Lennard-Jones potential calculations of the barrier to rotation around the glycosidic CN linkage in selected purine nucleosides and nucleotides. A direct comparison of the results of 6-12 potential calculations with results of semiempirical molecular orbital studies

Abstract

Lennard-Jones (6-12) potential energy calculations were performed on the barrier to rotation around the CN glycosidic linkage in purine nucleosides and nucleotides. While such calculations are strictly valid only for relatively non-polar substances the results of these simple and very inexpensive calculations appear to be in reasonable accord with the results of semi-empirical molecular orbital calculations. The effect of the assumed hydrogen van der Waals radius on rotational barrier was examined and use of the accepted value of 1·2 along with the newer 1·0 simultaneously is shown to be useful in determining the source of such barriers. The detailed curves indicated that those molecules found in the syn conformation in the solid state possessed relatively small barriers to rotation. Adenine nucleotides and nucleosides invariably were indicated to have very large barriers to rotation with notable exception of the 3′-O-acetyladenosine and 2′ and 3′-AMP. A systematic variation of the C(8) substituent from H to F to Cl to Br in guanosine and 8-bromoguanosine indicates that the preference of the syn conformation is primarily due to steric factors. However, a minor barrier which appears to be due to the fluorine electronegativity is also noticed when the C(8)F passes near the ribose O(1′)atom. Inclusion of electrostatic interaction (monopole-monopole) in the potential barrier calculation indicated a minor contribution from this term even in the molecules possessing considerable charge asymmetry. © 1973.