Chemical Sciences and Technology

DNA damage and cytotoxicity studies of viologen linked pyrene conjugates

dnaThe design of molecules that can efficiently interact and cleave DNA has been the subject of enormous interest from the point of developing new drugs and for studying the electron and energy transfer properties of DNA. A few water soluble novel viologen linked pyrene conjugates with varying spacer groups were synthesized and investigated their cellular permeability, DNA damage and cytotoxicity in the presence of light. These bifunctional conjugates showed significant DNA modifications that are sensitive to formamidopyrimidine glycosylase (Fpg). The observation of predominantly Fpg sensitive modifications in these conjugates confirm that the formation of photoinduced charge-separated base radical cation results in the oxidative DNA damage. The results demonstrate that the viologen linked pyrene conjugates undergo predominantly intercalative interactions with DNA, induce spacer length dependent DNA damage through a photoinduced electron transfer mechanism, localise inside the nucleus and exhibit cytotoxicity only upon photoexcitation (Chem. Commun. 2010, 46, 2064-2066).