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J. Bai, L. Zhang and Y. Qian
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 252 (2021) 119512
toxicity, higher phototoxicity and perfect lysosomal localization
ability. It is estimated that SBOP-Lyso could produce satisfactory
results during photodynamic therapy process.
boron (tri) fluoride etherate (9.00 mL) were added to the bottle
for another 12 h. The crude product was obtained by extraction
with water and DCM. Then residue was purified by column chro-
matography to get BOP as dark red solid (0.25 g, yield: 18%), 1H
NMR (600 MHz, CDCl3): d 7.28 (d, J = 6 Hz, 1H), 6.69 (d, J = 6 Hz,
2. Experimental part
1H), 6.01 (s, 2H), 2.55 (s, 6H), 1.68 (s, 6H). HRMS: m/z calcd for C17
-
H
16BF2IN2S [MÀH]À 455.0067, found 455.0040.
2.1. Materials and instruments
Synthesis of SBOP:
At room temperature, BOP (0.20 g, 0.44 mmol) and NIS (0.25 g,
The analytically pure chemicals and reagents involved could be
bought from common purchase platform and were used directly.
Reaction process was monitored by TLC which could realize the
real-time monitoring of chemical reaction. The products involved
in each step were purified by silica gel column with different polar
ratios solvents. UV absorption spectra were operated on Ultraviolet
visible spectrophotometer UV2600 and the corresponding fluores-
cence spectra were obtained from Fluoromax-4 fluorescence spec-
trometer. 1H NMR: AVANCE III HD 600 MHz spectrometer; mass
spectrometry: Ultraflextreme Matrix-assisted laser desorption ion-
ization time-of-flight mass spectrometer. Cell viability test data
were obtained from ThermoFisher Multiskan FC. Fluorescence
imaging of cells were obtained through the confocal laser scanning
microscopy (OLYMPUS FLUOVIEW FV3000). The common test
methods for calculation of Uf and UD, cell culture method, MTT
assay, DCFH-DA for ROS production assay, lysosomal co-
localization assay, AO/EB double staining and zebrafish imaging
were detailed in the additional materials.
1.11 mmol) were added to a round bottom flask with 50.00 mL
anhydrous dichloromethane as the solvent and the reaction was
monitored by TLC for about 5 h. Then excess solvent was removed
and residue was purified by column chromatography to get SBOP
as red solid (0.22 g, yield: 78%), 1H NMR (600 MHz, CDCl3): d
7.32 (d, J = 6 Hz, 1H), 6.70 (d, J = 6 Hz, 1H), 2.64 (s, 6H), 1.67 (s,
6H). HRMS: m/z calcd for C17H16BF2I3N2S [M] 707.8073, found
707.8090.
Synthesis of SBOP-Lyso:
Compound SBOP (0.20 g, 0.28 mmol) and 1-(2-morpholinoe
thyl)-1H-indole-3-carbaldehyde (0.09 g, 0.34 mmol) were added
to a two-necked flask with 15.00 mL toluene as the solvent. With
the addition of piperidine (15.00
lL) and glacial acetic acid
(150.00 L) as the condensation catalyst, it was refluxed under
l
nitrogen protection. Then real-time progress of the reaction was
monitored by TLC. After the reaction, the excess solvent was
removed by vacuum distillation. Then the crude product was puri-
fied by column chromatography to get photosensitizer SBOP-Lyso
as dark green solid (0.10 g, yield: 38%), 1H NMR (600 MHz, CDCl3):
d 8.58 (d, J = 18 Hz, 1H), 8.09–8.07 (m, 1H), 7.71 (d, J = 18 Hz, 1H),
7.63 (d, J = 6 Hz, 1H), 7.43 (d, J = 18 Hz, 1H), 7.316 (s, 1H), 7.322 (s,
1H), 7.31 (s, 1H), 6.71 (d, J = 6 Hz, 1H), 4.31 (s, 2H), 3.76–3.70 (m,
4H), 2.83 (s, 2H), 2.68–2.64 (m, 4H), 2.55 (s, 3H), 1.75 (s, 3H), 1.67
(s, 3H). HRMS: m/z calcd for C32H30BF2I3N4OS [M+H]+ 948.9408,
found 948.9425.
2.2. Synthesis route
The general synthetic route for SBOP-Lyso was illustrated in
Scheme 2.
In Scheme 2, intermediates compound (BOP, SBOP) involved
and photosensitizer (SBOP-Lyso) all passed nuclear magnetic reso-
nance spectroscopy and high resolution mass spectrometry (The
corresponding spectra could be found in the Supplementary Infor-
mation). The synthesis of BOP was based on previously reported
literature [29–31]. Under nitrogen protection, 5-iodothiophene-2-
carbaldehyde (0.72 g, 3.00 mmol) and 2, 4-Dimethyl-1H-pyrrole
(0.71 g, 7.50 mmol) were added to anhydrous dichloromethane
(100.00 mL). Then trifluoroacetic acid (100.00 mL) was added as
catalyst. The reaction progress was monitored by TLC and the
above mixed system was stirred at room temperature for about
12 h. Then tetra-chloro-benzoquinone (0.74 g, 3.00 mmol) in anhy-
drous dichloromethane (60.00 mL) was added to the above system
and stirred for another 5 h. Finally triethylamine (6.00 mL) and
3. Results and discussion
3.1. The design and synthesis of the NIR thiophene BODIPY
photosensitizer SBOP-Lyso
As shown in Scheme 2, thiophene-BODIPY PS SBOP-Lyso was
synthesized in three steps. Here, BODIPY was selected as the core
due to its countless advantages like high fluorescence quantum
yield, excellent molar absorption coefficient, narrow half-peak
width, good light stability, insensitive to solvent polarity and pH.
As shown in Scheme 3, thiophene was introduced through the
one-pot method, S atom in thiophene and heavy atom I had
enough ability to promote the ISC process. Although iodine atom
could ensure sufficient singlet oxygen yield, it brought the disad-
vantage of poor water solubility as well. To solve this problem,
M1 was introduced through Knoevenagel condensation reaction
with SBOP. It could not only ensure the absorption and emission
wavelength of SBOP-Lyso in the NIR region but also provide good
lysosome colocalization ability. Eventually, an NIR and lysosome-
targeted photosensitizer with enough water solubility was con-
structed. It was assumed that SBOP-Lyso had excellent properties
like NIR absorption and emission, higher singlet oxygen quantum
yield, higher phototoxicity, better biocompatibility and enough
intracellular lysosome localization ability.
3.2. Investigation on photodynamic therapy of SBOP-Lyso in cells and
zebrafish under 660 nm irradiation
Here, Fig. 1 (a) clearly showed the UV absorption spectra and
fluorescence emission spectra of intermediate compound SBOP. It
Scheme 2. Synthetic route for SBOP-Lyso.
3
Bai, Jin
