Efficient cycloreversion of cis,syn-thymine photodimer by a Zn2+ -1,4,7,10-tetraazacyclododecane complex bearing a lumiflavin and tryptophan by chemical reduction and photoreduction of a lumiflavin unit.

DNA photolyases (EC 4.1.99.3) are enzymes that catalyze photoreversion of cis,syn-thymine photodimer (T[c,s]T), which is one of major photolesion products in DNA, by utilizing UV light. In this work, we have designed and synthesized Zn2+ -1,4,7,10-tetraazacyclododecane complexes bearing a lumiflavin and L: -tryptophan (ZnL3) or L: -phenylalanine (ZnL4) as artificial DNA photolyases. We have found that (ZnL3)red, whose flavin unit was reduced in situ by Na2S2O4, accelerates the photoreversion of T[c,s]T utilizing near-UV light in aqueous solution at pH 7.6 and 11. Interestingly, more efficient photoreversion of T[c,s]T was achieved by UV irradiation of an oxidized form of ZnL3 [(ZnL3)ox] in the presence of an excess amount of Et3N at pH 11. UV-vis and fluorescence measurements and action spectra showed that an oxidized form of flavin of (ZnL3)ox was photoreduced by Et3N into its reduced form (ZnL3)red, which promoted the photoreduction of T[c,s]T. Comparison of the photochemical properties of ZnL3 with those of ZnL4 suggested that a tryptophan unit in ZnL3 contributed to the stabilities of the flavin through intramolecular photoinduced electron transfer.