Structure-fluorescence relationship of push-pull 2-phenylbenzothiazole derivatives designed based on the firefly light-emitter

Article abstract of DOI:10.1016/j.tetlet.2018.02.075

6-Dimethylamino-2-phenylbenzothiazole (1a) mimicking the firefly oxyluciferin structure and the derivatives with an electron-withdrawing substituent on the phenyl group were prepared, and their fluorescence properties were investigated in various solvents. 1a showed solvatochromic fluorescence with good fluorescence quantum yields (Φ_f >0.8). The introduction of an electron-withdrawing group led to a red-shift of the emission maximum. In particular, the derivatives with the 2,2-dicyanoethenyl and (1,3-dihydro-1,3-dioxo-2H-inden-2-ylidene)methyl groups showed near-infrared fluorescence in chloroform. In addition, the derivative with the phenylimine moiety showed efficient solid-state fluorescence, resulted from a molecular arrangement inhibiting intermolecular interactions for quenching the fluorescence state in crystals.

Full text of DOI:10.1016/j.tetlet.2018.02.075

Accepted Manuscript
Structure-fluorescence relationship of push-pull 2-phenylbenzothiazole deriv-
atives designed based on the firefly light-emitter
Tomoya Fujikawa, Takuya Uehara, Minoru Yamaji, Takuya Kanetomo,
Takayuki Ishida, Shojiro Maki, Takashi Hirano
PII:
S0040-4039(18)30275-2
https://doi.org/10.1016/j.tetlet.2018.02.075
TETL 49760
DOI:
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
3 February 2018
22 February 2018
26 February 2018
Please cite this article as: Fujikawa, T., Uehara, T., Yamaji, M., Kanetomo, T., Ishida, T., Maki, S., Hirano, T.,
Structure-fluorescence relationship of push-pull 2-phenylbenzothiazole derivatives designed based on the firefly
light-emitter, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.02.075
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Tetrahedron Letters
Structure-fluorescence relationship of push-pull 2-phenylbenzothiazole derivatives
designed based on the firefly light-emitter
Tomoya Fujikawaa, Takuya Ueharaa, Minoru Yamajib, Takuya Kanetomoa,†, Takayuki Ishidaa,
Shojiro Makia and Takashi Hiranoa,*
a Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, Chofu, Tokyo 182-8585,
Japan
b Division of Molecular Science, Graduate School of Science and Engineering, Gunma University, Kiryu, Gunma 376-8515, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
6-Dimethylamino-2-phenylbenzothiazole (1a) mimicking the firefly oxyluciferin structure and
the derivatives with an electron-withdrawing substituent on the phenyl group were prepared, and
their fluorescence properties were investigated in various solvents. 1a showed solvatochromic
fluorescence with good fluorescence quantum yields (Φf >0.8). The introduction of an electron-
withdrawing group led to a red-shift of the emission maximum. In particular, the derivatives
with the 2,2-dicyanoethenyl and (1,3-dihydro-1,3-dioxo-2H-inden-2-ylidene)methyl groups
showed near-infrared fluorescence in chloroform. In addition, it was found that the derivative
with the phenylimine moiety showed efficient solid-state fluorescence, resulted from a
molecular arrangement inhibiting intermolecular interactions for quenching the fluorescence
state in crystals.
Available online
Keywords:
Firefly oxyluciferin
Benzothiazole
Fluorophore
Solvatochromism
Push-pull structure
2009 Elsevier Ltd. All rights reserved.
Fireflies efficiently produce bioluminescent light with various
colors from green to red.1 The bioluminescence is caused by the
enzymatic reaction of firefly luciferin with ATP and O2 to
produce oxyluciferin (OLH) and light. The light emitting center
of the reaction is the keto-phenolate anion of OLH (OL−) in the
excited singlet (S1) state (Scheme 1).2 To confirm the reaction
mechanism, the spectroscopic property of OL− were clarified
based on that of the phenolate anion of 5,5-dimethyl OLH
(Me2OLH, Scheme 1).3 Because OL− is a solvatochromic
fluorophore with relatively high quantum yields, OL− is an
attractive prototype for designing new fluorophores. The
characteristic fluorescence property of OL− is originated from the
molecular structure consisted of the electron-donating and
withdrawing moieties (Scheme 1). The significance of the
electronically push-pull structure in OL− was supported by the
spectroscopic property of 6’-dimethylamino analogue
Me2NMe2OL (Scheme 1).4 We, thus, planned to design
benzothiazoles mimicking the push-pull structures of OL− and
Me2NMe2OL, while the benzothiazole ring has been widely used
for various fluorophore designs including solvatochromic
fluorophores.5 To tune spectroscopic properties of benzothiazole
fluorophores for various usages, it is needed to reveal
relationship between structure and fluorescence property of the
derivatives. For this purpose, we investigated here the
spectroscopic properties of 2-phenylbenzothiazoles 1 (Scheme 1)
with push-pull structures. In the course of the study, it was found
that one of the derivatives showed a moderate solid-state
fluorescence.
basic structure with an electron-donating moiety similar to
Me2NMe2OL. To introduce various electron-withdrawing
substituents to the 2-phenyl group in 1a, aldehyde 1b was
synthesized as a push-pull derivative. Then, push-pull derivatives
1c-e were prepared by condensation reactions with 1b.
Scheme 1. Structures of firefly oxyluciferin phenolate anion
(OL−), 5,5-dimethyloxyluciferin analogues (Me2OLH and
Me2NMe2OL), and push-pull 2-phenylbenzothiazole derivatives
1a-f.
Spectroscopic properties of 1a-f were investigated in solutions
of cyclohexane, chloroform, acetonitrile and methanol. Figure 1
shows the fluorescence spectra while the absorption spectra are
We adopted 6-dimethylamino-2-phenylbenzothiazole 1a as a

2
Tetrahedron
deposited in Supplementary data (SD). The numerical data are
Table 1. Fluorescence properties of 1a-f in various solvents at
listed in Tables 1 for the fluorescence and in Table S1 in SD for
the absorption. Phenyl derivative 1a showed a solvent-dependent
shift of fluorescence emission maxima (λf) with good quantum
yields (Φf) over 0.8, while electronic absorption maxima (λab) of
1a showed a small solvent-dependency. The λf values were red-
shifted with an increase in the solvent polarity to show a
variation in the range of 393 to 483 nm, indicating that the S1
state of 1a has electronically polarized character more than the
ground (S0) state.6 Introduction of only the pushing
dimethylamino group on the benzothiazole moiety caused push-
pull property in the π-electronic structure although 1a has no
pulling substituent on the 2-phenyl group. The λab and λf values of
1b-f in cyclohexane are red-shifted compared to those of 1a.
Similar to 1a, 1b-f showed solvent-dependent variations of the λf
values in contrast to a small solvent-dependency of the λab values.
The substituents on the 2-phenyl group of 1b-f were expected to
affect the spectroscopic properties by their electron withdrawing
properties together with expansion of the π-conjugated system. In
fact, the electron withdrawing strengths were quantified by using
the Hammett σp values for the formyl (0.42) in 1b, 2,2-
dicyanoethenyl (0.84) in 1c and (phenylimino)methyl (0.42) in
1e.7 At the same σp value for the formyl and (phenylimino)methyl
groups, the λf values of 1b and 1e in cyclohexane, chloroform,
and acetonitrile were similar to each other, while the Φf values of
1b were greater than those of 1e. Aldehyde 1b showed a blue-
shifted fluorescence spectrum in methanol, suggesting that the
formyl group of 1b gave a hemiacetal. Interestingly, 1e showed a
good Φf value (0.72) only in acetonitrile. Derivatives 1c and 1d
showed red-shifted λf values upon changing cyclohexane to
chloroform, while they showed no fluorescence in acetonitrile
and methanol. In particular, the λf values in chloroform reached
the near-infrared region. The 2,2-dicyanoethenyl in 1c and (1,3-
dihydro-1,3-dioxo-2H-inden-2-ylidene)methyl groups in 1d
induce a strongly polarized character of the S1 states lead to a
preferential nonradiative decay in polar solvents. Hydrazone 1f
showed lower Φf values than imine 1e, and a fluorescence
spectral change of 1f depending on the solvents was smaller than
that of 1e.
298 K.
Compd.
λf / nm (Φf)a
C6H12
CHCl3
CH3CN
CH3OH
1a
1b
1c
1d
1e
1f
393, 413 (0.84)
443 (0.84)
475 (0.83)
483 (0.94)
444, 469 (0.80)
526, 562 (0.85)
535, 572 (0.13)
445, 469 (0.057)
444, 469 (0.023)
550 (0.85)
683 (0.64)
727 (0.35)
534 (0.12)
626 (0.66)
N/Ab
N/Ab
494 (0.10)
N/Ab
N/Ab
610 (0.72)
639 (0.067)
517 (0.057) 541 (0.067) 545 (0.026)
a Emission maximum (λf) and quantum yield (Φf) in parenthesis. bNot
observed.
To understand the photophysical properties of the S1 states of
1a-f, fluorescence lifetimes (τf) of 1a-f in cyclohexane were
measured (Table 2). The decay profiles of the fluorescence are
deposited in Figure S2 in SD. The estimated rate constants (kf) of
the fluorescence emission processes for 1a-d were similar among
them. Introduction of the (1,3-dihydro-1,3-dioxo-2H-inden-2-
ylidene)methyl group causes an increase in the rate constant (knr)
of nonradiative decay, resulting in a small Φf value of 1d. The S1
states of 1e and 1f showed the kf values smaller than those of 1a-
d, resulting in the less fluorescent property of 1e and 1f.
Table 2. Photophysical properties of 1a-f in cyclohexane at
295 K.
Compd.
τfa / ns
2.1
Φfb
kfc/108 s−1
4.0
Φnr
knre/ 108 s−1
0.77
0.80
0.48
22
d
1a
0.84
0.80
0.85
0.12
0.057
0.023
0.16
0.20
0.15
0.88
0.94
0.98
1b
2.5
3.2
1c
3.1
2.7
1d
0.41
2.2
2.9
1e
0.26
4.3
1f
2.0
0.12
4.9
aFluorescence lifetime. bFluorescence quantum yield. cRate constant of the
fluorescence emission process determined by kf = Φf τf−1. dQuantum yield of
nonradiative decay processes determined by Φnr = 1−Φf. eRate constant of
nonradiative decay processes determined by knr = Φnr τf−1
.
To evaluate the correlation between the spectroscopic and π-
electronic properties of 1a-f, DFT and TD-DFT calculations of
1a-f were carried out with the B3LYP/6-31G(d) method8 (Table
3). The S0→S1 transitions of 1a-f correspond to π,π* transitions
with main contribution of the HOMO→LUMO configuration.
The λab values of 1a-f in cyclohexane and the wavelengths
estimated from the energies of the S0→S1 transitions (λtr)
increased with a decreased of the energy differences between
HOMO and LUMO (ΔEH−L). The HOMO and LUMO levels of
1b-e were lower than those of 1a, supporting that the substituents
on the 2-phenyl group effectively act as the electron withdrawing
groups. Electronic distributions of the HOMOs and LUMOs of
1a-e localized in the benzothiazole and 2-phenyl moieties,
respectively (Figure S3 in SD), resulting in enhanced polarized
character of the S1 states generated by the S0→S1 transitions. The
HOMO energy level of 1f was higher than that of 1a, and
electrons in the HOMO of 1f were distributed throughout the π-
electronic system. Thus, the phenylhydrazone moiety mainly
works for expanding the π-conjugated system. The oscillator
strength (f) for the S0→S1 transition of 1f was larger than those of
1a-e. This result supports the observation that the molar
absorptivities of 1f are larger than those of the other derivatives
Figure 1. Fluorescence spectra of 1a (A), 1b (B), 1c (C), 1d (D),
1e (E), and 1f (F) in cyclohexane (black), chloroform (blue),
acetonitrile (green), and methanol (red) at 298 K.

(Table S1 in SD).9 In contrast to this result, the kf value of 1f
together with that of 1e were less than those of 1a-d, suggesting
that a structural change in the C=N bonds of 1e and 1f in the S1
states decelerates the radiative process. In fact, the LUMOs of e
1e and 1f have nodal planes at the C=N bonds (Figure S3 in SD).
In
conclusion,
we
prepared
the
push-pull
2-
phenylbenzothiazoles 1a-f, and clarified the spectroscopic
properties. Phenyl derivative 1a shows solvatochromic
fluorescence with good Φf values in various solvents. The
introduced electron withdrawing groups in 1b-f lead to red-shifts
of the λf values compared to 1a. In particular, 1c and 1d show
near-infrared fluorescence in chloroform, and have ON/OFF
fluorescence functionality by switching polar and less polar
solvents. The Φf values of imine 1e and hydrazone 1f are less
than those of aldehyde 1b. Imine 1e shows efficient fluorescence
in the solid state, because the crystal packing inhibits a structural
change of 1e in the S1 state and the twisted phenyl group of the
imine moiety interferes intermolecular interactions for quenching.
Further fine tuning of the push-pull structure is in progress for
designing luminescent materials of soft crystals.
Table 3. Calculation data of 1 in vacuum with DFT and TD-
DFT using B3LYP/6-31G(d).
a
Compd.
HOMO
/eV
LUMO
/eV
ΔEH−L
/eV
λtr/nm (f) b
configurationc
1a
1b
1c
1d
1e
1f
−4.99
−1.25
3.74
359 (0.61) H → L (0.70)
428 (0.59) H → L (0.70)
537 (0.66) H → L (0.71)
531 (0.76) H → L (0.71)
433 (0.97) H → L (0.70)
423 (1.45) H → L (0.70)
−5.22
−5.40
−5.16
−5.06
−4.82
−2.10
−2.92
−2.62
−1.93
−1.64
3.12
2.48
2.54
3.13
3.18
Acknowledgments
a Energy difference between HOMO and LUMO. b Wavelength estimated
from the energy of the S0 → S1 transition. Oscillator strengths are in the
parentheses. c Configuration of excitation. Coefficients are in the parentheses.
H and L denote HOMO and LUMO, respectively.
This work was supported by JSPS KAKENHI Grant
(JP17H06371). We thank the Information Technology Center of
UEC for technical assistance in computing DFT calculations.
References and notes
It was found that only imine 1e showed solid state
fluorescence with the λf value at 600 nm (Fig. 3) with a moderate
Φf value (0.49). The crystal structure of 1e indicated that dimeric
units (A/A’ pairs) with a head-to-tail orientation make stair-like
stacked structures (Fig. 4). Imine 1e has an elongated shape, and
the long axes of the two molecules in the unit are nearly parallel.
Because the phenyl ring of the imine moiety is twisted at 30° in
the molecular structure of 1e, electronic interactions for
quenching the fluorescence state may be inhibited in the dimers.10
Concerning to 1e, the packing in the crystals would inhibit a
structural change in the C=N bond in the S1 state, resulting in
efficient solid-state fluorescence.
1.
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Figure 3. Fluorescence spectra of 1e in the solid state at 298 K.
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Valeur, B.; Berberan-Santos, M. N. In Molecular Fluorescence:
Principles and Applications, 2nd ed., Wiley-VCH: Weinheim,
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A
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A
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A'
A'
top view
(c)
A'
A
Figure 4. The crystal structures of 1e; the side views (a) and (b),
and the top view (c) of the stair-like stacked structure. A and A’
designate molecules making the A/A’ dimeric units.

4
Tetrahedron
Supplementary Material
* Corresponding author. E-mail address: thirano@uec.ac.jp (T.
Hirano).
Supplementary data (organic synthesis, UV-vis absorption and
fluorescence life time measurements, X-ray crystallographic data
for CCDC 1820886, and DFT calculation results with tables of
atom coordinates for the optimized geometries for compounds
1a-f) associated with this article can be found, in the online
version, at https://doi.org/###
†
Present address: Department of Chemistry, Faculty of
Science Division I, Tokyo University of Science, Tokyo 162-
8601, Japan.

Highlights
Structure-fluorescence relationship of
push-pull 2-phenylbenzothiazole
derivatives designed based on the firefly
light-emitter
Tomoya Fujikawa, Takuya Uehara, Minoru
Yamaji, Takuya Kanetomo, Takayuki Ishida,
Shojiro Maki and Takashi Hirano
• 2-Phenylbenzothiazoles were prepared by
mimicking the firefly oxyluciferin structure.
• Dimethylamino derivative shows solvatochromic
fluorescence with good quantum yields.
• Derivatives with a strong electron-withdrawing
group show near-infrared fluorescence.
• Phenylimine derivative shows efficient solid-state
fluorescence.

6
Tetrahedron Letters
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Structure-fluorescence relationship of push-pull 2-
phenylbenzothiazole derivatives designed based on
the firefly light-emitter
Leave this area blank for abstract info.
Tomoya Fujikawa, Takuya Uehara, Minoru Yamaji, Takuya Kanetomo, Takayuki Ishida, Shojiro Maki and
Takashi Hirano
electron donating electron withdrawing
Me N
6
2
S
N
moiety
moiety
2
R
O
6'
O
N
S
S
N
O
CH
1a: R = H
1b: R = CHO
1d: R =
O
firefly oxyluciferin
keto-phenolate anion
1c: R = CH=C(CN)
2
1e: R = CH=NPh
1f: R = CH=NNHPh