Heavy-atom-free charge transfer photosensitizers: Tuning the efficiency of BODIPY in singlet oxygen generation via intramolecular electron donor-acceptor interaction

Article abstract of DOI:10.1016/j.dyepig.2019.01.019

To test the tunability of charge transfer (CT)-based BODIPY photosensitizers in generating singlet oxygen (¹Δ_g), twelve meso-phenyl-BODIPY (donor-acceptor) type compounds have been synthesized and fully characterized, in which the ph

Full text of DOI:10.1016/j.dyepig.2019.01.019

Accepted Manuscript
Heavy-atom-free charge transfer photosensitizers: Tuning the efficiency of BODIPY in
singlet oxygen generation via intramolecular electron donor-acceptor interaction
Wenbin Hu, Yanhe Lin, Xian-Fu Zhang, Mingna Feng, Siwen Zhao, Jing Zhang
PII:
S0143-7208(18)32412-4
https://doi.org/10.1016/j.dyepig.2019.01.019
DYPI 7292
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 1 November 2018
Revised Date: 6 January 2019
Accepted Date: 14 January 2019
Please cite this article as: Hu W, Lin Y, Zhang X-F, Feng M, Zhao S, Zhang J, Heavy-atom-free
charge transfer photosensitizers: Tuning the efficiency of BODIPY in singlet oxygen generation
via intramolecular electron donor-acceptor interaction, Dyes and Pigments (2019), doi: https://
doi.org/10.1016/j.dyepig.2019.01.019.
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ACCEPTED MANUSCRIPT
Singlet oxygen formation yield of (CH3O)n-phenyl-BODIPY donor-acceptor
conjugate is proportional to the number of methoxy group.

ACCEPTED MANUSCRIPT
Heavy-atom-free charge transfer photosensitizers: Tuning the
efficiency of BODIPY in singlet oxygen generation via intramolecular
electron donor-acceptor interaction
Wenbin Hua, Yanhe Lina, Xian-Fu Zhangb,*, Mingna Fenga, Siwen Zhaoa, Jing
Zhanga
a
College of Chemical Engineering, Hebei Normal University of Science and
Technology, Qinhuangdao, Hebei Province, China, 066004
b MPC Technologies, Hamilton, Ontario, Canada L8S 3H4
*Corresponding author
E-mail addresses: zhangxianfu@tsinghua.org.cn, zhangxf111@hotmail.com
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Abstract
To test the tunability of charge transfer (CT)-based BODIPY photosensitizers in
generating singlet oxygen (1∆g), twelve meso-phenyl-BODIPY (donor-acceptor) type
compounds have been synthesized and fully characterized, in which the phenyl
moiety is modified with respective 0, 1, 2 and 3 methoxy groups to increase its
electron-donating ability. The UV-Vis absorption spectra, fluorescence emission
spectra, fluorescence quantum yield, fluorescence lifetime, excited triplet state
formation, and singlet oxygen formation properties are measured. DFT quantum
chemical computation is also carried out to explain the experiments. The occurrence
of intra-molecular CT is confirmed by UV-Vis absorption, fluorescence properties and
quantum chemical computation. The triplet excited state formation is evidenced by
laser flash photolysis technique. The quantitative photosensitized singlet oxygen
formation is demonstrated by DPBF (diphenylisobenzofuran) chemical trapping
method.
This type of BODIPY CT photosensitizers show good tunability in generating
singlet oxygen (1∆g). When the number of methoxy group on the donor is increased
(so that CT is enhanced), the efficiency of singlet oxygen generation becomes higher
from 0.070 to 0.30. When solvent polarity is increased (CT is also enhanced), the
efficiency of singlet oxygen generation is also increased significantly. The increase in
singlet oxygen generation is accompanied by the decrease in fluorescence quantum
yield and fluorescence lifetime values. These facts show that a higher CT efficiency in
a simple phenyl-BODIPY donor-acceptor conjugate can lead to significant higher
quantum yield of singlet oxygen generation. These results are useful in designing
novel CT-based heavy-atom-free photosensitizers for photodynamic therapy of tumor.
Keywords: Charge transfer photosensitizer; singlet oxygen; BODIPY; photodynamic
therapy
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1. Introduction
Photosensitizers (PSs) that generate singlet oxygen (1∆g) are the key of
photodynamic therapy of tumor (PDT) [1-5]. PDT has great potential for the
treatment of various cancers [6,7] and drug-resistant microbes [8,9], due to its many
advantages over the traditional chemotherapy [10-12], including higher precision of
the targets, lower systemic damage, non-invasion, reusable and controllable
characteristics. PDT relies on three basic elements: PS, light, and molecular oxygen. A
traditional PS molecule absorbs specific light and becomes an excited singlet state S1
(S0 + hv → S1), S1 then transforms to a triplet excited state T1 with slightly lower
energy (S1→T1), T1 then gives its energy to a surrounding oxygen molecule and
1
1
results in the formation of singlet oxygen O2 [13,14]: T1 + O2 → S0+ O2(1∆g).
1
Singlet oxygen O2 (1∆g) is considered to be the main reactive oxygen species (ROS)
for the tissue ablation in PDT [15,16].
Charge transfer (CT)-based photosensitizers (CTPSs) are new members of PS
family [17-21]. A traditional PS generates T1 from its S1 state via the spin flipping of
the electron in the molecular LUMO,
S1:HOMO(↑)LUMO(↓) or HOMO(↓)LUMO(↑)
→
T1: HOMO(↑)LUMO(↑) or HOMO(↓)LUMO(↓).
However, this type of electron spin reversing in S1 of some compounds is not efficient.
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives are such examples.
Nonhalogenated BODIPYs show very low T1 formation quantum yield because they
are highly fluorescence emissive. In recent years, BODIPYs have been proposed as
PSs for PDT due to their high molar extinction coefficient, good photochemical
stability, chemically robustness and good solubility in organic solvents [22,23]. To
this aim heavy atom effect have been attached to a BODIPY to make them efficiently
generate T1 [24,25]. In recent studies, however, PCT (Photoinduced CT) or PET
(Photoinduced electron transfer) are also found to be very efficient for causing T1 and
singlet oxygen formation, especially for BODIPY dyes [26-29]. The PCT/PET-based
PSs are advantageous because they are halogen-free and easily tailored to act as
activable PSs. A donor-acceptor (D-A) type molecular structure is a prerequisite for
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this type of PSs. The mechanism of T1 generation for these PSs is: S1 generates charge
separated state (CSS) via PET/PCT:
D-BODIPY(S1) → Dδ+-BODIPYδ− (0<δ≤1),
and then charge recombination of CSS produces T1:
Dδ+-BODIPYδ−→D-BODIPY(T1),
this is possible because S1 energy > CSS energy > T1 energy. The reported
PET/PCT-based BODIPY PSs are mainly meso-aryl-BODIPY conjugates, where the
aryl moiety is a relatively large electron donor, such as pyrene, anthracene, and
naphthalene [27-29].
Fig. 1. Structures of the methoxy-functionalized sensitizers
In order to make the PCT/PET-based BODIPY PSs easier use in vivo, we show in
this report that even the meso-phenyl-BODIPY can be easily modified to remarkably
increase the efficiency of BODIPY in T1 and singlet oxygen formation. We therefore
have synthesized a library of one to three meso-methoxys modified phenyl-BODIPY
conjugates. The increase in the number of methoxy on the phenyl makes the moiety a
better electron donor and enhances PCT/PET from the phenyl to BODIPY, which
significantly promotes the generation of T1. By changing the number and position of
methoxys on the phenyl, we expect to finely tune the singlet oxygen generation
efficiency. Fig. 1 shows the structures of the studied BODIPYs. BODIPY 2, 3 and 4
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contain one methoxy group, BODIPY 23, 24, 26, 34 and 35 contain two methoxys,
while BODIPY 234, 345 and 246 contain three methoxys on the phenyl. The starting
materials are cheap and commercially available, while the preparation procedure for
the compounds is simple and only involves one pot reaction.
2. Experimental section
2.1. Reagents and Apparatus
All chemicals were purchased from Sigma-Aldrich, Acros Organics, Merck or
Fluka at the highest commercial grade and were used without further purification. All
solvents were dried and redistilled before use. Dry solvents were prepared with
standard methods [30,31]. Merck 60 F254 silica gel precoated sheets (0.2 mm thick)
were used for analytical thin-layer chromatography (TLC). Silica gel (200-400mesh,
1
Merck) was used for flash column chromatography. H and 13C NMR spectra were
1
recorded with a Bruker dmx NMR spectrometer (600 MHz for H and 75 MHz for
1
13C). The spectra were recorded in CDCl3. H NMR chemical shifts are reported in
parts per million relative to tetramethylsilane (δ = 0.00 ppm), using the residual
solvent signal as the internal reference. 13C NMR chemical shifts are reported in ppm
with CDCl3 (δ = 77.67 ppm) as the internal standard. Carbon spectra were broad band
decoupled and calibrated on the particular solvent signal. Chemical shift multiplicities
were indicated by s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and br
(broad). The unit of the coupling constant is Herz (Hz). Mass spectra were registered
by atmospheric pressure chemical injection (APCI) in a LTQ Orbitrap XL TOF
spectrometer.
2.2. Synthesis
General Procedure for the Synthesis of BODIPYs: The synthetic procedure for
BODIPY (Fig. 1) is analogous to that described in ref [27-29]. An appropriate
aldehyde (1.0 mmol) and 2,4-dimethylpyrrole (0.200g, 2.1 mmol) were added to
absolute dichloromethane (20 mL). The color of the solution was turned into red after
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the addition of one drop of trifluoroacetic acid. The reaction mixture was then quickly
stirred at room temperature for 18 hours. 2,3-dicyano-5,6-dichlorobenzoquinone
(0.227g, 1.0 mmol) was added, and stirring was continued for 120 min.
N,N-Diisopropylethylamine (5ml) and boron trifluoride etherate (10ml) were added to
the solution sequentially. After stirring for 12 hours, the reaction mixture was washed
with water. Organic layer was dried with anhydrous MgSO4, filtered, and evaporated
under reduced pressure. The crude product was purified by silica gel column
chromatography using 20 % dichloromethane in n-hexane as mobile phase. The
brightly fluorescent fraction containing the product was collected then the solvent was
removed under reduced pressure.
5,5-difluoro-10-(2-methoxyphenyl)-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-
f][1,3,2]diazaborinin-4-ium-5-uide (2). Yield: 21%. Orange crystals. 1H NMR (CDCl3,
600 MHz): δ 7.44 (t, 1H, J=6.66), 7.14 (d, 1H, J=7.40), 7.08 (t, 1H, J=7.38), 6.99 (d,
13
1H, J=8.34), 5.96 (s, 2H), 3.77 (s, 3H), 2.55 (s, 6H), 1.43 (s, 6H). C NMR (CDCl3,
150 MHz): δ 156.41, 154.92, 142.60, 138.96, 131.56, 130.63, 129.52, 123.81, 121.51,
120.85, 111.14, 55.62, 14.61, 13.84. HRMS (APCI) m/z: 335.1714 [M-F]+ ([M-F]+
calcd. 335.1731).
Characterization data for eleven other compounds are given in supporting
information.
2.3. Photophysical characterization
Details of the photophysical properties of BODIPYs, including absorption,
fluorescence spectra, singlet oxygen and fluorescence quantum yields, and
fluorescence lifetime are given in our previous publication [28-29].
2.3.1. Absorption Measurements
Ground-state UV-visible absorption of BODIPYs were recorded on a Vary 8454
spectrometer from Agilent Technologies in a quartz cell of 1 cm path length at 20.0 ±
0.5 ºC.
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2.3.2. Fluorescence Measurements
Fluorescence excitation and emission spectra, fluorescence quantum yields, the
fluorescence and excited singlet state lifetimes were acquired on a FLS 920
Fluorescence Spectrometer from Edinburgh Instruments at 20 ºC. 1 cm pathlength
cuvettes were used, and the slit width was 2.5 nm for both excitation and emission.
All spectra were corrected for the sensitivity of the photomultiplier tube. All
measurements, both absorbance and emission, were acquired within 2 h of solution
preparation at room temperature (20-25 ºC),
(1). Fluorescence quantum yield (Φf) of the BODIPYs was determined by the
comparative method using equation (1).
F A0 ns2
Φf = Φ0f
s
⑴
F As n02
0
F is the area under the fluorescence emission curve, and the areas of the emission
spectra were integrated in the range of 480 - 700 nm. A represents the optical density
at which the sample was excited. The refractive indices (n) of the solvents were
employed in calculating the fluorescence quantum yields in different solvents. The
subscript 0 stands for a reference compound, and s represents samples. Fluorescein in
0.1 M NaOH was used as the reference (Φf0= 0.92) [32]. The excitation wavelength is
475 nm. The absorbance of the sample and reference solutions at the excitation
wavelength ranged between 0.08 and 0.10. All solutions were air saturated for Φf
measurements.
(2). Fluorescence lifetime was measured by Edinburgh FLS920
spectrophotometer via the time-correlated single photon counting (TCSPC) method
with excitation at 509 nm by a diode laser (50 ps fwhm). The emission was monitored
at the wavelength of emission maximum. The lifetime values were computed by the
F900 software supplied by Edinburgh Instruments Ltd.
2.3.3. Singlet oxygen quantum yield
The quantum yield of singlet oxygen production was determined by the chemical
trapping method using diphenylisobenzofuran (DPBF). The absorbance of the studied
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BODIPYs was adjusted around 1.0 at 509 nm (irradiation wavelength) in 1 cm path
length quartz cells (2 mL). The absorbance of DPBF was adjusted around 1.0 at 410
nm in order to avoid BODIPY aggregation. Singlet oxygen causes a remarkable
degradation of DPBF at 410 nm, where the DPBF absorbance decrease was measured
at fixed time intervals, as defined for each experiment. The quantum yields of singlet
oxygen generation were calculated by comparing with that of the reference compound
8-methylthio-2,6-diiodoBODIPY according to Equation (2)
k Iaref
kref Ia
Φ∆ =Φ∆ref
⑵
Where Φ∆ref is the singlet oxygen quantum yield for the standard
(8-methylthio-2,6-diiodoBODIPY, ΦΔR=0.85, practically independent of the solvent)
for excitation at 505 nm), k and kref represent the DPBF photobleaching rate constants
ref
in the presence of the respective samples and standard, respectively, and Ia and Ia
stand for the number of photons absorbed by the sensitizer and the standard at the
irradiation wavelength of 509 nm, respectively. Their ratio can be obtained by the
following equation:
Iaref
Ia
Aref
1−
10−
=
⑶
1−
10−
A
In which, A and Aref is the absorbance of a BODIPY and the reference compound
8-methylthio-2,6-diiodoBODIPY at excitation wavelength 505 nm, respectively.
2.4. Computational simulation
The calculations were carried out using density functional theory (DFT) method
as implemented in the Gaussian 09 package. The B3LYP exchange-correlation
functional was chosen together with a 6-311G basis set for structural optimization.
The solvent effect was modeled using the Polarizable Continuum Model (CPCM)
method. In all the cases frequency analysis was made after geometry optimization to
ensure the convergence to an energy minimum.
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3. Results and discussion
A meso-(OCH3)xphenyl-BODIPY (x=1, 2, 3) forms an intro-molecular
donor-acceptor (D-A) entity which act as the PCT-based photosensitizer in this study.
meso-(methoxy)xphenyl is the donor moiety, while the BODIPY is the acceptor.
Keeping the BODIPY unit unchanged, adding more methoxys onto the phenyl at
different positions, the charge transfer intensity from D to A is then affected by three
factors: the number of methoxys, the position of the methoxys, and solvent polarity.
By changing any one of the three factors, we can tune the efficiency of singlet oxygen
formation if the D-A entity is really a CT-based photosensitizer. To this purpose,
twelve meso-aryl BODIPYs have been synthesized by a facile three-step one-pot
1
procedure (Fig. 1) [28-29]. These BODIPYs have been structurally identified by H
13
NMR, C NMR, HRMS and UV-Vis absorption spectra. All the spectrum results are
consistent with the desired structures. These NMR and HRMS spectra are presented
in supplementary information.
Due to the presence of methoxy and the phenyl groups, these BODIPYs are all
well soluble in organic solvents, such as n-hexane, benzene, toluene, DCM,
chloroform, THF, ethyl acetate, acetone, ethanol, methanol, acetonitrile, DMF and
DMSO. Seven solvents ranging from nonpolar, low polar to high polar ones
(n-hexane, ethyl acetate, THF, pinacolone, acetone, methanol and acetonitrile) have
been used to measure their photophysical properties and singlet oxygen generation
ability.
3.1. Singlet oxygen formation tuned by methoxy and solvent polarity
The singlet oxygen formed by the BODIPY photosensitization was identified by
chemical trapping method using 1,3-diphenylisobenzofuran (DPBF). DPBF is a well
known specific chemical trapper of singlet oxygen (1
∆g) [33]. As shown in Fig. 2,
with light irradiation at 510 nm in air saturated acetonitrile (at which the light is
absorbed only by the BODIPY PS) DPBF absorption (peak at 410 nm) decreases with
time while the absorption of the BODIPY shows no change. In the absence of any one
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of oxygen (purged by bubbling argon), light irradiation, or a BODIPY PS, the
absorbance decrease of DPBF at 410 nm did not occur. These results mean that the
singlet oxygen formation is indeed due to photosensitization of the BODIPY.
0 s
1.4
1.3
1.2
1.1
1.0
0.9
0.8
0.7
0.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
10 s
20 s
30 s
40 s
50 s
60 s
70 s
80 s
90 s
100 s
400 420 440 460 480 500 520 540 560 580 600
Wavelength (nm)
0
20
40
60
80
100
Time (s)
Fig. 2. Left: Evolution of DPBF (60 µmol/L) absorption spectra in air saturated acetonitrile
containing BODIPY 246 (20 µmol/L) with light excitation at 510 nm. Right: Absorbance
decrease of DPBF at 410 nm with time (data extracted from spectra of Fig. 2 left ).
The quantum yield of singlet-oxygen formation (Φ∆) was obtained by measuring
the photooxidation kinetics of DPBF. The DPBF absorbance at 410 nm is plotted
against time (Fig. 2 right). A good linear relation between them indicates that the
reaction kinetics is zero order: c(t) = c(0) - k·t, in which k is the reaction rate constant,
t is time, and c(t) is the concentration of DPBF at time t. Singlet oxygen quantum
yields (Φ∆) of the studied BODIPYs were calculated according to the literature
[34,35]. The reference compound 8-methylthio-2,6-diiodoBODIPY has a singlet
oxygen quantum yield of 0.80 under the conditions of the study in all solvents [36].
Table 1 shows the Φ∆ values together with other photophysical parameters (also
see Table S1 of supporting information). Compared to BODIPY 1 that contains an
unsubstituted phenyl, the methoxy substitution leads to higher Φ∆ values. Fig. 3 plots
Φ∆ against
ε (solvent dielectric constant to represent polarity) and n (number of
methoxys), respectively. It shows that Φ∆ value increases with the increase in the
number of methoxy groups on the phenyl moiety, and this increase is more effective
in more polar solvent. The position of methoxys also affects Φ∆ values, but in a
complicated way as shown in Fig. 3 bottom. These BODIPYs exhibit very significant
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solvent effect: a higher Φ∆ value is observed in a more polar solvent. The data in
methanol for all compounds show deviation from the trend, likely because the strong
H-bonding O−H···F. In order to explain these results, UV-vis absorption spectra,
fluorescence emission spectra, fluorescence lifetimes, and transient absorption
properties were measured.
Fig. 3. Top: solvent polarity (ε) effect on Φ∆. Bottom: the influence of n (number of
methoxy on the phenyl) on Φ∆ (next to each data point is the compound number
), the
red line is the linear fitting results.
Table 1. Photophysical properties of the BODIPY PSs in different solvents**
abs
max
em
max
λ
λ
∆λ
(nm)
11
τf
Solvent
ε
Φf
Φ∆
χ2
(nm) (nm)
(ns)
3.81
3.65
3.39
3.98
3.73
3.37
3.9
36.6 0.52 0.068
20.7 0.46 0.050
497
498
499
498
500
501
498
508
509
511
510
512
511
510
1.00
1.24
1.18
1.18
1.12
1.27
1.22
CH3CN
Acetone
Pinacolone
EtOAc
11
12.8 0.55
0.11
12
6.02 0.58 0.057
7.52 0.56 0.033
2.02 0.56 0.038
12
12
THF
1
10
n-hexane
MeOH
33
0.58 0.031
12
abs
** Φ : fluorescence quantum yield, Φ : quantum yield for singlet oxygen formation, λ : UV−vis
max
f
∆
em
absorption maximum, λ : fluorescence emission maximum, ∆λ: the Stokes shift, τ : fluorescence
max
f
lifetime, χ2: chi squared value for fluorescence decay that obtaining τf.
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λabs
λem
∆λ
τ1
Solvent
ε
Φf
Φ∆
χ2
(nm) (nm) (nm)
(ns)
36.6 0.57
20.7 0.78
0.18
0.17
499
501
502
502
503
504
500
512
513
514
514
516
516
514
13
12
12
12
13
12
14
-
-
CH3CN
Acetone
Pinacolone
EtOAc
-
-
-
-
12.8 0.74 0.078
6.02 0.76 0.057
7.52 0.87 0.061
2.02 0.98 0.029
-
-
6.42
5.78
1.19
1.11
THF
n-hexane
MeOH
2
33
0.69 0.021
λabs
λem
∆λ
τ1
τ2
Solvent
ε
Φf
Φ∆
0.18
χ2
(nm) (nm) (nm)
(ns)
(ns)
36.6 0.54
500
503
505
504
506
507
503
513
516
520
520
520
519
518
13
13
15
16
14
12
15
-
-
-
-
-
-
-
-
-
-
-
-
CH3CN
Acetone
Pinacolone
EtOAc
20.7 0.72 0.082
12.8 0.64 0.081
6.02 0.47 0.073
7.52 0.64 0.051
2.02 0.71 0.040
5.77 1.38(.12) 1.08
THF
6.26
-
-
1.09
n-hexane
MeOH
26
33
0.58 0.036
--
λabs
λem
∆λ
τ1
τ2
solvent
ε
Φf
Φ∆
χ2
(nm) (nm) (nm)
(ns)
(ns)
36.6 0.55
20.7 0.80
12.8 0.69
0.31
0.11
0.16
501
503
505
503
506
505
513
515
517
511
517
520
12
12
12
8
-
-
-
-
-
-
-
-
-
-
-
-
CH3CN
Acetone
Pinacolone
EtOAc
6.02 0.64 0.063
7.52 0.78 0.059
2.02 0.95 0.024
11
15
5.70 1.35(.05) 1.14
THF
6.35
-
1.10
n-hexane
33
0.68 0.074
503
515
12
-
-
-
MeOH
246
3.2. UV-Vis absorption spectra and intra-molecular donor-acceptor charge transfer
The UV/vis absorption and fluorescence properties of these BODIPYs in
different solvents are also included in Table 1 (and Table S1 of supporting
information). Fig. 4 shows the spectra of compound 2, 26 and 246. Most compounds
display the typical UV-Vis absorption spectra of BODIPY type (supporting
information):37 a main band at about 500 nm with a shoulder at ca. 475 nm, and a
weak band at ca. 360 nm. For compound 26 and 246, however, an additional weak
band occurs at ca. 525 nm. This new band is red shifted relative to the usual main
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band, and the intensity of the new band is sensitive to the solvent polarity. These
characters suggest the new bands are due to CT (charge transfer) absorption. The CT
absorption occurs only for compound 26 and 246, likely because the two methoxys at
position 2 and 6 of the phenyl are the closest to the BODIPY unit and better facilitates
charge transfer compared to other methoxys.
As is evident from Table 1, the main absorption band for each compound is
centered between 497 and 507 nm and the peak maximum is not sensitive to either
solvent polarity or the number and position of methoxy group, because the methoxy is
not directly attached to the BODIPY chromophore but to the phenyl (which is nearly
orthogonal to the BODIPY).
Fig. 4. Top: Normalized UV-Vis absorption spectra of 2, 26, and 246 in different
solvents. Bottom: Normalized fluorescence emission spectra of 2, 26, and 246 in
different solvents (excitation at 475 nm, concentration ca. 5 µM).
3.3. Fluorescence Studies
The presence of the methoxys cause the change in fluorescence spectrum,
fluorescence quantum yield, and lifetime reflects the intensity of photoinduced charge
transfer from the donor to the acceptor. Fig. 4 shows the fluorescence spectra of the
BODIPY donor-acceptor conjugates in different solvents. These compounds exhibit
fluorescence in the range 500–550 nm, which is the typical emission characteristics of
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BODIPY fluorophores [38]. For compound 26 and 246, however, a new band occurs
at about 530 nm. This red shifted and weak emission shows the characteristics of CT
emission. The associated photophysical processes are given below.
Light absorption:
Fluorescence:
Charge transfer:
CT emission:
D-A(S0) + hv
→
D-A(S1),
(i)
D-A(S1)
→
→
hv’+ D-A(S0),
(ii)
(iii)
(iv)
(v)
D-A(S1)
Dδ+-Aδ-,
Dδ+-Aδ-
→
hv”+ D-A(S0),
Charge recombination: Dδ+-Aδ-
→ heat+ D-A(S0),
Since CT state Dδ+-Aδ- easily undergoes fast reverse thermal charge transfer in polar
solvents to form ground state (process v), CT emission is observed only in hexane.
The CT emission band occurs only for compound 26 and 246, because the two
methoxys at position 2 and 6 of the phenyl are closer to the BODIPY unit than other
methoxys, which better facilitates charge transfer.
Except for that of 26 and 246 in hexane, the fluorescence emission spectrum of
each BODIPY is the mirror image of the corresponding main absorption band, which
implies that the emission is due to S1 decay of the BODIPY unit [39]. The Stoke shifts
of the BODIPYs are in the range 10-17 nm. The small Stoke shift is typical for
BODIPY compounds, indicating that the S1 of BODIPY unit has similar nuclear
configurations to its ground state. All these BODIPYs share the same fluorophore and
therefore exhibit very similar emission shape in different solvents except hexane.
Increasing the solvent polarity for each compound causes only a slight shift in the
emission maximum to longer wavelength (~2-6 nm) while the shape of emission
spectra is not changed (except 26 and 246 in hexane). These results show that the
remarkable solvent dependence of Φ∆ values does not result from the interaction
between the solvent and the BODIPY (either S0 or S1 state).
The fluorescence quantum yield (Φf) values of each BODIPY in different
solvents are also listed in Table 1 (and Table S1 of supporting information). Fig. 5
shows how the substitution pattern and solvent polarity (represented by ε) affect the
Φf value of a BODIPY conjugate. It is known that
Φf = kf/(kf+kisc+kic+kCT),
(4)
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in which kf is the fluorescence rate constant, kisc is the intersystem crossing rate
constant for T1 formation, kic is the internal conversion rate constant for heat releasing,
and kCT is the charge transfer rate constant.
Fig. 5. Solvent polarity (represented by dielectric constant ε) effect on Φf. Left: mono
substituted BODIPY 2, 3, and 4. Middle: di substituted BODIPY 23, 24, and 26.
Right: tri substituted BODIPY 234, 246, and 345. The dashed line in each plot is for
unsubstituted BODIPY 1.
Several conclusions can be drawn from Fig. 5 as following. The Φf value of each
compound shows clear decrease trends with the increase in solvent polarity except the
slight positive deviation of a few solvent. This decrease trend is consistent with the
effect of solvent polarity on photoinduced charge transfer or electron transfer. Since
kCT of PCT/PET becomes larger in more polar solvent, so intramolecular PCT/PET
partially quenches emission process and leads to a lower Φf value according to eq. (4).
This change is opposite to the effect of solvent polarity on Φ∆ value, which implies
that singlet oxygen production is positively correlated to the intensity of PCT or PET.
Since singlet oxygen originates from the T1 of a photosensitizer, we conclude that T1
formation is positively correlated to PCT or PET.
Triplet formation from CT state: Dδ+-Aδ-
1O2 generation from T1: D-A(T1) + O2
→
D-A(T1),
(vi)
→
D-A(S0) + 1O2.
(vii)
Based on the processes (i) to (vii), we can easily understand Fig. 3 which shows how
solvent polarity and methoxy number affect Φ∆ value. Higher solvent polarity
enhances charge transfer process (iii) and leads to more CT state formation, then more
CT state favors process (vi) and causes more T1 formation, which further gives more
singlet oxygen through process (vii). The increase in the number of methoxy on the
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phenyl enhances the electron donating ability of the phenyl moiety, which favors
better charge transfer, and then leads to higher Φ∆ value. Φ∆ value is mainly
determined by kCT value for these BODIPYs, since kisc is negligible for BODIPYs and
not affected by the number and position of methoxy group.
Fig. 5 also indicates the effect of methoxy position on Φf. Φf value is influenced
by both kic and kCT for these OCH3 modified BODIPYs, since the position of methoxy
changes kic, while both the number and position of methoxys alter kCT. For mono
OCH3 compounds, compared 2 shows higher Φf than 1 (the dashed line) in each
solvent, but compound 4 always exhibits lower Φf than 1 in each solvent. This is due
to both steric and electronic effect. In addition to its electronic effect, the OCH3 group
in compound 2 obstructs the rotation of the phenyl, which reduces the kic value and
increases Φf. Therefore 2’-OCH3 is dominated by steric effect over its electronic
effect. The OCH3 group in compound 4, however, has no steric effect but exhibits
only electron donating effect which increases kCT and decreases Φf. The OCH3 group
in compound 3 is farther away than that in compound 2 but closer than that in
compound 4 from the BODIPY unit, and therefore it displays weaker steric effect than
that of compound 2 but stronger steric effect than that of compound 4. This explains
the Φf ranking 2>3>4 in each solvent. Di- and tri-methoxy substituted BODIPYs are
some complicated due to the mutual influence of steric and electronic effect of each
OCH3 group at different positions. Nevertheless, the Φf ranking of trisubstituted
BODIPYs is 246>234>345 in each solvent, because 246 contains two methoxys at
position 2 and 6 that both show strong steric effect, 234 contains one 2-methoxy,
while 345 contains none.
The fluorescence lifetime of 2, 26, and 246 in hexane and THF were measured
to confirm the presence of PCT in polar solvents. Fig. 6 shows the emission decay
curves of these BODIPYs. For 26 and 246, the decay in polar THF is faster than that
in non polar n-hexane. For compound 2, the solvent effect on the emission decay is
not significant. In hexane, the fluorescence decays can be described by a
single-exponential fit, and the calculated lifetime is 5.78, 6.26, and 6.35 ns for 2, 26,
and 246 respectively. In THF, however, the decays of BODIPY 26 and 246 become
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biexponential, the lifetime for 26 is 1.38 (12%) and 5.77 ns (88%), and the lifetime
for 246 is 1.37 (5%) and 5.70 ns (95%). Comparing the lifetime value of the
short-lived component in THF with the lifetime in n-hexane, we see a very significant
decrease from 6.26 to 1.38 ns for 26, and from 6.35 ns to 1.37 ns for 246. This large
decrease in more polar solvent supports the presence of intramolecular PCT/PET. By
using equation kCT = 1/τf − 1/τf0, the rate constant of PCT/PET (kCT) in THF can be
calculated as 0.564
time, the emission rate constant (kf = Φf
and 0.15
109 s-1 for 26 and 246, respectively. So kCT is much larger than kf in THF,
i.e. PCT becomes the predominant process of S1 decay in THF.
×
109 and 0.572
×
109 s-1 for 26 and 246, respectively. In the mean
τf in hexane) can be calculated as 0.11
109
/
×
×
Fig. 6. The emission decay curves of the BODIPY 2, 26, and 246 with excitation at
405 nm (50 ps pulsed laser).
3.4. CT from quantum chemical calculations
The molecular geometry of the D-A conjugates is optimized either by DFT (for
ground state S0) or TD DFT (for excited state S1) at the B3LYP 6-311g level. The
HOMO and LUMO of a compound are then obtained from the calculated geometry.
The HOMO and LUMO electron density distribution between the donor and acceptor
units provides the evidence of PCT occurrence within the D-A type conjugated
molecules. In Fig. 7, we compare the electron density change of frontier molecular
orbitals of compound 2, 24, and 246 upon the change of solvent and/or photo
excitation.
For compound 246 (Fig. 7), in either vacuum or non polar solvent hexane, the
HOMO and LUMO of both S0 and S1 are mainly located on the BODIPY unit (Fig. 7
Top), indicating that ground state CT or photoinduced CT must be weak in vacuum or
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non polar solvent hexane. In acetonitrile (ACN), however, the HOMO of S0 is located
on both BODIPY and the phenyl unit, but the LUMO of S0 is located only on
BODIPY unit, indicating that ground state CT can occur. This result shows the strong
effect of solvent polarity. On the other hand, the HOMO of S1 of 246 in acetonitrile is
located only on the phenyl unit, but the LUMO of S1 is located only on BODIPY unit,
suggesting that photoinduced electron transfer (complete charge transfer) occurs from
the trimethoxy phenyl unit to the BODIPY moiety, which causes the fluorescence
quenching and lowers Φf and τf values. This result shows the strong effect of
photoexcitation on PCT/PET.
For compound 24 (Fig. 7 bottom left), photoinduced CT occurs only for S1 state
in acetonitrile, because the HOMO of S1 is located on both BODIPY and the phenyl
unit, while the LUMO of S1 is located only on BODIPY unit. In other cases, CT or
PCT is not significant since both HOMO and LUMO are mainly on the BODIPY unit.
For compound 2 (Fig. 7 bottom right), no significant CT or PCT can occur since
both HOMO and LUMO are always mainly on the BODIPY unit. Based on Fig. 7, it
is obvious that the intensity of CT or PCT is ranked by 246>24>>2, which confirms
that the number of methoxy group shows large effect on CT and PCT.
Fig. 7. The HOMO/LUMO of S0 and S1 state of compound 2, 24, and 246 calculated by DFT
method using B3LYP exchange-correlation functional together with a 6-311G basis set. The
solvent effect was modeled using the Polarizable Continuum Model (CPCM) method.
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ACN=CH3CN, hex = n-hexane.
3.5. Triplet excited state identification
Nanosecond laser flash photolysis (LFP) was used to confirm the ability to form
excited triplet state T1 for the donor-BODIPY conjugate. Using 246 as an example,
the BODIPY moiety is excited at 510 nm (4 ns pulsed laser with energy of 4 mJ) in
nitrogen saturated CH3CN solution. Fig. 8 shows the transient absorption spectra
(TAS) and the triplet decay curves. The positive absorption bands were observed at
435 nm. No significant TAS signal was detected for compound 1. The band shape and
positions are similar to the reported triplet-triplet (T1-Tn) absorption of other BODIPY
analogues.16, 17 The negative signal matches the images of ground state absorption
spectra. From the spectra in Fig. 8, we can see that the decay of the positive signal is
accompanied by the rise of negative signal (formation of S0 state), during which an
isobestic point exists. The decay lifetime of the positive signal is the same as that of
the rise lifetime of the negative signal (Fig. 8 middle). Further more, the decay
lifetime is 0.35
s in N2 saturated CH3CN (Fig. 8 right). These results show that excited triplet state is
indeed formed by the (OMe)3-phenyl substituted BODIPY upon light excitation.
µs in air saturated CH3CN for 246, but it becomes much longer as 6.4
µ
Fig. 8. Left: the transient absorption spectra of 246 (20 µM) in nitrogen saturated
CH3CN solution. Middle: the triplet decay curve of 435 nm and the ground state
recovery at 465 nm in nitrogen saturated CH3CN solution. Right: the triplet decay of
420 nm in air saturated CH3CN solution. The BODIPY moiety is excited at 510 nm (4
ns pulsed laser with energy of 4 mJ).
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4. Conclusions
We have synthesized and characterized twelve methoxy-phenyl-BODIPY
donor-acceptor type new CT photosensitizers. Their absorption and fluorescence
properties were measured in different solvents, from which intramolecular CT is
evidenced and CT intensity is shown to depend on the number of methoxys on the
phenyl. The singlet oxygen formation quantum yields in seven solvents were
measured, from which it is established that Φ∆ is positively related to CT intensity.
The excited triplet state was identified by laser flash photolysis. The results show that
Φ∆ values are affected by the number and position of methoxys and solvent polarity.
With the increase in solvent polarity, the Φf and τf values of these BODIPYs decrease
but Φ∆ values increase. In short, a simple phenyl-BODIPY can be tailed easily to
donor-acceptor type halogen free CT photosensitizers. Further studies are in progress
to improve the water solubility of these PET-based BODIPY photosensitizers and to
develop their potential applications in destroying tumor cells through photodynamic
therapy.
Acknowledgements
We gratefully acknowledge financial support by the Natural Science Foundation of
Hebei Province (Contract B2016407084 and B2014407080), Youth Talent Program of
Hebei High School (Contract BJ2017028), the Technology Foundation for Selected
Overseas Chinese Scholar of Hebei Province (Contract C2015003046), Hebei
Provincial Hundred Talents Plan (Contract E2013100005).
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Highlights
ò Eight new charge transfer (CT)-based BODIPY photosensitizers are synthesized.
ò The CT efficiency is adjusted by adding 0 to 4 methoxys on meso-phenyl.
1
ò The increase in either the number of methoxys or solvent polarity enhances O2
formation.
ò Higher CT efficiency favors higher singlet oxygen generation quantum yield.