Synthesis and photophysical properties of a new BODIPY-based siloxane dye

Article abstract of DOI:10.1016/j.tetlet.2016.01.059

A fluorescent dye comprising four BODIPY derivatives conjugated to a cyclotetrasiloxane core was synthesized by consecutive hydrosilylation and esterification reactions. Photophysical properties of the dye in various organic solvents were investigated. It was shown that due to a fourfold extinction coefficient increase and a moderate quantum yield decrease the brightness of the tetra-BODIPY dye in low-polarity solvents, calculated per molecule, increased 3 times when compared to mono-BODIPY. By contrast, in polar solvents there was a dramatic drop in brightness apparently associated with intramolecular interactions of the low-polar BODIPY chromophores.

Full text of DOI:10.1016/j.tetlet.2016.01.059

Accepted Manuscript
Synthesis and photophysical properties of a new BODIPY-based siloxane dye
Alexey A. Pakhomov, Yuriy N. Kononevich, Maria V. Stukalova, Evgeniya A.
Svidchenko, Nikolay M. Surin, Georgy V. Cherkaev, Olga I. Shchegolikhina,
Vladimir I. Martynov, Aziz M. Muzafarov
PII:
S0040-4039(16)30058-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.01.059
TETL 47223
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
11 November 2015
15 January 2016
18 January 2016
Please cite this article as: Pakhomov, A.A., Kononevich, Y.N., Stukalova, M.V., Svidchenko, E.A., Surin, N.M.,
Cherkaev, G.V., Shchegolikhina, O.I., Martynov, V.I., Muzafarov, A.M., Synthesis and photophysical properties
of a new BODIPY-based siloxane dye, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.
2016.01.059
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Graphical Abstract
Synthesis and photophysical properties of a
new BODIPY-based siloxane dye
Leave this area blank for abstract info.
Alexey A. Pakhomov, Yuriy N. Kononevich, Maria V. Stukalova, Evgeniya A. Svidchenko, Nikolay M. Surin,
Georgy V. Cherkaev, Olga I. Shchegolikhina, Vladimir I. Martynov and Aziz M. Muzafarov

1
Tetrahedron Letters
Synthesis and photophysical properties of a new BODIPY-based siloxane dye
Alexey A. Pakhomova,*, Yuriy N. Kononevichb, Maria V. Stukalovab, Evgeniya A. Svidchenkoc, Nikolay
M. Surinc, Georgy V. Cherkaevc, Olga I. Shchegolikhinab, Vladimir I. Martynova and Aziz M. Muzafarovb,c
aM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russian Federation
bA.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation
cN.S. Enikolopov Institute of Synthetic Polymeric Materials, Russian Academy of Sciences, 117393 Moscow, Russian Federation
* Corresponding author. Tel.: +7-495-336-5111; e-mail: alpah@mail.ru (A.A. Pakhomov)
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A fluorescent dye comprising of four BODIPY derivatives conjugated to a cyclotetrasiloxane
core was synthesized by consecutive hydrosilylation and esterification reactions. Photophysical
properties of the dye in various organic solvents were investigated. It was shown that due to a
fourfold extinction coefficient increase and a moderate quantum yield decrease the brightness of
the tetra-BODIPY dye in low-polarity solvents, calculated per molecule, increased 3 times when
compared to mono-BODIPY. By contrast, in polar solvents there was a dramatic drop in
brightness apparently associated with intramolecular interactions of the low-polar BODIPY
chromophores.
Available online
Keywords:
BODIPY
siloxane
cyclotetrasiloxane
hydrosilylation
fluorescence
solvatochromism
2016 Elsevier Ltd. All rights reserved.
Bright and photostable fluorescent compounds are of
particular interest in the fields of modern photonics,
photochemistry and molecular biology. Derivatives of 4,4-
yield, which is the primary reason for fluorescence quenching of
chromophore bearing dendrimers.17 In the present work, we have
attempted to design a multichromophore compound with the
minimized effect of self-quenching. We presumed that the use of
TMB would prevent aggregation-induced quenching owing to the
BODIPY π-system being protected by four methyl groups.
difluoro-4-bora-3a,4a-diaza-s-indacene
(BODIPY)
display
outstanding photophysical properties and usually possess
considerable light-absorbing capacity, high quantum yield, sharp
absorption and emission bands, remarkable photostability and
solubility in organic solvents.1 Different BODIPY derivatives
span most of the visible and near infrared spectrum and offer
great potential for the development of biomolecular labels,2,3
chemosensors,4 energy transfer cassettes,5,6 dye-sensitized solar
cells (DSSC)7 and can be used in photodynamic therapy.8
BODIPYs were used as a base structure in the construction of
fluorescent molecular rotors9 and fluorescent liquid-crystalline
A new tetra-BODIPY-substituted siloxane fluorescent dye
was synthesized from two fragments: a siloxane ring and 3-(4,4-
difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl)-
propionic acid (TMB-propionic acid). The latter was prepared
analogously to the method described earlier.13 Briefly, the
reaction of succinic anhydride 1 with methanol followed by
thionyl chloride chlorination yielded chloroanhydride 3 (Scheme
1). Product 3 was reacted with 2,4-dimethylpyrrole 4 in dry
dichloromethane under argon at room temperature for 24 h
followed by neutralization using DIPEA and subsequent reaction
with boron trifluoride diethyl etherate. Addition of an extra
equivalent of dimethylpyrrole 4 (3:1 instead of the commonly
used 2:1) drastically improved the reaction yield. After
purification, the resultant TMB ester 5 was saponified using
LiOH in water-THF yielding TMB-propionic acid 6.
dendrimers.10 Herein, we have synthesized
a carboxylic
derivative of 1,3,5,7-tetramethyl-BODIPY (TMB) and
conjugated it with cyclotetrasiloxane. Cyclic and polyhedral
oligosiloxanes are known to be indispensable building blocks for
12
the preparation of a variety of organic polymer materials11,
improving their thermal and optical properties.13, Moreover,
14
these compounds display high chemical inertness and
16
biocompatibility.15,
As might be expected, conjugation of
several TMB fluorophores with the cyclosiloxane core structure
would enhance the total brightness, which is proportional to the
product of extinction (ε) and quantum yield (QY). Thus,
combining four fluorophores at the cyclotetrasiloxane matrix
might enhance the total brightness up to 4 times due to an
extinction increase. On the other hand, raising of the local
concentration of fluorophores may lead to the formation of
nonfluorescent aggregates and in turn lead to a drop in quantum
The synthesis of hydroxyl-bearing cyclotetrasiloxane began
from methyltriethoxysilane 7 (Scheme 2). The potassium cis-
tetramethylcyclotetrasiloxanolate 8 was synthesized in good yield
by the method previously reported by our group.18 The reaction
was carried out at room temperature in a mixture of ethanol and
hexane. It should be noted that in this reaction only the cis-
isomer can be formed, which was confirmed by X-ray analysis.19

2
At the next stage, modification of compound 8 by the
catalyst. Product 14 was obtained in 48% yield and purified by
silica column chromatography using toluene/ethylacetate (10:1)
as eluent. It should be noted that during the reaction,
isomerization of the siloxane ring with loss of the all-cis
configuration takes place as evident from the 29Si NMR spectrum
(see ESI). Probably, isomerization of the all-cis compound is the
result of DMAP base treatment. To verify this proposal we
incubated cis-cyclotetrasiloxanolate 13 with DMAP and observed
an analogous loss of the all-cis configuration. The obtained
compounds were characterized by 1H, 13C, 19F, 29Si NMR, IR, MS
and elemental analysis.
dimethylsilyl
Spectral properties of the obtained mono-TMB ether 5 and
tetra-TMB-siloxane 14 were studied in various solvents (Fig. 1).
In the case of mono-TMB compound 5, both absorbance and
emission spectra showed a moderate hypsochromic shift upon
increased solvent polarity (Table 1). The shape of the spectra did
not vary upon solvent change and the molar extinction coefficient
was constant, within the experimental error of determination. The
quantum yield slightly changed from 0.85 to 0.95, which
supported a lack of solvent quenching effect. Thus, there was no
detectable specific interactions of the chromophore with the
solvent. In the case of tetra-TMB siloxane 14, the expected
approximately fourfold molar extinction coefficient increase was
detected, along with a moderate increase in the absorbance and
emission bandwidths. The Stocks shift slightly increased in
Scheme 1. Synthesis of TMB-propionic acid 6.
group was accomplished. Reaction between salt
8 and
chlorodimethylsilane was carried out in dry toluene at room
temperature. The obtained compound 9 was used without further
purification. Allyloxytrimethylsilane 11 was used to introduce
the hydroxyl-bearing fragment into the siloxane ring. The
hydrosilylation reaction was carried out in dry toluene under an
inert atmosphere at room temperature. Product 12 was
sufficiently pure and was used at the next stage without any
purification. It should be noted that during the reaction only β-
addition occurred which was confirmed by NMR. The
trimethylsilyl protecting group was removed by stirring at room
temperature in methanol with acetic acid. Thus, for the first time
a hydroxyl-bearing cis-cyclotetrasiloxane 13 was prepared and
characterized.
toluene, dichloromethane and tetrahydrofuran.
A
slight
bathochromic shift and broadening of the fluorescence emission
spectra could be explained by alterations in a solvate shell
resulting from high density of intramolecular fluorophores in
tetra-TMB-siloxane. There was a considerable change of the
quantum yield, the most drastic decrease was observed in
acetonitrile (up to 11-fold). Compared to other solvents,
acetonitrile possesses the highest dielectric constant and dipole
moment, followed by tetrahydrofuran and dichloromethane. The
lowest reduction of the quantum yield was observed in toluene,
The final step of the synthesis of the star-shaped BODIPY-
bearing siloxane fluorescent dye was Steglich esterification
(Scheme 2). The reaction was carried out in dichloromethane at
room temperature using dicyclohexylcarbodiimide (DCC) as
condensing agent and 4-dimethylaminopyridine (DMAP) as
Scheme 2. Synthesis of star-shaped cyclotetrasiloxane with four terminal TMB fluorophores.

3
i.e. there was a correlation of QY with the dielectric constant
and solvent polarity. Apparently, quasi-concentration
a
quenching takes place: in a polar solvent, TMB-groups attached
by flexible spacers tend to move closer together to a distance
equivalent to one at very high fluorophore concentrations.
Generally, solvent properties have a significant influence on the
formation of concentration-induced aggregates. To verify
concentration-induced
TMB
interfluorophore
aggregate
formation, we prepared a solution of mono-TMB 5 in THF with a
concentration of 10-2 M. The average distance between the
fluorophores became close to that within tetra-TMB siloxane
under these conditions. For spectra measurement we further used
a 1 mm thin cuvette. In the absorption spectrum of the
concentrated solution of mono-TMB 5 we observed off-scale
readings of all bands and did not detect any new ones. In
contrast, in the fluorescence emission spectrum we observed a
new peak with a maximum at ~ 650 nm (Fig. 1с), that could be
21
referred to excimer emission.20, We reconstructed the whole
emission spectrum and estimated the QY of TMB in concentrated
solution to be 47%, which was close to QY of tetra-TMB 14 in
THF. In this way the formation of weakly fluorescent excimers
can cause quenching of fluorescence both in a concentrated TMB
solution and in tetra-TMB.
Thus, several BODIPY fluorophores combined together in a
single molecule can exhibit considerable solvatochromism that is
not characteristic for a single BODIPY molecule. Owing to a
considerable brightness increase in nonpolar media and a
fluorescence quenching effect in polar ones, TMB-siloxane
conjugates can be used as microenvironment sensitive probes in
real-time biomolecular imaging for monitoring biomolecular
interactions with the cellular membrane and for the study of
dynamic conformational transformations of biological
molecules.22 Another remarkable feature of tetra-TMB-siloxane
14 is its high solubility in organic solvents. Compared to the
original TMB 5, which is a crystalline powder, tetra-TMB 14 is
an oil, which is readily mixed with organic solvents. Therefore, it
is possible to generate TMB solutions of very high
concentrations.
Figure 1. Normalized absorption (—) and fluorescence emission
(-●-) spectra of mono-TMB 5 (a) and tetra-TMB cyclosiloxane 14
(b) in different solvents with fluorophore concentration 10-5 М. (с)
Normalized emission spectra (at 570 nm) of mono-TMB 5 in THF at
concentration 10-5 М (green ●), 10-2 М (red ■), full reconstructed
spectrum of mono-TMB 5 at a concentration of 10-2 М (red —) and
difference spectrum, which corresponds to excimer (blue —); insert
shows magnification of 600-750 nm interval.
In summary, a fluorescent dye comprising of four BODIPY
derivatives conjugated to the cyclotetrasiloxane core was
synthesized. Analysis of the spectral properties of the dye
showed that tetra-BODIPY cyclosiloxane remained fluorescent in
low-polarity solvents, whereas in polar solvents, there was a
considerable drop of the quantum yield due to intramolecular
interactions of BODIPY chromophores. Compared to mono-
BODIPY, the brightness of the dye in THF, DCM and toluene
Table 1. Spectral characteristics of mono-TMB 5 and tetra-TMB cyclosiloxane 14 in various solvents.
Δλ1/2a abs (cm-1)
Δλ1/2a em ( cm-1)
Compound
Solvent
Toluene
λmax abs (nm)
ε (M-1cm-1)
λmax em (nm)
Φf (%)
εab
µc (Db)
0.36
mono-TMB 5
505
79100
513
85
750
1190
2
DCM
THF
502
501
497
505
502
501
498
78300
80200
509
508
505
517
512
512
506
94
95
90
64
50
49
8
800
760
810
870
840
880
980
1130
1100
1220
1730
1480
1620
1480
9
8
1.58
1.63
3.2
ACN
Toluene
DCM
THF
75200
38
2
tetra-TMB 14
337200
325200
356000
300800
0.36
1.58
1.63
3.2
9
8
ACN
38
a half-width of absorbance or emission peak.
b dielectric constant of solvent.
с dipole moment of solvent.

4
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decrease. Consequently, the TMB-siloxane conjugate may serve
as a base structure in the design of compounds with high molar
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Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/
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