One consequence of life in an oxygen atmosphere is constant exposure to free radicals. Sunlight, redox-active transition metals, and the process of metabolism itself convert O₂ into oxygen-containing radicals that damage DNA sugars and bases. Work in the Burrows Lab has focused on reactions that generte such species by both photochemical means and the use of nickel, cobalt, manganese, copper, and iron-containing complexes. Peroxyl radicals, superoxide, and singlet oxygen are produced photochemically, while sulfate radical (from metal-catalyzed autooxidation of sulfite) and hyrdoxyl radical (the Fenton reaction) are formed via metal catalysis. Transition metal complexes may also directly serve as one-electron oxidants for DNA.

The nucleobase guanine is the most susceptible site in DNA toward oxidation. When G loses and electron or is attacked by an oxygen radical species, it initiates a complicated cascade of events leading to a large number of heterocyclic products. The preference for one product over another is highly influenced by pH, temperature, stacking interactions in the duplex, and the presence of additional oxidants and reductants. In addition, reactive intermediates along these pathways may be trapped by nucleophiles leading, for example, to DNA-protein crosslinking. Sorting out the various products, pathways, and likely mechanisms has been an adventure game, mostly played in the dark, but sunlighted somewhat with modern methods of mass spectrometry and biochemistry.

Having identified new lesions, or mistakes, arising from oxidative damage to DNA, we are currently attempting to understand the biochemical consequences of oxidized Gs. Are they copied accurately by polymerases? Are they recognized by DNA repair enzymes? Can we use these reactions as tools for manipulating DNA and RNA and understanding their structures? Collaborations with the laboratories of Profs. Sheila David, Peter Bean, and Brad Preston at the U of U are helping us to address these issues.