Acid-responsive fluorescent compounds based on nitro-group-substituted L-shaped pentacycles, pyrrolo[1,2- a ][1,8]naphthylidines

Article abstract of DOI:10.1021/ol501226x

Acid-responsive fluorescent compounds were prepared by introducing a nitrophenyl group to L-shaped pentacycles with a pyrrolo[1,2-a][1,8] naphthylidine backbone. These compounds show almost no fluorescence under neutral conditions, but emit green to orange fluorescence upon addition of trifluoroacetic acid. Acid titration experiments and NMR spectroscopy, plus DFT calculations, show that formation of a pyridinium cation species is responsible for the appearance of fluorescence.

Full text of DOI:10.1021/ol501226x

Letter
pubs.acs.org/OrgLett
Acid-Responsive Fluorescent Compounds Based on Nitro-Group-
Substituted L‑Shaped Pentacycles, Pyrrolo[1,2‑a][1,8]naphthylidines
Kotaro Tateno,† Rie Ogawa,† Ryota Sakamoto,‡ Mizuho Tsuchiya,‡ Takashi Otani,*,†,§
and Takao Saito*,†
†Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
‡Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
§Research Center for Chirality, Research Institute for Science & Technology, Tokyo University of Science, 1-3 Kagurazaka,
Shinjuku-ku, Tokyo 162-8601, Japan
S
* Supporting Information
ABSTRACT: Acid-responsive fluorescent compounds were prepared by
introducing a nitrophenyl group to L-shaped pentacycles with a
pyrrolo[1,2-a][1,8]naphthylidine backbone. These compounds show
almost no fluorescence under neutral conditions, but emit green to
orange fluorescence upon addition of trifluoroacetic acid. Acid titration
experiments and NMR spectroscopy, plus DFT calculations, show that
formation of a pyridinium cation species is responsible for the appearance
of fluorescence.
mall π-conjugated molecules have attracted much attention
in the research fields of both fundamental and applications
The nitro group is widely recognized as a strong quencher of
fluorescent dyes. Indeed, even if the nitro group is not directly
conjugated to the fluorophore but is located at a proximal
position, such compounds are usually nonfluorescent. Nitro
groups are strongly electron withdrawing and thus greatly lower
the lowest unoccupied molecular orbital (LUMO) energy level
of aromatic compounds. Therefore, in the nitroaryl-substituted
fluorophore, the intramolecular photoinduced electron transfer
(PeT) process from the excited fluorophore to the electron-
deficient nitro aryl moiety (donor-excited PeT; d-PeT)
dominates, which results in quenching of the fluorescence.4
Indeed, nitro-substituted fluorescent compounds are still rare
even now.5 On the other hand, Nagano et al. demonstrated that
an appropriate manipulation of the relative free energy change
of the PeT process (ΔGeT) may realize a fluorescent nitro-
substituted compound.4 In this context, we envisioned that
introduction of a nitroaryl group to an analyte-responsive
fluorophore would create a simple and diverse fluorescence
switching system. Thus, we have designed nitrophenyl-group-
substituted, acid-responsive fluorescent compounds6 based on
our L-shaped pyrrolo[1,2-a][1,8]naphthylidine compounds.
We anticipated that the introduction of nitrophenyl group(s)
would quench the fluorophore of the pentacycles and that
protonation of the pyridine site would turn on the fluorescence
as a consequence of drastically lowering the LUMOs of the
fluorophore.7 Herein, we report their synthesis and the
characterization of their photophysical properties.
S
chemistry. While linear polycyclic ring-fused aromatic com-
pounds such as pentacene derivatives have been investigated
extensively,1 L-shaped polycyclic ring-fused aromatic com-
pounds containing the 6−6−6−5−6 ring system as a corner
unit have been studied to a lesser extent.2 Recently, we reported
the synthesis of L-shaped penta- to heptacyclic compounds
(e.g., 2) having a pyrrolo[1,2-a][1,8]naphthylidine backbone
via fully intramolecular [2 + 2 + 2] cycloaddition of
bis(propargyl phenyl)carbodiimides 1 and naphthyl analogues
followed by oxidative aromatization (eq 1). In particular, the L-
shaped molecules contain spatially separated frontier molecular
orbitals (FMOs) and they are highly fluorescent, even in polar
solvents such as methanol (Figure 1).3
Scheme 1 depicts the synthesis of aryl-group-substituted L-
shaped compounds 5−7. Initially, 2a was brominated with N-
Figure 1. (a) HOMO, (b) LUMO, and (c) photograph under
irradiation with UV light (λ = 365 nm) in CH2Cl2 of 2b.
Received: April 29, 2014
© XXXX American Chemical Society
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Letter
reaction of 2,5-dibromide 4 provided the expected biscoupling
product 6 in moderate yield along with monocoupling product
7.
Scheme 1. Synthesis of Aryl-Substituted L-Shaped
Compounds
Table 1 summarizes some photophysical properties of the L-
shaped compounds (2a and 5−7) under neutral conditions,
and their fluorescence spectra are depicted in Figure S17. The
spectral data show that installation of an aryl group onto the 5-
position results in only a ca. 10 nm red shift, suggesting
ineffective conjugation between the aryl group and the
backbone. With regard to fluorescence properties, both phenyl-
and p-methoxyphenyl-substituted compounds 5a and 5b
strongly emit with high quantum yields and exhibit a similar
fluorescence lifetime (6.4 ns) to 2a (6.7 ns). Meanwhile, all
nitrophenyl-substituted compounds (5c, 5d, 6, and 7) exhibit
very weak emission, demonstrating the high fluorescence
quenching ability of the nitrophenyl group.
To evaluate the effects of acid on the photophysical
properties of nonfluorescent nitrophenyl-substituted com-
pounds 5c, 5d, 6, and 7, their electronic absorption spectra
and fluorescence spectra excited at two different wavelengths,
corresponding to the maximum absorption bands of neutral
(428−441 nm) and acidic compounds (500−510 nm), were
measured using a trifluoroacetic acid (TFA) titration.8 The
results are summarized in Table 2. In 5c, 5d, and 6, with
increasing amounts of TFA, a color change from green to
orange is observed: the original absorption bands at around 430
and 460 nm diminished and a new distinct band formed at
longer wavelengths of <500 nm (e.g., 5d, Figure 2a). In this
process, a well-defined isosbestic point was observed at around
460 nm, suggesting the production of one major protonated
product. Importantly, addition of TFA turns on fluorescence,
producing new distinct bands at ca. 590 and 630 (sh) nm when
excited at 510 nm (e.g., 5d, Figure 2b). In particular, 6, which
contains two nitrophenyl groups, exhibited fluorescence upon
addition of TFA (Figures S20 and S21). Meanwhile, in the
absorption spectrum of 7 upon addition of TFA, although a
well-defined isosbestic point was observed at 475 nm, distinct
absorption maxima were not observed (Figure 2c). When 7 was
excited at 440 nm after addition of TFA (Figure 2d), 7 showed
the highest quantum yield of 0.34 among the protonated L-
shaped compounds that we measured. The fluorescence
lifetime measurements revealed that protonated 7 features
relatively a long lifetime for organic fluorophores. On the other
hand, the fluorescence of protonated 5c, 5d, and 6 decays
biexponentially: Its contributions depend on the excitation
wavelength, suggesting dual fluorescence.9 We confirmed that
emission induced by TFA is quenched by addition of base and
this process is reversible: neutralization with triethylamine
(Figures S22 and S23) or with aqueous sodium hydrogen
a
Table 1. Photophysical Properties of L-Shaped Compounds
b
c
λem
Stokes shift
τs
b
compd
λmax (nm)
(nm)
(cm−1
)
ΦF
(ns)
d
d
d
d
d
d
d
d
2a
5a
5b
5c
5d
6
404, 425, 451
479, 512
496, 524
514
1296
1578
2237
1970
2097
1743
2096
0.71
0.72
0.89
6.72
6.35
6.36
−
d
412, 433, 460
d
412, 435, 461
d
e
409, 432, 456
501, 512
503
−
d
e
409, 428, 455
−
−
−
−
d
e
417, 440, 465
506
d
e
7
415, 437, 464
514
−
−
a
b
c
In CH2Cl2. Excitation at λmax. Fluorescence lifetime excited at 405
d
e
nm. Shoulder peak. ΦF < 0.01.
bromosuccinimide (NBS) to perform cross-coupling reactions.
When 2a was treated with an equimolar amount of NBS in
acetonitrile at room temperature, the reaction occurred highly
selectively on the 5-position to furnish 3 in 99% yield. When 2a
was treated with 3 equiv of NBS under the same conditions,
2,5-dibrominated compound 4 was formed in 65% yield. With
the bromide 3 and dibromide 4 in hand, we carried out the
Suzuki−Miyaura coupling reaction to install aryl groups. The
reactions of 3 with phenyl, p-methoxyphenyl, and m-nitro-
phenyl boronic acid delivered the corresponding aryl-
substituted compounds 5a, 5b, and 5d in moderate yields,
while the reaction with p-nitrophenyl boronic acid afforded the
product 5c in a relatively low yield of 43%. The coupling
a
Table 2. Photophysical Properties of Protonated L-Shaped Compounds
excited at 428−441 nm
excited at 500−510 nm
b
b
c
d
c
e
f
f
g
d
g
e
compd
λmax (nm)
λem (nm)
ΦF
τs1 (ns)
A1
τs2 (ns)
A2
λem (nm)
ΦF
τs1 (ns)
A1
τs2 (ns)
A2
h
h
h
h
h
h
5c+H
5d+H
6+H
472, 500, 545
526, 579
0.06
0.06
0.05
0.34
1.71
1.05
1.88
0.33
0.07
0.54
0.02
0.01
19.63
16.75
17.86
15.03
0.93
0.46
0.98
0.99
591, 629
0.07
0.07
0.06
1.77
1.09
0.73

0.77
0.56
0.52

14.47
20.19
18.70

0.23
0.44
0.48

h
h
473, 501, 540
511, 531, 582
589, 625
h
h
h
479, 510, 551
510, 534
539, 601
h
i
7+H
465, 507, 549
496, 515


a
b
Equivalents of TFA: 5c+H, 2.3 × 105; 5d+H, 2.3 × 105; 6+H, 5.6 × 104; 7+H, 1.2 × 105. Excitation at 432, 428, 441, 440 nm for 5c+H, 5d+H,
c
d
e
f
6+H, 7+H, respectively. Fluorescence lifetime excited at 405 nm. Contribution of τs1. Contribution of τs2. Excitation at 500, 501, 510, 507 nm
for 5c+H, 5d+H, 6+H, 7+H, respectively. Fluorescence lifetime excited at 470 nm. Shoulder peak. ΦF < 0.01.
g
h
i
B
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Figure 2. (a) UV−vis and (b) fluorescence spectra of 5d and (c) UV−vis and (d) fluorescence spectra of 7 in dichloromethane ((a) 20 μM, (b) 2
μM, (c) 20 μM, (d) 0.4 μM) on addition of different amounts of TFA (vol %).
Figure 3. 1H NMR of 5d in CF3CO2D/CDCl3: (a) 0 vol % and (b) 3 vol % of CF3CO2D. (c) Numbering of compound 5d. (d) Structure of 5d+H.
carbonate turned off the fluorescence without degradation of
5d and 7.
To identify the structure of the protonated compound,
quantitative 1H NMR titration experiments were carried out on
5d in CDCl3. As shown in Figure 3 and Table S1, upon
addition of CF3CO2D (0 to 3.0 vol %), H-2 showed the largest
upfield shift (9.86 to 8.60 ppm) and H-9 displayed the largest
downfield shift (8.39 to 8.78 ppm). In contrast, signals of the
nitrophenyl group hardly shifted. These observations strongly
support the predominant formation of structure 5d+H (Figure
3d) by protonation at the 14-nitrogen atom upon treatment
with TFA, which turns on fluorescence.
To elucidate the electronic structure of nitrophenyl-
substituted L-shaped compounds 5d, 6, and 7, density
functional theory (DFT) calculations at the B3LYP/6-31G**
level were performed on the neutral and 14-N-protonated
(pyridinium) forms (Figures 4 and S25). For all compounds in
both neutral and acidic forms, the HOMOs and LUMOs are
specially separated and the HOMOs reside primarily on the
indole-containing sides of the skeleton. As expected, the
LUMOs are localized on the m-nitrophenyl group in the neutral
compounds, implying an efficient intramolecular PeT process
from the excited fluorophore to the nitrophenyl group. In
contrast, in their protonated forms, the LUMOs reside
primarily on the pyridine-containing sides of the skeleton,
which is relevant to highly fluorescent 2 (Figure 1). Thus, we
conclude that the change in position of the LUMOs is
responsible for the turn-on of the fluorescence of 5c, 5d, 6, and
7.
In conclusion, we have succeeded in functionalizing the 2-
and 5-positions of L-shaped pentacycles 2 via bromination and
Suzuki−Miyaura coupling. Thus, synthesized nitrophenyl-
substituted L-shaped pentacyclic compounds behave as a
fluorescent switch by acid: they are nonfluorescent in neutral
conditions, but become emissive by addition of acid. The
resulting fluorescence is quenchable by neutralization with base,
and this process is reversible. This constitutes a rare example of
Figure 4. HOMOs and LUMOs of 7 and its 14-N protonated cation
[7+H]+.
a fluorescent dye containing a nitro group, which will
contribute to new designs of fluorescent dyes.
ASSOCIATED CONTENT
* Supporting Information
■
S
1
Experimental procedures, characterization data, copies of H
and 13C NMR spectra of all new compounds, photophysical
properties, and theoretical calculations. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: totani@rs.tus.ac.jp (T.O.).
C
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Letter
A.; Ihmels, H.; Pace, T. C. S.; Schnurpfeil, A.; Waidelich, M.; Yihwa, C.
J. Phys. Chem. A 2007, 111, 1036.
*E-mail: tsaito@rs.kagu.tus.ac.jp (T.S.).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported partly by Grants-in-Aid from MEXT
of Japan (No. 26107510, area 2406 [All Nippon Artificial
Photosynthesis Project for Living Earth]). M.T. appreciates
JSPS research fellowships for young scientists.
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