Bis-pyrene carbocations for chromogenic and fluorogenic dual-detection of fluoride anion in situ

Article abstract of DOI:10.1016/j.tet.2014.03.044

We have designed and synthesized a new carbocation precursor (carbinol) based on bis-pyrene derivative. The carbinol can be transformed to stable carbocations with quenched fluorescence and long wavelength absorption. The stable carbocations can be further used as fluoride anion detection in acidic environment, which show both chromogenic and fluorogenic responses in the presence of fluoride anion. UV-vis and fluorescence spectroscopy were utilized to monitor the changes during detection process. The responsive mechanism was studied by quantum chemical calculations and the results indicate that the carbocation mediated formation of C-F covalent bond leads to this dual responsive phenomenon. The bis-pyrene carbocations and corresponding F adduct was confirmed MALDI-TOF mass spectrum. The successful elucidation of this new mechanism opens a new avenue for carbocation-based sensor or biological labeling in the future.

Full text of DOI:10.1016/j.tet.2014.03.044

Tetrahedron 70 (2014) 3172e3177
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Bis-pyrene carbocations for chromogenic and fluorogenic dual-
detection of fluoride anion in situ
,
,
a,
Lei Wang a, Wei Li a b, Jing Lu b, Jing-Ping Zhang b , Hao Wang
*
*
a CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST),
Beijing 100190, PR China
b Faculty of Chemistry, Northeast Normal University, Changchun 130024, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
We have designed and synthesized a new carbocation precursor (carbinol) based on bis-pyrene de-
rivative. The carbinol can be transformed to stable carbocations with quenched fluorescence and long
wavelength absorption. The stable carbocations can be further used as fluoride anion detection in acidic
environment, which show both chromogenic and fluorogenic responses in the presence of fluoride anion.
UVevis and fluorescence spectroscopy were utilized to monitor the changes during detection process.
The responsive mechanism was studied by quantum chemical calculations and the results indicate that
the carbocation mediated formation of CeF covalent bond leads to this dual responsive phenomenon.
The bis-pyrene carbocations and corresponding F adduct was confirmed MALDI-TOF mass spectrum. The
successful elucidation of this new mechanism opens a new avenue for carbocation-based sensor or bi-
ological labeling in the future.
Received 28 October 2013
Received in revised form 5 March 2014
Accepted 13 March 2014
Available online 19 March 2014
Keywords:
Carbocations
Fluoride detection
In situ
Dual-responsive
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
to the intrinsic Lewis acidity, boron-centered receptors couple with
fluorides to afford fluoroborate complex via donation of an electron
Fluoride anion (Fꢀ) detection has attracted growing attentions
because of its pivotal importance in the fields of environmental
science and food industry.1 Appropriate amount of fluoride is often
added to drinking water and toothpaste for its beneficial effects in
dental and skeletal health.2 However, chronic exposure to high
levels of the fluoride leads to organ disorders, dental or even
skeletal fluorosis.3 To solve this problem, various receptor mole-
cules responded to Fꢀ have been reported.2e,g,4e6 Different from
other anions, fluoride anion shows small anionic diameter and
strong electronegativity, and it still remains challenge for design
and synthesis of the selective receptor for Fꢀ.1
Over the past decades, extensive efforts have been devoted to
develop new methods for selective detection of fluoride
anions.2e,g,4e6 Accordingly, various optically responsive molecules
for fluoride have been explored mainly based on three molecular
mechanisms, i.e., (i) hydrogen bonding formation between fluoride
and NH hydrogen (amide, pyrrole, indole, urea, and thiourea).2e,4
An optical-responsive chromophore covalently conjugate to
a skeleton containing H-bond donor sites, and the resulting re-
ceptor can selectively bind with fluoride to give H/Fꢀ type com-
plex; (ii) fluoroborate complexation mechanism. For example, due
pair of the fluoride anion into the pz-orbital of the boron center;2g,5
and (iii) fluoride mediated desilylation, i.e., Swager et al. developed
a fluoride-triggered SieO bond cleavage reaction for highly sensi-
tive detection fluoride by fluorescence spectroscopy.6
Carbocations have been intensively investigated owing to its
unique reaction selectivity and optically responsive properties.7
Carbocations are able to synthesize and stabilize in the presence
of acid. Many organic synthesis,8 biosynthesis,9 and pathogenic
mechanism10 involve carbocations as an intermediate of nucleo-
philic substitution reactions, such as N-heterocycles pharmaceuti-
cals, terpenes, and DNA alkylation according to reports. Recently,
carbocation has been utilized as a reaction-based probes and/or
labelers,11 in which the obviously colorimetric response of carbo-
cation was observed by coupling the labeler with active amine or
thiol residues of proteins.
Herein, we reported a new strategy for fluoride anion detection
in acidic environment based on bis-pyrene carbocations, which
exhibit both chromogenic and fluorogenic responses in the pres-
ence of fluoride. As depicted in Scheme 1, the solution of bis-pyrene
carbocations 4 shows negligible fluorescence intensity due to
intramolecular charge transfer (ICT).7b,12 Upon the bis-pyrene car-
bocations are substituted by fluoride anion in acid environment,
the color of the solution change from blue to transparent with re-
markably enhanced fluorescence emission.
* Corresponding authors. E-mail address: wanghao@nanoctr.cn (H. Wang).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.044

L. Wang et al. / Tetrahedron 70 (2014) 3172e3177
3173
directly visualized under the UV excitation (lex¼365 nm) (Fig. 1(b),
inset). The corresponding NMR spectra are not available due to the
low solubility of carbocations 4 in all tested solvents (CHCl3þTFA,
DMSOþTFA, and etc.).
Scheme 1. A plausible mechanism of the detection of Fꢀ by using stable bis-pyrene
carbocations. The bis-pyrene carbocations 4 with quenched fluorescence due to in-
tramolecular charge transfer (ICT) recovers its fluorescence upon coupling with fluo-
ride through nucleophilic substitution.
2. Result and discussion
2.1. Synthesis of compounds 2 and 3
Fig. 1. Changes in UVevis absorption (a) and fluorescence (b) of 3 upon gradual ad-
dition of TFA in chloroform. Inset: (a) photographs of 3 with visible color changes and
(b) fluorescence changes (UV illumination) in chloroform.
In this proof-of-concept study, a relatively stable carbocation
with optical activity is required to monitor the reaction process by
spectroscopy. Pyrene was chosen as fluorogenic group and delo-
calized
bocation precursor
p
system to stabilize the carbocation (Scheme 2). The car-
was synthesized from pyrene by
3
To utilize the carbocations for fluoride detection, the carboca-
tions should keep stable during employed. The large p-conjugated
FriedeleCrafts acylation and followed reduction. For the purpose of
comparison, the mono-substituted pyrene 2 as a reference com-
pound was prepared in a similar synthetic method. The full syn-
thetic details were shown in Experimental part (Figs. S1eS12).
pyrene unit could effectively stabilize the carbocations.14 Hence,
the bis-pyrene carbocation 4 are stable and the carbocations dis-
appeared in 15 h, which was characterized by the UVevis spec-
troscopy through monitoring the characteristic absorption change
of 4 at 645 nm. As shown in Fig. 2(b), the interval of each line was
150 min for 3. The next titration process with anions usually takes
5 min. Hence, we assure that the carbocations of 3 were stable
during next titration process. However, the carbocation of a refer-
ence compound 2 can only stabilize less than 2 h under the same
condition (Fig. 2(a)), which was not stable enough for next titration.
The results identified that the bis-pyrene carbocations 4 with two
pyrene units could be more benefit for delocalization and stabili-
zation of the positive charges of carbocations than one pyrene
unit14 (Fig. 2 and S13). The stable carbocations 4 were obtained by
us for further experiments.
Scheme 2. Synthetic route of compounds 2 and 3. Compound 2 is a mono-pyrene
reference molecule. i, terephthaloyl chloride (1 equiv for 3a, 0.5 equiv for 2a), AlCl3,
CH2Cl2; ii, NaBH4, ethanol.
Fig. 2. Stability of compound 2 (a) and 3 (b) carbocations under ambient condition,
indicating that the bis-pyrene can stabilize the carbocations.
2.2. Preparation and stability of carbocation 4
To obtain the carbocation 4, compound 3 in chloroform was
added with trifluoroacetic acid (TFA). This process could be moni-
tored by UVevis spectroscopy. Upon addition of TFA (from 100 to
2.3. Chromogenic and fluorogenic responses of carbocation 4
The fluorescence responses of 4 toward a series of anions (Fꢀ,
Clꢀ, Brꢀ, Iꢀ, CO32ꢀ, H2POꢀ4 , OAcꢀ, SO24ꢀ, and CNꢀ from their tetrabutyl
ammonium salts) were tested. Upon addition of variable anions
(10ꢀ5 M) into a CHCl3 solution containing 4 (c¼3.3ꢁ10ꢀ5 M), the
peaks at 440 and 645 nm of 4 became weak or disappeared and
some new peaks at 360 and 420 nm formed (Fig. S14), indicating
the formation of 4 and anion complexes.15 Furthermore, fluorescent
titration experiments of 4 (c¼3.3ꢁ10ꢀ5 M) with halide anions (from
0 to 10ꢀ4 M) in CHCl3 were performed to observe the fluorescence
intensity change. Upon addition of Fꢀ into a solution of 4, the
fluorescence intensity of the 4-Fꢀ adduct was remarkably enhanced
as the concentration of Fꢀ was increased. The fluorescence emission
maxima of the resulted 4-Fꢀ adduct formed at 380, 412, and
600 mL, 6.5 M) into a solution of chloroform (2 mL) containing 3
(c¼5ꢁ10ꢀ5 M), the absorption maxima of 3 at 330 and 347 nm
decreased and two new peaks appeared at 440 and 645 nm, re-
spectively. Accordingly, the color of the solution changed from
colorless to deep blue as shown in Fig. 1(a). These results indicated
the formation of bis-pyrene carbocations 4.13 Meanwhile, the for-
mation of 4 was monitored by fluorescence spectroscopy. With
addition of TFA from 2 to 200 mL (6.5 M) into a solution of chloro-
form (1 mL) containing 3 (c¼2ꢁ10ꢀ6 M), the fluorescence intensity
of 3 with emission peaks at 378, 398, and 423 nm was quenched
and a new peak formed at about 445 nm (Fig. 1(b)). The quenched
fluorescence upon formation of bis-pyrene carbocations 4 was

3174
L. Wang et al. / Tetrahedron 70 (2014) 3172e3177
436 nm (Fig. 3(a)). In a sharp contrast, the fluorescence intensity of
4 kept increasing slightly or even quenched in the presence of Clꢀ,
Brꢀ, and Iꢀ under the same condition owing to the heavy atom
effect (Fig. 3(b)).16 Other anions (CO32ꢀ, H2PO4ꢀ, OAcꢀ, SO24ꢀ, and
CNꢀ) were also investigated, no obvious fluorescence increases
were observed (Fig. S15).
(Fig. 5). It is reasonable that due to the order of nucleophilicities of
halide anions in protic solvents is Fꢀ>>Clꢀ>Brꢀ>Iꢀ and reversed
leaving capability,17 the Fꢀ is regarded as the strongest nucleophile
among halide anions and prefers the formation of CeF bond.8b,18
The MALDI-TOF mass spectrum was utilized for monitoring the
mixture of 4 and other halide anions (Clꢀ, Brꢀ, Iꢀ), there are no
molecular ion peak of CeX adduct were found.
Fig. 3. (a) The fluorescent spectral change of carbocations 4 (3.3ꢁ10ꢀ5 M) in chloro-
form with addition of Fꢀ (from 0 to 10ꢀ4 M), (b) fluorescence intensity of 4 in chlo-
roform upon addition of halide ions (from 0 to 10ꢀ4 M) inset: photos were taken under
UV illumination (from left to right, Fꢀ, Clꢀ, Brꢀ, Iꢀ).
An important aspect of Fꢀ sensors is their ability to detect Fꢀ
anions selectively over other competing anions. The competition
experiments were carried out in the presence of Fꢀ (10ꢀ4 M) mixed
with 10ꢀ4 M of another anion (Fig. 4). As shown in Fig. 4, no sig-
nificant interference in detection of Fꢀ was observed in the pres-
ence of many competitive anions except for Brꢀ and Iꢀ due to the
strong owing to the heavy atom effect.16 This demonstrates the
exceptional selectivity of 4 for Fꢀ. The fluorescent titration profile of
4 with Fꢀ (Fig. S16) demonstrated that the detection limit of Fꢀ is
3.0ꢁ10ꢀ5 M under the experimental conditions used here. The fast
chromogenic and fluorogenic responses of carbocation 4 to fluoride
anions could be used as fluoride anion detection in situ.
Fig. 5. MALDI-TOF mass spectrum of 5.
2.4. Quantum chemistry stimulations
To investigate fluorogenic response in the presence of fluoride,
we performed quantum chemical calculations of 3, 4, and 5 using
density function theory (DFT)19 and time-dependent density
function theory (TD-DFT)20 at the B3LYP/6-31G(d) level of the
Gaussian09 program. Meanwhile, in order to be consistent with the
experimental measurements, the emission properties have been
performed in chloroform using the well-known polarized contin-
uum model (PCM) approximation, which is adequate for the fluo-
rescence spectrum.21
As displayed in Fig. 6, the optimized structure of the lowest
singlet excited state (S1) has a dihedral angle about 166.1ꢂ between
the pyrene and terephthaloyl moieties for bis-pyrene carbocations
4, however, the dihedral angles of compounds 3 and 5 are 72.6ꢂ and
88.3ꢂ, respectively. Furthermore, the frontier molecular orbitals
(FMOs), which strongly affect the photophysical properties were
simulated in detail. The electron densities in the lowest unoccupied
molecular orbitals (LUMOs) and the highest occupied molecular
orbitals (HOMOs) are dominantly delocalized on pyrene moieties in
3 and 5, whereas relevant LUMOs and H-7 for bis-pyrene carbo-
cations 4 are mainly delocalized over the pyrene and terephthaloyl
moieties (Fig. 7).
On the basis of the optimized S1 structures, the emission
wavelengths, emission energies, transition nature, and oscillator
strength (f ) were calculated by TD-B3LYP method. As shown in
Table 1, strong emission wavelengths are predicted at 387 nm
(f ¼0.0843) and 376 nm (f ¼1.1769) for 3, in good agreement with
experimental values, these bands are ascribed to LUMO/HOMO
(72%) and Lþ1/H-1 (71%) transitions, respectively, and described
Fig. 4. Fluorescence response of 4 (2.0ꢁ10ꢀ5 M) in CHCl3 to 10ꢀ4 M of various tested
anions (green bar) and to the mixture of 10ꢀ4 M of anions with Fꢀ anion (10ꢀ4 M, red
bar). Blue bar¼4þFꢀ, black bar¼4. lex¼350 nm.
Given the fact that the complexation between 4 and Fꢀ is not
reversible, we deduce that the significant spectral response of 4
towards Fꢀ is not attributed to the electrostatic interaction but the
formation of new compound 5 through nucleophilic substitution
reactions between Fꢀ and 4. The proposed mechanism was further
confirmed by MALDI-TOF, which was carried out right after the
titration of Fꢀ to carbocation 4 and validated the formation of 5
as p*/p character of the pyrene moieties. However, the calculated
weak emission wavelengths of 4 are 393 nm, 369 nm, respectively,
and a new peak formed at about 449 nm (f ¼0.0579), this new
emission originates from Lþ1 to H-7 [
p*/p character of the pyr-
ene and terephthaloyl moieties]. For 5, the experimental emission
spectrum presents two major bands, centered around 412 nm and

L. Wang et al. / Tetrahedron 70 (2014) 3172e3177
3175
Table 1
The fluorescence emission wavelength (lem), corresponding transition contribution,
and oscillator strength (f) of 3, 4, and 5
E (eV)
lem (nm) in
f
Major transition
Expt. (nm)
chloroform
in chloroform
3
4
5
3.20
3.30
2.76
387
376
449
0.0843
1.1769
0.0579
LUMO/HOMO
Lþ1/H-1
72%
27%
71%
26%
75%
18%
90%
86%
74%
26%
73%
24%
398
378
445
Lþ1/H-1
LUMO/HOMO
Lþ1/H-7
LUMO/H-11
Lþ1/H-8
3.16
3.36
3.19
393
369
388
0.0088
0.0137
0.0989
398
378
412
Lþ1/H-9
LUMO/HOMO
Lþ1/H-1
3.30
376
1.1610
Lþ1/H-1
380
LUMO/HOMO
380 nm, TD-B3LYP method also predicts two strong emission bands
at 388 nm (f ¼0.0989) and 376 nm (f ¼1.1610), which have the same
character as 3. These results are in good agreement with experi-
mental values (fluorescence response) and prove the mechanism of
the fluoride anions detection.
Fig. 6. Optimized structures of 3 (a), 4 (b), and 5 (c) in the lowest singlet excited states
(S1) at TD-B3LYP/6-31G (d) level.
3. Conclusion
We demonstrated a new molecular mechanism for in situ
fluoride anion detection in acidic environment based on stable
p-
conjugated carbocations. First, we have designed and synthesized
a new bis-pyrene based carbocation precursor, which could form
stable carbocations with weak fluorescence and long wavelength
absorption. The carbocations show both chromogenic and fluoro-
genic responses in the presence of fluoride anion. We proposed that
the carbocations react with fluoride anion to form CeF covalent
bond, which leads to this dual responsive phenomenon. The re-
sponsive mechanism was supported by quantum chemical calcu-
lations and the MALDI-TOF spectrum. The successful elucidation of
this new mechanism opens new avenue for carbocation-based
sensor or biological labeling in the future.
4. Experimental
4.1. General
All reagents and solvents were purchased from commercially
available sources and used without further purification. All the
reactions were performed under an inert atmosphere of nitrogen.
1H NMR spectra were recorded on an Advance Bruker 400M
spectrometer in deuterated chloroform. Chemical shifts are quoted
in parts per million (ppm) and referenced to tetramethylsilane. The
13C NMR spectra were recorded at 100 MHz on the same spec-
trometer in deuterated chloroform. Chemical shifts were defined
relative to the 13C resonance shift of chloroform (77.0 ppm).
Microflex LRF MALDI-TOF was used to determine the molecular
mass. Elemental analyses were performed on a Flash EA 1112 an-
alyzer. The UV absorption was determined with a PE Lambda 650
UVevis spectrometer. Fluorescence spectrum was recorded on F-
280 spectrometer from Tianjin Gangdong Sci&Tech. Development.
Co., Ltd.
4.2. FriedeleCrafts acylation procedure for compound 3a
Pyrene 1 (2.02 g, 10.00 mmol) and p-phthanoyl chloride (1.01 g,
5.00 mmol) were dissolved in dichloromethane (50 mL), the mix-
ture was cooled to 0 ꢂC. After the portionwise addition of AlCl3
(2.00 g, 15.00 mmol), the mixture was allowed to react overnight at
room temperature, then poured into ice-water and the resulting
Fig. 7. Contour plots of LUMOs and HOMOs in the first excited states for 3, 4, and 5 in
detail.

3176
L. Wang et al. / Tetrahedron 70 (2014) 3172e3177
mixture was stirred until the color of the organic phase turned from
black to yellow. The aqueous phase was extracted with dichloro-
methane, the combined organic phases were dried with MgSO4,
and the solvent was evaporated. The residue was purified by col-
umn chromatography (elute CH2Cl2/PE¼4:1), and compound 3a
was obtained (1.62 g, 63%). Mp>300 ꢂC. IR (KBr, cmꢀ1) 3084, 3040,
1643, 1595, 1509, 1390, 1250, 1203, 1065, 935, 870, 844, 832, 806,
1H NMR (CDCl3, 400 MHz) (
d
, ppm) 8.31 (d, J¼9.6 Hz, 1H), 8.21e8.15
(m, 4H), 8.06e7.98 (m, 4H), 7.44 (d, J¼8.0 Hz, 2H), 7.32 (d, J¼8.0 Hz,
2H), 6.87 (s, 1H), 4.66 (s, 2H), 2.53 (s, 1H), 1.62 (s, 1H). 13C NMR
(CDCl3, 100 MHz) (d, ppm) 143.14, 140.23, 138.53, 131.33, 131.07,
130.61, 128.07, 127.86, 127.52, 127.45, 127.22, 127.21, 126.03, 125.40,
125.34, 125.23, 125.06, 124.92, 124.81, 124.77, 124.70, 123.03, 73.42,
65.10. MALDI-TOF: calcd for C24H18O2 338.13, found 338.02. Ele-
mental analysis: calcd (%) for C24H18O2: C, 85.18; H, 5.36. Found: C,
85.16; H, 5.29.
710. 1H NMR (CDCl3, 400 MHz) (
d
, ppm) 8.40 (d, J¼9.6 Hz, 2H), 8.27
(t, J¼8.8 Hz, 4H), 8.22e8.06 (m, 12H), 7.94 (d, J¼8.0 Hz, 4H). 13C
NMR (CDCl3, 100 MHz) (d, ppm) 197.74, 142.28, 134.10, 133.59,
132.15, 131.20, 130.68, 130.50, 130.07, 129.56, 129.34, 127.41, 127.21,
126.57, 126.36, 126.19, 124.92, 124.60, 124.41, 123.80. MALDI-TOF:
calcd for C40H22O2 534.16, found 534.30. Elemental analysis: calcd
(%) for C40H22O2: C, 89.87; H, 4.15. Found: C, 89.88; H, 4.18.
Acknowledgements
This work was supported by National Basic Research Program of
China (973 Program, No. 2013CB932701), the 100-Talent Program of
the Chinese Academy of Sciences, Beijing Natural Science Founda-
tion (No. 2132053) and Young Scientists Fund of National Natural
Science Foundation (No. 51102014).
4.3. Reduction with NaBH4 for compound 3
Compound 3a (0.53 g, 1.00 mmol) and NaBH4 (0.15 g, 4 mmol)
was dissolved in ethanol (30 mL), the mixture was stirred at room
temperature until the compound 3a reacted completely about 3 h.
Then the 1 M HCl was added until the pH value reached 7. The
solvent was evaporated and the residue was washed with deion-
ized water. The compound 3 was purified by column chromatog-
raphy (elute CH2Cl2, 0.50 g, 93%). Mp>300 ꢂC. IR (KBr, cmꢀ1) 3410,
3046, 2919, 1434, 1384, 1362, 1254, 1108, 1026, 953, 926, 785, 705.
Supplementary data
This material contains the details of 1H and 13C NMR, MALDI-
TOF-MS spectra, and UVevis and fluorescence spectra. Supple-
mentary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.03.044.
1H NMR (DMSO-d6, 400 MHz) (
d
, ppm) 8.46 (dd, J¼11.2, 1.7 Hz, 2H),
References and notes
8.28e8.21 (m, 8H), 8.16e8.08 (m, 6H), 8.03 (t, J¼7.6 Hz, 2H), 7.38 (s,
4H), 6.70 (d, J¼4.2 Hz, 2H), 6.23 (d, J¼4.2 Hz, 2H). 13C NMR (DMSO-
1. (a) Rochat, S.; Severin, K. Chem. Commun. 2011, 4391e4393; (b) Sole, S.; Gabbai,
F. P. Chem. Commun. 2004, 1284e1285; (c) Guha, S.; Saha, S. J. Am. Chem. Soc.
2010, 132, 17674e17677; (d) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40,
486e516; (e) Youngmin, K.; Gabbai, F. P. J. Am. Chem. Soc. 2009, 131, 3363e3369;
(f) Wade, C. R.; Broomsgrove, A. E. J.; Aldridge, S.; Gabbai, F. P. Chem. Rev. 2010,
110, 3958e3984; (g) Yu, G.; Zhang, Z.; Han, C.; Xue, M.; Zhou, Q.; Huang, F.
Chem. Commun. 2012, 2958e2960; (h) Xu, Z.; Kim, S. K.; Yoon, J. Chem. Soc. Rev.
2010, 39, 1457e1466; (i) Moragues, M. E.; Manez, R. M.; Sancenon, F. Chem. Soc.
Rev. 2011, 40, 2593e2643; (j) Ke, I.-S.; Myahkostupov, M.; Castellano, F. N.;
Gabbai, F. P. J. Am. Chem. Soc. 2012, 134, 15309e15311.
2. (a) Briancon, D. Rev. Rheum. 1997, 64, 78e81; (b) Dreisbuch, R. H. Handbook of
Poisoning; Lange Medical: Los Altos, CA, 1980; (c) Xu, G.; Tarr, M. A. Chem.
Commun. 2004, 1050e1051; (d) Bhosale, S. V.; Bhosale, S. V.; Kalyankar, M. B.;
Langford, S. J. Org. Lett. 2009, 11, 5418e5421; (e) Miyaji, H.; Sato, W.; Sessler, J. L.
Angew. Chem., Int. Ed. 2000, 39, 1777e1780; (f) Bucklr, D.; Bhosale, S. V.;
Langford, S. J. Tetrahedron Lett. 2011, 52, 1990e1992; (g) Cho, E. J.; Ryu, B. J.; Lee,
Y. J.; Nam, K. C. Org. Lett. 2005, 7, 2607e2609; (h) Cametti, M.; Rissanen, K.
Chem. Commun. 2009, 2809e2829.
3. (a) Riggs, B. L. Bone and Mineral Research, Annual 2; Elsevier: Amsterdam, The
Netherlands, 1984; (b) Carton, R. J. Fluoride 2006, 39, 163e172; (c) Environ-
mental Health Criteria 227. IPCS International Programme on Chemical Safety;
World Health Organization: Geneva, Switzerland, 2002; (d) Broomsgrove, A. E.
J.; Addy, D. A.; Paolo, A. D.; Morgan, I. R.; Bresner, C.; Chislett, V.; Fallis, I. A.;
Thompson, A. L.; Vidovic, D.; Aldridge, S. Inorg. Chem. 2010, 49, 157e173.
4. (a) Sessler, J. L.; Davis, J. M. Acc. Chem. Res. 2001, 34, 989e997; (b) Gale, P. A.
Coord. Chem. Rev. 2003, 240, 191e221; (c) Sessler, J. L.; Camiolo, S.; Gale, P. A.
Coord. Chem. Rev. 2003, 240, 17e55; (d) Gale, P. A.; Garcia-Garrido, S. E.; Garric,
J. Chem. Soc. Rev. 2008, 37, 151e190; (e) Martinez-Manez, R.; Sancenon, F. Chem.
Rev. 2003, 103, 4419e4476; (f) Choi, K.; Hamilton, A. D. Coord. Chem. Rev. 2003,
240, 101e110; (g) Arnendola, V.; Bonizzoni, M.; Esteban-Gomez, D.; Fabbrizzi,
L.; Licchelli, M.; Sancenon, F.; Taglietti, A. Coord. Chem. Rev. 2006, 250,
1451e1470; (h) Lee, D. H.; Lee, K. H.; Hong, J.-I. Org. Lett. 2001, 3, 5e8; (i) Cao,
X.; Lin, W.; Yu, Q.; Wang, J. Org. Lett. 2011, 13, 6098e6101; (j) Qu, Y.; Hua, J.;
Tian, H. Org. Lett. 2010, 12, 3320e3323.
5. (a) Yamaguchi, S.; Akiyama, S.; Tamao, K. J. Am. Chem. Soc. 2000, 122,
6793e6794; (b) Aldridge, S.; Bresner, C.; Falls, I. A.; Coles, S. J.; Hursthouse, M.
B. Chem. Commun. 2002, 740e741; (c) Arimori, S.; Davidson, M. G.; Fyles, T. M.;
Hibbert, T. G.; James, T. D.; Kociok-Kohn, G. I. Chem. Commun. 2004, 1640e1641;
(d) Zhou, Y.; Xiao, Y.; Chi, S.; Qian, X. Org. Lett. 2008, 10, 633e636; (e) Li, J.;
Zhang, G.; Zhang, D.; Zheng, R.; Shi, Q.; Zhu, D. J. Org. Chem. 2010, 75,
5330e5333; (f) Vadavi, R. S.; Kim, H.; Lee, K. M.; Kim, T.; Lee, J.; Lee, Y. S.; Lee,
M. H. Organometallics 2012, 31, 31e34; (g) Swamy, K. M. K.; Lee, Y. J.; Lee, H. N.;
Chun, J.; Kim, Y.; Kim, S.-J.; Yoon, J. J. Org. Chem. 2006, 71, 8626e8628; (h) Sun,
H.; Dong, X.; Liu, S.; Zhao, Q.; Mou, X.; Yang, H. Y.; Huang, W. J. Phys. Chem. C
2011, 115, 19947e19954; (i) Madhu, S.; Ravikanth, M. Inorg. Chem. 2012, 51,
4285e4292; (j) Hudnall, T. W.; Gabbai, F. P. Chem. Commun. 2008, 4596e4597;
(k) Galbraith, E.; James, T. D. Chem. Soc. Rev. 2010, 39, 3831e3842; (l) Padie, C.;
Zeitler, K. New J. Chem. 2011, 35, 994e997.
d6, 100 MHz) (d, ppm) 143.75, 138.97, 130.79, 130.09, 131.20, 129.85,
127.39, 127.11, 127.08, 126.91, 126.54, 126.12, 125.13, 124.94, 124.91,
124.80,124.02,123.97,123.67, 71.30. MALDI-TOF: calcd for C40H26O2
538.19, found 538.00. Elemental analysis: calcd (%) for C40H26O2: C,
89.19; H, 4.87. Found: C, 89.22; H, 4.82.
4.4. FriedeleCrafts acylation procedure for compound 2a
Pyrene 1 (2.02 g, 10.00 mmol) and p-phthanoyl chloride (2.03 g,
10.00 mmol) were dissolved in dichloromethane (100 mL), the
mixture was cooled to 0 ꢂC. After the portionwise addition of AlCl3
(1.33 g, 10.00 mmol), the mixture was allowed to room temperature
for 10 min, then poured into ice-water and the resulting mixture
was stirred until the color of the organic phase turned from black to
yellow. The aqueous phase was extracted with dichloromethane,
the combined organic phases were dried with MgSO4, and the
solvent was evaporated. The residue was purified by column
chromatography, and compound 2a was obtained (1.41 g, 40%). Mp:
192 ꢂC. IR (KBr, cmꢀ1) 3437, 3044, 1773, 1653, 1595, 1507, 1263,
1202, 1065, 938, 876, 847, 837, 814, 693. 1H NMR (CDCl3, 400 MHz)
(
d
, ppm) 8.44 (d, J¼9.2 Hz, 1H), 8.28 (t, J¼8.0 Hz, 2H), 8.24e8.04 (m,
8H), 7.99 (d, J¼8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz) (
d, ppm)
197.96, 168.87, 145.23, 137.21, 134.77, 132.42, 132.25, 132.21, 132.06,
131.77, 131.57, 131.50, 131.10, 130.73, 130.49, 128.49, 128.07, 127.57,
127.46, 127.26, 125.82, 125.32, 125.22, 124.70. MALDI-TOF: calcd for
C
24H14O3 350.09, found (MþH)þ 350.88. Elemental analysis: calcd
(%) for C24H14O3: C, 82.27; H, 4.03. Found: C, 82.31; H, 4.02.
4.5. Reduction with NaBH4 for compound 2
Compound 2a (0.35 g, 1.00 mmol) and NaBH4 (0.15 g, 4 mmol)
was dissolved in ethanol (30 mL), the mixture was stirred at room
temperature until the compound 2a reacted completely about 3 h.
Then the 1 M HCl was added until the pH value reached 7. The
solvent was evaporated and the residue was washed with deion-
ized water. The pure compound 2 was obtained by column chro-
matography (0.30 g, 89%). Mp: 140 ꢂC. IR (KBr, cmꢀ1) 3423, 3261,
3041, 2921, 2869, 1417, 1383, 1209, 1062, 1028, 1016, 843, 758, 717.
6. (a) Kim, T.-H.; Swager, T. M. Angew. Chem., Int. Ed. 2003, 42, 4803e4806; (b) Hu,
R.; Feng, J.; Hu, D.; Wang, S.; Li, S.; Li, Y.; Yang, G. Angew. Chem., Int. Ed. 2010, 49,
4915e4918; (c) Kim, S. Y.; Hong, J. I. Org. Lett. 2007, 9, 3109e3112; (d) Kim, S. Y.;

L. Wang et al. / Tetrahedron 70 (2014) 3172e3177
3177
Park, J.; Koh, M.; Park, S. B.; Hong, J. I. Chem. Commun. 2009, 4735e4737; (e)
Bozdemir, O. A.; Sozmen, F.; Buyukcakir, O.; Guliyev, R.; Cakmak, Y.; Akkaya, E.
U. Org. Lett. 2010, 12, 1400e1403; (f) Yang, X. F.; Qi, H. P.; Wang, L. P.; Su, Z.;
Wang, G. Talanta 2009, 80, 92e97; (g) Hudnall, T. W.; Gabbai, F. P. J. Am. Chem.
Soc. 2007, 129, 11978e11986; (h) Hirano, J.; Miyata, H.; Hamase, K.; Zaitsu, K.
Tetrahedron Lett. 2007, 48, 4861e4864; (i) Lee, M. H.; Quang, D. T.; Jung, H. S.;
Yoon, J.; Lee, C.-H.; Kim, J. S. J. Org. Chem. 2007, 72, 4242e4245; (j) Kim, D.;
Singha, S.; Wang, T.; Seo, E.; Lee, J. H.; Lee, S.-J.; Kim, K. H.; Ahn, K. H. Chem.
Commun. 2012, 10243e10245.
11. (a) Shchepinov, M. S.; Korshun, V. A.; Egeland, R. D.; Southern, E. M. Tetrahedron
Lett. 2000, 41, 4943e4948; (b) Wetzl, B. K.; Yarmoluk, S. M.; Craig, D. B.; Wolfbeis,
O. S. Angew. Chem., Int. Ed. 2004, 43, 5400e5402; (c) Gorris, H. H.; Saleh, S. M.;
Groegel, D. B. M.; Ernst, S.; Reiner, K.; Mustroph, H.; Wolfbeis, O. S. Bioconjugate
Chem. 2011, 22,1433e1437; (d) Royo, S.; Gotor, R.; Costero, A. M.; Parra, M.; Gil, S.;
Martinez-Manez, R.; Sancenon, F. New J. Chem. 2012, 36, 1485e1489.
12. This is supported by our calculation result and the reference of Paci, B.;
Schmidt, C.; Fiorini, C.; Nunzi, J.-M.; Arbez-Gindre, C.; Screttas, C. G. J. Chem.
Phys. 1999, 111, 7486e7492.
7. (a) Das, P. K. Chem. Rev. 1993, 93, 119e144; (b) Samanta, A.; Gopidas, K. R.; Das,
P. K. J. Phys. Chem. 1993, 97, 1583e1588; (c) Laursen, B. W.; Krebs, F. C. Chem.
dEur. J. 2001, 7, 1773e1783; (d) Hamacek, J.; Besnard, C.; Mehannac, N.; Lacour,
J. Dalton Trans. 2012, 41, 6777e6782; (e) Kel, O.; Sherin, P.; Mehanna, N.; Laleu,
B.; Lacour, J.; Vauthey, E. Photochem. Photobiol. Sci. 2012, 11, 623e631.
8. (a) Emer, E.; Sinisi, R.; Capdevila, M.; Petruzziello, G.; Vincentiis, D. F.; Cozzi, P.
G. Eur. J. Org. Chem. 2011, 647e666; (b) Nolte, C.; Ammer, J.; Mayr, H. J. Org.
Chem. 2012, 77, 3325e3335; (c) Zhang, Y.; Sheets, M. R.; Raja, E. K.; Boblak, K.
N.; Klumpp, D. A. J. Am. Chem. Soc. 2011, 133, 8467e8469.
9. (a) Hastings, C. J.; Backlund, M. P.; Bergman, R. G.; Raymond, K. N. Angew. Chem.,
Int. Ed. 2011, 50,10570e10573; (b) Rajamani, R.; Gao, J. J. Am. Chem. Soc. 2003,125,
12768e12781; (c) Torre, M. C.; Sierra, M. A. Angew. Chem., Int. Ed. 2004, 43,
160e181.
13. Wang, C.; Chen, Q.; Xu, H.; Wang, Z.; Zhang, X. Adv. Mater. 2010, 22, 2553e2555.
14. Thorley, K. J.; Hales, J. M.; Anderson, H. L.; Perry, J. W. Angew. Chem., Int. Ed.
2008, 47, 7095e7098.
15. Nenajdenko, V. G.; Shevchenko, N. E.; Balenkova, E. S. Chem. Rev. 2003, 103,
229e282.
16. (a) Carrigan, S.; Doucette, S.; Jones, C.; Marzzacco, C. J.; Halpern, A. M. J. Pho-
tochem. Photobiol., A 1996, 99, 29e35; (b) Giri, R. Spectrochim. Acta, Part A 2004,
60, 757e763.
17. Asubiojo, O. I.; Braurnan, J. I. J. Am. Chem. Soc. 1979, 101, 3715e3724.
18. Wang, H.; Webster, C. E.; Perez, L. M.; Hall, M. B.; Gabbai, F. P. J. Am. Chem. Soc.
2004, 126, 8189e8196.
19. Runge, E.; Gross, E. K. U. Phys. Rev. Lett. 1984, 52, 997e1000.
20. Stratmann, R. E.; Scuseria, G. E.; Frisch, M. J. J. Chem. Phys. 1998, 109,
8218e8244.
10. (a) Meehan, T.; Wolfe, A. R.; Negregete, G. R.; Song, Q. Proc. Natl. Acad. Sci. U.S.A.
1997, 94, 1749e1754; (b) Laali, K. K.; Okazaki, T.; Hansen, P. E. J. Org. Chem. 2000,
65, 3816e3828; (c) Laali, K. K.; Hansen, P. E.; Houser, J. J.; Zander, M. J. Chem.
Soc., Perkin Trans. 2 1995, 1781e1790.
21. Cossi, M.; Scalmani, G.; Rega, N.; Barone, V. J. Chem. Phys. 2002, 117, 43e54.