Abstract
The results of semiempirical quantum chemical calculations performed on the tautomeric forms of four modified anionic nucleic acid bases, i.e. the anions of the 1-methyl-5-hydroxyuracil, 1- methyl-5-hydroxycytosine, 9-methyl-8-hydroxyadenine, and 9-methyl-8-hydroxyguanine, allow prediction of the mutagenically most active forms of these compounds. Preliminary calculations on base pairs between modified and normal bases indicate strong bonding to the most stable anionic tautomers of modified bases.
Highlights
It has been shown by us that the quantum chemical self-consistent reaction field (SCRF) method, in combination with AM1 (Austin Model 1)[1] and PM3 (Parametric Model 3)[2] semiempirical parameterization, gives confident predictions of the tautomeric equilibrium constants of different classes of heterocyclic compounds in aqueous solutions.[3,4,5,6,7] Other investigators using different levels of quantum theory[8,9,10] have later confirmed the applicability of the SCRF method for the description of tautomeric equilibria in solutions
The results of semiempirical quantum chemical calculations performed on the tautomeric forms of four modified anionic nucleic acid bases, i.e. the anions of the 1-methyl-5-hydroxyuracil, 1methyl-5-hydroxycytosine, 9-methyl-8-hydroxyadenine, and 9-methyl-8-hydroxyguanine, allow prediction of the mutagenically most active forms of these compounds
This has encouraged us to use the same approach for prediction of the tautomeric constitution of chemically modified nucleic acid bases in aqueous solutions
Summary
It has been shown by us that the quantum chemical self-consistent reaction field (SCRF) method, in combination with AM1 (Austin Model 1)[1] and PM3 (Parametric Model 3)[2] semiempirical parameterization, gives confident predictions of the tautomeric equilibrium constants of different classes of heterocyclic compounds in aqueous solutions.[3,4,5,6,7] Other investigators using different levels of quantum theory[8,9,10] have later confirmed the applicability of the SCRF method for the description of tautomeric equilibria in solutions. It has been demonstrated that the relative stability of nucleic acid pyrimidine and purine bases and their 1-methyl analogues in solutions is correctly predicted using the AM1 and PM3 SCRF method.[7] This has encouraged us to use the same approach for prediction of the tautomeric constitution of chemically modified nucleic acid bases in aqueous solutions It has been known for some time that the 8-hydroxy- or 8-oxo-substituted purines exhibit substantial mutagenic activity.[11,12,13,14] The 5-hydroxyuracil and, in particular, 5-hydroxycytosine are predicted to be some of the most efficient mutagenic agents.[15, 16] It has been suggested that the active form would be the anion of the modified bases. The structure and energetics of mixed normal base – modified base pairs was investigated quantum-chemically
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