ExcitedState Proton Transfer of Natural Flavonoidsand Their Chromophores in Duplex and Tetraplex DNAs

摘要

Fisetin (3,7,3′,4′-tetrahydroxyflavone) and quercetin (3,5,7,3′,4′-pentahydroxyflavone) are the bioactive plant flavonoids that are potentially useful therapeutic drugs for the treatment of a broad spectrum of diseases, including atherosclerosis, cardiovascular disease, obesity, hypertension, and cancer. 3-Hydroxyflavone (3HF) and 7-hydroxyflavone (7HF) are the synthetic chromophores of fisetin and quercetin. We have exploited dual luminescence properties of fisetin and quercetin along with 3-HF and 7HF to examine their efficacy of binding and compare their interactions with DNA, which is one of the macromolecular targets of flavonoids in physiological systems. Following the sequence of the human telomeric DNA 5′-d (CCCTAA-)n/(-TTAGGG)n-5′, two single-stranded DNA oligonucleotides, 5′-d(C3TA2)3C3-3′ and 5′-d(T2AG3)4-3′, and their duplex were used as receptors to study binding by the ligands quercetin, fisetin, and their chromophores. Circular dichroism, differential absorption, UV thermal melting, and size exclusion chromatographic studies indicated the formation of unusual DNA structures (such as C4 andG4 tetraplexes) for both the C- and G-rich single-strandedDNAs. Upon binding to DNA, dramatic changes were observed in the intrinsicfluorescence behavior of the flavonoids. Molecular docking studieswere performed to describe the likely binding sites for the ligands.The spectroscopic studies on flavonoid–DNA interactions describedherein demonstrate a powerful approach for examining their DNA bindingthrough exploiting the highly sensitive intrinsic fluorescence propertiesof the flavonoids as their own “reporter” for theirinteractions with macromolecular targets.