Density functional study of the influence of C5 cytosine substitution in base pairs with guanine

Theoretical Chemistry Accounts vol. 122  p. 179-188  DOI: 10.1007/s00214-008-0497-5
PMID/PMCID: PMC2771868 Published: 2009-03-01 


Adam Moser, Rebecca Guza, Natalia Y. Tretyakova, Darrin M. York [ ]

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Abstract

<p>The present study employs density-functional electronic structure methods to investigate the effect of chemical modification at the C5 position of cytosine. A series of experimentally motivated chemical modifications are considered, including alkyl, halogen, aromatic, fused ring, and strong s and p withdrawing functional groups. The effect of these modifications on cytosine geometry, electronic structure, proton affinities, gas phase basicities, cytosine&ndash;guanine base pair hydrogen bond network and corresponding nucleophilicity at guanine are examined. Ultimately, these results play a part in dissecting the effect of endogenous cytosine methylation on the reactivity of neighboring guanine toward carcinogens and DNA alkylating agents.</p>