Energetic basis for structural preferences in 5/6-hydroxy-5,6-dihydropyrimidines: products of ionizing and ultraviolet radiation action on DNA bases.
The structures of all diastereoisomers of 5/6-hydroxy-5,6-dihydropyrimidines have been optimized with ab initio quantum chemical calculations using a 6-31G basis set. The energies of the optimized structures were calculated at the MP2/6-31G* level. The hydroxyl group prefers an equatorial over an axial orientation at the C(5) position of pyrimidines by 3-4 kcal/mol. At the C(6) position, the axial orientation of hydroxyl is preferred by 3-4 kcal/mol. The factors responsible for the different preferences result from dipolar intramolecular interactions between the hydroxyl and C(4) = O(4) on the one hand, and the N(1)-H(1) on the other hand. As a consequence of these structural preferences, the pseudo axial positions at C(5) and C(6), which are perpendicular to the molecular plane, can be occupied by different substituents. These pseudo axial groups are expected to be a major source of distortions to DNA structure with more bulky groups having a greater effect. This may constitute a structural basis for interpretation of experimental results on the biological consequences of pyrimidine lesions. The conclusions drawn from the calculations correlate well with experimental observations on the biological activities of thymine lesions.
Miaskiewicz
K
K
Department of Physiology and Biophysics, Mount Sinai School of Medicine of the City University of New York, NY 10029.
Miller
J
J
Osman
R
R
D002151:Calorimetry; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000528:radiation effects; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry* / Q000528:radiation effects*; D011839:Radiation, Ionizing; D013237:Stereoisomerism; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000528:radiation effects
D011743:Pyrimidines; D014498:Uracil; D003596:Cytosine; D004247:DNA; D013941:Thymine