title: Comparison of gas phase intrinsic properties of cytosine and thymine nucleobases with their O-alkyl adducts: different hydrogen bonding preferences for thymine versus O-alkyl thymine.
abstract: In recent years, there has been increasing interest in damaged DNA and RNA nucleobases. These damaged nucleobases can cause DNA mutation, resulting in various diseases such as cancer. Alkylating agents are mutagenic and carcinogenic in a variety of prokaryotic and eukaryotic organisms. The present study employs density functional theory (DFT/B3LYP) with the 6-311++G(d,p) basis set to investigate the effect of chemical damage in O-alkyl pyrimidines such as O(4)-methylthymine, O(2)-methylcytosine and O(2)-methylthymine. We compared the intrinsic properties, such as proton affinities, gas phase acidities, equilibrium tautomerization and nucleobase pair's hydrogen bonding properties, of these molecules with those in the normal nucleobases thymine and cytosine. The results are of interest for chemical reasons and also possibly for biological purposes since biological media can be quite non-polar. Furthermore, we found that N1-H of O(4)-methylthymine is less acidic than N1-H of thymine, suggesting that alkyl DNA glycosylase enzyme cannot discriminate this damaged nucleobase from a normal thymine nucleobase. This result indicates that the conjugated base anion of O(4)-methylthymine would be a worse leaving group and O(4)-methylthymine is repaired in genome by demethylation rather than enzyme-catalyzed excision at N1.
authors.affiliation: Department of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Aliakbar Tehrani
authors.forename: Alireza
authors.initials: A
authors.lastname: Fattahi
mesh_terms: D003596:Cytosine / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D019175:DNA Methylation; D005740:Gases / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D011522:Protons; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics; D013941:Thymine / Q000737:chemistry*
chemical_list: D018736:DNA Adducts; D005740:Gases; D011522:Protons; D003596:Cytosine; D013941:Thymine
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