10.1002/chem.202101918
Chemistry - A European Journal
FULL PAPER
(m), 1558 (m), 1462 (m), 1425 (m), 1249 (m), 1048 (s), 755 s); HRMS
(ES+): m/z: calcd for C28H16N2: 382.1470 [M]; found 382.1464 [M].
trapping reagent and the photosensitizers, except for the ortho
derivative 2o. Several control experiments under anaerobic
conditions and use of deuterated solvents confirm two reaction
1
Bis-9,10-(3-pyridylethynyl)anthracene 5m: Yield 319 mg (87%), yellow
crystals. Mp. 270-273 °C. 1H NMR (400 MHz, CDCl3): δ=7.42 (2H, dd,
J=3.4Hz, 7.85 Hz, 3-HPy), 7.70 (4H, J=3.4 Hz, 9.9 Hz, H-1, H-4, H-5, H-
8), 8.07 (2H, d, J=7.9 Hz, 4-HPy), 8.67-8.69 (6H, H-2, H-3, H-6, H-7, 6-
HPy), 9.04 (2H, s 2-HPy). 13C NMR (80 MHz, CDCl3): δ=89.5 (AlkynylANT),
98.9 (s, AlkynylPy), 118.2 (s, C9, C10), 120.5 (s, CPy3), 123.2 (s, C11,
C12, C13, C14, C15), 127.1 (d, C2, C3, C6, C7), 127.2 (d, C1, C4, C5,
C8), 132.1 (CPy4), 138.4 (CPy5), 149.0 (CPy2), 152.2 (d, CPy6); IR (cm-
1, ATR) ꢀꢁ=3667 (m), 2979 (s), 2903 (s), 2196 (m), 1901 (w), 1715 (w), 1476
(m), 1404 (m), 1232 (m), 1184 (m), 1017 (m); HRMS (ES+): m/z: calcd for
C28H16N2: 382.1470 [M]; found 382.1447 [M].
pathways, one involving O2, the other electron transfer from the
trapping reagent to the excited pyridinium anthracene. By use of
cyclic voltammetry and UV/vis spectroscopy, the excited state
reduction potentials of the three sensitizers were determined.
These data reveal that 2o and 2p act as strong oxidants in their
excited states, which leads to an ET processes. Also, the inherent
anthracene units of the pyridinium alkynylanthracenes undergo
ET. Because of these ET processes, the three compounds are
1
unsuitable as sensitizers for the generation of O2 in their free
forms.
In contrast, the ability to generate 1O2 is switched on for all
three derivatives in the presence of poly(dA:dT), as clearly
indicated by the increased oxidation of GLYANT. The prevalence
Bis-9,10-(4-pyridylethynyl)anthracene 5p: Yield 321 mg (89%), yellow
crystals. Mp. 283-286 °C. 1H NMR (400 MHz, CDCl3): δ=7.65 (4H, d,
J=5.6 Hz, 3-HPy, 5-HPy), 7.72 (4H, dd, J=3.4Hz, 9.9 Hz, H-2, H-3, H-6, H-
7), 8.67 (dd, J=9,9 Hz, 3.4 Hz, H-1, H-4, H-5, H-8), 8.75 (4H, d, J=5.6 Hz,
2-HPy, 6-HPy). 13C NMR (80 MHz, CDCl3): δ=90.6 (AlkynylANT), 99.7 (s,
AlkynylPy), 118.2 (s, C9, C10), 125.4 (s, C11, C12, C13, C14, C15), 127.0
(d, C2, C3, C6, C7), 127.4 (d, C1, C4, C5, C8), 131,2 (s, CPy4), 132.2 (d,
CPy3, CPy5), 150.0 (d, CPy2, CPy6); IR (cm-1, ATR) ꢀꢁ=3667 (m), 2979 (s),
2902 (s), 2200 (m), 1587 (m), 1403 (m), 1213 (m), 1062 (s); HRMS (ES+):
m/z: calcd for C28H16N2: 382.1470 [M]; found 382.1437 [M].
1
of the O2 pathway over the ET path is confirmed by the lack of
reactivity under anaerobic conditions and the strong reactivity
enhancement in deuterated solvents. The main advantage gained
from this interaction is that the sensitizers are stabilized and their
self-decomposition is suppressed. This effect is caused by the
hydrophobic environment provided within the intercalation pocket.
However, for the ortho isomer 2o with the highest oxidation
potential in its excited state, ET from adenine bases can also
Synthesis of the methyl 9,10-(pyridiniumalkynyl)anthracenes 2o─p.
The pyridylalkynyl anthracenes 5o─p (0.5 mmol) were methylated by
heating in DMF in the presence of 3 eq of dimethyl sulfate at 100 °C for 24
h. After removal of DMF at reduced pressure, the methyl 9,10-
(pyridiniumalkynyl)anthracenes 2o─p were recrystallized in methanol.
occur causing
a
quenching of fluorescence and self-
decomposition of the sensitizer. The para isomer 2p, where the
reaction of the trapping reagent exhibits the highest reactivity, is
the only example, where a switching is also achieved by
polynucleotides carrying guanine. It is therefore persistent against
self-decomposition but does not provide sufficient oxidation
power to oxidize the polynucleotide bases. Future studies will
focus on the application of these new pyridinium
alkynylanthracenes to selectively damage DNA in vitro and in vivo.
9,10-Bis(2-methylpyridinium-1-yl-ethynyl)anthracene sulfate 2o:
Yield 290 mg (96 %), orange solid. Mp. > 300 °C (Decomposition). 1H NMR
(400 MHz, DMSO-d6): δ=4.70 (6H, CH3), 7.97 (4H, dd, J=2.8 Hz, 6.4 Hz,
H-1, H-4, H-5, H-8), 8.22 (2H, m, 4-HPy), 8.75 (6H, m, 2-H, 3-H, 6-H, 7-H,
5-HPy), 8.85 (2H, d, J=7.8 Hz, 3-HPy), 9.28 (2H, d, J=5.9 Hz, 6-HPy). 13
C
NMR (80 MHz, DMSO-d6): δ=48.3 (s, CH3), 94.0 (s, AlkynylANT), 100.9 (s,
AlkynylPy), 117.5 (s, C9, C10), 127.2 (d, CPy4), 127.8 (s, C11, C12, C13,
C14, C15), 130.0 (d, C2, C3, C6, C7), 132.4 (d, C1, C4, C5, C8), 132.8 (d,
CPy3), 137.2 (s, CPy2), 145.3 (d, CPy5), 147.9 (d, CPy6); IR (cm-1, ATR)
ꢀꢁ=3063 (w), 3032 (w), 2196 (m), 1628 (m), 1506 (m), 1452 (m), 1229 (s),
1165 (s), 1032 (s), 839 (s), 761 (s); HRMS (ES+): m/z: calcd for C30H22N2:
410.1782 [M]; found 205.0887 [M2+].
Experimental Section
Detailed information about the materials used, all spectroscopic
techniques, DNA melting studies, determination of binding constants,
irradiation experiments, calculations and molecular modelling is given in in
the Supporting Information.
9,10-Bis(3-methylpyridinium-1-yl-ethynyl)anthracene sulfate 2m:
Yield 285 mg (92 %), orange solid. Mp. > 300°C (Decomposition). 1H NMR
(400 MHz, DMSO-d6): δ=4.45 (6H, CH3), 7.91 (4H, J=3.4 Hz, 9.7 Hz, H-1,
H-4, H-5, H-8), 8.30 (2H, dd, J=6.1 Hz, 7.7 Hz, 5-HPy), 8.83 (4H, dd, J=3.4
Hz, 9.7 Hz, 2-H, 3-H, 6-H, 7-H), 9.09 (2H, d, J=6.1 Hz, 4-HPy), 9.12 (2H,
d, J=8.2 Hz, 6-HPy), 9.75 (2H, s, 2-HPy). 13C NMR (80 MHz, DMSO-d6):
δ=48.7 (s, CH3), 92.3 (s, AlkynylANT), 96.5 (s, AlkynylPy), 117.1 (s, C9,
C10), 122.9 (s, C11, C12, C13, C14, C15), 127.3 (d, CPy5), 128.1 (d,
CPy4), 129.1 (d, C2, C3, C6, C7), 132.1 (d, C1, C4, C5, C8), 147.1 (d,
CPy2), 145.6 (s, CPy3), 148.6 (d, CPy6); IR (cm-1, ATR) ꢀꢁ=3667 (w), 2979
(s), 2902 (s), 2198 (m), 1505 (m), 1452 (m), 1230 (s), 1170 (m), 1034 (s),
840 (m); HRMS (ES+): m/z: calcd for C30H22N2: 410.1782 [M]; found
205.0894 [M2+].
Synthesis of bis-9,10-(pyridylalkynyl)anthracenes 5o─p by
Sonogashira coupling. Anthracenes 5o─p were prepared according to
an
established
procedure,
affording
yields
of
>80%.[37]
Dibromoanthracene (4) (336 mg, 1 mmol), [Pd(PPh3)2Cl2] (60 mg, 0.08
mmol) and CuI (100 mg, 0.52 mmol) were placed in a round bottom flask
and dissolved in dry THF (8 mL) and dry iPr2NH (8 mL). After degassing
by three freeze-pump-thaw cycles, the flask was filled with argon and
sealed with a septum. At 80 °C the literature known pyridyl acetylenes (2.1
mmol) (3o─p)[64] were added in neat via syringe pump over a period of 4.5
h. Thereafter, the solvent was evaporated and the residue was suspended
in methanol. The precipitate was filtered and the residue was dissolved in
hot CHCl3. After hot filtration, the product precipitated upon cooling.
9,10-Bis(4-methylpyridinium-1-yl-ethynyl)anthracene sulfate 2p:
Yield 292 mg (94 %), orange solid. Mp. > 300 °C (Decomposition). 1H NMR
(400 MHz, DMSO-d6): δ=4.39 (6H, CH3), 7.94 (4H, dd, J=3.4 Hz, 9.8 Hz,
H-1, H-4, H-5, H-8), 8.67 (4H, d, J=9.1 Hz, 3-HPy, 5-HPy), 8.85 (4H, dd,
J=3.4 Hz, 9.8 Hz), 2-H, 3-H, 6-H, 7-H), 9.15 (4H, d, J=9.1 Hz, 2-HPy, 6-
HPy). 13C NMR (80 MHz, DMSO-d6): δ=48.3 (CH3), 97.6 (s, AlkynylANT),
99.3 (s, AlkynylPy), 118.1 (s, C9, C10), 127.4 (d, C2, C3, C6, C7), 129.5
(d, C1, C4, C5, C8), 129.7 (s, C11, C12, C13, C14, C15), 132.5 (CPy2,
CPy4), 138.1 (CPy1), 146.1 (CPy3, CPy5); IR (cm-1, ATR) ꢀꢁ=3064 (w),
Bis-9,10-(2-pyridylethynyl)anthracene 5o: Yield 315 mg (84%), yellow
crystals. Mp. > 300 °C (Decomposition). 1H NMR (400 MHz, CDCl3):
δ=7.35 (2H, J=4.2 Hz, 13.6 Hz, 4-HPy), 7.69 (4H, dd, J=3.45 Hz, 9.89 Hz,
H-1, H-4, H-5, H-8), 7.81 (4H, 2d, J=3.65 Hz, 9.89 Hz, 3-HPy, 5-HPy),
8.76-8.78 (6H, m, 2-H, 3-H, 6-H, 7-H, 6-HPy). 13C NMR (80 MHz, CDCl3):
δ= 86.1 (s, AlkynylANT), 101.6 (s, AlkynylPy), 118.2 (C9, C10), 123.0 (s,
C11, C12, C13, C14, C15), 127.2 (d, C1, C2, C3, C4, C5, C6, C7, C8),
127.6 (d, CPy4), 132.4 (d, CPy3), 136.3 (d, CPy5), 143.5 (s,CPy2), 150.4
(d, CPy6); IR (cm-1, ATR) ꢀꢁ=3666 (m), 2982 (s), 2903 (s), 2199 (m), 1575
10
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