MECHANISMS OF NUCLEOPHILIC-ADDITION TO ACTIVATED DOUBLE-BONDS - 1,2-MICHAEL AND 1,4-MICHAEL ADDITION OF AMMONIA

The molecular mechanisms for nucleophilic addition of an ammonia molec ule to three small molecules with activated double bonds-acrolein (ACR ), acrylonitrile (ACN), and acrylic acid (AA)-have been examined with ab initio quantum chemical methods in reactions modeling their interac tions with biological targets. The calculations include the nucleophil ic addition reaction of either an ammonia molecule or an NH3 hydrogen bonded to a discrete water molecule (NH3.OH2) to ACR, ACN, and AA. Opt imizations of the geometries of reactants and transition structures fo r the 1,2- and 1,4-addition mechanisms were done at the restricted Har tree-Fock level with 6-31G basis sets, and electron correlation energy was calculated at the MP2 level with 6-31G basis sets. Reaction ener gies were corrected for zero-point energies calculated from the harmon ic vibrational frequencies of the 6-31G optimized structures. Hydratio n enthalpies were evaluated with the solvent described as a polarizabl e dielectric continuum. The barriers calculated for the addition react ions were found to be significantly reduced by the assistance of a sol vent molecule in the intramolecular proton-transfer process. The order of reactivities, based on energies of activation of the 1,4-addition to ACR, either 1,2- or 1,4-addition to AA, and 1,2-addition to ACN, is as follows: ACR > AA > ACN, in very good agreement with experimental results. The results provide inferences regarding the relative capabil ities of the molecules in this class to interact with DNA and reflect on their relative potencies in reactions determining the biological ef fects of these environmentally important chemical species.