Formation of Transient Intermediates in Low-Temperature Photosensitized Oxidation of an 8-¹³C-Guanosine Derivative

Abstract

An 8-(13)C-labeled guanosine derivative, 2',3',5'-O-tert-butyldimethylsilyl-N-tert-butyldimethylsilyl-8-(13)C-guanosine, was synthesized and its photosensitized oxidation with singlet oxygen carried out below -100 degrees C. Two transient intermediates that decompose directly to the final major product 5 and CO(2) were detected by (13)C NMR between -100 and -43 degrees C. The two intermediates are carbamic acids based on (13)C NMR and 2D NMR (HMQC, HMBC) spectra and the formation of final product 5 and of 8-CO(2). No endoperoxide intermediate could be detected by low-temperature NMR spectroscopy even at -100 degrees C. A reaction mechanism is proposed involving initial [4 + 2] cycloaddition of singlet oxygen to the imidazole ring to form an unstable endoperoxide, subsequent rearrangement of the endoperoxide to a dioxirane, and decomposition of the dioxirane to the two observed intermediates. Both oxygen atoms of CO(2) are derived from a single oxygen molecule, which strongly supports a dioxirane structure for the precursor of the two observed intermediates. The distribution of products estimated by (13)C NMR accounts for all the (13)C-containing products in the reaction mixture.

Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways

“…The tert ‐butyldimethylsilyl (TBDMS) groups provided solubility to 8‐methylguanosine in CD 2 Cl 2 at low temperature, where two diastereomeric endoperoxides form. Unstable peroxide products from 1 O 2 reactions with guanine and imidazoles have been suitably detected by low‐temperature NMR spectroscopy thanks to their isotopic labeling with 13 C and 15 N atoms .…”

Formation and processing of DNA damage substrates for the hNEIL enzymes

“…The path to understanding G oxidation by 1 O 2 has led to many challenges in determination of the products observed and their mechanisms of formation [120, 121]. The mechanism by which G is oxidized via 1 O 2 remains a topic of study in the literature [122–124].…”

Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

“…9). Typically, hydroperoxides generated in the course of oxidative degradation of guanine bases are very unstable at room temperature (52). According to the mechanism proposed by Cadet and co-workers (31), the cleavage of 5-HOO-G(ϪH) occurs via the opening of the pyrimidine ring at the C-5-C-6 bond in 5-HOO-G(ϪH) leading to an unstable intermediate that is easily hydrated at the 7,8-CϭN double bond (Fig.…”