An ab initio study of model compounds of fecapentaenes

Abstract

Total geometry optimizations at the STO-3G and 3-21G basis levels, as well as single point energy determinations using the 6-31G* basis set for all relevant minima and selected first- and second-order critical points on the unprotonated and protonated potential energy surfaces (PES's) of vinyl alcohol, methyl vinyl ether and 1,3-butadien-1-ol were determined. The proton affinities for each minimum isomer on the PES's of these compounds were also determined. These three systems were chosen as initial compounds to model the highly potent mutagenic “fecapentaenes” which are found in the bowel mucosa of people who have a high risk of developing colon cancer. These model compounds were chosen for two reasons: (1) to determine if a simplified glycerol moiety (i.e. a methyl group in methyl vinyl ether) can be further simplified to a hydrogen atom as in vinyl alcohol, and (2) to compare and contrast the differences obtained in the PES when the double bond moiety in vinyl alcohol is extended to a conjugated carbon—carbon double bond system as in 1,3-butadien-1-ol. The calculations reveal that the glycerol moiety of the enol ether type compounds may be simplified to a hydrogen atom using enol aldehyde compounds. In general, the PES's of the model fecapentaene compounds behave as would be predicted by chemical intuition, i.e. secondary carbonium ions are found to be more stable than primary carbonium ions, and the anti or trans configurations for (CCCC), (CCCO) and (HOCC) torsional angles are favored over the syn or cis configurations respectively (unless the cis/syn configurations are part of a ring system formed by H-bond or covalent type bonds). Configurations about carbon—carbon double bonds favor trans over cis, and finally, when three-, five- and six-membered rings can form, the calculations reveal that in all likelihood they will do so. The most important features at each basis level were that the energy barriers for methyl, methoxyl and hydroxyl rotations were very low, corresponding to virtually free rotations, and that the energy differences between conformers of a given isomer were small. The geometries determined by the 3-21G basis set should be superior to those determined with the STO-3G basis set, and some unusual features were present with the STO-3G basis set, especially when the protonation site was oxygen.