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 molecule 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 interactions with biological targets. The calculations include the nucleophilic addition reaction of either an ammonia molecule or an NH3 hydrogen bonded to a discrete water molecule (NH3.OH2) to ACR, ACN, and AA. Optimizations of the geometries of reactants and transition structures for the 1,2- and 1,4-addition mechanisms were done at the restricted Hartree-Fock level with 6-31G basis sets, and electron correlation energy was calculated at the MP2 level with 6-31G* basis sets. Reaction energies were corrected for zero-point energies calculated from the harmonic vibrational frequencies of the 6-31G optimized structures. Hydration enthalpies were evaluated with the solvent described as a polarizable dielectric continuum. The barriers calculated for the addition reactions were found to be significantly reduced by the assistance of a solvent 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 capabilities of the molecules in this class to interact with DNA and reflect on their relative potencies in reactions determining the biological effects of these environmentally important chemical species.