The C8 position of guanine is known to be vulnerable to forming adducts that cause damage to DNA, and these adducts are often used as biomarkers to indicate conditions such as oxidative stress. Forming guanine adducts synthetically usually occurs via Pd-catalysed coupling reactions, as radical-based approaches generally have poor yields. Water has also seldom been used as a reaction medium, despite its relevance to biomimetic chemistry.
However, this HOT article from Chryssostomos Chatgilialoglu et al. describes the successful radical-based alkylation of two guanine derivatives in aqueous solution via γ-radiolysis. The mechanism of α-hydroxylalkyl radical addition to the C8 position of the purine ring, which results in intermolecular C-C bond formation, is discussed in detail and provides useful insights into the radical chemistry of 8-bromoguanines.
This paper is free to access until 26th April and is part of the forthcoming OBC special web themed issue on radical chemistry.
Radical-based alkylation of guanine derivatives in aqueous medium
Chryssostomos Chatgilialoglu, Clara Caminal and Quinto G. Mulazzani
Org. Biomol. Chem., 2011, Advance Article