ENERGETIC BASIS FOR STRUCTURAL PREFERENCES IN 5 6-HYDROXY-5,6-DIHYDROPYRIMIDINES - PRODUCTS OF IONIZING AND ULTRAVIOLET-RADIATION ACTION ONDNA BASES/

The structures of all diastereoisomers of 5/6-hydroxy-5,6-dihydropyrim idines have been optimized with ab initio quantum chemical calculation s using a 6-31G basis set. The energies of the optimized structures we re calculated at the MP2/6-31G level. The hydroxyl group prefers an e quatorial over an axial orientation at the C(5) position of pyrimidine s by 3-4 kcal/mol. At the C(6) position, the axial orientation of hydr oxyl is preferred by 3-4 kcal/mol. The factors responsible for the dif ferent preferences result from dipolar intramolecular interactions bet ween 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 th e molecular plane, can be occupied by different substituents. These ps eudo 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 resu lts on the biological consequences of pyrimidine lesions. The conclusi ons drawn from the calculations correlate well with experimental obser vations on the biological activities of thymine lesions.