Regular Article

Theoretical Chemistry Accounts

, Volume 122, Issue 3, pp 179-188

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

  • Adam MoserAffiliated withDepartment of Chemistry, University of Minnesota
  • , Rebecca GuzaAffiliated withDepartment of Medicinal Chemistry and the Cancer Center, University of Minnesota
  • , Natalia TretyakovaAffiliated withDepartment of Medicinal Chemistry and the Cancer Center, University of Minnesota
  • , Darrin M. YorkAffiliated withDepartment of Chemistry, University of Minnesota Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

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 σ and π withdrawing functional groups. The effect of these modifications on cytosine geometry, electronic structure, proton affinities, gas phase basicities, cytosine–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.