In this context, we previously studied EET in DNA contain-
ing 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol,
Tg), which forms a less stable base pair with the comple-
mentary 2′-deoxyadenosine, to investigate radiation-induced
reductive DNA damage mechanisms and demonstrated that
excess electrons could be transported beyond the Tg/A site.5
The results can be explained by the low electron affinity of
Tg, slow decomposition of the corresponding radical anion,
and the flexibility of the duplex structures. The third factor
might be a critical issue for the investigation of the structural
effects of mismatched base pairs on EET in the duplex
because exact location of the electron donor cannot be
determined. Because of our interest in this aspect and to
explore the effect of modified DNA bases on EET in detail,
here we developed a novel diaminostilbene (DAS)-capped
hairpin DNA and undertook mechanistic investigation of
EET through mismatched DNA bases.
(E*ox ) -2.53 V vs SCE)6 or a flavin (E*ox ) -2.6 V vs
NHE)3c-e as photoinducible electron injectors have been
reported previously. Our newly developed electron-donor
DAS shows absorption in the wavelength range 280-430
nm (Figure 2), has a high excited-state oxidation potential,
Previously, we developed DNA duplexes tethered to
phenothiazine (PTZ, E*ox ) -2.67 V vs SCE) by a
trimethylene linker for the investigation of reductive repair
of Tg in DNA.5 Similar assemblies were employed for
quantification of EET from PTZ to an irreversible electron
acceptor, 5-bromo-2′-deoxyuridine (BrU),3g,h through inter-
vening mismatched base pairs (DS, Figure 1). For compari-
Figure 2. UV absorption (1 and 2) and fluorescence (3-5) spectra
of 1 µM diaminostilbene derivative 2 in 0.1% acetonitrile/H2O (1
and 3) and 1 µM HP [X/Y ) T/A (2 and 5) and X/Y ) A/A (4)]
in phosphate buffer (90 mM phosphate, 10 mM NaCl). Fluorescence
spectra were obtained by excitation at 365 nm.
E*ox ) -2.73 V vs SCE,7 which is comparable to that of
PTZ, and does not require any additive for activation of the
chromophore.3c-e Furthermore, the planar aromatic ring
might allow for capping at one end of the duplex, leading to
efficient electron injection because of orbital overlap between
nucleobases and the chromophore.
The phosphoramidite of DAS was synthesized from the
t-butyldimethylsilyl-protected benzaldehyde (1) in three steps
(Scheme 1). Synthesis of N,N′-di(2-hydroxyethyl)-diaminos-
tilbene derivative (2) from the nonprotected benzaldehyde
by McMurry reaction has been reported previously.8 How-
ever, the reported coupling reaction gave multiple products
which were hardly isolable by flash chromatography. We
thus attempted the synthesis of 2 starting from the benzal-
dehyde 1, by which we could obtain 2 as an exclusive
product. After dimethoxytrityl derivatization of 2, the cor-
responding phosphoramidite derivative (4) was obtained by
the reaction of 3 with N,N-diisopropylmethyl phosphona-
midic chloride (DIMPACl). The diaminostilbene unit was
introduced into DNA using a DNA synthesizer via conven-
Figure 1. Sequences of oligodeoxynucleotides.
son, we designed novel electron-donor-DNA conjugates
(HP) to study the effects of structural distortion on EET
(Figure 1). Similar hairpin structures bearing a stilbenediether
(6) (a) Lewis, F. D.; Liu, X.; Wu, Y.; Miller, S. E.; Wasielewski, M. R.;
Letsinger, R. L.; Sanishvili, R.; Joachimiak, A.; Tereshko, V.; Egli, M.
J. Am. Chem. Soc. 1999, 121, 9905–9906. (b) Lewis, F. D.; Liu, X. J. Am.
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(7) Excited-state oxidation potential was calculated using E*ox ) Eox
-
E00 with the oxidation potential of N,N,N′,N′-tetramethyl-4,4′-diaminostil-
bene (Eox) 0.42 V (Kubota, T.; Uno, B.; Matsuhisa, Y.; Miyazaki, H.; Kano,
K. Chem. Pharm. Bull. 1983, 31, 373–385) and zero excitation energy (E00)
evaluated from λ00 () 394 nm) in aqueous solution
(8) (a) Wang, X.; Zhou, G.; Wang, D.; Wang, C.; Fang, Q.; Jiang, M.
Bull. Chem. Soc. Jpn. 2001, 74, 1977–1982. (b) Wang, X.; Wang, D.; Zhou,
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(5) Ito, T.; Kondo, A.; Terada, S.; Nishimoto, S. J. Am. Chem. Soc.
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Org. Lett., Vol. 11, No. 4, 2009