Acridine-Viologen Dyads: Selective Recognition of Single-Strand DNA through Fluorescence Enhancement Elizabeth Kuruvilla, †,‡ Paramjyothi C. Nandajan, † Gary B. Schuster, ‡ and Danaboyina Ramaiah* ,† Photosciences and Photonics, Chemical Sciences and Technology DiVision, National Institute for Interdisciplinary Science and Technology (NIIST), TriVandrum 695 019, India, and School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400 d_ramaiah@rediffmail.com; rama@csrrltrd.res.nic.in Received July 29, 2008 ABSTRACT Tolylacridine-viologen dyads show distinct fluorescence emission changes in the presence of double-strand DNA (dsDNA) and single-strand DNA (ssDNA) depending on the position of the linkage. The para isomer shows fluorescence quenching in the presence of both dsDNA and ssDNA, while the ortho isomer interacts selectively with ssDNA with enhancement in fluorescence intensity. Study of interactions of small molecules with nucleic acids is important from the viewpoint of developing new probes for quantification of nucleic acids, in establishing carcino- genic potential of a chemical and in developing drugs targeted to DNA. 1 A better understanding of the ligand-DNA interactions can lead to the development of probes that can discriminate between various nucleic acid structures. 2 An example is distinguishing between single (ssDNA) and double strand (dsDNA) to quantify single-strand or double- strand breaks in DNA. 3 In this context, the direct measure- ment of ssDNA and dsDNA through optical methods have several advantages. Of the optical methods, the fluorescence- based techniques offer high sensitivity. 4 These methods rely on measuring either changes in fluorescence intensity or lifetimes of the probe when bound to DNA. 3b,5 However, many of the available probes cannot efficiently differentiate between dsDNA and ssDNA. 5-7 As a result, the development † National Institute for Interdisciplinary Science and Technology. ‡ Georgia Institute of Technology. (1) (a) Levy, M. S.; Lotfian, P.; O’Kennedy, R.; Lo-Yim, M. Y.; Shamlou, P. A. Nucleic Acids Res. 2000, 28, e57. (b) Rogers, K. R.; Apostol, A.; Madsen, S. J.; Spencer, C. W. Anal. Chem. 1999, 71, 4423. (c) Seo, Y. J.; Ryu, J. H.; Kim, B. H. Org. Lett. 2005, 7, 4931. (d) Landreau, C. A. S.; LePla, R. C.; Shipman, M.; Slawin, A. M. Z.; Hartley, J. A. Org. Lett. 2004, 6, 3505. (2) (a) Xu, Y.; Zhang, Y. X.; Sugiyama, H.; Umano, T.; Osuga, H.; Tanaka, K. J. Am. Chem. Soc. 2004, 126, 6566. (c) Carreon, J. R.; Mahon, K. P.; Kelley, S. O. Org. Lett. 2004, 6, 517. (d) Kimura, T.; Kawai, K.; Majima, T. M. Org. Lett. 2005, 7, 5829. (3) (a) Cosa, G.; Focsaneanu, K.-S.; McLean, J. R. N.; McNamee, J. P.; Scaiano, J. C. Photochem. Photobiol. 2001, 73, 585. (b) Cosa, G.; Vinette, A. L.; McLean, J. R. N.; Scaiano, J. C. Anal. Chem. 2002, 74, 6163. (4) (a) Luo, W.; Gujuar, R.; Ozbal, C.; Taghizadeh, K.; Lafleur, A.; Dasari, R. R.; Zarbl, H.; Thilly, W. G. Chem. Res. Toxicol. 2003, 16, 74. (b) Haugland, R. P., Ed. Handbook of Fluorescent Probes and Research Products; Molecular Probes, Inc.: Carlsbad, CA, 2002. (5) Chen, Q.; Li, D.; Zhao, Y.; Yang, H.; Zhu, Q.; Xu, J. Analyst 1999, 124, 901. (6) (a) Blackburn, G. M., Gait, M. J., Eds. Nucleic Acids in Chemistry and Biology; Oxford University Press: Oxford, 1996. (b) Booth, C.; Griffith, E.; Brady, G.; Lydall, D. Nucleic Acids Res. 2001, 29, 4414. (c) Singleton, S. F.; Shan, F.; Kanan, M. W.; McIntosh, C. M.; Stearman, C. J.; Helm, J. S.; Webb, K. J. Org. Lett. 2001, 3, 3919. ORGANIC LETTERS 2008 Vol. 10, No. 19 4295-4298 10.1021/ol801731k CCC: $40.75  2008 American Chemical Society Published on Web 09/10/2008