Interplay of Intra-and Intermolecular H-Bonds for the Addition of a Water Molecule to the Neutral and N-Protonated Forms of Nordrenaline

摘要

The conformational flexibility of noradrenaline in its N-protonated nd neutral forms was considered at the Hartree-Fock (HF)/6-31G~* level, taking into account the orientaiton of the two hydroxy groups located on the catechol ring and the interconversion pathways between their stable arrangements. The difference in stability among the various forms of N-protonated noradrenaline was maintained including either more diffuse functions on the heteroatomns or Moller-Plesset second order (MP2) correlation corrections. The embedding in aqueous solution, in the polarizable continuum model framework, of the conformers kept rigid at their in vacuo geometries favored the T conformers with respect to the G ones at the HF level (for neutral noradrenaline at the MP2 level as well). The addition of a single were molecule to noradrenaline (either N-protonated or not) caused the intramolecular H-bond within the side chain to weaken until formation of one or two intermolecular H-bonds with water. This fact, coupled to the intramolecular H-bond strain relaxation, further stabilized the G1 and T conformers. Continuum solvation of the hydrated clusters of neutral noradenaline favored significantly the T…water adducts at the HF level, but only slightly at the MP2 level, because of their large energy gap in vcuo with respect to G1…water, even enhanced by MP2 geometry optimizations. The dependenceof the poential energy profile for the NH_2 group rotation on the catechol ring and side chain OH group orientation was examined in noradrenaline and compared to the trend shown by dopamine.