Naphthalimide hydroperoxides as photonucleases: Substituent effects and structural basis

A variety of naphthalimide hydroperoxides as novel photochemical DNA cleavers were synthesized and evaluated. Their photochemical DNA-cleaving abilities depend on the substituents on the aromatic moiety. The DNA-cleaving differences of these hydroperoxides may result from the differences of the intercalating ability of the naphthalene moiety. X-ray single crystal structure of a representative compound 1 Light-induced cleavage of DNA by naphthalimide hydroperoxides. Supercoiled DNA runs at position I, nicked DNA at position II. pUC19 DNA (1.0 μg) was incubated in 10 μl of 1×TBE with drugs (400 μM concentration) at room temperature in the dark for 2 h, and irradiation for 30 min. The samples were analysed by gel electrophoresis in 1% agarose and the gel was stained with ethidium bromide. Lane 1: DNA control, Lane 2: 6, Lanes 3: 8, 4: 9:10≈1:1, 5: 12, 6: 1 X-ray single crystal structure of 1 was determined, and showed that all endocyclic atoms were coplanar, indicating a structural basis for potential and efficient DNA intercalation by 1.