Photochemical Control of DNA Structure through Radical Disproportionation

Photolysis of an aryl sulfide‐containing 5,6‐dihydropyrimidine ( 1 ) at 350 nm produces high yields of thymidine and products resulting from trapping of a 5,6‐dihydrothymidin‐5‐yl radical by O₂ or thiols. Thymidine is believed to result from disproportionation of the radical pair originally generated from C? S bond homolysis of 1 on the microsecond timescale, which is significantly shorter than other photochemical transformations of modified nucleotides into their native forms. Duplex DNA containing 1 is destabilized, presumably due to disruption of π‐stacking. Incorporation of 1 within the binding site of the restriction endonuclease EcoRV provides a photochemical switch for turning on the enzyme's activity. In contrast, 1 is a substrate for endonuclease VIII and serves as a photochemical off switch for this base excision repair enzyme. Modification 1 also modulates the activity of the 10–23 DNAzyme, despite its incorporation into a nonduplex region. Overall, dihydropyrimidine 1 shows promise as a tool to provide spatiotemporal control over DNA structure on the miscrosecond timescale.