THIOGUANINE AND THIOURACIL - HYDROGEN-BONDING AND STACKING PROPERTIES

Base stacking and H-bonding properties of thioguanine and thiouracils were studied using an ab initio quantum chemical method with inclusion of electron correlation (second-order Moller-Plesset perturbational m ethod). Hydrogen-bonded base pairs containing thiobases are only sligh tly less stable (up to 2 kcal/mol) than the unmodified base pairs. The N ... S distances are larger by 0.4-0.7 Angstrom compared to the N .. . O distances in the standard base pairs. The thio group enhances pola rizability of the monomers and their dipole moments. Thus, in stacked complexes of thiobases, both dispersion attraction and electrostatic i nteractions are enhanced. Mutual contact of the sulfur atoms and their interaction with second-row elements lead to steric clashes destabili zing the stacking, though, in DNA, such clashes should be eliminated b y rather small adjustments of the local DNA conformation. The thio gro up significantly destabilizes the hydration of the 6-position of thiog uanine with respect to guanine. The first hydration shell in the major groove might be significantly altered by thioguanine.