First principles calculation of pKa values for 5-substituted uracils

Yun Hee Jang, Lawrence C. Sowers, Tahir Çagin, William A. Goddard

Research output: Contribution to journalArticlepeer-review

198 Scopus citations


Oxidation of uracil (U) and thymine (5-Me-U) are believed to play a role in genetic instability because of the changes these oxidations cause in the ionization constants (pKa values), which in turn affects the base pairing and hence coding. However, interpretation of the experimental evidence for the changes of pKa with substitution at U has been complicated by the presence of two sites (N1 and N3) for ionization. We show that a procedure using first principles quantum mechanics (density functional theory with generalized gradient approximation, B3LYP, in combination with the Poisson-Boltzmann continuum-solvation model) predicts such pKa values for a series of 5-substituted uracil derivatives in excellent correlation with experiment. In particular, this successfully resolves which cases prefer ionization at N1 and N3. Such first principles predictions of ionization constant should be useful for predicting and interpreting pKa for other systems.

Original languageEnglish (US)
Pages (from-to)274-280
Number of pages7
JournalJournal of Physical Chemistry A
Issue number1
StatePublished - Jan 11 2001
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry


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