Quadrupolar benzobisthiazole-cored arylamines as highly efficient two-photon absorbing fluorophores

Article abstract of DOI:10.1021/ol503137p

A computer-aided design of novel D-π-A-π-D styrylamines containing five isomeric benzobisthiazole moieties as the electron-accepting core has revealed the linear centrosymmetric benzo[1,2-d:4,5-d′]bisthiazole as the most promising building block for engin

Full text of DOI:10.1021/ol503137p

Letter
pubs.acs.org/OrgLett
Quadrupolar Benzobisthiazole-Cored Arylamines as Highly Efficient
Two-Photon Absorbing Fluorophores
Peter Hrobarik,*,† Veronika Hrobarikova,† Vladislav Semak,‡,§ Peter Kasak,∥ Erik Rakovsky,⊥
́
́
́
́
́
Ioannis Polyzos,# Mihalis Fakis,*,# and Peter Persephonis#
†Institute of Chemistry, Technical University of Berlin, Strasse des 17. Juni 135, D-10623 Berlin, Germany
‡Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fed
erale de Lausanne, CH-1015 Lausanne, Switzerland
cesta 9, SK-84541 Bratislava, Slovakia
́
́
§Polymer Institute, Slovak Academy of Sciences, Dubravska
́
́
∥Center for Advanced Materials, Qatar University, P.O. Box 2713, Doha, Qatar
⊥Department of Inorganic Chemistry, Faculty of Natural Sciences, Comenius University, SK-84215 Bratislava, Slovakia
#Department of Physics, University of Patras, GR-26504 Patras, Greece
S
* Supporting Information
ABSTRACT: A computer-aided design of novel D−π−A−π−D
styrylamines containing five isomeric benzobisthiazole moieties as
the electron-accepting core has revealed the linear centrosymmetric
benzo[1,2-d:4,5-d′]bisthiazole as the most promising building block
for engineering chromophores displaying high two-photon absorp-
tion (TPA) in the near-IR region, as also confirmed experimentally.
The ease of synthesis of quadrupolar derivatives thereof, combined
with extraordinarly high TPA action cross sections (δTPAΦf > 1500
GM), makes these heteroaromatic systems particularly attractive as
diagnostic agents in 3D fluorescence imaging.
ring onto photochemically stable, π-deficient benzothiazole
might offer a useful design strategy for enhancing TPA.
While a reasonable number of benzobisthiazole dyes has been
reported to date, predominantly in the form of variously
substituted 2,6-di(hetero)arylbenzo[1,2-d:4,5-d′]bisthiazoles,6,9
TPA properties of these derivatives have remained unexplored.
To the best of our knowledge, there was only one attempt to
characterize a benzobisthiazole-containing polymer (trans-PBT),
which was however unsuccessful due its limited solubility.10
Synthesis and spectral properties of bis(styryl)benzobisthiazole
dyes, which may be viewed as analogues of the previously
characterized benzothiazole fluorophores and could thus allow a
direct comparison of these systems, were not reported so far.
Additionally, two thiazole rings could be connected to the central
benzene in several different ways, resulting in five constitutional
isomers (Scheme 1), namely, benzo[1,2-d:5,4-d′]bisthiazole (1),
benzo[1,2-d:4,5-d′]bisthiazole (2), benzo[1,2-d:4,3-d′]-
bisthiazole (3), benzo[2,1-d:3,4-d′]bisthiazole (4), and benzo-
[1,2-d:3,4-d′]bisthiazole (5).
hiazole and thiazole-annulated scaffolds are among the
Tmost prominent building blocks in chromophores with
potential applications in fields such as nonlinear optics
(NLO),1−4 organic light-emitting diodes,5 organic field-effect
transistors,6 and dye-sensitized solar cells.7 Most of these
applications rely on the electron-withdrawing ability of the
thiazole ring, which is frequently used as the edge substituent.
Recently, we demonstrated use of the 1,3-benzothiazole moiety
as an electron-accepting core in quasi-quadrupolar fluorophores
with the D−π−A−π−D setup, which display high two-photon
absorption (TPA).2 This feature enables the activation of
chemical and photophysical processes by low-energy near-IR
excitation, which is beneficial in deeper light penetration through
materials or living tissues as compared to excitations by visible or
UV light (lower-energy photons are also less likely to cause
damage outside the focal volume). Dependency of the TPA rate
on the square of the incident laser light intensity allows for better
control and higher spatial resolution, which is exploited in
microfabrication, high-resolution imaging and 3D data storage.
To fully benefit from the advantages of the TPA process and to
meet specific application requirements, a quest for dyes
possessing larger TPA cross sections (δTPA) in a suitable
excitation window, in conjunction with additional properties,
such as high emission quantum yields, excelent photostability,
and good cell permeability (keeping the molecular size as small as
possible), is still a hot topic inmaterial science.8 In thisrespect, we
were curious as to whether the introduction of a second thiazole
To evaluate the influence of an additional thiazole ring and the
effect of positional isomerism on TPA properties, a series of linear
and V-shaped quadrupolar benzobisthiazole-derived dyes,
bearing N,N-dialkylaniline and triphenylamine moieties as the
electron-donating groups, have been investigated in this work
(Scheme 1).
Received: October 27, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol503137p | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Structure of the Parent Benzobisthiazoles (1−5)
a
and Quadrupolar Chromophores Q1−Q5
Figure 1. Frontier molecular orbitals in Q2-Ph.
relative position of two thiazole rings on the central benzene plays
a key role.
Irrespective of the R substituent, benzobisthiazole dyes are
ranked according to increasing TPA cross sections as follows: Q5
< Q4 < Q1 < Q3 < Q2, with a difference of >900 GM between the
least and the most efficient TPA dye! The additional thiazole ring
has a beneficial effect only in the case of Q2-Ph, whereas δTPA of
Q2-Me is virtually identical with its benzothiazole analogue.
Using a three-state model,14 the great variation of δTPA within the
isomeric benzobisthiazole series and the strikingly lower TPA
cross sections of Q1 and Q3−Q5 as compared to the
benzothiazole congeners can be primarily attributed to the
differerent excited-to-excited state transition moments μ12 and
the somewhat larger detuning energies (E1 − E2/2) in the former
series (cf. Table S5, Figure S1 in SI for more detailed analysis of
the observed trends). In contrast, the superiority of dyes derived
from benzobisthiazole 2 over its isomers is related to a favorable
combination of all parameters involved in the three-state model
(the highest transition dipole moments μ01 and μ12 and the
reduced detuning energy). This results from the most efficient
coupling between two branches connected to the heteroaromatic
ring with two nitrogen and two sulfur atoms in mutual para
position, respectively. The lowest μ12 values are computed for
dyes derived from l and 5, where two N and two S atoms,
respectively, are in unfavorable meta position. Benzobisthiazoles
3 and 4 are intermediate cases, where one of the N,N or S,S
couples is positioned para, while the other one is placed in the
ortho position. Substantially higher δTPA of Q3 over Q4 indicate
more important placement of two azole N atoms into a mutual
para position, compared to the two sulfur atoms.
To prove these findings, quadrupolar chromophores contain-
ing benzobisthiazoles 2 and 3 as the central moiety were prepared
and subjected to measurements of δTPA via a two-photon excited
fluorescence (TPEF) method with femtosecond laser excitation
at wavelengths of 750−850 nm. The synthesis of other isomers
was not attempted due to their anticipated lower TPA activity.
A key step in the synthesis of Q2 and Q3 was a double aldol-
type condensation between 4-donor-substituted benzaldehydes
and benzobisthiazoles with two active methyl groups (2-Me or 3-
Me) under strongly basic conditions (Scheme 2). The starting 2-
Me was prepared by a condensation of the commercially available
2,5-diaminobenzene-1,4-dithiol dihydrochloride (6) with acetic
anhydride in the presence of triethylamine as a cosolvent. Ac2O
was efficient enough in the one-step formation of a
benzobisthiazole scaffold and the use of orthoesters and rare-
earth metal triflates as catalysts was not necessary, albeit the latter
method provides the desired product in somewhat higher yield.15
3-Me was prepared from 6-amino-2-methylbenzothiazole (7),2
which was first reacted with KSCN and Br2 to afford the
thiocyanate 8. This was consequently transformed in one pot to
3-Me via reduction with Na2S and ring-closing reaction between
a
R substituents in the arylamine part are indicated by the suffix at the
end of the dye label. TPA cross sections, δTPA (S0 → S2) given in GM
(1 GM = 1 × 10−50 cm4·s·photon−1), excitation energies En, and
ground-to-excited and excited-to-excited state transition dipole
moments μ01 and μ12, respectively, were computed at the CAM-
B3LYP/6-311++G** level using a PCM solvation model (toluene as
the solvent).
A computer-aided prescreening of chromophores with the
highest TPA activity has been done by means of the quadratic
response time-dependent DFT method, employing the
CAM‑B3LYP functional and a polarizable continuum model
(PCM) accounting for bulk solvent effects, as implemented in the
Dalton program.11 δTPA associated with the five lowest excitations
are collected in Supporting Information, SI. Since we found a
strong dependency of the TPA cross sections on the
conformation of the two styryl branches with respect to a
heteroaromatic core (s-cis and/or s-trans arrangement), all low-
energy conformers were included in our calculations, and the
results were Boltzmann-averaged.12 Note that δTPA values for
different conformers of the same molecule vary, in some cases, by
several hundreds of GM, underlining the necessity to consider
conformational flexibility in rational design of TPA-active
materials.13
In all cases, the highest δTPA with maxima positioned in the red
and near-IR region (En < 4.0 eV) are related to the excitation from
the ground state to the second excited state (S0 → S2), and the
corresponding TPA cross sections are reported in Scheme 1. The
S0 → S2 transition takes place from both HOMO−1 and HOMO
to the LUMO and LUMO+1 (Figure 1 and Table S3) and
corresponds to a charge transfer from the arylamine edges to the
π-deficient heteroaromatics. Although all five benzobisthiazoles
possess stronger electron-accepting ability than the parent
benzothiazole, as indicated by NPA charge analysis (Table S4),
this feature does not necessarily guarantee a higher NLO
response, and no relationship between δTPA and the acceptor
strength of the π-deficient core can be established. Instead, the
B
dx.doi.org/10.1021/ol503137p | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Synthetic Routes to Fluorophores Q2 and Q3
Figure 3. UV−vis absorption (solid line) and emission (dashed line)
spectra of Q2-Ph (c = 10 μM) in toluene, THF, acetone, and DMSO
(left). Fluorescence of Q2-Ph in various organic solvents (right).
Figure 4. TPA action cross sections δTPA·Φf (left) and TPA cross
sections δTPA (right) of the quadrupolar dyes in toluene.
visible region with maxima λabs in the range of 440−451 nm (11−
23 nm bathochromically shifted compared to the Qbtz series),
with one shoulder peak on the low-energy side. This multi-
component pattern is also seen in emission spectra (Figure S5)
and can be related to the vibronic coupling. The fluorescence in
toluene is observed in the blue-green spectral region with the
most intense peaks at 490−500 nm. While λabs remains essentially
unchanged upon increasing solvent polarity, a pronounced red
shift is observed for fluorescence maxima λf (Figure 3).
TPEF spectra of the prepared dyes are in toluene shown in
Figure 4. All benzobisthiazole chromophores exhibit moderate to
excellent TPA cross sections (975−1815 GM), with maxima λTPA
positioned at 790−810 nm (Table 1). This is substantially less
than twice that of the single-photon absorption λabs (S0 → S1),
implying a S0 → S2 transition as expected for quadrupolar dyes
due to parity selection rules. λTPA of Qbtz-Me and Qbtz-Ph are
blue-shifted to 750 and 770 nm, respectively, consistent with the
somewhat higher second excitation energies E2 calculated for
these derivatives. The highest δTPA (>1600 GM) are observed for
Q2-Do, Q2-Ph, and Q3-Do.
The efficiency of central heteroaromatic rings is assessed by
comparing δTPA of triphenylamine end-capped derivatives,
establishing the following order: Q3-Ph < Qbtz-Ph < Q2-Ph.
This is in agreement with our computations and confirms (a) a
slight superiority of the linear centrosymmetric benzobisthiazole
2 over benzothiazole and (b) lower TPA activity of dyes derived
from angular benzobisthiazole 3 compared with its linear
congener 2 and benzothiazole analogue (this is also evident
from comparing Q3-Do to Q2-Do and Q3-Me to Qbtz-Me).
Although the difference between δTPA of Q2-Ph and Qbtz-Ph is
rather small, the former exhibits a fluorescent quantum yield
more than twice as large, resulting in substantially higher TPA
action cross section, δTPA·Φf (Figure 4, left). Since the latter
quantity is vital in TPEF microscopy, where both strong TPA and
one-photon emission are required, Q2-Ph is an excellent
candidate for two-photon imaging.
Figure 2. Intermolecular π−π stacking in the unit cell of Q2-Ph·2CHCl3
(solvent molecules are omitted for clarity, and the displacement
ellipsoids are drawn at 50% probability level). The benzobisthiazole
molecules are mutually π-stacked with interplanar distance of 3.502(3) Å
and slippage of 0.812 Å (see SI for more details).
Table 1. Photophysical Properties of Quadrupolar Dyes in
Toluene
λabs
εmax
λf
[nm]
λTPA δTPAΦf
δTPA
dye
[nm] [M−1cm−1
]
Φf
[nm] [GM] [GM]
Qbtz-Me
Qbtz-Ph
Q2-Ph
417
431
445
451
440
442
448
68500
72400
83900
85800
62300
74600
77200
493
491
496
499
492
493
497
0.17
0.56
0.94
0.48
0.20
0.50
0.31
750
770
810
810
790
810
810
232
864
1575
871
195
619
503
1365
1543
1676
1815
975
Q2-Do
Q3-Me
Q3-Ph
1238
1622
Q3-Do
Ac2O and the intermediately formed 6-amino-2-methylbenzo-
thiazol-7-thiol.16
The presence of a second thiazole ring allows avoiding metal-
catalyzed cross-coupling reactions to attach the second styryl arm
to the central ring, making the synthesis more convenient, cost
friendly, and amenable to large-scale production as compared to
that of the Qbtz series. Q2-Me was not isolated due to its high
insolubility in common organic solvents, presumably due to π−π
stacking interactions (see Figure 2). No insolubility issue
occurred when preparing Q3-Me and all the other derivatives
with phenyl (Ph) and dodecyl (Do) substituents at the periphery.
All double bonds in the target chromophores formed under the
Knoevenagel condensation were trans-configured, as confirmed
by the coupling constants of the vinyl protons (3JH,H ≈ 16 Hz) in
1H NMR spectra and the X-ray structure of Q2-Ph.
The absorption spectra of benzobisthiazole dyes in toluene
(Table 1, Figure 3, Figure S5) feature one intense band in the
C
dx.doi.org/10.1021/ol503137p | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Similar to our previous findings, derivatives decorated with a
diphenylamino group exhibit larger NLO response than their
dimethylamino analogues (Qbtz-Me vs Qbtz-Ph, Q3-Me vs Q3-
Ph). TPA enhancement is even more pronounced when
employing a didodecylamino group (Q2-Ph vs Q2-Do, Q3-Ph
vs Q3-Do). This somewhat counterintuitive behavior is
confirmed by our calculations17 and can be rationalized by
involving additional optical channels in triphenylamine series,
which to some extent reduce the δTPA values obtained from the
three-state model (cf. Table S6). Both the elongation of pendant
alkyl chains and the extension of π-conjugation using a
diarylamino moiety offer thus a useful strategy not only to
increase the solubility but also to amplify δTPA, where the latter
modification is revealed as more suitable for engineering highly
emissive fluorophores.
To conclude, the fusion of the additional π-deficient
heteroaromatic ring to the central electron-accepting core must
not necessarily lead to TPA enhancement, as intuitively expected,
and may even have a detrimental effect on the NLO response
(Qbtz vs Q1, Q3−Q5). To benefit from this structural
modification, the relative position of heteroaromatic moieties
attached to the central ring has to be optimized to ensure an
efficient electronic coupling, which results in favorable one-
photon absorption parameters and an enhanced TPA response.
In this respect, the Q2 series with excellent TPA cross sections
(δTPA > 1600 GM), high emission quantum yields, and a facile
method for synthesis provides a low-cost and very efficient
alternative to many TPA fluorophores currently used.18 In
addition, all benzobisthiazoles have further possible points of
attachment, allowing for more modifications to modulate and
improve TPA cross sections using the same building block, for
example, by introducing auxiliary electron donor or acceptor
substituents on the heteroaromatic ring or by building multi-
branched structures via coordination of heterocyclic nitrogen
atoms to metal ions.
REFERENCES
■
(1) (a) Breitung, E. M.; Shu, C. F.; McMahon, R. J. J. Am. Chem. Soc.
2000, 122, 1154. (b) Hrobarik, P.; Zahradník, P.; Fabian, W. M. F. Phys.
Chem. Chem. Phys. 2004, 6, 495. (c) Hrobarik, P.; Sigmundova, I.;
́
́
́
́
Zahradník, P.; Kasak, P.; Arion, V.; Franz, E.; Clays, K. J. Phys. Chem. C
2010, 114, 22289. (d) Ma, X. H.; Ma, F.; Zhao, Z. H.; Song, N. H.;
Zhang, J. P. J. Mater. Chem. 2010, 20, 2369. (e) Raposo, M. M. M.;
Castro, M. C. R.; Belsley, M.; Fonseca, A. M. C. Dyes Pigm. 2011, 91, 454.
(f) El-Shishtawy, R. M.; Borbone, F.; Al-Amshany, Z. M.; Tuzi, A.;
Barsella, A.; Asiri, A. M.; Roviello, A. Dyes Pigm. 2013, 96, 45.
(2) Hrobar
Persephonis, P.; Zahradník, P. J. Org. Chem. 2010, 75, 3053.
(3) Hrobarik, P.; Hrobarikova, V.; Sigmundova, I.; Zahradník, P.; Fakis,
́ ́ ́ ̌
ikova, V.; Hrobarik, P.; Gajdos, P.; Fitilis, I.; Fakis, M.;
́
́
́
́
M.; Polyzos, I.; Persephonis, P. J. Org. Chem. 2011, 76, 8726.
(4) Belfield, K. D.; Morales, A. R.; Kang, B. S.; Hagan, D. J.; Van
Stryland, E. W.; Chapela, V. M.; Percino, J. Chem. Mater. 2004, 16, 4634.
(5) Yu, G.; Yin, S. W.; Liu, Y. Q.; Shuai, Z. G.; Zhu, D. B. J. Am. Chem.
Soc. 2003, 125, 14816.
(6) (a) Ando, S.; Murakami, R.; Nishida, J.; Tada, H.; Inoue, Y.; Tokito,
S.; Yamashita, Y. J. Am. Chem. Soc. 2005, 127, 14996. (b) McEntee, G. J.;
Vilela, F.; Skabara, P. J.; Anthopoulos, T. D.; Labram, J. G.; Tierney, S.;
Harrington, R. W.; Clegg, W. J. Mater. Chem. 2011, 21, 2091. (c) Lin, Y.
Z.; Fan, H. J.; Li, Y. F.; Zhan, X. W. Adv. Mater. 2012, 24, 3087.
(7) (a) Zhang, W. Y.; Feng, Q. Y.; Wang, Z. S.; Zhou, G. Chem.Asian
J. 2013, 8, 939. (b) Saeki, A.; Tsuji, M.; Yoshikawa, S.; Gopal, A.; Seki, S.
J. Mater. Chem. A 2014, 2, 6075.
(8) (a) He, G. S.; Tan, L. S.; Zheng, Q.; Prasad, P. N. Chem. Rev. 2008,
108, 1245. (b) Pawlicki, M.; Collins, H. A.; Denning, R. G.; Anderson, H.
L. Angew. Chem., Int. Ed. 2009, 48, 3244. (c) Kim, H. M.; Cho, B. R.
Chem. Commun. 2009, 153.
(9) (a) Reinhardt, B. A.; Unroe, M. R.; Evers, R. C.; Zhao, M. T.;
Samoc, M.; Prasad, P. N.; Sinsky, M. Chem. Mater. 1991, 3, 864.
(b) Intemann, J. J.; Mike, J. F.; Cai, M.; Barnes, C. A.; Xiao, T.; Roggers,
R. A.; Shinar, J.; Shinar, R.; Jeffries-EL, M. J. Polym. Sci., Part A: Polym.
Chem. 2013, 51, 916. (c) Bon, J. L.; Feng, D. J.; Marder, S. R.; Blakey, S.
B. J. Org. Chem. 2014, 79, 7766.
(10) Belfield, K. D.; Yao, S.; Morales, A. R.; Hales, J. M.; Hagan, D. J.;
Van Stryland, E. W.; Chapela, V. M.; Percino, J. Polym. Adv. Technol.
2005, 16, 150.
(11) DALTON, a molecular electronic structure program, 2011
(available from http://www.daltonprogram.org). See SI for computa-
tional details.
(12) The cis-configured isomers are energetically disfavored by >26 kJ/
mol, giving rise to a negligible Boltzmann weighting factor.
(13) Conformational dependence of δTPA has been recently reported
also in: Silva, D. L.; Murugan, N. A.; Kongsted, J.; Rinkevicius, Z.;
Canuto, S.; Agren, H. J. Phys. Chem. B 2012, 116, 8169.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental and computational details, computed TPA cross
sections and one-photon absorption characteristics, detailed
quantum-chemical analysis, synthetic procedures, and crystal
structure data for Q2-Ph·2CHCl3. This material is available free
of charge via the Internet at http://pubs.acs.org.
(14) δTPA(S0→S2) of quadrupolar dyes is usually dominated by the
three-state term, which is proportional to the product |μ01|2|μ12|2 and
inversely proportional to the square of the detuning energy (E1 − E2/2).
(15) (a) Mike, J. F.; Inteman, J. J.; Ellern, A.; Jeffries-El, M. J. Org. Chem.
AUTHOR INFORMATION
■
̌
2010, 75, 495. (b) Cibova,
́
A.; Magdolen, P.; Fulopova, A.; Zahradník, P.
́
̈
̈
Corresponding Authors
Chem. Pap. 2013, 67, 110.
(16) (a) Fridman, S. G.; Golub, D. K. Chem. Heterocycl. Compd. 1965, 1,
713. (b) Kiprianov, A. I.; Mikhailenko, F. A. Chem. Heterocycl. Compd.
1967, 3, 270.
(17) See Figure S2 for a dependence of δTPA on the pendant alkyl chain
length in Q2-R series, where δTPA increases steadily to reach a plateau for
the dioctylamino group. Despite the higher μ01 and μ12 values for the
NPh2 end-capped derivative, its TPA activity is comparable to that of the
NHex2 analogue.
(18) For recent examples of quadrupolar dyes with large δTPA, see:
́
(a) Wilkinson, J. D.; Wicks, G.; Nowak-Krol, A.; Łukasiewicz, Ł. G.;
Wilson, C. J.; Drobizhev, M.; Rebane, A.; Gryko, D. T.; Anderson, H. L. J.
Mater. Chem. C 2014, 2, 6802. (b) Belfield, K. D.; Bondar, M. V.; Yao, S.;
Mikhailov, I. A.; Polikanov, V. S.; Przhonska, O. V. J. Phys. Chem. C 2014,
118, 13790. (c) Grzybowski, M.; Hugues, V.; Blanchard-Desce, M.;
Gryko, D. T. Chem.−Eur. J. 2014, 20, 12493.
*E-mail: peter.hrobarik@tu-berlin.de
*E-mail: fakis@upatras.gr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
P. H. gratefully acknowledges the Alexander von Humboldt
foundation for a research fellowship. We thank Dr. M. Cigan
(Comenius University) for measuring fluorescence quantum
́
yields, and Dr. J. Kozısek (STU, Bratislava) for assistance with the
̌
̌
X-ray crystallographic determination. The authors also thank Dr.
S. Gerber (EPFL) for generously providing the laboratory
facilities for final characterizations.
́
̌
D
dx.doi.org/10.1021/ol503137p | Org. Lett. XXXX, XXX, XXX−XXX