BisBODIPY as PCT-based halogen free photosensitizers for highly efficient excited triplet state and singlet oxygen formation: Tuning the efficiency by different linking positions

Article abstract of DOI:10.1016/j.dyepig.2017.07.051

Four covalent BODIPY hetero-dimers, formed by different linking positions at (2,2′), (2,8′), (3,8′) and (8,8′) respectively, were designed and synthesized to compare their ability for excited triplet state (T₁) and singlet oxygen generation. In

Full text of DOI:10.1016/j.dyepig.2017.07.051

Accepted Manuscript
BisBODIPY as PCT-based halogen free photosensitizers for highly efficient excited
triplet state and singlet oxygen formation: Tuning the efficiency by different linking
positions
Xian-Fu Zhang
PII:
S0143-7208(17)31304-9
10.1016/j.dyepig.2017.07.051
DYPI 6140
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 7 June 2017
Revised Date: 11 July 2017
Accepted Date: 21 July 2017
Please cite this article as: Zhang X-F, BisBODIPY as PCT-based halogen free photosensitizers for
highly efficient excited triplet state and singlet oxygen formation: Tuning the efficiency by different linking
positions, Dyes and Pigments (2017), doi: 10.1016/j.dyepig.2017.07.051.
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ACCEPTED MANUSCRIPT
BisBODIPY as PCT-based halogen free photosensitizers for highly
efficient excited triplet state and singlet oxygen formation: Tuning
the efficiency by different linking positions
a,b,*
Xian-Fu Zhang
a
Institute of Applied Photochemistry & Center of Analysis and Measurements, Hebei
Normal University of Science and Technology, Qinhuangdao, Hebei Province, China
0
66004.
b
MPC Technologies, Hamilton, ON, Canada L8S 3H4.
To whom correspondence should be addressed
*
E-mail: zhangxianfu@tsinghua.org.cn. Fax: 86 3358387040. Tel: 86 3358387040
1

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Abstract
Four covalent BODIPY hetero-dimers, formed by different linking positions at (2,2’),
2,8’), (3,8’) and (8,8’) respectively, were designed and synthesized to compare their
(
ability for excited triplet state (T ) and singlet oxygen generation. In contrast to
1
BODIPY monomers that show negligible photosensitizing ability, the four dimers are
very efficient for T and singlet oxygen formation depending on the individual linking
1
style and solvent polarity. Laser flash photolysis, time-resolved/steady state
fluorescence, quantum chemical calculation and thermodynamic analysis revealed
that the mechanism of triplet state T formation is different from the traditional
1
intersystem crossing mechanism. The T formation is due to charge recombination of
1
the twisted charge separation state (TCSS), while the TCSS is generated by
photoinduced intramolecular charge transfer (PCT) from one BODIPY monomer
moiety to another within the dimer. The PCT based photosensitizers are also medium
polarity sensitive which may be very useful in designing and synthesizing of
photosensitizers for photodynamic therapy of tumor, photobiology and organic
photochemistry.
Keywords: singlet oxygen; BODIPY dimer; excited triplet state; twisted charge
transfer state; laser flash photolysis
2

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1
. Introduction
BODIPY (abbreviation for boron-dipyrromethene, the official IUPAC name is
,4-difluoro-4-bora-3a,4a-diaza-s-indacene) compounds have been advocated as
4
photosensitizers (PSs) in generating excited triplet state and singlet oxygen.[1-3]
BODIPYs have high molar absorption coefficients, are environment insensitive,
exhibit good resistance to photobleaching, and show higher light–dark toxicity ratios
than other PDT agents, these features make them ideal to act as good photosensitizers
for PDT.[1-3] Among them, bisBODIPYs (Scheme 1) have been undergoing
extensive investigations due to their halogen- and heavy metal-free nature.[4-11]
halogen- and heavy metal- contained drugs are not desirable due to the potential
harmful side effect. The type of BODIPY dimer PSs is unique because they are able
to significantly increase the quantum yields of singlet oxygen formation (Φ up to
∆
0
.90) whereas the corresponding BODIPY monomer compounds show little
photosensitizing ability (Φ <0.10).[5, 9] In addition, the BisBODIPY PSs can be
∆
structurally tailored to get high medium polarity selectivity which is a desirable
,
feature for activable PSs in photodynamic therapy of tumors.[7] [9]
Fig. 1. The chemical structures of BODIPY monomers and dimers in this study.
3

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The bisBODIPY PSs reported are mainly formed by the monomers directly
linked at the position (2, 8’), such as d-2-8’ shown in Scheme 1. However, a
bisBODIPY compound can be synthesized by linking two monomeric BODIPY units
at different positions, e.g. 2-2’, 2-8’, 3-8’, and 8-8’, as shown in Scheme 1.[12] It is
still not clear whether and how the linking position can affect the photosensitizing
capability of a bisBODIPY. Although a few types of BODIPY dimers have been
examined by us and other authors, each type of them was studied separately from
other types and has not been compared under the same condition.[4-11] In this report
we compare these different types of BODIPY dimers to understand how their
efficiency and mechanism are influenced by the linking positions.
2
. Experimental Section
2
.1. General
Reagents and solvents for synthesis were used as received from commercial
suppliers unless stated otherwise. All reactions were performed in oven-dried or
flame-dried glassware unless otherwise stated, and were monitored by TLC using
1
13
0
.25 mm silica gel plates with UV indicator (60F-254). H and C NMR are obtained
on a 600 MHz Bruker Top Spin NMR spectrometer at room temperature. Chemical
1
13
shifts (δ) are given in ppm relative to CDCl (7.26 ppm for H and 77 ppm for C) or
3
1
to internal TMS (0 ppm for H). High-resolution mass spectra were obtained on a
Thermo Fisher mass spectrometer using APCI-TOF or ESI in positive mode. IR
spectra were recorded at room temperature on a Shimadzu FTIR-8900 spectrometer.
4

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UV-visible spectra were recorded on an Agilent 8454 spectrophotometer using 1 cm
matched quartz cuvettes. Fluorescence was measured using Edinburgh Instruments
FLS920 spectrometer.
All solvents for spectrum, photophysics and DPBF photosensitized oxidation
are dried and redistilled according to standard procedures. Details on the
measurements for photophysics and singlet oxygen are given in the supporting
information.
2
.2. 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 6-31G(d) 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.
2
2
.3. Synthesis
.3.1.m1 (4,4-difluoro-8-phenyl-1,3,5,7-tetramethyl-4-boron-3a,4a-diaza-s-indacene
)
m1 was prepared according to the general procedure using an aldehyde as a
precursor. 50 ml anhydrous dichloromethane (СH Cl ) containing benzaldehyde (2.0
2
2
mmol) and 2,4-dimethyl-pyrrole (4.0 mmol) was stirred under argon protection. After
1
5 min, one drop of trifluoroacetic acid (CF COOH) was added, and the solution was
3
5

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stirred for 12 h at room temperature. Then 2.0 mmol of DDQ (2,3-dichloro-5,6-
dicyano-1,4-benzoquinone) was added and the solution was stirred for 30 min. The
excess of boron trifluoride diethyl etherate (BF O(Et) , 4 ml) and triethylamine
3
2
(
N(Et) , 4 ml) was added and stirring was continued for 30 min. The intense
3
fluorescence of reaction mixture was observed on that stage. The formation of
intermediates and BODIPY products on every stage was monitored by UV-Vis
absorption spectra. After that the reaction mixture was washed with water (100
mL×3), the organic layer was dried over anhydrous MgSO , filtered and evaporated.
4
The crude product was purified by silica gel chromatography (eluent
СH Cl /hexane=2:1 v/v) to afford pure samples. The product is dark red crystals.
2
2
o
-1
Yield: 154 mg, 20 %. mp 127-130 C; IR (KBr)/cm : 723, 978, 1072, 1155, 1196,
1
471, 1508, 1543 (ν BODIPY ring); 1508, 1543 (ν B-F); 1308, 2854, 2924 (ν CH3);
1
UV/vis (DCM) λmax/nm: 501; H NMR (600 MHz, Chloroform-d) δ 7.54–7.47 (m,
3
H), 7.31–7.28 (m, 2H), 6.00 (s, 2H), 2.58 (s, 6H), 1.39 (s, 6H). HRMS (APCI): m/z
+
calcd for C H BF N [M+H] 325.1682, found 325.1682; HRMS (APCI): m/z calcd
1
9
20
2
2
+
for C H BFN [M-F] , 305.1625, found 305.1623.
1
9
19
2
2
.3.2. m2 (4,4-difluoro-1,3,5,7-tetramethyl-4-boron-3a,4a-diaza-s-indacene)
m2 was synthesized by modifying a literature procedure.[14] 250 mL
1
,2-dichloroethane was deaerated by bubbling N . 2,4-dimethyl pyrrole (1 mL, 11.37
2
mmol), triethylorthoformate (0.95 mL, 5.69 mmol) and POCl (0.58 mL, 6.25 mmol)
3
were added to the deaerated solvent. Reaction was allowed to stir for 2 hours at room
6

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temperature. Then 11.5 mL NEt and 11.5 mL BF -etherate were added. After 1 hour
3
3
the reaction was washed with water (3×250 mL), the organic layer separated, dried on
anhydrous NaSO and evaporated in vacuo. Column chromatography with CHCl as
4
3
1
the eluent yielded the pure product as reddish solid (400 mg, 28 %). H NMR (600
1
3
MHz, Chloroform-d) δ 7.07 (s, 1H), 6.07 (s, 2H), 2.55 (s, 6H), 2.27 (s, 6H). C NMR
(151 MHz, Chloroform-d) δ 156.69, 133.35, 120.06, 118.99, 14.67, 11.29.
The dimer d2-2’, d2-8’, d3-8’, and d8-8’ were prepared by the paths shown in
Scheme 1, and the detailed procedure for each compound is given below.
Scheme 1. The synthetic reaction for d2-2’, d2-8’, d3-8’, and d8-8’.
2
.3.3. d2-2’ synthesis
d2-2’ was synthesized by modifying the procedure in reference.[15, 16] FeCl3•
6
H O (245 mg, 0.90 mmol) was refluxed in SOCl (2 mL) for 1 h. After SOCl was
2
2
2
7

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evaporated under vacuum, dried CH Cl (10 mL) containing monomer 1 (130 mg,
2
2
0
.40 mmol) was added, the resulted solution turned red and then purple immediately
o
from deep green. It was then stirred at 20 C for 30 min, MeOH (10 mL) was added to
quench the reaction. The solution was then added to deionized water (100 mL) and
stirred for 2 hrs. The organic layer was separated and washed by water three times
(
3×150 mL), then dried by MgSO and filtered. The filtrate was evaporated to give
4
the solid, which was then purified by column chromatography (CH Cl : petroleum
2
2
-1
ether = 2: 1). Yield: 7 mg, 6%. IR (KBr)/cm : 723, 983, 1084, 1161, 1188, 1357,
1
402, 1465, 1514, 1539 (ν BODIPY ring); 1305, 2854, 2924 (ν CH ); UV/vis (DCM)
3
+
λmax/nm: 533; HRMS (APCI): m/z calcd for C H B F N [M+H] 647.3135, found
38
37
2
4
4
+
6
6
7
2
47.3134; HRMS (APCI): m/z calcd for C H B F N [M-F] 627.3078, found
38 36 2 3 4
1
27.3078. H NMR (600 MHz, Chloroform-d) δ 7.52 (ddd, 2H, J = 9.3, 4.5, 2.4 Hz),
.49 – 7.47 (m, 3H), 7.33 (d, 2H, J = 7.5 Hz), 7.27 (dt, 3H, J = 4.3, 2.3 Hz), 6.01 (s,
1
3
H), 2.58 (s, 6H), 2.37 (s, 6H), 1.39 (s, 6H), 1.14 (s, 6H). C NMR (151 MHz,
Chloroform-d) δ 155.99, 154.68, 143.62, 141.68, 141.22, 135.04, 131.75, 131.24,
1
29.28, 129.14, 129.02, 127.95, 127.83, 124.73, 121.47, 14.68, 14.44, 13.34, 12.88.
2
.3.4. Synthesis of d2-8’
Compound m3 was synthesized by the procedure in our previous report.[5] Under
ice bath, DMF (7.5 mL) in 100 mL three-necked round bottom flask was saturated by
N with bubbling the gas for 20 min, POCl (7.5 mL) was added drop wise with
2
3
stirring in 5 min. Ice bath was then removed, and the resulted solution was stirred at
room temperature for 20 min. which resulted in a white sticky mixture. Monomer m1
(
194 mg, 0.6 mmol) in 1,2-ClCH CH Cl (70 mL) was added drop wise into the white
2 2
o
mixture, it was then stirred for 6 hrs. at 50 C. After cooling down, the solution was
8

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added drop wise into saturated NaHCO aq. solution (400 mL) with stirring for 30
3
min. The organic layer was extracted by dichloromethane, washed by water (2×200
mL), dried by MgSO and filtered. Red solid was obtained after evaporating the
4
filtrate under vacum. The crude compound m3 was purified by column
chromatography (eluent CH Cl : n-hexane = 2: 1). Yield, 180 mg, 85%. Then d2-8’
2
2
was prepared. CH Cl (10 mL, redistilled and dried) containing compound m3 (62 mg,
2
2
0
2
.18 mmol) was saturated by N with bubbling the gas for 30 min. Pyrrole (2 mL,
2
.80 mmol) and trifluoro acetic acid (9 µL, 0.12 mmol) were added, the resulted
solution was stirred at room temperature for 4 hrs. NaOH aqueous solution (0.2 M, 30
mL) was added to quench the reaction. The organic layer was extracted by
dichloromethane, washed by water (2×200 mL), dried by excessive MgSO and
4
filtered. The filtrate was added by p-chloranil (60 mg, 0.24 mmol) and stirred for 1 h
at room temperature, then triethyl amine (1 mL, 7.12 mmol) was put in under ice bath.
After the disappearance of white smog, BF -etherate (1 mL, 7.77 mmol) was added,
3
and the resulted solution was stirred at room temperature for 3hrs. 100 mL water was
added, and the organic layer was extracted by dichloromethane, washed by water
(
2×200 mL), dried by MgSO , filtered, and evaporated by rotavapor. The crude
4
compound was purified by column chromatography (eluent CH Cl : n-hexane = 1: 1).
2
2
-1
Dark red solid, yield: 10 mg, 11%. mp 220-223℃ ; IR (KBr)/cm : 721, 976, 1074,
114, 1191, 1263, 1409, 1473, 1508, 1541 (ν BODIPY ring); 1309, 2852, 2924 (ν
CH ); UV/vis (DCM) λ /nm: 506; HRMS (ESI): m/z calcd for C H B F N Na
1
3
max
28 24
2
4
4
+
[
[
M+Na] 537.2015, found 537.2011; HRMS (ESI): m/z calcd for C H B F N
28 24 2 3 4
+
1
M-F] 495.2134, found 495.2131. H NMR (600 MHz, Chloroform-d) δ 8.10 (d, 1H,
J = 8.4 Hz), 7.81 (s, 1H), 7.63 – 7.47 (m, 3H), 7.28 (s, 3H), 7.10 (d, 1H, J = 4.4 Hz),
6
.87 (d, 1H, J = 8.4 Hz), 6.68 (d, 1H, J = 4.5 Hz), 6.02 (d, 1H, J = 8.7 Hz), 1.60 (s,
9

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1
3
6
1
1
H), 1.28 (s, 6H); C NMR (151 MHz, Chloroform-d) δ 155.87, 146.84, 142.64,
40.96, 140.07, 136.25, 135.70, 134.56, 133.56, 133.44, 133.27, 131.71, 131.37,
30.48, 129.33, 128.76, 121.51, 120.04, 15.29, 14.66.
2
.3.5. Synthesis of d3-8’
The first step is the synthesis of m4. 1,3,5,7,8-tetramethyl-2,6-diethyl BODIPY
(
64 mg, 0.2 mmol) in THF/H O (8/0.08 mL) was titrated drop wisely by THF (2 mL)
2
containing DDQ (180 mg, 0.8 mmol) under ice bath and stirring. The mixture was
then stirred for 12 hrs at room temperature. Water (20 mL) was added to quench the
reaction. The organic phase was extracted by dichloromethane (3×50 mL), dried
(
anhydrous Na SO ), and rotavapored. The crude product was purified by column
2 4
chromatography (300-400 mesh silica, PE/EA = 6:1 v/v) afforded red solid m4. Yield
1
3
0 mg, 45%. H NMR (300 MHz, CDCl ) δ10.29 (s,1H), 2.76 (q, 2H, J=7.0 Hz),
3
2
.72(s, 3H), 2.64 (s, 3H), 2.38 (q, 2H, J=7.5 Hz), 2.34 (s, 3H), 2. 27 (s, 3H), 1.19 (s, 3
H), 1.03 (s, 3H).
nd
The 2 step is the synthesis of m5. m4 (0.5 mmol) was dissolved in pyrrole (5
mL) under argon protection, one drop of trifluoroacetic acid was added, the resulted
solution was stirred at r. t. for 0.5 h, then water (20 mL) was added to it. Organic
phase was extracted by dichloromethane (3×50 mL), washed by water (3×50 mL),
dried by anhydrous Na SO and rotavapored. The crude product was purified by
2
4
column chromatography (300-400 mesh silica, PE/EA = 5:1 v/v) afforded orange
1
solid m5. Yield 67 mg, 30%. H NMR (300 MHz, CDCl3) δ 8.51 (s, 2H), 6.68 (s, 2H),
6
.27 (s, 3H), 6.16 (s, 2H), 2.62 (s, 3H), 2.52 (s, 3H), 2.44-2.39 (m, 2H), 2.36 (s, 3H),
1
0

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2
.32 (d, 2H, J=7.5 Hz), 2. 27 (s, 3H),1.06 (t, 3H, J=7.4 Hz), 0.50 (t, 3H, J=7.2 Hz).
C NMR (75 MHz, CDCl3) δ153.4, 151.6, 140.8, 138.3, 137.7, 133.3, 132.5, 132.1,
1
3
1
31.1, 129.0, 116.9, 108.2, 106.6, 36.7, 30.3, 17.4, 17.1, 14. 8, 14.5, 14.3, 13.5, 12.5.
+
HRMS (APCI) calcd. for C H BF N [M+H] : 449. 2683, found 449.2674.
26
32
2
4
rd
The 3 step is d3-8’ Synthesis. m5 (0.1 mmol) was dissolved in DCM (10 mL),
then DDQ (45 mg, 0.2 mmol) was added under ice bath. 10 min later, triethyl amine
(
0.8 mL) was added and reacted for 30 min. BF -etherate (1 mL) was injected and
3
stirred at r.t. for 4 h. Water (20 mL) was added to quench the reaction. Organic phase
was extracted by dichloromethane (3×50 mL), washed by water (3×50 mL), dried by
anhydrous Na SO and rotavapored. The crude product was purified by column
2
4
chromatography (300-400 mesh silica, n-hexane/EE = 6:1 v/v) afforded orange solid
1
d3-8’. Yield 10 mg, 20%. H NMR (600 MHz, Chloroform-d) δ 7.92 (s, 2H), 6.89 (d,
2
2
0
1
1
4
H, J = 4.1 Hz), 6.49 (dd, 2H, J = 4.2, 1.7 Hz), 2.46 (s, 3H), 2.42 (s, 3H), 2.40 (s, 3H),
.32 (q, 2H, J = 7.5 Hz), 1.27 (s, 3H), 1.03 (t, 3H, J = 7.6 Hz), 0.93 (t, 3H, J = 7.5 Hz),
1
3
.90 (t, 2H, J = 6.9 Hz). C NMR (75 MHz, CDCl ) δ 159.6, 144.3, 141.5, 140.2,
3
38.4, 137.5, 136.3, 135.7, 133.4, 133.1, 131.4, 130.4, 118.2, 17.4, 17.1, 15.5, 14.7,
+
4.5, 14.2, 13.0. HRMS (APCI) calcd. for C H B F N [M-F] : 475.2452, found
2
6
28
2
3
4
75.2451.
2
.3.6. Synthesis of d8-8’
To a mixture of m6 (40 mg, 0.16 mmol) and pyrrole (2 ml, 28 mmol) in CH Cl
2
2
(10 mL) trifluoroacetic acid (0.021 mL, 0.27 mmol) was added under argon. After the
1
1

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reaction mixture was stirred at room temperature for 30 min, 0.2 mol/L NaOH (30
mL) aqueous solution was added to quench the reaction. The mixture was extracted
with CH Cl (3×25mL) and dried (anhydrous Na SO ). Column chromatography
2
2
2
4
(
silica, CH Cl ) afforded dipyrromethanes intermediate. A solution of the above
2 2
dipyrromethane in CH Cl (20 ml) was treated with DDQ (125 mg, 0.55 mmol) for 1
2
2
hr at room temperature, after the solution was treated with triethylamine (1 ml, 7.2
mmol) for 20 min, boron trifluoride etherate (3 ml, 23.9 mmol) was added and the
resulting solution was stirred for 2 hrs at room temperature. The solvent was removed
and the reside was column chromatographed (silica, hexane: ethyl acetate = 3:1) to
1
afforded a red solid (13 mg, 20%). H NMR (600 MHz, Chloroform-d) δ 7.99 (s, 2H),
7
4
1
.08 (d, 2H, J = 4.3 Hz), 6.84 (d, 2H, J = 4.3 Hz), 6.55–6.51 (m, 2H), 6.28 (d, 2H, J =
13
.2 Hz), 1.29 (s, 6H). C NMR (151 MHz, Chloroform-d) δ 159.78, 158.38, 145.74,
34.42, 131.00, 129.73, 123.60, 121.98, 120.17, 118.92, 14.79. HRMS (APCI
+
positive): C H B F N [M-F] calcd. 391.1513, found 391.1513; C H B F N
2
0
16
2
3
4
20 17
2
4
4
+
[
M+H] calcd. 411.1575, found 411.1571.
3
. Results and discussion
After the synthesis and purification, the UV-Vis, HRMS, and NMR data were
collected, these data are well consistent with the chemical structures of the targeting
bis-BODIPYs. To understand the mechanism and the linking position effect on the
singlet oxygen formation ability, we carried out a detailed study on their
photophysical properties in various solvents.
1
2

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3
.1. UV-Vis absorption spectra
The linking position shows strong influence on the UV-vis absorption spectra
Fig. 2). Compared to the monomer m1, all bis-BODIPYs exhibit either red-shifted
(
and broader spectra or a new red-shifted band appeared (d2-8’ and d8-8’), indicating
the J-type electronic coupling between the two components in each BODIPY dimer.
Fig. 2: The normalized UV-vis absorption spectra of BODIPY monomer m1 and different dimers
in air saturated CCl solutions.
4
The UV-Vis ground state absorption spectra in different solvents for each dimer
are shown in Fig. 3. The solvent change (from low to high polarity) showed little
effect on the spectra of each bis-BODIPY, so the ground state molecular structures of
the bisBODIPYs are little affected by the solvent polarity, i.e. ground state interaction
between the monomers in a bisBODIPY is not remarkably changed by the solvent
nature.
1
3

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Fig. 3. The UV-Vis absorption spectra of BODIPY dimers in different solvents.
3
.2. Fluorescence spectra
The fluorescence spectra of the dimers are displayed in Fig. 4 and compared to
that of the monomer m1. m1 shows the typical spectrum of a BODIPY with the band
maximum at ca. 510 nm which is only slightly modified by solvent polarity. In the
non polar hexane, all compounds show a single fluorescence band. However, a dimer
can exhibit dual fluorescence when the polarity of a solvent is sufficiently high (Fig.
4
), for example d-2,8’ and d-8,8’ exhibit dual emission in DCM, i.e. a new broad and
structureless band appears. The short-wavelength band of the dual fluorescence for a
dimer M -M (M and M are two linked BODIPY monomers) matches the
1
2
1
2
*
fluorescence from the local excited state of the dimer (LE band, [M -M ] → [M -M ]
1
2
1
2
+
hν’). The second band of the dual emission (which is broad, structureless and
largely red-shifted) has the typical feature of ICT (intra-molecular charge transfer)
•
δ+
•δ−
emission, suggesting the occurrence of following process: M1 -M2 → M -M +
1
2
hν’’. An ICT state is formed by PCT (photoinduced intramolecular charge transfer)
process (ii) after the light absorption process (i):
*
*
(
i) M -M + hν → M -M or M -M , then
1 2 1 2 1 2
1
4

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*
*
PETorPCT
•δ+
•δ−
(
ii) M -M or M -M     → M1 -M2 (δ<1 for PCT, δ=1 for PET).
1 2 1 2
If a whole electron is transferred, then it is a PET (photoinduced electron transfer)
process.
Fig. 4. Top: comparison of fluorescence spectra between monomer m1 with each dimer. Middle
and Bottom: solvent effect on the fluorescence spectra of BODIPY dimers. Ex. Wavelength is 470
nm. The emission is normalized at the emission maximum.
3
.3. Fluorescence quantum yield, lifetime and PCT process within a bisBODIPY
1
5

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Φf and τf were measured in different solvents (Table 1). The Φf value of three
dimers (d-2,8’, d-3,8’ and d-8,8’) shows the same behavior upon the increase of
solvent polarity. Dimer d-2,8’, for example, has high Φf value in non polar n-hexane
(
0.81) and c-hexane(0.70), but it decreases sharply in polar solvents, i.e. toluene
0.078), DCM (0.0050), and acetonitrile (0.0033). This strong solvent polarity effect
(
on Φf indicates that fast photoinduced charge transfer occurs within a dimer for three
*
*
PCT
•δ+
•δ−
dimers (d-2,8’, d-3,8’ and d-8,8’): M -M or M -M   → M1 -M2 , (0<δ≤1).
1
2
1
2
The dimer d-2,2’, on the other hand, shows significant Φf decrease only in high polar
acetonitrile but not in non or low polar hexane, toluene and DCM.
Table 1. Photophysical data
Solvent
λabs (nm) λem (nm) Φf
τ (ns)
m1
n-hexane 501
512
0.57
2.76 5.11 (51%)
c-hexane
toluene
DCM
503
503
501
497
508
510
501
513
0.48
2.67 5.24 (31%)
516
0.60
4.04
513
0.62
4.28
CH CN
508
0.63
3.97
3
m2
c-hexane
benzene
514
0.96
5.85
517
0.90
5.17
CH CN
508
1.00
5.70
3
d-2,2' n-hexane 534
575
0.29
3.79
c-hexane
toluene
DCM
536
536
533
528
576
0.25
3.40
519, 575
516, 575
512, 566
545
0.31
3.21
0.21
3.69
CH CN
0.017
0.81
0.29 3.71 (12%)
4.31
3
d-2,8' n-hexane 505
c-hexane
toluene
DCM
507, 530
549
0.70
4.18
509
506
503
515
516
518
517, 610
526, 740
517
0.078
0.0050
0.0033
0.34
1.95
0.53 4.38 (4%)
2.13 5.89 (56%)
4.24
CH CN
3
d-3,8' c-hexane
benzene
594
552, 645
550
0.045
0.036
1.57 4.97 (8%)
1.88 5.89 (87%)
DCM
1
6

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CH CN
507
523
524
519
510
546
0.025
0.80
1.39 6.29 (90%)
13.5
3
d-8,8' c-hexane
benzene
597
530, 674
534
0.080
0.0045
0.0051
6.07 8.59 (86%)
2.36 6.10 (75%)
4.27 7.45 (26%)
DCM
CH CN
543
3
The fluorescence lifetime (τf) of the dimers is also strongly affected by the solvent
polarity. The fluorescence decay curves are shown in Fig. 5, from which the
fluorescence lifetime values were calculated. d-2,8’, d-3,8’ and d-8,8’ shows mono
exponential decay only in non polar solvent with τf value 4.18, 4.24, and 13.5 ns in
c-hexane, respectively. With the increase in solvent polarity, the decay becomes
biexponential in DCM and MeCN, the smaller one of the two τf values is due to the
*
*
local excited state M -M or M -M , the larger one is due to the ICT state
1
2
1
2
•
δ+
•δ−
M1 -M2 . Because PCT is enhanced by solvent of higher polarity, τf value of the
local excited state in polar solvent ( f) is significantly smaller than that in non polar
τ
0
*
*
solvent (τf ), due to the intramolecular quenching of M1 by M or M by M1.
2
2
Therefore the fluorescence decay study supports the conclusion from previous
section.
1
7

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Fig. 5. The fluorescence decay of the dimers in different solvents with excitation at 509 nm (70 ps
diode laser), the emission was monitored at fluorescence peak maximum of LE state.
3
.4. Geometry of the bisBODIPYs calculated from quantum chemical methods
We calculated their optimal geometry and show them in Fig. 6. Apparently,
these covalent dimers are all formed by the head-to-head linking of two planar
π
-systems, and belong to the J-type dimers according to molecular exciton theory.[17]
o
o
o
The dihedral angle
θ
in the dimer is 67.5 (d2-2’), 62.9 (d2-8’), 70.0 (d8-8’), and
o
o
7
3.2 (d3-8’), respectively. The average
θ
is 68.4 (±5.5) , indicating these
compounds have the similar orientation between the two BODIPY units within a
dimer.
1
8

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Fig. 6: optimized dimer structures that show the change of the dihedral angle from d2-2’, d2-8’,
d3-8’ to d8-8’ (left to right), H atoms are hidden for clear viewing. Structural optimization were
carried out by Gaussian 09 on DFT B3LYP/6-31G level with toluene as solvent (cpcm model).
o
o
o
o
The calculated dihedral angle in the dimers: 67.5 (d2-2’), 62.9 (d2-8’), 73.2 (d3-8’), 70.0
(d8-8’), respectively. Every BODIPY chromophore in a monomer or dimer is strictly planar.
3
.5. PCT based on quantum chemical calculation
For the optimal molecular structure calculated by Gaussian09, the HOMO and
LUMO are obtained and shown in Fig. 7. For example, the HOMO of d-2,8’ is
located on the m1 moiety, while the LUMO is mainly on the m2 unit, which means
that upon deexcitation of S state one electron will be transferred from m2 unit to m1
1
moiety. So are the cases for d-3,8’ and d-8,8’. However, both the HOMO and LUMO
of d-2,2’ are equally distributed on two moieties, indicating that PCT is very difficult
to occur, and ICT state is not formed, so that T is very difficult to form. This
1
quantum chemical result is consistent with the previous study.
1
9

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Fig. 7. HOMO, LUMO of d2-2’, d2-8’. d3-8’, and d8-8’ in acetonitrile from Left to Right , Top
to Bottom.
3
.6. Identification of singlet oxygen from NIR luminescence
Fig. 8 shows the NIR luminescence spectra with excitation at 505 nm. An
emission band at 1270 nm was observed for all the bis-BODIPYs in air saturated
solutions, their signal intensity is much higher than that of m1. The emission decay at
1
5
270 nm after the excitation pulse was used to obtain the lifetime which has the value
9 ms.[18] The spectral shape and the lifetime value are consistent with that of singlet
1
oxygen ( ∆g) reported in literature, this result and the high signal intensity indicate
that the four dimers have good ability to produce singlet oxygen. Apparently d-2,8’
and d-8,8’ have much higher intensity than d-3,8’ and d-2,2’, suggesting the linking
position has a strong effect on the photosensitizing capability of a bisBODIPY. Even
the weakest PS d-2,2’ still shows much stronger signal than the monomer m1,
2
0

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indicate that the covalent dimerization can very significantly increase the
photosensitizing capability of BODIPY compounds.
1
Fig. 8. NIR Luminescence band of singlet oxygen (1270 nm band for ∆ emission) using
g
different BODIPY monomer m1 and dimers as photosensitizers in air saturated CCl solutions
4
with excitation at 505 nm (Absorbance is 0.18 at 505 nm).
3
.7. Identification of singlet oxygen by DPBF chemical trapping
2
1

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Fig. 9. The change of absorption spectrum upon irradiation time in air saturated solution
containing 20 µM DPBF and 5 µM photosensitizer with irradiation at 505 nm. Bottom Right: the
linear plot of absorbance at 410 nm against irradiation time.
Fig. 9 shows the change of absorption spectra of DPBF (diphenylisobenzofuran)
in the presence of BODIPY dimers as photosensitizers in air saturated solutions. The
absorption of DPBF decreases quickly with irradiation time, while the absorption
peak of the BODIPY photosensitizer showed little change. DPBF is a specific trapper
of singlet oxygen, it decomposes upon the reaction with singlet oxygen. The
decomposition did not occur in the absence of either a photosensitizer or oxygen,
which confirms that BODIPY dimers can really act as photosensitizers.
The formation quantum yield of singlet oxygen (Φ ) was determined for each
∆
compound in three solvents and their values are listed in Table 2. In toluene, three
dimers with 8’-linkage can generate singlet oxygen in high quantum yield (Φ is 0.63,
∆
0
.81, and 0.87 for d-3,8’, d-2,8’, and d-8,8’), but the Φ values decreased in solvents
∆
with lower polarity, while Φ of d-2,2’ is relatively low in all three solvents. In
∆
contrast, the monomers show negligible ability to produce singlet oxygen (Φ is from
∆
0
.023 to 0.083). In most cases, a solvent with higher polarity increases Φ . Also
∆
noticed is that Φ (d-8,8’) > Φ (d-2,8’) > Φ (d-3,8’) > Φ (d-2,2’), which clearly
∆
∆
∆
∆
indicates the linking position effect on Φ∆.
Table 2. The formation quantum yield of singlet oxygen
Toluene
CCl4
n-Hexane
d-2,2'
d-2,8'
0.053
0.81
0.047
0.31
0.040
0.19
2
2

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d-3,8'
d-8,8'
m1
0.63
0.076
0.29
0.38
0.87
0.23
0.065
0.083
0.023
0.080
0.052
0.041
m2
Solvent polarity shows little effect on the absorption spectra of a BisBODIPY
Fig. 3), but has large influence on the formation efficiency of singlet oxygen (Table
(
2
). It can then be concluded that the large solvent effect on Φ value is due to the
∆
excited state interaction between the monomers in a bisBODIPY. The exciton
coupling is not the major factor for enhancing the ability in singlet oxygen formation,
because d-2,2' has the strongest exciton coupling (according to its largest spectral red
shift in Fig. 2) but it has the lowest ability to generate singlet oxygen. It is apparent
that Φf correlates with Φ∆, i.e. with the increase in solvent polarity, Φf is decreased
but Φ∆ is increased. Since polar solvent enhances PCT, we must conclude that T state
1
•
δ+
•δ−
is generated from charge separation state: M1 -M2
→ M (T )-M or M -M (T ),
1 1 2 1 2 1
(0<δ≤1).
3
.8. Triplet excited state generation by the BODIPY dimers
1
To confirm that O is truly generated by the photosensitization of the dimers, we
2
identified their excited triplet state (T ) by laser flash photolysis (LFP). LFP was
1
carried out with excitation at 355 nm (4 ns pulse) in argon and air saturated solutions,
respectively. The transient absorption spectra (TAS) are shown in Fig. 10.
BODIPY m1 and m2 did not yield well detectable (TAS) within ns to µs range,
i.e. the formation yield of excited triplet state for the BODIPY monomers is too low
to be recorded, i.e. ISC (intersystem crossing) from S to T for the monomers are not
1
1
2
3

ACCEPTED MANUSCRIPT
efficient. On the other hand, the dimers all show well resolved transient absorption
spectra in argon-saturated solution, which are assigned to triplet–triplet (T -T )
1
n
absorption as described below.
Fig. 10. Transient absorption spectra (Left) and the decay of positive transient absorbance (Right)
in argon purged 20 µM solution, excitation wavelength is 355 nm (4 ns Nd:YAG pulsed laser).
2
4

ACCEPTED MANUSCRIPT
All spectra show a positive peak and a negative peak (Fig. 10), and the negative
absorption of a dimer matches its ground state absorption. With the decrease in the
positive signal (T decay), the negative signal increases (S formation), and the
1
0
positive bands are separated from the ground state bleaching with well defined
isosbestic points. The presence of isosbestic points indicates only two states are
involved in the transformation (T →S ). These are all the typical spectral behavior of
1
0
the T -T absorption. TAS of the bis-BODIPYs differs by their peak position, due to
1
n
their difference in the absorption of ground state (Fig. 2). The shape and position of
the TAS are similar to the T -T spectra of the BODIPY dyes in previous report.[9]
1
n
This similarity suggests that the positive signal of is also due to T -T absorption.
1
n
The decay of the positive signal, and the rise of the negative signal, can be well
fit by mono exponential function (Fig. 10 right), the rise time and the corresponding
decay time are the same, indicating that only one transient species (triplet state T ) is
1
present in the solutions. The triplet lifetime (τT) was computed to be 41 µs for d-2,2’,
2
3
µ
s for d-2,8’, 45 s for both d-3,8’ and d-8,8’, which are all long enough for
µ
photosensitizing the production of singlet oxygen.
In air saturated solution, the τT value is shortened dramatically. For example, τT
of d-8,8’ was decreased from 45 to 0.25
.23 s, but the TAS spectral shape and position were not altered by the presence of
oxygen. The rate constant of triplet quenching by oxygen can be then evaluated to be
µs, τT of d-2,8’ was decreased from 23 to
0
µ
9
9
-1 -1
2 ×10 and 2.2×10 M s , respectively, which is close to the 1/9 of diffusion rate
.0
constant. This effective oxygen quenching also suggests that the positive bands are
2
5

ACCEPTED MANUSCRIPT
indeed due to T -T absorption. Since TA spectra were not changed by O quenching,
1
n
2
1
the oxygen quenching to T must be a physical process, i.e. T + O
→ S + O . In
0 2
1
1
2
summary, LFP study evidences the T formation for the bis-BODIPYs and the
1
enhancement of T formation by the covalent dimerization.
1
4
. Conclusions
We have synthesized and characterized four BODIPY dimers linked at
different positions. We measured the triplet T and singlet oxygen formation
1
properties of the dimers. The tuning of the photosensitizing properties by different
linkages are significant, since dimer d-2,8’ and d-8,8’ can generate excited triplet
state and singlet oxygen with high quantum yields up to 0.81 and 0.87, respectively,
while their corresponding monomer compounds are non photoactive. Based on
UV-Vis absorption spectra, we conclude that T formation is from a twisted charge
1
separation state via charge recombination. We show that the photosensitizing
efficiency can be tuned not only by the linkage but also by solvent polarity. This
photosensitizing mechanism provides a novel strategy for designing efficient and
activable photosensitizers which are heavy metal and halogen free and
micro-environment sensitive. This type of PCT photosensitizers may find important
applications in photodynamic therapy of tumor, photobiology and organic
photochemistry.
Acknowledgements
2
6

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We thank the financial support from Hebei Provincial Hundred Talents Plan
Contract E2013100005), Hebei Provincial Science Foundation (Contract
(
B2014407080) and HBUST (Contract CXTD2012-05).
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