A pyrene dihydrodioxin with pyridinium “arms”: A photochemically active DNA cleaving agent with unusual duplex stabilizing and electron trapping properties

• Pyrene dihydrodioxins (PDHDs) are very effective DNA binding agents.
• Pyrenequinone is released photochemically from PDHDs.
• Pyrenequinone cleaves DNA ribose backbones and damages bases in a localized fashion.
• Pyrenequinone initiates its photochemical release from PDHD autocatalytically.
• Electron capture by the coordinated action of two pyridinium rings is described.

Pyrene dihydrodioxins (PDHD) comprise effective DNA intercalation agents that are masked ortho-quinones, which can be released by near ultraviolet or visible irradiation. We have studied the binding and photoreactions of chiral dipyridinium PDHDs with herring sperm DNA and an 11-mer duplex DNA containing all 10 basepair steps. Binding affinities to herring sperm DNA were determined for purified enantiomers (Kb = 1.6 ± 0.15 × 105 and 2.3 ± 0.2 × 105 M−1). UV-melting experiments using the 11-mer DNA revealed significant stabilization of duplex DNA, (ΔTm = 11.5° and ΔTm = 15.3° C). Both enantiomers linearized (double-strand cleavage) supercoiled ΦX174 plasmid DNA with high efficiency. PDHDs have specificity to cleave and/or damage DNA duplexes at Gs and have preferable binding to GG DNA sites.A full range of transient absorption spectroscopy from the ultrafast femtosecond to the microsecond domains has been applied in the study of this system. These studies have revealed a novel mechanism for quinone release via the pyrene radical cation and the entrapment of the released electron by the coordinated action of the two pyridinium rings. These same studies have shown that the released pyrenequinone can photochemically initiate the further release of pyrenequinone. Thus, this reaction is autocatalytic and can be initiated with visible light.

Figure optionsDownload as PowerPoint slide