Proton-coupled electron transfer in the oxidation of guanines by an aromatic pyrenyl radical cation in aqueous solutions

Abstract

Electron transfer reactions between nucleic acid residues in DNA and strong oxidants are often the critical initial steps that initiate oxidative, irreversible DNA damage. Employing laser Ñash photolysis transient absorption spectroscopic techniques, we investigated the characteristics of electron transfer reactions in aqueous solutions between the 2@-deoxynucleoside 5@-monophosphates, dGMP, dAMP, dCMP and dTMP and a representative one-electron oxidant. The latter was a radical cation of a pyrene derivative with enhanced water-solubility, 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT). The BPT radical cation was BPT~`, generated by intense nanosecond laser pulse (308 or 355 nm, 50È70 mJ pulse~1 cm~2) by a non-linear consecutive two-photon absorption process. No electron transfer reactions were observed with dAMP, dTMP and dCMP, consistent with their unfavorable redox potentials. However, efficiently oxidized dGMP BPT~ẁ ith a rate constant M~1 s~1, which is smaller than the di †usion-controlled value by a k b \ 1.7 ^0.1) ] 109 factor of only D3. The dGMP(-H) neutral radicals formed on time scales of a few microseconds, were ĩdentiÐed by their characteristic transient absorption spectrum mn). The rate constant of electron (j max D 310 transfer from dGMP to was smaller in by a factor of D1.5 than in This kinetic isotope BPT~`D 2 O H 2 O. e †ect indicates that the electron transfer reaction from dGMP to is accompanied by the deprotonation BPT~ò fand therefore appears to be a proton-coupled electron transfer reaction. dGMP~`,

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

“…The rate constants were determined by least squares fits of the appropriate kinetic equations to the experimentally measured transient absorption profiles as described in detail elsewhere. 28,32 The values reported are averages of five independent measurements. The relevant and important steps leading to the oxidation of oligonucleotides by BPT •+ radicals are summarized in Table 1.…”

“…32,34 In the presence of oxygen, the hydrated electrons are rapidly scavenged by O 2 to form superoxide radical anions (reaction 2) that do not react directly with DNA. 36 Thus, the BPT •+ radicals can be used to oxidize guanine in oligonucleotides (reaction 3).…”

“…36 Thus, the BPT •+ radicals can be used to oxidize guanine in oligonucleotides (reaction 3). 32 The CO 3 •− radicals are generated by two consecutive reactions that begin with the photodissociation of persulfate anions into SO 4 •− radical anions (reaction 5, Table 2) induced by intense 308 nm excimer laser pulses. In turn, SO 4 •− radicals detectable via their characteristic absorption band at 455 nm with extinction coefficient 37 of 1600 M −1 cm −1 , oxidize bicarbonate anions into CO 3 •− radical anions (reaction 4, Table 2).…”

“…32 The rate constant k 1 , k 2 and amplitudes a 1 and a 2 for different duplexes are summarized in Table 4.…”

“…As shown previously, the decay of BPT •+ radicals occurs by a one-electron transfer reaction from guanine, while the decay of BPT •+ radicals by dTMP, dAMP, and dCMP is more than 10 4 times less efficient than for dGMP. 32 …”