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K. Duskova et al. / Bioorg. Med. Chem. 20 (2012) 7112–7118
TSQ Quantum LC/MS or an Agilent 6210 LC/MS/TOF instruments.
FAB mass spectra were obtained on a V.G. AutoSpec spectrometer
with 3-nitrobenzyl alcohol as matrix. UV–visible spectra were re-
corded on a Lambda 18 Perkin-Elmer spectrometer. Merck silica
gel 60 (230–400 ASTM mesh) was employed for flash column chro-
matography. TLC was performed on precoated aluminum silica gel
plates (Merck or Macherey-Nagel 60 F254 0.25 mm). Distilled,
deionized water was utilized in the preparation of all buffers and
all aqueous reactions. Chemicals were of the highest available pur-
ity and were used without further purification. Sodium phosphate
dibasic, and sodium phosphate monobasic were obtained from the
Aldrich Chemical Company. The concentration of CT DNA solutions
was determined by UV–visible spectrophotometry using the
3017, 2980, 1639, 1603, 1518, 1510, 1472, 1413, 1151 cmÀ1 1H
;
NMR (DMSO-d6, 500 MHz) d (ppm): 3.05 (2H, t, J 8.1 Hz, CH2CH2),
3.2 (2H, t, J 8.1 Hz, CH2CH2), 5.95 (2H, s, Py+CH2Naph), 7.27 (2H,
d, J 5.9 Hz, HbPy), 7.55–7.59 (3H, m, H-3, H-6, H-7 Naph), 7.91–
7.95 (2H, m, H-5, H-8 Naph), 7.98 (1H, d, J 8.5 Hz, H-4 Naph),
8.04 (1H, br s, H-1 Naph), 8.07 (2H, d, J 6.5 Hz, HbPy+), 8.44 (2H,
d, J 5.9 Hz, H Py), 9.13 (2H, d, J 6.5 Hz, H Py+); 13C NMR (DMSO-
a
a
d6, 75 MHz) d (ppm): 33.7, 34.9, 62.9, 124.1, 125.8, 127.1, 127.3,
127.9, 128.2, 128.3, 128.5, 129.2, 132.1, 132.8, 133.1, 144.4,
149.1, 149.8, 161.8.
4.2.4. 1-(Anthracen-9-ylmethyl)-4-(2-(pyridin-4-yl)ethyl)
pyridinium chloride (2)
extinction coefficient
e
260 = 12,824 MÀ1 (bp) cmÀ1
.
To a solution of 1,2-bis(4-pyridyl)ethane (200 mg, 1.08 mmol)
in dry acetone (2 mL) a solution of 9-chloromethylanthracene
(78 mg, 0.36 mmol) in dry acetone (2 mL) was added dropwise.
The reaction mixture was stirred at room temperature for 24 h.
The solid was filtered, washed with cold acetone and dried at
50 °C affording pure product 2 (114 mg, 77%); mp 224–226 °C;
[Found: C, 79.15; H, 5.72; N, 6.50. C27H23ClN2 requires C, 78.91;
4.2. Synthesis
4.2.1. Synthesis of 2-methylphenazine
4-Methylcatechol (3.72 g, 30 mmol) was dissolved in water
(300 mL) at room temperature and sodium periodate (6.37 g,
31.4 mmol) was added. The mixture was stirred vigorously for
1 min before extraction with methylene chloride (2 Â 70 mL). The
organic extract was immediately added to a solution of o-phenyl-
enediamine (3.24 g, 30 mmol) in methylene chloride (40 mL) with
stirring. Then glacial acetic acid (20 mL) was added dropwise over
a period of 10 min and the solution was left to stir for 30 min at
room temperature before being heated to reflux for 4 h. The solu-
tion was cooled and washed successively with water (100 mL),
aqueous sodium hydrogen carbonate (2 Â 100 mL) and finally
brine (100 mL). The organic layer was dried and evaporated to dry-
ness giving a brown solid. Filtration through a plug of alumina
using methylene chloride afforded an orange solid, which was
purified by flash chromatography through silica gel (5:1 hexane/
ethyl acetate, Rf = 0.3) affording the title compound (1.4 g, 24%) as
a yellow solid, mp 117–119 °C (lit.13 117 °C); 1H NMR (300 MHz,
CDCl3): d (ppm) 2.66 (3H, s, CH3), 7.70 (1H, dd, J 9.2, 1.8 Hz, H-3),
7.80–7.91 (2H, m, H-7, H-8), 8.06 (1H, br s, H-1), 8.17 (1H, d, J
9.2 Hz, H-4), 8.25–8.32 (2H, m, H-6, H-9). HRMS (ESI-TOF): m/z
found 195.0925 (M+H)+, C13H11N2 requires 195.0922.
H, 5.64; N, 6.82%]; IR (KBr):
m 3015, 1633, 1602, 1515, 1467,
1419, 1143 cmÀ1 1H NMR (DMSO-d6, 300 MHz) d (ppm): 2.97
;
(2H, t, J 8.1 Hz, CH2CH2), 3.20 (2H, t, J 8.1 Hz, CH2CH2), 6.89 (s,
2H, Py+CH2Anthr), 7.23 (2H, d, J 6.3 Hz, HbPy), 7.60–7.70 (4H, m,
H-2, H-3, H-6, H-7 Anthr), 7.93 (2H, d, J 6.9 Hz, HbPy+), 8.25 (2H,
d, J 8.2 Hz, H-4, H-5 Anthr), 8.34 (2H, d, J 8.9 Hz, H-1, H-8 Anthr),
8.42 (2H, d, J 6.3 Hz, H Py), 8.75 (2H, d, J 6.9 Hz, H Py+), 8.91
a
a
(1H, s, H-10 Anthr). 13C NMR (DMSO-d6, 75 MHz) d (ppm): 33.6,
34.7, 55.3, 122.4, 123.4, 124.1, 125.9, 128.2, 128.4, 129.7, 131.2,
131.3, 131.5, 143.5, 149.1, 149.6, 161.5.
4.2.5. 1-(Phenazin-2-ylmethyl)-4-(2-(pyridin-4-yl)ethyl)
pyridinium bromide (3)
To a solution of 1,2-bis(4-pyridyl)ethane (200 mg, 1.08 mmol)
in dry acetone (2 mL)
a solution of 2-bromethylphenazine
(100 mg, 0.36 mmol) in dry acetone (10 mL) was added dropwise.
The reaction mixture was stirred at room temperature for 28 h
and then the solid was filtered, washed with cold acetone and
dried at 50 °C affording pure product 3 (128 mg, 78%); mp 273–
275 °C; [Found: C, 65.52; H, 4.71; N, 12.43. C25H21BrN4 requires
4.2.2. Synthesis of 2-bromomethylphenazine
C, 65.65; H, 4.63; N, 12.25%]; IR (KBr):
m 3052, 1645, 1605, 1513,
2-Methylphenazine (200 mg, 1 mmol) was dissolved in carbon
tetrachloride (10 mL) at room temperature. Freshly recrystallized
N-bromosuccinimide (NBS) (196 mg) was added, followed by ben-
zoyl peroxide (8 mg) and the reaction mixture was gentle refluxed
for 71 h. Then it was cooled at room temperature, filtered, and the
filtrate washed successively with water (10 mL) and brine (10 mL).
The organic extract was dried, evaporated and dried overnight in a
desiccator to give the crude product, which was purified by flash
chromatography (5:1 hexane/ethyl acetate, Rf = 0.23) to give the ti-
tle compound as a yellow product (149 mg, 53%), mp 157–159 °C
(lit.13 156–162 °C); 1H NMR (300 MHz, CDCl3): d (ppm) 4.74 (2H,
s, CH2Br), 7.84–7.88 (3H, m, ArH), 8.21–8.26 (4H, m, ArH); HRMS
(ESI-TOF): m/z found 273.0035 (M+H)+, C13H10BrN2 requires
273.0027.
1475, 1176, 1153 cmÀ1 1H NMR (DMSO-d6, 300 MHz) d (ppm):
;
3.05 (2H, t, J 7.8 Hz, CH2CH2), 3.27 (2H, t, J 7.8 Hz, CH2CH2), 6.13
(2H, s, Py+CH2Phenazine), 7.28 (2H, d, J 6.0 Hz, HbPy), 7.98–8.03
(3H, m, H-3, H-7, H-8 Phenazine), 8.12 (2H, d, J 6.7 Hz, HbPy+),
8.25À8.29 (3H, m, H-1, H-6, H-9 Phenazine), 8.33 (1H, d, J 9.1 Hz,
H-4 Phenazine), 8.46 (2H, d, J 6.0 Hz, H Py), 9.21 (2H, d, J 6.7 Hz,
a
H Py+). 13C NMR (DMSO-d6, 75 MHz) d (ppm): 33.7, 35.0, 62.5,
a
124.2, 128.5, 129.3, 129.5, 129.6, 130.6, 130.7, 131.9, 137.4,
142.6, 142.7, 143.4, 143.5, 144.8, 149.4, 149.6, 162.2.
4.2.9. Bis-[4-(2-(1-(naphthalen-2-ylmethyl)pyridinium-4-
yl)ethyl)pyridinium-1-yl](1,2-ethylendiamine)platinum(II)
(tetrakis)hexafluorophosphate (4)
A suspension of PtCl2(en)2 (40 mg, 0.12 mmol) in water (10 mL)
was heated at reflux until to obtain a clear solution. Then a solution
of 1 (100 mg, 0.24 mmol) in methanol-water (1:10) (3 mL) was
added. The reaction mixture was heated at reflux for 6 h. The solid
was filtered and the filtrate concentrated under reduced pressure
affording a colorless oil. The crude product was purified by column
chromatography on silica gel and methanol-374 mM aqueous
ammonium chloride solution (2:1) as eluent. The combined frac-
tions were concentrated at reduced pressure and the residue thus
obtained was dissolved in water and treated with ammonium
hexafluorophosphate. The precipitate was filtered, washed with
water and dried in a oven at 50 °C yielding 40 mg (22%) of pure
4.2.3. 1-(Naphthalen-2-ylmethyl)-4-(2-(pyridin-4-yl)ethyl)
pyridinium bromide (1)
To a solution of 1,2-bis(4-pyridyl)ethane (200 mg, 1.08 mmol)
in dry acetone (2 mL) a solution of 2-bromomethylnaphtalene
(83 mg, 0.36 mmol) in dry acetone (2 mL) was added dropwise.
The reaction mixture was stirred under argon at room temperature
for 24 h and then cooled at 0 °C. The solid was filtered, washed
with cold acetone and dried affording pure product 1 (108 mg,
74%); mp 189–191 °C; [Found: C, 68.18; H, 5.39; N, 7.15.
C23H21BrN2 requires C, 68.15; H, 5.22; N, 6.91%]; IR (KBr): m