Supporting Information
© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2009
Construction of Helical J-Aggregates Self-Assembled from a Thymidylic
Acid-Appended Anthracene Dye and DNA as a Template
Rika Iwaura,*†‡ Mayumi Ohnishi-Kameyama,† and Tomohiko Iizawa†
†
National Food Research Institute (NFRI), National Agriculture and Food Research Organization (NARO),
2-1-12 Kannondai, Tsukuba, Ibaraki, 305-8642 Japan
‡
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology
Agency (JST).
1
Synthesis
of
2,
6-bis-(5-hydroxy-pentyloxy)anthracene.
6-Bis(5-hydroxy-penthyloxy)anthraquinone
was
prepared
according
to
2,
previously
described procedures.[1] A mixture of 2, 6-dihydroxyanthraquinone (1.2 g, 5 mmol) and
potassium carbonate (3.5 g, 25 mmol) in 100 ml dimethyl formamide (DMF) was warmed
until complete dissolution had occurred. 5-Bromo-1-pentanol (3.7 g, 22 mmol) was then
added over 20 min. The reaction mixture was refluxed for 12 h, cooled to room temperature,
and the solvent was evaporated under reduced pressure. Water was added to the remaining
solid and the aqueous layer was extracted with dichloromethane. The collected
dichloromethane extract was dried with magnesium sulfate overnight and filtered. Silica gel
column
chromatography
using
chloroform/methanol
(9/1)
gave
2,
6-bis(5-hydroxy-pentyloxy)anthraquinone. After the removal of the solvent in vacuo and
recrystallization from chloroform/methanol, yellow needle crystals were obtained (1.0 g,
2.4 mmol, 50%). TLC: (silica gel, chloroform/methanol = 9/1, v/v) Rf = 0.66. IR: ν (cm-1) =
3312, 3100, 2937, 2860, 1666, 1585, 1490, 1469, 1432, 1371, 1327, 1309, 1295, 1232,
1218, 1168, 1148, 1089, 1078, 1055, 1025, 966, 904, 892, 873, 845, 740, 710. ESI-MS:
(m/z) Calcd. for C24H29O6+ [M+H]+; 413.20, Found; 413.43.
Isopropanol (25 ml) was added to 500 mg (1.2 mmol) of 2, 6-bis
2
(5-hydroxypentyloxy)anthraquinone and solid sodium borohydride (1.0 g, 23 mmol) was
then added in small portions. The mixture was refluxed for 3 h. After cooling, hydrochloric
acid (35%) and ice water were added to the mixture, which was then extracted three times
with dichloromethane. The organic layers were collected, washed with sodium hydroxide
solution, and dried with magnesium sulfate overnight. Filtration and evaporation of the
solution gave 2, 6-bis(5-hydroxy-penthyloxy)-10H-anthracen-9-one as a yellow powder.
TLC: (silica gel, chloroform/methanol = 9/1, v/v) Rf = 0.38. ESI-MS: (m/z) Calcd. for
C24H30NaO5+ [M+Na]+; 421.20, Found; 421.36.
The residue was dissolved in isopropanol (25 ml) and portions of sodium borohydride
(1.7 g, 20 mmol) were added. The mixture was refluxed for 4 h under an atmosphere of
nitrogen. After cooling, hydrochloric acid (35%) and ice water were added to the mixture
and
the
precipitate
was
filtered.
The
residue
was
recrystallized
from
dichloromethane/methanol (1/1, v/v) to give 2, 6-bis(5-hydroxypentyloxy)anthracene as an
orange powder (0.16 g, 33%). TLC: (silica gel, ethyl acetate/chloroform = 3/1, v/v) Rf =
1
0.46.
H
NMR:
(400
MHz
in
CDCl3
at
25°C)
δ
1.60−1.63
(m,
4H,
OCH2CH2CH2CH2CH2OH), 1.67−1.73 (m, 4H, OCH2CH2CH2CH2CH2OH), 1.91 (quintet,
4H,
J
=
7.5 Hz,
OCH2CH2CH2CH2CH2OH),
3
3.72
(t,
4H,
J
=
6.22 Hz,
OCH2CH2CH2CH2CH2OH), 4.12 (t, 4H, J = 6.4 Hz, OCH2CH2CH2CH2CH2OH), 7.12 (d,
2H, J = 2.45 Hz, H3 and H7), 7.15 (s, 2H, H1 and H5), 7.82 (d, 2H, J = 8.9 Hz, H4 and H8),
8.17 (s, 2H, H9 and H10). FTIR: ν (cm-1) = 3357, 2939, 2856, 1630, 1589, 1465, 1434,
1389, 1347, 1364, 1294, 1200, 1060, 1030, 983, 88, 800, 744. ESI-MS: (m/z) Calcd. for
C24H30NaO4+ [M+Na]+; 405.20, Found; 405.43.
O
OH
O
HO
O
OH
O
OH
O
OH
O
OH
O
OH
O
(i)
HO
O
O
OH
O
OH
( ii )
OH
O
( iii )
O
HO
OH
O
OH
( iv )
(v)
HO
O
Figure S1. Route for the synthesis of 2, 6-bis(5-hydroxypentyloxy)anthracene. (i) K2CO3,
Br-(CH2)5-OH, DMF, (ii) NaHB4, isopropanol, (iii) HCl/water, (iv) NaBH4, isopropanol, (v)
4
HCl/water.
Synthesis of 2，
，6-bis[5-(3’-thymidylic acid)pentyloxy]anthracene (1). The synthesis of
compound 1 was carried out essentially as previously described.[2] The dried THF (30 ml)
was added to 0.5 g (0.65 mmol) 3′-O-[2-cyanoethoxy (N, N-diisopropylamino)
phosphino]-5′-O-(4, 4′-dimethoxytrityl) thymidine and the solution was mixed with 2,
6-bis(5-hydroxypentyloxy)anthracene 1 (0.1 g, 0.26 mmol) and 1H-tetrazole (0.1 g, 1.4
mmol), and stirred for 2 days. To this reaction mixture, 0.3 ml of 70% t-butylhydroperoxide
aqueous solution was added and the mixture was stirred for 1 h. The reaction mixture was
evaporated under reduced pressure, and the residue was used for further reactions without
purification. The removal of the protecting cyanoethyl group was carried out with 10 ml of
28% aqueous ammonia and 5 ml of methanol for 1 day, and the solution was evaporated.
The residue was purified by silica gel column chromatography using chloroform and
methanol (9/1 to 4/1, v/v). The compound was treated with a chloroform solution
containing 5% trifluoroacetic acid to remove the protecting dimethoxytrityl group. After the
removal of the solvent, the residual solid was reprecipitated from acetone, and the
precipitate was filtered and dried. The final compound 1 was obtained as a reddish brown
5
powder (52 mg, 20%). TLC: (silica gel, chloroform/methanol = 4/1, v/v) Rf = 0.1. 1H NMR:
(500 MHz in d6-DMSO at 25°C) δ 1.48−1.53 (m, 4H, OCH2CH2CH2CH2CH2OP), 1.62
(quintet, 4H, J = 6.6 Hz, OCH2CH2CH2CH2CH2OP), 1.75 and 1.77 (s, 6H, 5-CH3), 1.80 (m,
4H, OCH2CH2CH2CH2CH2OP), 2.15−2.30 (m, 4H, 2′-H), 3.61 (br. s, 4H, 5′-H), 3.96 (br. s,
4H, OCH2CH2CH2CH2CH2OP), 4.03 (br. s, 4H, OCH2CH2CH2CH2CH2OP), 4.09 (t, 2H, J
= 6.4 Hz, 4′-H), 4.74 (br. s, 2H, 3′-H), 6.16 (br. s, 2H, 1′-H), 7.12−7.15 (m, 2H, H3 and H7),
7.26−7.31 (m, 2H, H1 and H5), 7.73 (s, 2H, H9 and H10), 7.89 (dd, 2H, J = 3.65 and 3.84,
H4 and H8), 8.26 (s, 2H, 6-H), 11.3 (s, 2H, 3-NH).
13
C NMR (500 MHz, in d6-DMSO at
25 °C) δ 12.2, 22.2, 38.2, 61.4, 64.2, 67.4, 83.6, 86.0, 104.5, 109.4, 120.4, 135.8. FT-IR: ν
(cm-1) = 3339, 3218, 3062, 2939, 2868, 1667, 1632, 1588, 1465, 1275, 1198, 1130, 1100,
1057, 1004, 885, 832, 799, 768. ESI FTICR MS: (m/z) Calcd. for C44H54N4O18P22[M-2H]2- 494.1449, Found; 494.1443. m.p = 196ºC.
6
Figure S2. Route for the synthesis of 2，6-bis[5-(3’-thymidylic acid)pentyloxy]anthracene.
(vi) 3′-O-[2-cyanoethoxy (N, N-diisopropylamino) phosphino]-5′-O-(4, 4′-dimethoxytrityl)
thymidine, 1H-tetrazol, THF (vii) t-butylhydroperoxide, (viii) 28% aqueous ammonia
solution, (ix) trifluoroacetic acid.
7
Synthesis of 1, 5-bis-(5-hydroxy-pentyloxy)-anthracene. The synthesis was carried out
by a procedure that was similar to that used for 2, 6-bis(5-hydroxypentyloxy) anthracene
using
1,
5-dihydroxyanthraquinone
as
a
starting
material.
1,
5-Bis(5-hydroxypentyloxy)anthracene was obtained as a brown powder (0.51 g, 74%).
TLC: (silica gel, chloroform/methanol = 4/1, v/v) Rf = 0.75. 1H NMR: (800 MHz in CDCl3
at 25°C) δ 1.70−1.75 (m, 8H, OCH2CH2CH2CH2CH2OH, OCH2CH2CH2CH2CH2OH), 2.05
(quintet, 4H, J = 7.5 Hz, OCH2CH2CH2CH2CH2OH), 3.74 (t, 4H, J = 6.22 Hz,
OCH2CH2CH2CH2CH2OH), 4.22 (t, 4H, J = 6.3 Hz, OCH2CH2CH2CH2CH2OH), 7.33 (t,
2H, J = 7.4 Hz, H3 and H7), 7.62 (d, 2H, J = 8.4 Hz, H2 and H6), 8.76 (s, 2H, H9 and H10).
FTIR: ν (cm-1) = 3332, 2933, 28636, 1660, 1587, 1457, 1255, 1168, 1113, 1055, 893, 785,
722. ESI-MS: (m/z) Calcd. for C24H31O4+ [M+H]+; 383.22, Found; 383.28.
Synthesis of 1，
，5-bis[5-(3’-thymidylic acid)pentyloxy]anthracene (2). The synthesis of
compound 2 was carried out using a procedure that was similar to that used for [2,
6-bis(5-pentyloxy)anthracene]bis(3’-thymidylic
acid)
(1),
using
1,
5-bis-(5-hydroxy-pentyloxy)-anthracene as a starting material. 1，5-bis[5-(3’-thymidylic
8
acid)pentyloxy]anthracene was obtained as a brown powder (20 mg, 10%). TLC: (silica gel,
chloroform/methanol = 4/1, v/v) Rf = 0.1. 1H NMR: (800 MHz in d6-DMSO at 25°C) δ
1.70−1.75 (m, 8H, OCH2CH2CH2CH2CH2OH, OCH2CH2CH2CH2CH2OH), 1.78 (s, 6H,
5-CH3), 1.94 (br. 4H, OCH2CH2CH2CH2CH2OH ), 2.15−2.31 (m, 4H, 2′-H), 3.61 (br. 8H,
5′-H and OCH2CH2CH2CH2CH2OP), 4.03 (br. 6H, OCH2CH2CH2CH2CH2OP and 4′-H),
4.78 (br. s, 2H, 3′-H), 6.16 (br. s, 2H, 1′-H), 6.84−7.343 (m, 4H, H3, H4, H6 and H7), 7.72
(s, 2H, 6-H), 7.76 (br, 2H, H2 and H6), 8.13 (s, 1H, H9 andH10), 11.3 (s, 2H, 3-NH).
FT-IR: ν (cm-1) = 3371, 2947, 2868, 1667, 1588, 1543, 1460, 1271, 1203, 1101, 1059, 1004,
891, 787. ESI FTICR MS: (m/z) Calcd. for C44H54N4O18P22- [M-2H]2- 494.1449, Found;
494.1451. m.p = 222ºC (decomposition).
Figure S3 Temperature dependence of the UV/Vis spectra of 1/dT20 in 0.1 × TE buffer
solution ([1] = 1.0 × 10-3 M, [dT20] = 1.0 × 10-4 M, l = 0.1 cm).
9
Figure S4 CD spectra of compound 1 (dashed line) and 1/dA20 (solid line) in 0.1 × TE
buffer at 20 °C.
References
[1]
Pozzo, J. L.; Clavier, G. M.; Colomes, M.; BouasLaurent, H. Tetrahedron 1997, 53,
6377-6390.
[2]
Iwaura, R.; Yoshida, K.; Masuda, M.; Yase, K. Shimizu, T., Chem. Mater. 2002, 14,
3047-3053.
10