Novel benzimidazolium-urea-based macrocyclic fluorescent sensors: Synthesis, ratiometric sensing of H2PO4- and improvement of the anion binding performance via a synergistic binding strategy

Article abstract of DOI:10.1039/c3cc43184c

A modular approach to obtain benzimidazolium-urea-based, fluorophore-appended macrocyclic receptors was developed. This class of receptors could be used as selective ratiometric fluorescent sensors for H ₂PO₄^- due to the synergistic binding effect of benzimidazolium and urea moieties. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc43184c

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Novel benzimidazolium–urea-based macrocyclic
fluorescent sensors: synthesis, ratiometric sensing
of H2PO4 and improvement of the anion binding
performance via a synergistic binding strategy†
Cite this: Chem. Commun., 2013,
49, 6149
ꢀ
Received 30th April 2013,
Accepted 21st May 2013
a
a
Dawei Zhang,z Xiaozhi Jiang,z Haiqiang Yang,a Zhao Su,a Enqing Gao,a
DOI: 10.1039/c3cc43184c
Alexandre Martinez*b and Guohua Gao*a
www.rsc.org/chemcomm
A modular approach to obtain benzimidazolium–urea-based, fluorophore-
appended macrocyclic receptors was developed. This class of
receptors could be used as selective ratiometric fluorescent sensors
for H2PO4ꢀ due to the synergistic binding effect of benzimidazolium
and urea moieties.
The sensing of anions by fluorescent sensors is an expanding area of
molecular recognition,1 especially for the biologicallꢀy important
H2PO4ꢀ.2 A number of fluorescent sensors for H2PO4 have been
reported via fluorescence quenching or enhancement.3 However, the
ratiometric sensing of H2PO4ꢀ is still a challenging task.4 Apart from
the fluorescence-response behavior towards the anions, the binding
site and structure of the sensors are also important. It is known
that imidazolium/benzimidazolium and urea groups are effective
hydrogen bond donors through formation of (C–H)+ꢁꢁꢁX and
N–HꢁꢁꢁX hydrogen bonds with anions respectively.5 Even though a
few efficient imidazolium/benzimidazolium-based3a,4c,6 macrocyclic
receptors have been reported, there is no reported macrocyclic sensor
simultaneously involving benzimidazolium and urea moieties. Never-
theless, it could be expected that with the assistance of urea, the
benzimidazolium-based macrocyclic sensors would exhibit an
improved anion binding performance due to their well defined
cavities bearing multiple hydrogen binding sites. Hence, it
is highly desirable to develop a facile method for synthesizing
benzimidazolium–urea-based macrocyclic sensors and investigate
the synergistic binding effect of benzimidazolium and urea moieties.
Recently, our group reported a class of benzimidazolium–acridine-
based macrocyclic fluorescent sensors, such as sensor 2 (Scheme 1),
Scheme 1 Synthesis of fluorescent sensors 1–4.
ꢀ
which achieved ratiometric detection of H2PO4 via an anion-
induced assembly mechanism.4c Bearing in mind the above concept,
herein, we reported a new class of macrocyclic sensors (1 and 3)
which contain two building blocks: benzimidazolium–urea linkage
(7) and the model fluorophore (Scheme 1). Acridine and anthracene
were, respectively, chosen as model fluorophores. Hence, this work
provided an unprecedented opportunity to combine the benzimida-
zolium and urea moieties in the same macrocyclic moꢀlecule to
strongly improve the recognition properties toward H2PO4
.
The synthetic routes to obtain sensors 1 and 3 are illustrated
in Scheme 1 and Scheme S1 (ESI†). 1,3-Bis-(3-hydroxyl-propyl)-
urea 5 was reacted with SOCl2 in CHCl3 at r.t. to achieve 1,3-bis-
(3-chloro-propyl)-urea 6 in 34% yield. Then 6 underwent a
substitution reaction with benzimidazole in the presence of
NaH in DMF resulting in 1,3-bis-(3-benzoimidazol-1-yl-propyl)-
urea 7 in 39% yield. A [1+1] macrocyclization between 8/9 and 7
occurred in CH3CN under high dilution conditions to afford the
bromide salt of 1/3 in 85%/75% yield. Finally, the [PF6]ꢀ salts of
1 and 3 were obtained by counterion exchange reaction using
NH4PF6 in water. For comparison, sensors 2 and 4 bearing only
benzimidazolium moieties were also prepared (see ESI†).
a Shanghai Key Laboratory of Green Chemistry and Chemical Processes,
Department of Chemistry, East China Normal University,
3663 North Zhongshan Road, Shanghai, 200062, P. R. China.
E-mail: ghgao@chem.ecnu.edu.cn; Fax: +86 (21)62233323; Tel: +86 (21)62233323
b
´
´
Laboratoire de Chimie, CNRS, Ecole Normale Superieure de Lyon, 46,
´
Allee d’Italie, F-69364, Lyon, France. E-mail: alexandre.martinez@ens-lyon.fr
† Electronic supplementary information (ESI) available: 1H–13C NMR spectra of
sensors 1–4, a summary of the crystallographic data, fluorescence titrations and
Job’s plots etc. CCDC 914122. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c3cc43184c
‡ Dawei Zhang and Xiaozhi Jiang contributed equally to this work.
c
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Fig. 1 Crystal structure of 2ꢁ2(PF6ꢀ)ꢁ(CH3COCH3). Nonacidic hydrogen atoms, some
ꢀ
PF6 counterions, some CH3COCH3 solvent molecules and one of the two sets of
disorders in the sensor molecule are omitted for clarity. Dashed lines represent
hydrogen bonds, anion–p and p–p interactions. Symmetry codes: A = 2 ꢀ x, 1 ꢀ y, ꢀz.
The single crystal of sensor 2 revealed the self-assembly nature of
the benzimidazolium-based sensors, as shown in Fig. 1 and Fig. S5
(ESI†). Hydrogen bonds formed by benzimidazolium C(2)–H and
PF6ꢀ/CH3COCH3, p–p interactions between two benzimidazoliums
and between two acridines were the main driving forces for the
assembly behavior. It is worth mentioning that the formation of the
assembled acridine dimer shown in Fig. 1 could also be induced by
ꢀ
Fig. 2 Fluorescence titrations of 5 mM sensor 1 excited at 357 nm (a) and sensor
H2PO4 in solution and resulted in bathochromic-shifted fluores-
ꢀ
cence emission, as we reported previously.4c
3 excited at 362 nm (b) with H2PO4 in CH3CN. Insets: normalized emission
developments at the wavelength of monomer and excimer peaks as a function of
ꢀ
Binding performance of sensors 1–4 toward H2PO4 was then
ꢀ
H2PO4 equivalents, and the fluorescent color of sensor 1/3 in the absence or
evaluated by the fluorescent changes of the 5 mM sensor in CH3CN
upon addition of the tetrabutylammonium H2PO4ꢀ salt. As shown in
Fig. 2a and Fig. S6a (ESI†), a significant decrease in the fluorescence
ꢀ
presence of H2PO4 under a UV lamp excited at 365 nm.
emission at 430 nm and increase in emission at 501 nm with clear curve of sensor 4 was much gentler and lower than that of sensor 3
isoemission points at 459 and 476 nm, respectively, were observed (Fig. S7b, ESI†). Job’s plots demonstrated the 1 : 1 complexes of
ꢀ
upon addition of H2PO4ꢀ to the solution of sensors 1 and 2. Adding sensors 1–4 with H2PO4 (Fig.ꢀS8, ESI†). Binding constants of
3.0 equiv. of H2PO4 to the solution of sensor 1 resulted in sensors 1, 3 and 4 with H2PO4 were 2.9 ꢂ 106, 2.6 ꢂ 105 and
ꢀ
quenching of fluorescence by 68% at 430 nm and enhancement of 1.6 ꢂ 105 Mꢀ1 respectively (Fig. S9, ESI†). The binding constant of
ꢀ
fluorescence by 4.3-fold at 501 nm, changing the fluorescent color sensor 2 with H2PO4 could not be calculated because of the two-
from blue to green. However, 4 equiv. of H2PO4ꢀ only caused 2.6-fold step process of the titration profile (Fig. S9, ESI†).4c All these results
fluorescence enhancement at 501 nm of sensor 2. The new fluores- indicated that compared with sensors 2 and 4, sensors 1 and 3
cence peaks of sensors 1 and 2 at 501 nm could be assigned to the which bear both benzimidazolium and urea binding sites exhibited
ꢀ
anion-induced acridine excimer.4c Interestingly, such a H2PO4
-
better anion binding performance toward H2PO4ꢀ owing to the urea-
induced fluorophore dimer displayed by acridine derivatives 1 and assisted synergistic binding effect.
2 was also exhibited by the anthracene derivative 3. Similarly, a In order to check the sensing selectivity of 1 and 3 as H2PO4
ꢀ
significant decrease in the monomer peak at 428 nm and increase in ratiometric fluorescent sensors, the fluorescence responses of sensors
the excimer peak at 500 nm with a clearꢀisoemission point at 479 nm 1 and 3 toward other common anions, such as Fꢀ, Clꢀ, Brꢀ, Iꢀ,
were observed upon addition of H2PO4 to the solution of sensor 3 HSO4ꢀ, AcOꢀ, SCNꢀ and ClO4ꢀ, were evaluated, as shown in Fig. S10
(Fig. 2b). It seems to be a versatile principle for the class of (ESI†). Obviously, sensor 3 displayed excellent selectivity towards
benzimidazolium–urea-based receptors that they could be used as H2PO4ꢀ since only H2PO4ꢀ resulted in the unique excimer emission
ꢀ
ratiometric fluorescent sensors for H2PO4 even with the varying output at 500 nm. However, in terms of this view, both H2PO4ꢀ and
ꢀ
fluorophores. In contrast, the excimer peak of the anthracene HSO4 could give rise to the excimer peak of sensor 1 at 501 nm.
ꢀ
derivative 4 induced by H2PO4 was not so obvious upon addition Hence, special attention was paid to H2PO4ꢀ selectivity of sensor 1 in
of H2PO4ꢀ, since only a feeble fluorescence enhancement at longer the presence of other competing anions. As shown in Fig. 3 and
wavelength was observed (Fig. S6b, ESI†).
Fig. S11 (ESI†), no significant variations in the intensity ratio (I501/I430)
ꢀ
In order to further evaluate the H2PO4 ratiometric sensing and the excimer wavelength were found for the detection of 2 equiv. of
performance of sensors 1–4, ratiometric curves of Iexcimer/Imonomer H2PO4ꢀ when in the presence of 20 equiv. of other background anions.
ꢀ
ꢀ
as a function of H2PO4 concentration were studied. As shown in Sensor 1 has the ability to ratiometrically sense H2PO4 with high
ꢀ
Fig. S7a (ESI†) sensor 1 could achieve ratiometric sensing of H2PO4
at a much lower concentration than sensor 2 (1.0 vs. 6.5 mM). In
selectivity even in the mixture containing other competing anions.
To fully explore the interaction modes between sensor 1/3 and
addition, the curve with a good linear relationship from 1.0 to 7.5 mM H2PO4ꢀ, the 1H NMR titration experiments were carried out
ꢀ
H2PO4 could serve as the calibration curve of sensor 1 for the in DMSO-d6 due to the precipitation in CD3CN. As shown in
detection of H2PO4ꢀ. Fig. S7b (ESI†) indicates that the linear range Fig. 4, effective binding between sensor 3 and H2PO4 occurred in
ꢀ
ꢀ
for H2PO4 of sensor 3 was 5.0–15 mM. However, the ratiometric DMSO-d6 which can be confirmed by the vivid fluorescent color
c
6150 Chem. Commun., 2013, 49, 6149--6151
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urea moieties of sensor 1/3 participated in the anionꢀcomplexation
and exhibited a synergistic effect for binding H2PO4
.
In summary, we have designed and synthesized the first two
novel macrocyclic compounds 1 and 3 bearing benzimidazolium
and urea groups based on acridine and anthracene fluorophores
respectively. This new class of cyclic compounds could be used
as highly selective ratiometric fluorescent sensors for H2PO4ꢀ via
the anion-induced fluorophore dimer formation. Compared with
sensors 2 and 4, sensors 1 anꢀd 3 exhibited better anion binding
performance towards H2PO4 due to the synergistic binding
effect of benzimidazolium and urea moieties.
Fig. 3 Fluorescence responses of sensor 1 (5 mM) upon addition of 2 equiv. of
ꢀ
H2PO4 and subsequent addition of 20 equiv. of other anions.
The authors are grateful to financial support from the
National Natural Science Foundation of China (Grant No.
21072061) and Shanghai Leading Academic Discipline Project
(Grant No. B409).
Notes and references
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ꢀ
Fig. 4 1H NMR titrations of sensor 3 (15 mM) upon addition of H2PO4 in
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ꢀ
3 equiv. of H2PO4 in DMSO-d6 under a UV lamp excited at 365 nm.
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1
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Based on the above discussions, the possible binding mode
between sensor 1/3 and H2PO4ꢀ was proposed and is illustrated in
Scheme 2. It is worth mentioning that both benzimidazolium and
ꢀ
Scheme 2 Possible binding mode of sensor 1/3 with H2PO4
.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 6149--6151 6151