close proximity of double-stranded nucleic acids, i.e. at a
position where mercury develops its genotoxicity; and there
is no interfering background signal due to association with
Hg2+ or DNA alone, respectively. Most remarkably, the
strong influence of the Hg2+ concentration on the CD spectrum
of the ternary complex is also not influenced by separate
1a–Hg2+ or 1a–DNA interactions, so that the combination
of fluorimetric and polarimetric titrations even enables the 3D
analysis of the Hg2+ concentration (cf. ESIw, Fig. S7).
Notes and references
1 (a) G. L. Eichhorn and J. J. Butzow, Proc. Int. Symp. Biomol.
Struct. Interactions, Suppl. J. Biosci., 1985, 8, 527;
(b) M. T. Rodgers and P. B. Armentrout, J. Am. Chem. Soc.,
2000, 122, 8548; (c) I. Onyido, A. R. Norris and E. Buncel, Chem.
Rev., 2004, 104, 5911; (d) J. Muller, Eur. J. Inorg. Chem., 2008,
¨
3749; (e) C. Ruan and M. T. Rodgers, J. Am. Chem. Soc., 2009,
131, 10918.
2 (a) E. Sletten and W. Nerdal, in Metal Ions in Biological Systems,
ed. A. Sigel and H. Sigel, Marcel Dekker, 1997, p. 479; (b) H. Sigel,
Chem. Soc. Rev., 1993, 22, 255; (c) J. V. Burda, J. Sponer,
J. Leszczynski and P. Hobza, J. Phys. Chem. B, 1997, 101, 9670;
(d) Y. Miyake, H. Togashi, M. Tashiro, H. Yamaguchi, S. Oda,
M. Kudo, Y. Tanaka, Y. Kondo, R. Sawa, T. Fujimoto,
T. Machinami and A. Ono, J. Am. Chem. Soc., 2006, 128, 2172;
(e) Y. Tanaka, S. Oda, H. Yamaguchi, Y. Kondo, C. Kojima and
A. Ono, J. Am. Chem. Soc., 2007, 129, 244.
3 M. E. Crespo-Lopez, G. L. Macedo, S. I. D. Pereira, G. P.
F. Arrifano, D. L. W. Picanco-Diniz, J. L. M. do Nascimento
and A. M. Herculano, Pharmacol. Res., 2009, 60, 212.
4 (a) M. Tabata, A. K. Sarker and E. Nyarko, J. Inorg. Biochem.,
2003, 94, 50; (b) S. S. Babkina and N. A. Ulakhovich, Bio-
electrochemistry, 2004, 63, 261; (c) Z. Hossain and F. Huq,
J. Inorg. Biochem., 2002, 91, 398.
5 (a) A. P. H. de Silva, Q. Gunaratne, T. Gunnlaugsson, A. J.
M. Huxley, C. P. McCoy, J. T. Rademacher and T. E. Rice, Chem.
Rev., 1997, 97, 1515; (b) B. Valeur, Molecular Fluorescence:
Principles and Applications, Wiley-VCH, Weinheim, 2002.
6 E. M. Nolan and S. J. Lippard, Chem. Rev., 2008, 108, 3443.
7 X. Xue, F. Wang and X. Liu, J. Am. Chem. Soc., 2008, 130, 3244.
8 A. Granzhan, H. Ihmels and G. Viola, J. Am. Chem. Soc., 2007,
129, 1254.
Fig. 4 Deactivation pathways of the excited state of 1a (path a:
rotation about N–Car bond; path b: photoinduced electron transfer),
and schematic representation of fluorimetric detection of Hg2+ ions in
the microenvironment of ds DNA by suppression of both deactivation
pathways in the excited state.
Notably, neither the complexation of Hg2+ nor the inter-
calation into DNA has a significant influence on the very weak
emission intensity of 1a. This behavior may be explained by
the two possible pathways through which the excited state may
be deactivated, namely photoinduced electron transfer from
the aminophenyl unit to the excited benzo[b]quinolizinium
(Fig. 4, path b) and rotation about the C–N bond
(Fig. 4, path a), as has been demonstrated in detail for
the 9-[(4-dimethylamino)phenyl]-aminobenzo[b]quinolizinium.8
Thus, if only one of these deactivation pathways is suppressed,
namely by complexation of the azacrown ether donor
functionality or by intercalation of the ligand, the emission
is still efficiently quenched. However, if both pathways are
suppressed by simultaneous complexation and intercalation,
the emission intensity increases as observed for the ligand 1a in
the presence of DNA and Hg2+. Thus the combination of 1a,
DNA, and Hg2+ constitutes a DNA-based molecular logic
gate of the AND type,7,14 i.e. the output (fluorescence
enhancement) of the gate occurs only if both inputs, DNA
and Hg2+, are present. In addition, this system enables the
sensitive and selective detection of Hg2+ ions under physio-
logical conditions, even in the presence of potentially competing
metal cations. Specifically, the sensitivity of fluorimetric
detection of Hg2+ was determined to be 39 nM, i.e., 7.8 ppb
(cf. ESIw). Even more notable is the fact that the fluorescent
probe 1a enables the unambiguous detection of Hg2+ in the
9 J. Polster and H. Lachmann, Spectrometric Titrations: Analysis of
Chemical Equilibria, Wiley, VCH, Weinheim, 1989.
10 (a) H. Ihmels and D. Otto, Top. Curr. Chem., 2005, 258, 161;
(b) U. Pindur, M. Jansen and T. Lemster, Curr. Med. Chem., 2005,
12, 2805; (c) M. Sinan, M. Panda, A. Ghosh, K. Dhara,
P. E. Fanwick, D. J. Chattopadhyay and S. Goswami, J. Am.
Chem. Soc., 2008, 130, 5185.
11 J. D. McGhee and P. H. von Hippel, J. Mol. Biol., 1974, 86, 469.
12 B. Norden and T. Kurucsev, J. Mol. Recognit., 1994, 7, 141.
13 H. Ihmels, K. Faulhaber, C. Sturm, G. Bringmann, K. Messer,
N. Gabellini, D. Vedaldi and G. Viola, Photochem. Photobiol.,
2001, 74, 505.
14 K. Szacilowski, Chem. Rev., 2008, 108, 3481. Most recent
examples: T. Li, E. Wang and S. Dong, J. Am. Chem. Soc.,
2009, 131, 15082; T. Konry and D. R. Walt, J. Am. Chem. Soc.,
2009, 131, 13232.
ꢁc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 5719–5721 | 5721