Comparison of transition metal-mediated oxidation reactions of guanine in nucleoside and single-stranded oligodeoxynucleotide contexts

As the most readily oxidized of DNA’s four natural bases, guanine is a prime target for attack by reactive oxygen species (ROS) and transition metal-mediated oxidants. The oxidation products of a modified guanosine nucleoside and of a single-stranded oligodeoxynucleotide, 5′-d(TTTTTTTGTTTTTTT)-3′ have been studied using oxidants that include CoII, NiII, and IrIV compounds as well as photochemically generated oxidants such as sulfate radical, electron-transfer agents and singlet oxygen. The oxidized lesions formed include spiroiminodihydantoin (Sp), guanidinohydantoin (Gh), imidazolone (Iz), oxazolone (Z) and 5-carboxamido-5-formamido-2-iminohydantion (2-Ih) nucleosides with a high degree of dependence on the exact oxidation system employed. Interestingly, a nickel(II) macrocyclic complex in conjunction with KHSO5 leads to the recently reported 2-Ih heterocycle as the major product in both the nucleoside and oligonucleotide contexts.

Graphical abstractThe oxidation of guanosine as a nucleoside or in single-stranded DNA yields a suite of hydantoin products depending on the metal complex and oxidation method employed.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► A broad spectrum of G oxidation products form in nucleosides and DNA. ► The recently characterized 2-iminohydantoin nucleoside was a major product from Ni(II). ► Spiroiminodihydantoin was formed in other reactions mediated by Co(II), and Ir(IV).