Structural analyses of DNA oligonucleotides indicate the presence of strongly bound water molecules in the major and minor grooves. These water molecules may react with guanosine radical cation to form 8-oxo-7,8-dihydroguanine and other oxidation products, which can result in strand scission or other DNA damage. We probed the reaction of guanosine radical cation with water by incorporating alkyl-substituted cytidines and thymidines into anthraquinone-linked DNA duplexes and irradiating them with UV light at 350 nm. The incorporation of these hydrophobic substituents disrupts the DNA spine of hydration and we have observed that these modifications do not affect the trapping or long-distance hopping of radical cations in DNA.