A series of modified thiazole orange dye as the highly fluorescent G-quadruplex DNA binders: The study of electronic effects of the substituent on 1-methylquinolinium moiety

Abstract

The molecular of scaffold of thiazole orange has a number of merits for being as a fluorescent dye with tailor-made structure advancement for many useful applications. Structural modification based on 1-methylquinolinium moiety of thiazole orange is able to induce critical effects on fluorescent signal discrimination ability towards certain secondary or tertiary DNA structures. The electronic effect of the substituent on both molecular signaling and binding preference were investigated in the present study. We systematically compared the structural influence on the fluorescence signaling and binding preference towards nucleic acids in vitro through the addition of a number of substituent groups including p-methylstrylyl, p-hydroxylstyryl, p-chlorostyryl, p-bromostyryl, p-fluorostyryl, and (p-fluorobenzyl)-1,3-butadien-1-yl. The dyes synthesized were investigated with 19 nucleic acids for their interaction kinetics and fluorescent signal response with fluorescence titration experiments. The experimental results indicate that both the electronic effect and the molecular size of the dyes show significant influence on achieving higher binding affinity and fluorescent signal discrimination for G-quadruplex DNA. In addition, the dye with the introduction of a p-fluorostyryl substituent exhibits excellent linear relationship of the enhanced signal with respect to the concentration of telo21 DNA in vitro. The limit of detection (LOD) obtained was found to be 9 nM, which is much better than other analogues under the same conditions.