110.5, 109.4, 35.6. (s, -n-ch -, 2h). c nmr (dmso-d ... · solution of compound 4 (3.723 g, 11.18...
TRANSCRIPT
Synthesis
O
O
O
Br
Br
N
O
O
Br
BrO
N
O
O
I
IO
4 5
a b
Scheme S1. Synthesis of compound 4 and 5. (a) furfurylamine, acetic acid, 22 h; (b)
KI, acetic acid, 5 h.
3,4-dibromo-1-(furan-2-ylmethyl)-1H-pyrrole-2,5-dione (Compound 4). 3,4-
dibromomaleic anhydride (6.14 g, 24.3 mmol) was dissolved in acetic acid (60 mL)
with slowly addition of furfurylamine (2.748 g, 28.3 mmol), the solution was stirred
at room temperature until the white smoke disappeared, then the system was heated at
120 ºC for 22 h. After removal of solvent, the crude residue was separated by column
chromatography on silica gel (hexane/ethyl acetate = 15/1) to give compound 4 as a
light yellow solid (5.645 g, 70.1 %). 1H NMR (DMSO-d6, 400 MHz, ppm): 7.33-7.32
(d, -O-CH=CH, 1H), 6.35-6.34 (m, -CH=CH-, 1H), 6.30-6.29 (d, -C=CH-, 1H), 4.75
(s, -N-CH2-, 2H). 13C NMR (DMSO-d6, 100MHz, ppm): 163.1, 148.0, 142.7, 129.5,
110.5, 109.4, 35.6.
3,4-diiodo-1-(furan-2-ylmethyl)-1H-pyrrole-2,5-dione (Compound 5). A
solution of compound 4 (3.723 g, 11.18 mmol) and potassium iodide (7.427 g, 44.74
mmol) in 50 mL acetic acid was heated at 120 ºC and stirred for 5 h. After removal of
acetic acid, the crude residue was separated by column chromatography on silica gel
(hexane/ethyl acetate = 10/1) to give compound 5 as a light yellow solid (3.03 g, 63.2
%). 1H NMR (DMSO-d6, 400MHz, ppm): 7.27-7.20 (d, -O-CH=, 1H), 6.28 (m, -
CH=CH-, 1H), 6.24-6.23 (d, -C=CH-, 1H), 4.72 (s, -N-CH2-, 2H). 13C NMR (DMSO-
d6, 100MHz, ppm): 166.6, 148.9, 142.7, 119.2, 110.6, 108.3, 35.7. HRMS (ESI): m/z
cald. for C9H5I2NO3Na (M+Na)+: 451.8256; found: 451.8254.
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry B.This journal is © The Royal Society of Chemistry 2015
Sc
N
O
O
I
I
N
O
OO
+O
7NO O
N
O
ON NO
NNN
O
O
8
(PTAD)
N
O
O
I
I
N
O
O
9
5
OEtOEt
OEt
N
O
O
EtO
OEtOEt
EtO
OEtOEt
10
heme S2. Synthesis of fluorescent enediyne compounds.
ppm (t1)4.505.005.506.006.507.007.508.00
0
5000
7.3317.3297.327
6.3476.3396.3046.2996.2966.291
4.756
1.00
0.97
0.94
2.00
N
O
O
Br
BrO
Figure S1. 1H NMR spectrum of compound 4
ppm (t1)50100150
0
5000
10000
163.111
148.041
142.749
129.495
110.533
109.406
35.639
N
O
O
Br
BrO
Figure S2. 13C NMR spectrum of compound 4
ppm (t1)4.505.005.506.006.507.007.508.00
0
1000
2000
3000
4000
7.567
6.3926.3846.3806.3606.352
4.650
2.00
2.05
0.95
N
I
I
O
O
O
Figure S3. 1H NMR spectrum of compound 5
ppm (t1)50100150
0
1000
2000
3000
4000
5000
6000
166.623
148.873
142.708
119.156
110.543108.298
35.696N
I
I
O
O
O
Figure S4. 13C NMR spectrum of compound 5
ppm (t1)1.02.03.04.05.06.07.0
0
2500
5000
7500
10000
7.265
6.2676.2596.2406.2366.228
4.646
3.6913.6743.6563.638
1.2031.1851.167
12.9
3
2.00
1.01
0.98
1.06
23.7
7
N
O
O
O
OO
O
OO
O
Figure S5. 1H NMR spectrum of enediyne 1
ppm (t1)255075100125150
0
2500
5000
7500
10000
165.158
148.166
142.738
128.826
110.495
109.205109.061103.714
72.806
59.419
35.149
14.829
N
O
OO
O
OO
O
OO
Figure S6. 13C NMR spectrum of enediyne 1
ppm (t1)4.505.005.506.006.507.007.508.00
0
5000
100007.6757.6587.6047.5847.5667.5597.5497.5377.5187.501
6.418
4.688
2.02
4.08
1.03
5.88
2.00
N
O
OO
Figure S7. 1H NMR spectrum of enediyne 7
ppm (t1)5075100125150175
0
1000
2000
3000
4000
5000
6000
7000
8000165.763
148.736
142.737
132.085
130.911129.132127.304120.252
110.579108.700108.286
80.295
34.970
N
O
OO
Figure S8. 13C NMR spectrum of enediyne 7
3470 3480 3490 3500 3510 3520 3530 3540 3550 3560
Magnetic Field (G)
Figure S9. EPR spectrum of DA-product (enediyne 2) in CHCl3. Enediyne 2 was
dissolved in CHCl3 with the addition of one drop of TFA.
0.6 1.3 2.5 5 10 20 400
20
40
60
80
100
Cytotoxicity of DA-product 2 on A549 cell
Concentration(µM)
Cell
viab
ility
(% o
f con
trol
)
24h 48h 72h
Figure S10.Effect of DA-product (enediyne 2) on cell viability of tumor model cell
lines A549 cells
1.5 3.1 6.25 12.5 25 50 100 2000
20
40
60
80
100
Concentration(µM)
Cell
viab
ility
(% o
f con
trol
)
48 h L-02 A549
Figure S11. Effect of enediyne 1 on cell viability of tumor model cell lines A549 cells
and normal model cell lines L-02 cells. Cells were incubated with enediyne 1 for 48 h
and cell viability was determined and analyzed by MTT assay.
1.5 3.1 6.25 12.5 25 50 100 2000
20
40
60
80
100
Concentration(µM)
Cell
viab
ility
(% o
f con
trol
)
72 h L-02 A549
Figure S12. Effect of enediyne 1 on cell viability of tumor model cell lines A549 cells
and normal model cell lines L-02 cells. Cells were incubated with enediyne 1 for 72 h
and cell viability was determined and analyzed by MTT assay.
24 48 720
20
40
60
80
100
Effect of acetone on cells
Time (h)
Cell
viab
ility
(% o
f con
trol
)
A549cell L-02cell
Figure S13. Effects of 0.1% acetone on cell viability of tumor and normal cells. The
cells were incubated with acetone for 24 h, 48 h, and 72 h respectively. Cell viability
was determined and analyzed by MTT assay.
Figure. S14. Cellular distribution of enediyne 7 entering in A549 cell at 12 h observed
by CLSM. Blue-nucleus; green-enediyne; red-lysosome.
Figure. S15. Cellular distribution of enediyne 8 in A549 cell at 12 h observed by
CLSM. Blue-nucleus; green-enediyne; red-lysosome.
Figure. S16. Cellular distribution of enediyne 10 entering in A549 cell at 12 h
observed by CLSM. Blue-nucleus; green-enediyne; red-lysosome.