AIM study of pyrimidyl carbocyclic analogues of nucleosides based on cyclopentene rings

A topological charge electron density analysis using the atoms in molecules (AIM) theory with HF/6‐31++G**// HF/6‐31G* wave functions was performed on cis ‐pyrimidyl and cis ‐5/6‐halopyrimidyl derivatives of 1,2‐disubstituted analogues of carbocyclic nucleosides. In these analogues, which belong to an important class of antiviral or antitumoral compounds, the usual ribose or deoxyribose is replaced by a carbocycle with a hydroxymethyl group and a heterocyclic base on adjacent carbons and a double bond between positions 2 and 3 of the carbocycle. The results obtained demonstrate that 5‐halogenation does not alter the relative energy sequence of the conformers and gives rise to no meaningful distortion of the electron distribution in the cyclopentene ring. In fact, the difference in the total electron population of this cycle between the parent and any of the halogenated molecules is never larger than 7×10 −3 a.u. It has been found that the electron population of the α C atom in the chloro derivatives is enlarged with respect to the unhalogenated species. The 5‐halogenation results in a destabilization of the C4, C5, and C6 atoms of the heterocyclic base. According to the AIM computed energy properties this destabilization originates from larger interelectronic repulsions in the C5 basin that are consistent with its reduced volume and its lower first moment of the electron density. On the other hand, 6‐halogenation produces a significant modification of the conformational equilibrium, modifying the relative energy sequence of conformers. The electronic properties are also significantly modified by 6‐halogenation. The charge transfer from the cyclopentene ring to the base reaches 0.71 a.u. in the 6‐fluoro derivative and 0.69 a.u. in the 6‐chloro derivative. © 2002 John Wiley & Sons, Inc. Int J Quantum Chem 86: 67–78, 2002