A novel fluoride selective optical chemosensor based on internal charge transfer signaling

Article abstract of DOI:10.1016/j.tetlet.2009.11.050

A new internal charge transfer probe, NAPH-1, synthesized by incorporating photoemitive naphthalimide core with an acidic imidazolium ring, offers highly selective colorimetric and ratiometric 'off-on' signaling for targeting F^-, while Cl^-, Br^-, I^-, HSO₄^-, SCN^-, AcO^-, and NO₃^- do not appreciably perturb the photophysical properties of the probe even at relatively higher concentrations than the F^-. Deprotonation of the imidazolium ring, supported by the ¹H NMR and theoritical studies, seems to cause the spectral modulations.

Full text of DOI:10.1016/j.tetlet.2009.11.050

Tetrahedron Letters 51 (2010) 596–599
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel fluoride selective optical chemosensor based on internal charge
transfer signaling
a
a
b
b
Sabir H. Mashraqui a, , Rupesh Betkar , Mukesh Chandiramani , David Quinonero , Antonio Frontera
*
a Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz-E, Mumbai 400098, India
b Department de Quimica, Universitat de les Illes Balears, Palma de Mallorca 07122, Baleares, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A new internal charge transfer probe, NAPH-1, synthesized by incorporating photoemitive naphthalimide
core with an acidic imidazolium ring, offers highly selective colorimetric and ratiometric ‘off–on’ signal-
Received 14 October 2009
Revised 11 November 2009
Accepted 13 November 2009
Available online 20 November 2009
À
À
ing for targeting FÀ, while ClÀ, BrÀ, IÀ, HSO4À, SCN , AcO , and NO3 do not appreciably perturb the
photophysical properties of the probe even at relatively higher concentrations than the FÀ. Deprotonation
of the imidazolium ring, supported by the 1H NMR and theoritical studies, seems to cause the spectral
modulations.
À
Ó 2009 Elsevier Ltd. All rights reserved.
Anion recognition constitutes an area of fundamental impor-
tance because of the key roles anions play in a range of chemical
and biological processes.1 In biological systems, anion interactions
primarily occur via hydrogen bonding at the specific H-donor sites
on proteins. By analogy, the design criteria for artificial optical an-
ion sensors during past years have typically relied upon anion
interactions with different neutral and cationic H-donor receptors,
while the optical transductions have been expressed by exploiting
different photophysical protocols which include photoinduced
electron transfer, metallo-ligand charge transfer, internal charge
transfer (ICT) mechanisms, and excimer formation.2
For a number of medical, clinical, and environment-related is-
sues, the selectiveandpractical detectionof fluorideion are a subject
of major current interest.3 With this perspective, many optical fluo-
ride sensors featuring either ‘off–on’4 or ‘on–off’5 type responses and
with or without additional colorimetric sensing have been recently
investigated. Though, not as extensively studied, however by far
the most appealing fluoride ion sensors are those offering dual, col-
orimetric, and ratiometric ‘off–on’ type optical readouts.6
Since the ICT probes experience both ground and excited state
perturbations upon analyte binding,7 the ICT protocol can be used
to harness dual colorimetric–fluoregenic sensors. On this ground,
we have incorporated a chromogenic naphthalimide core with
the acidic imidazolium ring to access a novel ICT chemosensor,
NAPH-1. It may be noted that though the photoemitive naphthali-
mide8 and the acidic imidazolium9 moieties have in the past been
separately used as a part of chemosensors, to the best of our
knowledge, their joint incorporation in the sensor design is
unprecedented.
The design concept behind NAPH-1 is based on the understanding
thatthe -deficientnaphthalimidering,byvirtueofitselectron-with-
p
drawingnaturewouldboosttheacidityoftheimidazoliumring.Inthe
eventofstronganion binding, the forming negative chargeonthe imi-
dazolium ring would induce the ICT character into the system. Conse-
quently, significant optical modulations by ways of optical spectral
shift and intensity variation can be expected in the probe upon anion
complexations.
The synthesis of NAPH-1 was achieved by condensing 4-nitro-1,
8-naphthalic anhydride 1 with p-methoxybenzylamine 2 in reflux-
ing AcOH to afford naphthalimide 3 (Scheme 1). Heating the latter
with imidazole in dry DMF gave imidazole-substituted napthali-
mide 4. Quarternization of 4 with CH3I in anhydrous CH3CN gave
iodide salt 5 which upon anion exchange with an excess of
Mg(ClO4)2 in CH3CN afforded NAPH-1 as a pale yellow solid in good
overall yield.
Addition of 100 equiv (1.5 Â 10À3 M) of the tetra-n-butylammo-
nium salt (TBA) of FÀ exhibited remarkable spectral variations,
exhibiting a new red-shifted absorption band at 585 nm (extinc-
tion coefficient, em 5.08 Â 104 MÀ1 cmÀ1), and the shift of the LE
band from 335 to 360 nm.
As depicted in Fig. 1, the longer wavelength absorption at
585 nm is attributable to the ICT transition, which originates as a
consequence of the FÀ binding interaction with the imidazolium
receptor. In contrast, addition of up to 1000 equiv of TBA salts of
À
ClÀ, BrÀ, IÀ, HSO4À, SCN , and NO3 did not detectably alter the
UV–vis profile of NAPH-1, while exposing the probe to 1000 equiv
of the acetate ion induced a red-shifted band around 585 nm, but
À
with a drastically low em value of 1.3 Â 102 MÀ1 cmÀ1
.
The spectrophotometric titration of NAPH-1 (1.5 Â 10À5 M)
with TBAF (0–1.5 Â 10À3 M) is depicted in Figure 2. The inset
depicts a graphical representation of the steady changes in the
* Corresponding author. Tel.: +91 22 26526091; fax: +91 22 26528547.
E-mail address: sh_mashraqui@yahoo.com (S.H. Mashraqui).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.050

S. H. Mashraqui et al. / Tetrahedron Letters 51 (2010) 596–599
597
OMe
OMe
O
O
O
O
O
N
O
O
N
OMe
CH I / CH CN
1)
3
3
1) AcOH,
+
Mg(ClO ) /
2) Imidazole/
2)
4
2
CH3CN
DMF,
NO2
R
N
+
H
NH2
N
CH3
X
3 : R = -NO2
1
2
5 : X = I
X =
ClO4
N
:
4
R =
NAPH-1
N
Scheme 1. Synthesis of chemosensor, NAPH-1.
Noteworthily, many reported fluoride sensors exhibit varying
degrees of competitive binding, especially from the acetate ion10
having a basicity comparable to that of the FÀ.4a Gratifyingly, the
probe NAPH-1 shows highly selective and strong ground state
interactions only with FÀ, thereby allowing its unequivocal visual
detection.
probe,Cl-, I-, Br-, SCN-, HSO4-, NO3-.
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
}
F-
Excitation of NAPH-1 at the isosbestic point at 353 nm pro-
duced an emission maximum at 373 nm. The fluorescence behav-
ior of the probe was essentiallÀy insensitive to the added TBA
AcO-
salts of ClÀ, BrÀ, IÀ, HSO4À, SCN , and NO3 up to 1.2 Â 10À3 M.
À
On the other hand, striking changes in the emission profile of the
probe (1.5 Â 10À5 M) occurred upon incremental addition of FÀ
(0–1.2 Â 10À4 M). As shown in Figure 3, the original emission at
373 nm gradually diminished, while a red-shifted dual emission
emerged at 438 and 545 nm, with an isoemissive point at
200
300
400
500
600
700
800
Wavelength (nm)
Figure 1. UV–vis of NAPH-1 (1.5 Â 10À5 M) in the absencÀe and with added FÀ
390 nm. The shorter wavelength emission at 438 nm is attributable
À
À
À
(1.5 Â 10À3 M) and (1.5 Â 10À2 M) of AcOÀ, HSO4À, SCN , Br , I , Cl , and NO3 in
À
*
to the radiative return of the
p–p state, whereas the emission
DMSO.
band at 545 nm with a Stokes shift of 210 nm could originate from
the ICT emission.11 In comparison with the 438 nm emission band,
the weaker intensity of the emission band at 545 nm is in accord
with many known ICT systems which reportedly undergo deactiva-
tion via internal conversion.8,12
1.6
1.0
0.8
1.4
0.6
At a limiting concentration of 1.2 Â 10À4 M of FÀ, the original
band at 373 nm is virtually replaced by the dual emissions. Rela-
tive to the probe’s emission band at 373 nm, a ca. 29-fold fluores-
cence enhancement is observed in the new emission band at
438 nm in the presence of FÀ. A similar, but truncated emission re-
0.4
0.2
1.2
0.0
0.0 0.4 0.8 1.2 1.6
Conc.of F
M
1.0
0.8
0.6
0.4
0.2
0.0
585 nm
80
438 nm
200
300
400
500
600
700
800
60
Wavelength (nm)
Figure 2. Spectrophotometric titration of NAPH-1 (1.5 Â 10À5 M) with TBAF
(0–1.5 Â 10À3 M) in DMSO.
40
373 nm
545 nm
600
20
0
UV–vis profile upon incremental addition of FÀ. An isosbestic point
centered at 353 nm indicates a well-defined equilibrium involving
the receptor and FÀ interaction. A DMSO solution of the probe in-
stantly changed color from light yellow to purple only in the pres-
ence of FÀ, whereas no perceptible color changes occurred with
350
400
450
500
550
Wavelength (nm)
À
À
ClÀ, BrÀ, IÀ, HSO4À, SCN , AcO , and NO3 even at a concentration
À
Figure 3. Fluorimetric titration of NAPH-1 (1.5 Â 10À5 M) with TBAF
(0–1.2 Â 10À4 M) in DMSO.
10-fold higher than the FÀ (see Supplementary data).

598
S. H. Mashraqui et al. / Tetrahedron Letters 51 (2010) 596–599
sponse was also induced by the AcOÀ at 10 times higher than the
limiting concentration of FÀ.
To understand the anion binding, we performed DFT calculations
at the level of RI-BP86/def-TZVP in DMSO solvent. To facilitate the
calculations, we replaced the p-methoxybenzene by a methyl group.
In the optimized structure (Fig. 5), the torsional angle of the naph-
thyl-imidazolium bond in the protonated form is 66 degrees (COS-
MO computation). Calculations show that only FÀ is able to
withdraw the C(2)–H hydrogen with a distance of approximately
1.6 Å. Furthermore, the torsional angle is reduced to 50 degrees in
one conformation and to 51 degrees in another conformation upon
FÀ interaction. The ca. 15 degrees reduction in torsional angle re-
Thus, in the presence of 1.2 Â 10À3 M of AcOÀ, the emission
intensity measured at 438 nm was enhanced only by 4-fold and
moreover, under this condition, the probe’s emission band at
373 nm was only partially diminished. Job’s plot derived from
the fluorimetric titration with FÀ suggested 1:1 binding interaction
and the association constant, log K calculated using the nonlinear
curve fitting method was found to be 2.49. For the case of AcOÀ,
the log K was determined to be 0.46, which is nearly two orders
of magnitude lower than that found for the FÀ. The log Ks for other
anions could not be reliably calculated due to insignificant
interactions.
flects increasing conjugative tendency between the
p-deficient
naphthalimide ring and the deprotonated imidazolium ring. This
phenomenon appears to be responsible for the dramatic effects ob-
served in the optical properties of the probe in the presence of fluo-
ride ion.
The superior affinity of the FÀ was validated by a competitive
fluorescence experiment. No significant variations in the emission
profile of the probe containing 1.2 Â 10À4 M of FÀ were detected
upon adding 1.2 Â 10À3 M each of ClÀ, BrÀ, IÀ, HSO4À, SCNÀ, AcOÀÀ,
and NO3À. These findings bear out that ClÀ, BrÀ, IÀ, HSO4À, SCN ,
Though the optimized geometries of the selected complexes of
the selected anions ClÀ, BrÀ, and AcOÀ do show the formation of H-
bonding, however the acidic C(2)–H remain attached to the imi-
dazolium ring. The computed binding energies for the selected an-
ions both in the gas phase and in the DMSO solvent were found in
the order FÀ ꢀ AcOÀ > ClÀ > BrÀ, implying the superior binding
affinity of the fluoride ion.
AcOÀ, and NO3 do not or only scarcely perturb the excited states
À
of NAPH-1. The detection limit of FÀ, determined fluorimetrically,
was found to be 3.86 Â 10À6 M, which is lower among numerous
reported fluoride sensors.4–6 The emission intensity ratio, I438/
I373 increased linearly with respect to increasing fluoride concen-
trations. Thus, in addition to the ‘naked eye’ sensing, the fluores-
cence ratiometric protocol is available, enhancing the utility of
NAPH-1 for the fluoride ion detection.
The theoretically calculated 1H NMR values of the imidazolium
C(2)–H of the probe and its fluoride complex were found to be 7.49
and 12.5 ppm, respectively. Although the absolute value
(Dd = 5.01 ppm) is lower than the experimental one (Dd = 6.1 ppm),
The strong binding interaction of FÀ with NAPH-1 was also cor-
roborated by the 1H NMR experiment (Fig. 4). Addition of 5 equiv
of TBAF resulted in the broadening and downfield shift of the imi-
dazolium C(2)–H from 9.1 to 15.2 ppm, whereas the N–Me group
moved upfield from 4.1 to 2.7 ppm. These results imply the devel-
opment of a high degree of negative charge at the C-2 position of
the imidazolium ring. We assume that the electron-withdrawing
naphthalimide ring increases the acidity of the imidazolium ring,
thereby facilitating the interaction by the strongly basic fluoride
ion.
the theoretical downfield shift prediction is acceptable. This result
gives reliability to the theoretical model, especially since chemical
shifts are sensitive to the geometry of the compound.
Though our theoretical work seems to indicate deprotonation,
the available optical and 1H NMR data do not allow distinction be-
tween the strong C(2)–HÁ Á ÁFÀ interaction and the extreme case of
full deprotonation by the strongly basic fluoride ion to generate
the carbene.13 Nevertheless, the FÀ induced ICT process, that is,
red shift in the UV–vis spectrum and the high Stokes shift in the
ICT emission maximum, can be reasonably reconciled taking into
Figure 4. 1H NMR spectrum (a) of NAPH-1 and (b) of NAPH-1 + TBAF (5 equiv) in DMSO-d6.
Figure 5. RI-BP86/def-TZVP optimized structures, right: conformation of N-methyl analog of NAPH-1; middle and left: two different conformations involving the FÀ
interaction.

S. H. Mashraqui et al. / Tetrahedron Letters 51 (2010) 596–599
599
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uted to its high basicity which makes it a strong contender to en-
gage the receptor, while its small size should allow an
unencumbered access to the imidazolium ring held in a twisted
conformation. However, effective interactions with other anions
could be precluded or limited due to their lower basicities and/or
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To summarize, our strategy of directly attaching a naphthali-
mide core with an imidazolium receptor has yielded the chemo-
sensor, NAPH-1 as one of the rare examples of the internal
charge transfer probes, which delivers dual-mode colorimetric
‘naked eye’ detection as well as an efficient ratiometric lumines-
cent ‘turn-on’ sensing for targeting the fluoride ion. Importantly,
several other anions, including the commonly interfering AcOÀ,
caused none or minimal optical perturbations even at relatively
higher concentrations than the fluoride ion. A large downfield shift
of the imidazolium C(2)–H confirms the strong binding interaction
with the highly basic FÀ. The DFT calculations predict FÀ induced
deprotonation as well as reduction in the torsional angle of the
probe. The ensuing electronic conjugation between the deproto-
nated imidazolium ring and the electron deficient naphthalimide
ring appears to cause the observed spectral modulations.
9. Yoon, J.; Kim, S. K.; Singh, N. J.; Kwang, S.; Kim, K. S. Chem. Soc. Rev. 2006, 35,
Supplementary data
355–360.
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Experimental details, selected 1H/13C NMR spectra, graph for
anion induced emission enhancements, Job’s plot, ratiometric
graph, competitive fluorescence binding profile, detection limit,
and Table for anion binding energies are available. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.tetlet.2009.11.050.
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