 nm. Inset: near-linear correlation curve of 1
monitored at 512 nm (black) and 637 nm (red) versus fluoride equiv concentration
in CH3CN excited at 392 nm.
Figure 6. 1H NMR (300 MHz) titration of 1 with FÀ (as the TBAF salt from 0 to
2 equiv) in d6-DMSO.

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C. Wang et al. / Tetrahedron Letters 54 (2013) 2633–2636
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Q.Z. acknowledges financial support from AcRF Tier 1 (RG 18/
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CREATE program (Nanomaterials for Energy and Water Manage-
ment) from NRF, and the New Initiative Fund from NTU, Singapore.
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