S. Zhu et al.
Dyes and Pigments 178 (2020) 108353
À 1
2
1
3
0.27, 14.19. FT-IR (KBr, v, cm ): 3231, 3072, 2957, 2871, 2155, 1699,
7.31 (d, J ¼ 3.7 Hz, 1H), 7.29 (d, J ¼ 3.7 Hz, 1H), 6.98–6.95 (m, 1H),
6.95–6.92 (m, 1H), 4.24–4.15 (m, 2H), 3.86 (s, 3H), 1.73 (tt, J ¼ 7.7, 6.6
655, 1360, 1231. HR-MS (m/z) (ESI): calcd for C16
H
14BrNO
2
[M þ H]þ:
1
3
32.0286, found: 332.0285.
Hz, 2H), 1.46 (dd, J ¼ 15.1, 7.5 Hz, 2H), 0.99 (t, J ¼ 7.4 Hz, 3H).
C
NMR (100 MHz, CDCl
3
) δ 164.20, 163.93, 159.71, 146.85, 139.04,
2
1
.2.2. Synthesis of 2-butyl-6-(thiophen-2-yl)-1H-benzo[de]isoquinoline-
,3(2H)-dione (6)
137.96, 132.30, 131.33, 130.70, 129.95, 129.72, 128.90, 128.20,
127.14, 126.49, 122.93, 121.68, 114.48, 55.42, 40.31, 30.23, 20.43,
À 1
Under nitrogen protection, compound 5 (300 mg, 0.90 mmol), 2-
13.90. FT-IR (KBr, v, cm ): 3459, 2961, 1697, 1656, 1585, 1359, 1252,
thienylboronic acid (127 mg, 0.99 mmol), K
Pd (dba) (16.5 mg, 18 mol), P(o-tol)
CH NCl (10 mg, 90 mol) were added into a three-neck round-bottom
2
CO
3
(997 mg, 7.2 mmol),
1236, 1182, 781. HR-MS (m/z) (ESI): calcd for C27
H
24NO
3
S [M þ H]þ:
2
3
μ
3
(22.0 mg, 72
μmol) and
442.1399; found 442.1388.
(
3
)
4
μ
flask. After the mixture was degassed for 30 min, toluene (10 mL) and
2.2.5. Synthesis of 2-butyl-6-(5-(4-hydroxyphenyl)thiophen-2-yl)-1H-
distilled water (2 mL) were added. The reaction contents were subse-
benzo[de]isoquinoline-1,3(2H)-dione (9)
ꢀ
quently heated at 80 C for 24 h. The resulting mixture was extracted
Compound 8 (50 mg, 0.11 mmol) was dissolved in dry CH
2
Cl
2
(3 mL)
ꢀ
with dichloromethane and washed with brine and distilled water. The
organic extract was dried over sodium sulfate and collected under
reduced pressure. The crude material was purified through column
chromatography on silica to obtain 6 as a yellow solid (153 mg), 50.5%
and the solution was cooled to 0 C by an ice bath. A solution of BBr
3
2 2
(569 mg, 2.3 mmol) in CH Cl (2 mL) was added dropwise to the cold
solution using a syringe. After the addition was completed, the stirring
ꢀ
was continued for 1 h at 0 C and then at rt. After the reaction was
ꢀ
1
yield, m.p. 134–136 C. H NMR (400 MHz, CDCl
3
) δ 8.57–8.46 (m, 3H),
completed, the mixture was poured onto ice and was extracted with
7
7
1
0
1
1
4
1
.75–7.68 (m, 1H), 7.68–7.61 (m, 1H), 7.46 (dd, J ¼ 5.1, 0.8 Hz, 1H),
dichloromethane. The organic layer was washed with saturated NaHCO
3
.29–7.22 (m, 1H), 7.16 (ddd, J ¼ 5.1, 1.8, 0.8 Hz, 1H), 4.11 (dd, J ¼
0.7, 4.2 Hz, 2H), 1.70–1.59 (m, 2H), 1.37 (dd, J ¼ 15.0, 7.5 Hz, 2H),
solution and brine and dried over sodium sulfate. The crude material
was purified by column chromatography on silica gel to obtain red solid
1
3
ꢀ
1
.90 (t, J ¼ 7.4 Hz, 3H). C NMR (100 MHz, CDCl
3
) δ 164.16, 163.90,
9 (20 mg), 41.7% yield, m.p. 149–151 C. H NMR (400 MHz, DMSO‑d
6
)
39.77, 139.02, 132.25, 131.30, 130.60, 129.93, 128.89, 128.60,
27.93, 127.62, 127.15, 126.90, 122.93, 121.94, 77.33, 77.07, 76.75,
δ 9.81 (s, 1H), 8.67 (d, J ¼ 8.5 Hz, 1H), 8.47 (d, J ¼ 7.1 Hz, 1H), 8.40 (d,
J ¼ 7.7 Hz, 1H), 7.85 (dt, J ¼ 8.1, 4.0 Hz, 2H), 7.56 (d, J ¼ 8.5 Hz, 2H),
7.49 (d, J ¼ 3.7 Hz, 1H), 7.43 (d, J ¼ 3.7 Hz, 1H), 6.86 (d, J ¼ 8.5 Hz,
À 1
0.30, 30.21, 20.42, 13.89. FT-IR (KBr, v, cm ): 3450, 2960, 2930,
697, 1658, 1610, 1592, 1390, 1291, 781. HR-MS (m/z) (ESI): calcd for
2H), 4.01 (t, J ¼ 7.4 Hz, 2H), 1.68–1.55 (m, 2H), 1.36 (dd, J ¼ 14.8, 7.4
þ
13
C
20
H
18NO
2
S [M þ H] : 336.0980; found 336.1008.
Hz, 2H), 0.94 (t, J ¼ 7.3 Hz, 3H). C NMR (100 MHz, DMSO‑d ) δ
6
1
63.15, 162.84, 157.79, 146.50, 137.96, 136.37, 131.78, 130.74,
2
.2.3. Synthesis of 6-(5-bromothiophen-2-yl)-2-butyl-1H-benzo[de]
130.21, 128.56, 127.97, 127.61, 126.91, 124.14, 122.97, 122.32,
À 1
isoquinoline-1,3(2H)-dione (7)
120.88, 115.93, 29.56, 19.78, 13.68. FT-IR (KBr, v, cm ): 3257, 2959,
Compound 6 (70 mg, 0.21 mmol) and acetic acid (3 mL) were
charged with a single-neck round-bottom flask under ambient condi-
tions. After the compound was completely dissolved, liquid bromine
1688, 1637, 1607, 1583, 1444, 1354, 1276, 1236, 1172, 780. HR-MS
þ
(m/z) (ESI): calcd for C26
H
22NO
3
S [M þ H] : 428.1320; found
428.1318.
(
2
Br ) (40 mg, 0.25 mmol) in dichloromethane (1 mL) was added. The
reaction was kept stirring at room temperature for 1 h. Then the reaction
mixture was extracted with dichloromethane and washed with saturated
2
.3. Quantum yields
Absorption spectra were recorded on a Varian Cary 100 spectrom-
3
NaHCO solution and brine. The organic extract was dried over sodium
sulfate and collected under reduced pressure. The crude material was
purified by column chromatography on silica gel to obtain pale yellow
solid 7 (63 mg), 73.3% yield, m.p. 162–164 ꢀC. H NMR (400 MHz,
eter. Fluorescence spectra were measured with a Hitachi F-4500 fluo-
rescence spectrometer with slit widths routinely set at 2.5 nm. Quantum
yields (Φ) were determined relative to Rhodamine 6G (Q ¼ 0.95, exci-
tation ¼ 440 nm) [51] and calculated according to the following
formula:
1
CDCl
3
) δ 8.61 (dd, J ¼ 7.3, 1.0 Hz, 1H), 8.59–8.53 (m, 2H), 7.75 (dd, J ¼
9
4
7
1
1
.4, 7.5 Hz, 2H), 7.20 (d, J ¼ 3.8 Hz, 1H), 7.09 (d, J ¼ 3.8 Hz, 1H),
.22–4.13 (m, 2H), 1.77–1.67 (m, 2H), 1.51–1.40 (m, 2H), 0.98 (t, J ¼
.4 Hz, 3H). 13C NMR (100 MHz, CDCl
3
) δ 164.05, 163.78, 141.25,
Fu Au
Fs As
Φ
u
¼ Φ
s
�
�
(3)
37.80, 131.79, 131.44, 130.76, 130.55, 129.77, 129.14, 128.65,
27.41, 123.04, 122.39, 114.46, 40.34, 30.20, 20.40, 13.88. FT-IR (KBr,
À 1
Φ
s
equals the fluorescence quantum yield of the standard, typically
v, cm ): 3450, 2963, 2931, 1698, 1655, 1613, 1590, 1388, 1231, 784.
þ
taken from the literature; F presents the integrated spectral fluorescence
photon flux at the detector and A presents the absorbance at the
maximum excitation [52].
HR-MS (m/z) (ESI): calcd for C20
H
17BrNO
2
S [M þ H] : 414.1185; found
4
14.1170.
2
.2.4. Synthesis of 2-butyl-6-(5-(4-methoxyphenyl)thiophen-2-yl)-1H-
2
.3.1. Cell culture
benzo[de]isoquinoline-1,3(2H)-dione (8)
Human adenocarcinoma A549 cells, human breast carcinoma MCF-7
Under nitrogen protection, compound 7 (60 mg, 0.14 mmol), 4-
cells, human ovarian carcinoma SKOV-3 cells, and human colorectal
adenocarcinoma HT-29 cells were purchased from the cell bank of the
Chinese Academy of Sciences (Shanghai, China). A549 cells were
cultured in F12 media. MCF-7 cells and SKOV-3 cells were cultured in
DMEM media. HT-29 cells were cultured in McCoy’s 5A medium. All
media were supplemented with 10% (v/v) fetal bovine serum (FBS) and
methoxyphenylboronic acid (25 mg, 0.16 mmol), K
mmol), Pd (dba) (2.6 mg, 3 mol), P(o-tol) (3.5 mg, 10
CH NCl (1.6 mg, 14 mol) were added into a three-neck round-bot-
2
CO
3
(160 mg, 1.1
2
3
μ
3
μ
mol) and
(
3
)
4
μ
tom flask. After the mixture was degassed for 30 min, toluene (5 mL) and
distilled water (1 mL) were added. The reaction contents were subse-
ꢀ
quently heated at 80 C for 24 h. The resulting mixture was extracted
1
% (v/v) penicillin/streptomycin. Cells were incubated in a humid at-
with dichloromethane and washed with brine and distilled water. The
organic extract was dried over sodium sulfate and collected under
reduced pressure. The crude material was purified through column
chromatography on silica to obtain 8 as a yellow solid (37 mg), 57.8%
ꢀ
mosphere of 5% CO
2
at 37 C.
2.4. In vitro cellular uptake
ꢀ
1
yield, m.p. 158–160 C. H NMR (400 MHz, CDCl
.9 Hz, 1H), 8.63 (dd, J ¼ 7.2, 0.9 Hz, 1H), 8.58 (d, J ¼ 7.6 Hz, 1H), 7.82
d, J ¼ 7.6 Hz, 1H), 7.75 (dd, J ¼ 8.5, 7.3 Hz, 1H), 7.63–7.55 (m, 2H),
3
) δ 8.71 (dd, J ¼ 8.5,
0
For the purpose of observing the cellular uptake behavior of com-
(
pound 9, cells were plated in 20 mm glass-bottomed culture dishes at
3