Nucleic Acid Oxidation Mediated by Naphthalene and Benzophenone Imide and Diimide Derivatives: Consequences for DNA Redox Chemistry

The rate constants for electron transfer from guanosine 5‘-monophosphate (GMP), adenosine 5‘-monophosphate (AMP), cytidine 5‘-monophosphate (CMP), and thymidine 5‘-monophosphate (TMP) to the triplet excited states of N-(3-propanol)-1,8-naphthalimide (NI), N,N ‘-(3-propanol)-1,4,5,8-naphthaldiimide (NDI), and N,N ‘-(3-propanol)-3,3‘,4,4‘-benzophenonediimide (BPDI) have been determined in 1:1 H2O/CH3CN solution. Upon 355-nm (8 ns) laser flash excitation of each of the imide or diimides in solution, the triplet states decayed by first-order kinetics under conditions of low excitation energy. Photoinduced electron transfer to the lowest electronically excited triplet state of N-(3-propanol)-1,8-naphthalimide from GMP occurred with a rate constant of 2.0 × 107 M-1 s-1. Electron-transfer quenching by the other nucleotides was almost 2 orders of magnitude slower. In the case of BPDI, photooxidation rate constants ranged from 2.3 × 108 M-1 s-1 for quenching by CMP to 1.1 × 109 M-1 s-1 by GMP. In all cases, the imide radical anion was observed by laser flash photolysis, and the yields were quantified. From these investigations, nucleotide oxidation by the triplet state of a series of redox-active photosensitizers has been demonstrated. The results represent a systematic study of nucleotide oxidation by the triplet states of a series of structurally related organic photosensitizers in which the reduction potential can be tuned by ca. 800 mV. The greater than 100-fold variation in bimolecular rate constants for oxidation of base monophosphates by these photosensitizers offers the prospect of kinetic “selectivity” of oxidative damage in random-sequence DNA.