Asymmetric meso-CF3-BODIPY dyes based on cycloalkanopyrroles

Article abstract of DOI:10.1016/j.dyepig.2020.108228

New meso-CF₃-substituted BODIPY derivatives have been synthesized using the methodology that includes as a key step the condensation of pyrroles with trifluoro(2,3-cycloalkanopyrrol-2-yl)ethanols. The further reaction of dipyrromethanes thus obtained with DDQ followed by complexation with BF₃ leads to either benzo[b]-fused (in the case of dipyrromethanes obtained from trifluoro(4,5,6,7-tetrahydroindol-2-yl)ethanol) or cycloheptano[b]-fused saturated or partially saturated BODIPY dyes. The latter exhibit strong red fluorescence (λ_em = 588–634 nm, Φ_f = 0.54–0.68), while benzo[b]-fused do not fluoresce at all in either polar or non-polar solvents. The performed quantum-chemical calculations (TD-CAM-B3LYP/SVP) explain the spectroscopic results.

Full text of DOI:10.1016/j.dyepig.2020.108228

Dyes and Pigments 176 (2020) 108228
Contents lists available at ScienceDirect
Dyes and Pigments
journal homepage: http://www.elsevier.com/locate/dyepig
Asymmetric meso-CF3-BODIPY dyes based on cycloalkanopyrroles
Denis N. Tomilina, Elena F. Sagitovaa, Konstantin B. Petrushenkoa, Lyubov N. Sobeninaa,
,
,*
Igor A. Ushakova, Guoqiang Yangb c, Rui Hub, Boris A. Trofimova
a A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Science, 1 Favorsky Str., 664033, Irkutsk, Russian Federation
b Beijing National Laboratory for Molecular Sciences, Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China
c University of Chinese Academy of Sciences, Beijing, 100049, China
A R T I C L E I N F O
A B S T R A C T
Keywords:
New meso-CF3-substituted BODIPY derivatives have been synthesized using the methodology that includes as a
key step the condensation of pyrroles with trifluoro(2,3-cycloalkanopyrrol-2-yl)ethanols. The further reaction of
dipyrromethanes thus obtained with DDQ followed by complexation with BF3 leads to either benzo[b]-fused (in
the case of dipyrromethanes obtained from trifluoro(4,5,6,7-tetrahydroindol-2-yl)ethanol) or cycloheptano[b]-
fused saturated or partially saturated BODIPY dyes. The latter exhibit strong red fluorescence (λem ¼ 588–634
nm, Φf ¼ 0.54–0.68), while benzo[b]-fused do not fluoresce at all in either polar or non-polar solvents. The
performed quantum-chemical calculations (TD-CAM-B3LYP/SVP) explain the spectroscopic results.
Cycloalkano[b]-fused BODIPY
benzo[b]-fused BODIPY
meso-CF3-Dipyrromethanes
2,2,2-Trifluoro-1-(pyrrol-2-yl)-1-ethanols
Aromatization
1. Introduction
of strong acceptor - perfluoroalkyl or perfluoroaryl groups at the mes-
o-position of the BODIPY molecule also causes a significant red-shift of
The discovery of fluorescent 4,4-difluoro-4-bora-3a,4a-diaza-s-inda-
cenes, better known as BODIPY dyes, has established a new class of
fluorophores with a variety of highly important and useful representa-
tives possessing tunable properties [1]. The most frequent and important
applications of these dyes in medicine and related areas comprise pho-
tosensitizers for photodynamic therapy [2,3], highly sensitive detectors
of specific targets in biological media [4–7], probes, sensors and label-
ling agents for biochemical research [8–10]. Fluorescent BODIPY dyes
are also widely used in OLEDs and laser dyes [11], nonlinear optics [12,
13], fluorescent markers and sensors for contamination [14], organic
photovoltaics [15], solar batteries [16,17] and so on [1].
the absorption and fluorescence spectra [21–24]. Another effective
method for the construction of boron dipyrromethene dyes of the above
types, i.e. absorbing and emitting in IR or NIR region, is a fusion of
saturated or unsaturated cycles with the
α
,β-positions of the BODIPY
core [18,20].
Unlike BODIPY with an extended
π-system [25–29], BODIPY dyes
with annulated cyclic aliphatic substituents are less studied. There is
information [30] that symmetrical meso-methyl BODIPYs with fused
cycloalkyl substituents exhibit strong fluorescence, high extinction co-
efficient and show good laser activity. The symmetric fused bis
(cyclohexyl)-BODIPYs possess intense chromophore properties compa-
rable to those of alkyl-substituted ones [20,31,32] The quantum chem-
ical calculations also show bathochromic shift for these dyes [20,33]. A
representative of the fused cycloalkyl BODIPY was used as fluorescent
part of a probe with no dye-induced distortions in lipid membrane
research [34]. A lipophilic dye (LD540) derived from cycloalkyl BODIPY
is a multicolor probe for microscopic imaging of lipid droplets in living
cells [35–37]. The same compound due to its enhanced lipophilicity was
successively tested to stain lipids and related biological material within
sebaceous fingermarks [38]. The polymer compositions of fused cyclo-
alkyl BODIPYs are incorporated in securing elements to protect the
identity documents [39].
Especially promising for practical applications are BODIPY de-
rivatives that exhibit absorption and emission in the deep-red and near
infrared (NIR) spectral regions (>650 nm). The search for these fluo-
rophores is progressively growing [18]. This research activity is inspired
by the fact that such BODIPYs fit well in vivo bioimaging because they
lesser photo-damage the biological objects, deeper penetrate in organic
tissues, and demonstrate minimum interference from background
auto-fluorescence in the living systems [19]. Among the important ways
to access NIR BODIPYs are the extension of π-conjugation by introduc-
tion of aromatic or heteroaromatic substituents to the bor-
adiazaindacene core or the desymmetrization of their molecules to
impart them inner donor-acceptor properties [18,20]. The introduction
Commonly, symmetrically and asymmetrically fused cycloalkyl
* Corresponding author.
E-mail address: boris_trofimov@irioch.irk.ru (B.A. Trofimov).
https://doi.org/10.1016/j.dyepig.2020.108228
Received 11 December 2019; Received in revised form 13 January 2020; Accepted 19 January 2020
Available online 22 January 2020
0143-7208/© 2020 Published by Elsevier Ltd.

D.N. Tomilin et al.
Dyes and Pigments 176 (2020) 108228
2. Results and discussion
Cyclohexano- and cycloheptano[b]-fused BODIPYs were synthesized
on the basis of cycloalkanones, i.e. cyclohexanone and cycloheptanone
using the modified one-pot Trofimov assembly from oximes and acety-
lene gas in the system KOH-DMSO (Scheme 1) [43]. The tri-
fluoroacetylation of pyrroles and reduction of trifluoroacetyl derivatives
thus prepared were performed accordingly to the improved protocol
[22].
Scheme 1. Synthesis of cycloheptano[b]pyrrole by Trofimov reaction.
BODIPYs are synthesized by the treatment of substituted pyrroles with
chloroanhydrides [40] or by the POCl3-promoted condensation of
2-acylpyrroles/pyrrole-2-carbaldehydes with other pyrrole molecule
The key intermediates of BODIPYs 1 synthesis, meso-CF3-dipyrro-
methanes 2a-e, were obtained by the upgraded condensation of trifluoro
(pyrrol-2-yl)ethanols 3a,b with pyrroles 4a-c in the presence of P2O5
(Table 1) [22]. Notably, pyrrolyldihydroisoxazolol 4a upon condensa-
tion with trifluoroethanols 3a,b undergoes dehydration to afford
dipyrromethanes 2a and 2e with phenylisoxazolyl substituent (Table 1).
First, we attempted to oxidize dipyrromethane 2a by equimolar
amount of DDQ (CH2Cl2, rt, 1 h) followed by chelation with BF3∙Et2O as
it was done earlier [22]. Regretfully, in this case, even no traces of the
expected BODIPYs were detected in the crude, only mixture of
difficult-to-identify compounds being formed.
having free α-position [20,41,42]. To our knowledge, only one protocol
provides BODIPYs with fused substituents and meso-CF3 group, but it is
limited to symmetric ones [23]. Evidently, a further progress in this field
requires more structural diversity and functional complexity in the
BODIPY series. In this context, asymmetric representatives of the mes-
o-CF3-BODIPY, fused with cycloalkyl substituents, could cardinally
contribute to potential of these compounds as high effective fluo-
rophores exhibiting absorption and emission in red and near infrared
(NIR) spectral regions.
Recently [22], we have reported a new approach to the design of
symmetric and asymmetric meso-trifluoromethyl-substituted BODIPYs
including as a key step condensation of trifluoropyrrolylethanols with
pyrroles followed by the conventional procedure, i.e. oxidation with
DDQ and complexation with BF3⋅Et2O.
When replacing the solvent (CH2Cl2) for toluene (other conditions
being the same), in 1H NMR spectra characteristic indole signals were
identified. Surprisingly, the entire aromatization of tetrahydroindole
part of the molecule 2a happened, if threefold molar excess of DDQ (rt,
1 h) was employed: benzo[b]-fused dipyrromethane 5a was obtained in
48% yield, though the expected dipyrromethene was not discernible
among the reaction products (Scheme 2). Such ease of dehydrogenation
of the cyclohexane ring condensed with the pyrrole moiety draws
attention. Usually, the reactions of this type require high temperature
and special, often noble metal catalysts [44–46]. For instance, full
This approach may open a convenient path to the synthesis of
asymmetric meso-CF3 2,3-cycloalkano-fused BODIPY dyes.
In this work, we describe a further unfolding of advantageous fea-
tures of the above multi-purpose methodology as applied to the syn-
thesis of asymmetric cycloalkano[b]-fused meso-CF3 BODIPYs 1 and
their major fluorescent characteristics.
Table 1
Synthesis of dipyrromethanes 2a-e from trifluoro(pyrrolyl)ethanols 3a,b and pyrroles 4a-c.
.
Entry
1
Trifluoro(pyrrolyl)ethanol
Pyrrole
Dipyrromethane
Yield, %
94
2
92
3
4
94
95
5
97
Reaction conditions: trifluoropyrrolylethanols 3a-c (1 mmol), pyrroles 4a-c (1 mmol), P2O5 (1 mmol), CH2Cl2, rt, 16 h.
2

D.N. Tomilin et al.
Dyes and Pigments 176 (2020) 108228
Scheme 2. Aromatization of dipyrromethane 2a with DDQ.
Scheme 3. Formation of BODIPY dyes 1a,b.
aromatization of 4,5,6,7-tetrahydroindole is realized in the presence of
Ni2S/Al2O3 catalyst [45,47,48]. Eventually, when the reaction of 2a
with DDQ was carried out at a higher temperature (80 �C), the desired
benzo[b]-dipyrromethene 6a was isolated in 60% yield (Scheme 2). This
compound turned out to be highly reactive, decomposing in a freezer
after a few days.
Obviously, less prone to dehydrogenation would be cycloheptano[b]
pyrrole, because of its inability to be aromatized. Therefore, this pyrrole
was involved, for the first time, in a BODIPY dye assembly via the same
sequence: the trifluoroacetylation, reduction (NaBH4) to the corre-
sponding trifluoromethyl alcohol and further condensation with
pyrroles.
Consequently, benzo[b]-fused BODIPYs 1a,b were assembled from
dipyrromethanes 2a,b by one-pot manner (without isolation of unstable
dipyrromethenes 6), employing 3 mol excess of DDQ (toluene, 80 �C, 1
h) and BF3⋅Et2O (i-Pr2NEt, toluene, 0 �C, 1 h). However, the isolated
yields of the target products (Scheme 3, Table 2) were 7–8%, obviously
due to the above-mentioned instability of the intermediate dipyrrome-
thene 6.
Transformation of dipyrromethanes 2c-e to dipyrromethenes and
their following complexation with BF3⋅OEt2 (i-Pr2NEt, 2 h) into fluo-
rophores BODIPYs 1c-f were carried out according to the methodology
[22].
It appeared that despite the lesser tendency of the cycloheptane ring
to be dehydrogenated, dipyrromethane 2c after 1.5 h of contact with one
equivalent of DDQ followed by the treatment BF3⋅OEt2 (i-Pr2NEt, 2 h) at
room temperature was transformed into a mixture of cycloheptane- and
cycloheptene-fused boradiazaindacenes 1c and 1d, their isolated yields
being 2 and 16% correspondingly. Under the same conditions, from
dipyrromethane 2d, only partially dehydrogenated BODIPY 1e was
Thus, as shown above, the aromatization of a cyclohexano[b]pyrrole
moiety precedes the formation of dipyrromethene and, hence, it pre-
vents receiving the BODIPY with cyclohexano[b]pyrrole counterpart via
this route.
Table 2
Synthesis of BODIPY dyes 1a-f from dipyrromethanes 2a-e.
Dipyrromethane
BODIPY
Yield, %
7a
Dipyrromethane
BODIPY
Yield, %
8a
2a
2b
2c
2d
12b
10b
2c
2e
16b
12b
Reference compd
Reference compd
Reaction conditions.
a
b
dipyrromethanes 2a,b (1 mmol), DDQ (3 mmol), i-Pr2NEt (10 mmol), BF3⋅Et2O (11 mmol), toluene, 0 �C, 1 h.
dipyrromethanes 2c-e (1 mmol), DDQ (1 mmol), i-Pr2NEt (10 mmol), BF3⋅Et2O (11 mmol), CH2Cl2, 20–25 �C, 2 h.
3

D.N. Tomilin et al.
Dyes and Pigments 176 (2020) 108228
Fig. 1. Cross-peaks in compound 1d.
isolated in 10% yield. When the contact time of dipyrromethane 2c with
DDQ was reduced to 0.5 h, fluorophores 1c and 1d were isolated in 12
and 10% yields, respectively. Likewise, from dipyrromethane 2e only
saturated cycloheptano[b]-fused boradiazaindacene 1f was isolated in
12% yield.
Fig. 2. Normalized absorption spectra of 1e (1) and 1b (2) in MeCN.
of BODIPY 1f with the shortest conjugate system, in turn, is slightly less
than that of the reference molecule.
Compounds 1c-f exhibit strong red fluorescence (λem ¼ 588–634
nm). The fluorescence excitation spectra perfectly match the absorption
spectra (Figs. S1–S4) and fluorescence lifetimes are in the normal range.
The Φf values of 1c-f are higher than 0.50 (Table 3). As follows from the
comparison with the reference molecule, the fusion with cycloheptyl
moiety does not decrease Φf. Unexpectedly, benzo[b]-fused (indole-
derived) BODIPYs 1a and 1b do not fluoresce at all in both polar and
non-polar solvents.
The structure of the synthesized fluorophores, in particular, with
respect to the position of the double bond in the cycloheptene moiety of
BODIPY dyes 1d and 1e, was proved by 1H and 13C spectroscopy using
2D HMBC and HSQC methods. For instance, the 1H NMR spectrum of
compound 1d contains a doublet at 7.11 ppm (J ¼ 12.4 Hz) and a
doublet of triplets at 6.47 ppm (J ¼ 12.4, 5.0 Hz) of the olefin fragment.
In the high-field part of the spectrum, characteristic multiplets of 3 CH2
groups were preserved. The presence of cross peaks in the 2D NOESY
spectrum between proton signals at 7.04 ppm (H-3 pyrrole) and 2.77
(CH2 group) indicated the position of the olefin fragment (See Fig. 1).
Spectroscopic and photophysical data [the positions of the maxima
of the absorption, emission, and fluorescence excitation bands, Stokes
shifts (ΔνSt), fluorescence lifetimes (τf), and fluorescence quantum
yields (Φf)] for the fused asymmetric BODIPY dyes 1a-f are summarized
in Table 3, while individual spectra (absorption, emission and excita-
tion) are placed in the ESI (Figs. S1–S5). Additionally, for the compar-
ison, Table 3 shows data for their unfused asymmetric analog 8-CF3-5-
Ph-BODIPY (1g) [22].
The reasons for the low fluorescence quantum yield of a series of the
asymmetric indole-derived BODIPYs (1h is typical example) have been
already mentioned in literature [51,52]. However, due to the fact that
all these dyes in the meso-position contain a phenyl substituent
(sp2-bonded type), which is an effective quencher of BODIPY fluores-
cence [53,54], their weak emission properties were attributed to the free
rotation of the meso-phenyl group [51,52]. On the other hand, in our
case the meso-position is bonded to sp3 carbon. Such BODIPY dyes
usually strongly fluoresce relative to their sp2-bonded congeners [54].
As compared to the reference molecule, the presence of a cyclo-
heptane[b]-fused moiety in 1c and a cycloheptene[b]-fused moiety in 1d
leads to a red shift of the main absorption bands by 16 nm and 50 nm,
respectively (for reference BODIPY 1g and BODIPY 1c and 1d dissolved
in n-hexane). This bathochromic displacement is in accordance with a
stronger inductive electron-donating effect of alkyl groups and the
Table 4
Calculated electronic excitation energies and oscillator strengths (f) in the gas
phase for BODIPY 1b and 1e molecules computed at the TD-CAM-B3LYP/SVP
level of theory.
Transition
BODIPY
Energy,
eV
f
Main
Contribute,
%
configuration
expansion of the π-system of b-annulated cyclic substituents relative to
S0 → S1
1e
1b
2.48
2.49
0.74
0.16
Ha-Lb
98
37
60
92
63
35
82
13
95
the reference BODIPY 1g having no substituents in the positions 2 and 3.
Replacement of the phenyl ring in the position 5 in compound 1d for
the isoxazole moiety (cycloheptene[b]-fused BODIPY 1e) and further
replacement of cycloheptene moiety for an indole in BODIPY 1b do not
considerably change the length and character of the conjugation chain
in these molecules, and, therefore, maxima of the main absorption bands
for 1d, e and 1b almost coincide (Table 3). The main absorption bands of
BODIPY 1b relative to isomeric 1a are red-shifted by 24 nm, in accor-
dance with reference [50]. The absorption wavelength of the main band
H-L
H-1-L
H-4-L
H-L
→ S2
→ S3
1e
1b
3.67
2.55
0.07
0.69
H-1-L
H-5-L
H-3-L
H-2-L
1e
1b
3.93
3.73
0.001
0.001
a
b
designation for HOMO.
designation for LUMO.
Table 3
Photophysical properties of BODIPY dyes 1a-f in MeCN at 293K
BODIPY
λabs(max), nm
ε
(max),
λex(max), nm
λem(max), nm
Δ
νSt, cmÀ 1
τf, ns
Φfa
MÀ 1cmÀ 1
1a
1b
1c
1d
1e
1f
580
50,000
47,500
31,000
39,500
47,000
36,000
N.F.c
N.F.
572
605
608
553
N.F.
N.F.
600
632
634
588
N.F.
N.F.
820
700
670
1010
N.F.
N.F.
6.09
5.91
5.57
5.04
N.F.
N.F.
0.57
0.63
0.68
0.54
604
572; 577b
605; 611b
609
555
Reference BODIPY 1g in n-hexane [22]
1g
561
36,000
561
578
520
4.5
0.56
a
Relative to 4,4-difluoro-3-[(4-methyl)phenyl]-5-phenyl-8-trifluoromethyl-4-bora-3a, 4a-diaza-s-indacene (Φf ¼ 0.87 in MeCN [49]).
Measured in n-hexane. Given to show similarity with spectra in MeCN and for comparison with reference compound 1g.
N.F. – non fluorescence.
b
c
4

D.N. Tomilin et al.
Dyes and Pigments 176 (2020) 108228
Fig. 3. The electron density difference plot between
the Si (i ¼ 1, 2) and S0 state of the benzo[b]-fused
derivative 1b (plotted for the isosurface value of
0.001 a.u.). Red and blue correspond to positive (
ρ
>
0) and negative (
ρ < 0) regions, respectively, and
thus represent increase and decrease in electron
density due to the excitation. μ(S1) and μ(S2) - dipole
moment S1 and S2 states, respectively. (For inter-
pretation of the references to color in this figure
legend, the reader is referred to the Web version of
this article.)
As far as many known meso-CF3-BODIPY dyes [21–24,49,50,55–58], as
well as some here synthesized CF3-BODIPY exhibit excellent fluorescent
properties, it seems that the lack of fluorescence in derivatives 1a and 1b
should be caused by other reasons than in the case of meso-Ph-BODIPY
[51,52], probably by the presence of fused indole substituent.
Aggregation-caused emission quenching effect for BODIPYs 1a,b could
be excluded because of their high solubility in n-hexane/MeCN and low
concentration of solutions used.
may be due to the competition of the radiative transition from the 1LE
fluorescent state and the additional nonradiative transition from the 1LE
state to the 1CT non-fluorescent state, as shown schematically in Fig. S7.
3. Conclusions
In conclusion, an expedient strategy for the synthesis of highly effi-
cient BODIPY fluorophores of novel family of meso-CF3-cycloheptane-
and cycloheptene[b]-fused BODIPY dyes fluorescing in a 588–634 nm
region with good quantum yields (Φf ¼ 0.54–0.68) has been developed.
The key step of this strategy is the P2O5-promoted condensation of
readily accessible trifluoro-1-(2,3-cycloalkanopyrrol-2-yl)ethanols with
diverse pyrroles. The strategy proved to be a general easy route to
previously inaccessible asymmetric BODIPY fluorophores.
In order to better understand the quenching mechanism, we
compared the photophysical properties of benzo[b]-fused (indole-
derived) derivatives 1b (and 1a) with those of cycloheptene[b]-fused
derivative 1e, which intensively fluoresces unlike benzo[b]-fused de-
rivatives. Other substituents (in the positions 3 and 8) were the same for
pair 1b and 1e. The maxima of the absorption bands of these derivatives
almost coincide (Table 3), that is very convenient for the comparison.
Fig. 2 displays the absorption spectra of compounds 1b and 1e. It is
seen that the main absorption band of the benzo[b]-fused dye 1b is much
wider and extends up to 700 nm, while the absorption of dye 1e ends at
� 650 nm.
Declaration of competing interests
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Taking into account these differences, we assume that in the case of
benzo[b]-fused dyes, another one weak transition is located on the red
side of the main transition. Due to the strong overlap of bands, the
maximum of this second band cannot be determined accurately.
Therefore, only the red tail of this absorption band is observed.
To test this hypothesis, TD-CAM-B3LYP/SVP calculations (Gaussian
09, Revision B.01 [59]) for the first five electronic transitions of dyes 1a,
1b and 1e have been performed and their results are presented in
Table S1 (ESI). The molecular orbitals involved into these transitions are
shown in Fig. S6. Results for the first three transitions for 1b and 1e are
shown in Table 4.
CRediT authorship contribution statement
Denis N. Tomilin: Investigation. Elena F. Sagitova: Investigation.
Konstantin B. Petrushenko: Software, Validation. Lyubov N. Sobe-
nina: Project administration, Writing - original draft. Igor A. Ushakov:
Visualization, Validation, Software. Guoqiang Yang: Investigation,
Validation. Rui Hu: Investigation, Validation. Boris A. Trofimov:
Conceptualization, Methodology.
TD-DFT calculations reveal that the longest absorption bands in 1e is
the envelope of a single and intense (f ¼ 0.74) S0 → S1 transition, which
is due to the one electron excitation from the HOMO to the LUMO (98%)
(Table 4). The weaker S0 → S2 and S0 → S3 transitions, which are far
enough from the transition S0 → S1 located in the high-energy spectral
region form the second absorption band in the spectrum of 1e.
A completely different picture is observed for benzo[b]-fused de-
rivatives 1a and 1b. Here, the long-wavelength part of the spectra is
formed by two closely spaced transitions, the main contribution to
which are done by HOMO-LUMO and HOMO-1-LUMO single-electron
excitations (Table 4 for 1b as example and Table S1). The first of them,
the S0 → S1 transition, is relatively low-intense and has a moderate
charge transfer (CT) character, and the second, intense S0 → S2 transi-
tion, is a local excited type (LE) transition. This is obvious from the
electron density difference plot (Fig. 3) and the picture of the molecular
orbitals of derivatives 1a and 1b involved in these transitions (Fig. S6).
As a result, the absence of fluorescence of the derivatives 1a and 1b
Acknowledgements
This work was supported by the Russian Foundation for Basic
Research (project no. 19-53-53008 NSFC_a). The main results were ob-
tained using the equipment of the Baikal Analytical Center for Collective
Use, Siberian Branch of the Russian Academy of Sciences.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.dyepig.2020.108228.
References
~
[1] Sola-Llano R, Banuelos J. Bodipy dyes. A privilege molecular scaffold with tunable
properties. IntechOpen; 2018. https://doi.org/10.5772/intechopen.75220.
5

D.N. Tomilin et al.
Dyes and Pigments 176 (2020) 108228
[2] Awuah SG, You Y. Boron dipyrromethene (BODIPY)-based photosensitizers for
photodynamic therapy. RSC Adv 2012;2(30):11169–83. https://doi.org/10.1039/
C2RA21404K.
[28] Shimogawa H, Mori H, Wakamiya A, Murata Y. Impacts of dibenzo- and dithieno-
fused structures at the b, g bonds in the BODIPY skeleton. Chem Lett 2013;42(9):
986–8. https://doi.org/10.1246/cl.130360.
[3] Kamkaew A, Lim SH, Lee HB, Kiew LV, Chung LY, Burgess K. BODIPY dyes in
photodynamic therapy. Chem Soc Rev 2013;42(1):77–88. https://doi.org/
10.1039/C2CS35216H.
[29] Zhou Z, Zhou J, Gai L, Yuan A, Shen Z. Naphtho[b]-fused BODIPYs: one pot
Suzuki–Miyaura–Knoevenagel synthesis and photophysical properties. Chem
Commun 2017;53(49):6621–4. https://doi.org/10.1039/C7CC02918G.
[30] Boyer JH, Haag AM, Sathyamoorthi G, Soong M-L, Thangaraj K, Pavlopoulos TG.
Pyrromethene–BF2 complexes as laser dyes: 2. Heteroat Chem 1993;4(1):39–49.
https://doi.org/10.1002/hc.520040107.
[4] Dorh N, Zhu S, Dhungana KB, Pati R, Luo F-T, Liu H, et al. BODIPY-based
fluorescent probes for sensing protein surface-hydrophobicity. Sci Rep 2015;5:
18337. https://doi.org/10.1038/srep18337.
[5] Kowada T, Maeda H, Kikuchi K. BODIPY-based probes for the fluorescence imaging
of biomolecules in living cells. Chem Soc Rev 2015;44(14):4953–72. https://doi.
org/10.1039/C5CS00030K.
[31] Kritskaya AY, Bumagina NA, Antina EV, Ksenofontov AA, Berezin MB,
Semeikin AS. Synthesis and photochemical properties of 2,3;5,6-bis(cyclohexano)-
BODIPY. J Fluoresc 2018;28(1):393–407. https://doi.org/10.1007/s10895-017-
2201-4.
[6] Gao Y-G, Zhang Y, Shi Y-D, Hao H-J, Gong B, Lu Z-L. Fluorescent sensors based on
[12] aneN3-modified BODIPY: discrimination of different biological thiols in
aqueous solution and living cells. Bioorg Med Chem 2016;24(7):1550–9. https://
doi.org/10.1016/j.bmc.2016.02.024.
[32] Wu L, Burgess K. A new synthesis of symmetric boraindacene (BODIPY) dyes.
Chem Commun 2008;(40):4933–5. https://doi.org/10.1039/B810503K.
[33] Momeni MR, Brown A. Why do TD-DFT excitation energies of BODIPY/Aza-
BODIPY families largely deviate from experiment? Answers from electron
correlated and multireference methods. J Chem Theor Comput 2015;11(6):
2619–32. https://doi.org/10.1021/ct500775r.
[7] Kolemen S, Akkaya EU. Reaction-based BODIPY probes for selective bio-imaging.
Coord Chem Rev 2018;354:121–34. https://doi.org/10.1016/j.ccr.2017.06.021.
[8] Chen Y, Tsao K, Acton SL, Keillor JW. A green BODIPY-based, super-fluorogenic,
protein-specific labelling agent. Angew Chem 2018;130(38):12570–4. https://doi.
org/10.1002/ange.201805482.
[34] Tretiakova DS, Alekseeva AS, Galimzyanov TR, Boldyrev AM, Chernyadyev AY,
Ermakov YA, et al. Lateral stress profile and fluorescent lipid probes. FRET pair of
probes that introduces minimal distortions into lipid packing. BBA Biomembranes
2018;1860(11):2337–47. https://doi.org/10.1016/j.bbamem.2018.05.020.
[35] Spandl J, White DJ, Peychl J, Thiele C. Live cell multicolor imaging of lipid
droplets with a new dye, LD540. Traffic 2009;10(11):1579–84. https://doi.org/
10.1111/j.1600-0854.2009.00980.x.
[9] Kong X, Di L, Fan Y, Zhou Z, Feng X, Gai L, et al. Lysosome-targeting turn-on red/
NIR BODIPY probes for imaging hypoxic cells. Chem Commun 2019;55(77):
11567–70. https://doi.org/10.1039/C9CC04416G.
[10] Kaur P, Singh K. Recent advances in the application of BODIPY in bioimaging and
chemosensing. J Mater Chem C 2019;7(37):11361–405. https://doi.org/10.1039/
C9TC03719E.
[36] Thiele C. Fluorescence-based imaging and analysis of cells and cellular components
using lipophilic dyes with improved specificity, spectral property and
photostability. 2011. EP2284541 (A1).
[11] Chapran M, Angioni E, Findlay NJ, Breig B, Cherpak V, Stakhira P, et al. An
ambipolar BODIPY derivative for a white exciplex OLED and cholesteric liquid
crystal laser toward multifunctional devices. ACS Appl Mater Interfaces 2017;9(5):
4750–7. https://doi.org/10.1021/acsami.6b13689.
[37] Astanina K, Koch M, Jüngst C, Zumbusch A, Kiemer AK. Lipid droplets as a novel
cargo of tunnelling nanotubes in endothelial cells. Sci Rep 2015;5:11453. https://
doi.org/10.1038/srep11453.
[12] Shi W-J, Lo P-C, Singh A, Ledoux-Rak I, Ng DKP. Synthesis and second-order
nonlinear optical properties of push-pull BODIPY derivatives. Tetrahedron 2012;68
(42):8712–8. https://doi.org/10.1016/j.tet.2012.08.033.
[38] Qi A, Miskelly GM. Staining using the lipid dye LD540 in fluorous media:
application to sebaceous latent fingermarks. Anal Methods 2015;7(4):1265–8.
https://doi.org/10.1039/C4AY02925A.
[13] Wang H-Q, Ye J-T, Zhang Y, Zhao Y-Y, Qiu Y-Q. A thorough understanding of the
nonlinear optical properties of BODIPY/carborane/diketopyrrolopyrrole hybrid
chromophores: module contribution, linear combination, one-/two-dimensional
difference and carborane’s arrangement. J Mater Chem C 2019;7(25):7531–47.
https://doi.org/10.1039/C9TC01750J.
[39] Prete C. Use of 4-bora-3a,4a-diaza-s-indacenes for security purposes. 2019.
US2019016953 (A1).
[40] Chen J, Burghart A, Derecskei-Kovacs A, Burgess K. 4,4-Difluoro-4-bora-3a,4a-
diaza-s-indacene (BODIPY) dyes modified for extended conjugation and restricted
bond rotations. J Org Chem 2000;65(10):2900–6. https://doi.org/10.1021/
jo991927o.
[14] Maity A, Ghosh U, Giri D, Mukherjee D, Maiti TK, Patra SK. A water-soluble
BODIPY based ‘OFF/ON’ fluorescent probe for the detection of Cd2þ ions with high
selectivity and sensitivity. Dalton Trans 2019;48(6):2108–17. https://doi.org/
10.1039/C8DT04016H.
[41] Leen V, Leemans T, Boens N, Dehaen W. 2- and 3-monohalogenated BODIPY dyes
and their functionalized analogues: synthesis and spectroscopy. Eur J Org Chem
2011;2011(23):4386–96. https://doi.org/10.1002/ejoc.201100324.
[42] Kang D, Eom D, Mo J, Kim H, Sokkalingam P, Lee C-H, et al. Synthesis of BODIPY
chromophores bearing fused-carbocycles. Bull Kor Chem Soc 2010;31(2):507–10.
https://doi.org/10.5012/BKCS.2010.31.02.507.
[15] Chen JJ, Conron SM, Erwin P, Dimitriou M, McAlahney K, Thompson ME. High-
efficiency BODIPY-based organic photovoltaics. ACS Appl Mater Interfaces 2015;7
(1):662–9. https://doi.org/10.1021/am506874k.
[16] Klfout H, Stewart A, Elkhalifa M, He H. BODIPYs for dye-sensitized solar cells. ACS
Appl Mater Interfaces 2017;9(46):39873–89. https://doi.org/10.1021/
acsami.7b07688.
[43] Trofimov Reaction. Comprehensive organic name reactions and Reagents. 2010.
p. 2793–6. https://doi.org/10.1002/9780470638859.conrr626.
[44] Kazuyuki D, Miwako M. Short step synthesis of 4-substituted indoles using
palladium-catalyzed C-C bond forming reaction. Heterocycles 1996;42(1):113–6.
https://doi.org/10.3987/COM-95-S34.
[17] Thumuganti G, Gupta V, Singh SP. New dithienosilole- and dithienogermole-based
BODIPY for solar cell applications. New J Chem 2019;43(22):8735–40. https://doi.
org/10.1039/C9NJ00550A.
[18] Lu H, Mack J, Yang Y, Shen Z. Structural modification strategies for the rational
design of red/NIR region BODIPYs. Chem Soc Rev 2014;43(13):4778–823. https://
doi.org/10.1039/C4CS00030G.
[45] Trofimov BA, Mikhaleva AI, Schmidt EY, Protsuk NI, Ivanov AV, Ryapolov OA.
A Catalyst for the selective dehydrogenation of 4,5,6,7-tetrahydroindole into
indole. Dokl Chem 2011;437(2):95–7. https://doi.org/10.1134/
S0012500811040057.
[19] Yuan L, Lin W, Zheng K, He L, Huang W. Far-red to near infrared analyte-
responsive fluorescent probes based on organic fluorophore platforms for
fluorescence imaging. Chem Soc Rev 2013;42(2):622–61. https://doi.org/
10.1039/C2CS35313J.
[46] Forberg D, Kallmeier F, Kempe R. Iridium catalyzed synthesis of tetrahydro-1H-
indoles by dehydrogenative condensation. Inorganics 2019;7(8):97. https://doi.
org/10.3390/inorganics7080097.
[20] Boens N, Leen V, Dehaen W, Wang L, Robeyns K, Qin W, et al. Visible absorption
and fluorescence spectroscopy of conformationally constrained, annulated BODIPY
dyes. J Phys Chem A 2012;116(39):9621–31. https://doi.org/10.1021/
jp305551w.
[47] Mikhaleva AI, Platonov VB, Riapolov OA, Schmidt EY, Trofimov BA. Catalyst for
dehydrogenation of 4,5,6,7-tetrahydroindole into indole and method for preparing
thereof. 2008. WO2008147246A1.
[48] Trofimov BA, Mikhaleva AI, Vasil’tsov AM, Ivanov AV, Schmidt EY, Protsuk NI,
et al. Selective dehydrogenation of 4,5,6,7-tetrahydroindole to indole with a nickel
sulfide catalyst. Dokl Chem 2010;434(2):257–9. https://doi.org/10.1134/
S0012500810100022.
[21] Li L, Nguyen B, Burgess K. Functionalization of the 4,4-difluoro-4-bora-3a,4a-
diaza-s-indacene (BODIPY) core. Bioorg Med Chem Lett 2008;18(10):3112–6.
https://doi.org/10.1016/j.bmcl.2007.10.103.
[22] Sobenina LN, Vasil’tsov AM, Petrova OV, Petrushenko KB, Ushakov IA, Clavier G,
et al. General route to symmetric and asymmetric meso-CF3-3(5)-Aryl(hetaryl)- and
3,5-Diaryl(dihetaryl)-BODIPY dyes. Org Lett 2011;13(10):2524–7. https://doi.org/
10.1021/ol200360f.
[49] Sobenina LN, Petrova OV, Petrushenko KB, Ushakov IA, Mikhaleva AI, Meallet-
Renault R, et al. Synthesis and optical properties of difluorobora-s-diazaindacene
dyes with trifluoromethyl meso-substituents. Eur J Org Chem 2013;2013(19):
4107–18. https://doi.org/10.1002/ejoc.201300212.
[23] Jiang X-D, Fang T, Liu X, Xi D. Synthesis of meso-CF3-substituted BODIPY
compounds with redshifted absorption. Eur J Org Chem 2017;34:5074–9. https://
doi.org/10.1002/ejoc.201700800.
[50] Tomilin DN, Sobenina LN, Petrushenko KB, Ushakov IA, Trofimov BA. Design of
novel meso-CF3-BODIPY dyes with isoxazole substituents. Dyes Pigments 2018;152:
14–8. https://doi.org/10.1016/j.dyepig.2018.01.026.
�
[24] Schoder S, KordDaorounKalai S, Reissig H-U. Novel alkoxy-substituted dipyrrins
and near-IR BODIPY dyes—preparation and photophysical properties. Chem Eur J
2017;23(51):12527–33. https://doi.org/10.1002/chem.201701108.
[25] Hayashi Y, Obata N, Tamaru M, Yamaguchi S, Matsuo Y, Saeki A, et al. Facile
synthesis of biphenyl-fused BODIPY and its property. Org Lett 2012;14(3):866–9.
https://doi.org/10.1021/ol2033916.
[51] Bessette A, Auvray T, Desilets D, Hanan GS. Non-symmetric benzo[b]-fused
BODIPYs as a versatile fluorophore platform reaching the NIR: a systematic study
of the underlying structure–property relationship. Dalton Trans 2016;45(18):
7589–604. https://doi.org/10.1039/C5DT04444H.
[52] Wakamiya A, Murakami T, Yamaguchi S. Benzene-fused BODIPY and fully-fused
BODIPY dimer: impacts of the ring-fusing at the b bond in the BODIPY skeleton.
Chem Sci 2013;4(3):1002–7. https://doi.org/10.1039/C2SC21768F.
[53] Kee HL, Kirmaier C, Yu L, Thamyongkit P, Youngblood WJ, Calder ME, et al.
Structural control of the photodynamics of BoronÀ Dipyrrin complexes. J Phys
Chem B 2005;109(43):20433–43. https://doi.org/10.1021/jp0525078.
[54] Prlj A, Fabrizio A, Corminboeuf C. Rationalizing fluorescence quenching in meso-
BODIPY dyes. Phys Chem Chem Phys 2016;18(48):32668–72. https://doi.org/
10.1039/C6CP06799A.
[26] Sarma T, Panda PK, Setsune J-i. Bis-naphthobipyrrolylmethene derived BODIPY
complex: an intense near-infrared fluorescent dye. Chem Commun 2013;49(84):
9806–8. https://doi.org/10.1039/C3CC44834G.
[27] Ni Y, Zeng W, Huang K-W, Wu J. Benzene-fused BODIPYs: synthesis and the impact
of fusion mode. Chem Commun 2013;49(12):1217–9. https://doi.org/10.1039/
C2CC38380B.
6

D.N. Tomilin et al.
Dyes and Pigments 176 (2020) 108228
[55] Umezawa K, Nakamura Y, Makino H, Citterio D, Suzuki K. Bright, color-tunable
fluorescent dyes in the VisibleÀ Near-infrared region. J Am Chem Soc 2008;130(5):
1550–1. https://doi.org/10.1021/ja077756j.
the 3-position: synthesis and optical properties. Dyes Pigments 2017;136:488–95.
https://doi.org/10.1016/j.dyepig.2016.09.009.
[58] Petrushenko KB, Petrushenko IK, Petrova OV, Sobenina LN, Ushakov IA,
Trofimov BA. Environment-Responsive 8-CF3-BODIPY dyes with aniline groups at
the 3 position: synthesis, optical properties and RI-CC2 calculations. Asian J Org
Chem 2017;6(7):852–61. https://doi.org/10.1002/ajoc.201700117.
[59] Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al.
Gaussian 09. Wallingford, CT, USA: Gaussian, Inc.; 2009.
[56] Tomilin DN, Petrushenko KB, Sobenina LN, Gotsko MD, Ushakov IA,
Skitnevskaya AD, et al. Synthesis and optical properties of meso-CF3-BODIPY with
acylethynyl substituents in the 3-position of the indacene core. Asian J Org Chem
2016;5(10):1288–94. https://doi.org/10.1002/ajoc.201600303.
[57] Petrushenko KB, Petrushenko IK, Petrova OV, Sobenina LN, Trofimov BA. Novel
environment-sensitive 8-CF3-BODIPY dye with 4-(dimethylamino)phenyl group at
7