A direct-dynamics study of the zwitterion-to-neutral interconversion of glycine in aqueous solution

The mechanism of interconversion between the neutral and zwitterionic forms of glycine in aqueous solution is studied theoretically. It is argued that indirect transfer via a water bridge is a plausible alternative to the generally assumed direct transfer mechanism. The argument is based on model calculations in which the system glycine-water is represented by a 1:6 supermolecule embedded in a dielectric continuum. Optimized geometries and vibrational frequencies are obtained at the Hartree-Fock level with a 6-31G* basis set, and at the second-order Moller-Plesset frozen-core level with the 6-31 + G* basis set for the neutral and zwitterionic forms, and for their transition state. At both levels the energetics are corrected by single-point quadratic configuration interaction calculations, including single and double substitutions with frozen-core inner-shell orbitals. Both models reproduce the observed endothermicity of the transfer better than models that use only a limited number of discrete water molecules without a continuum and models solely based on the continuum approximation. In the optimized structures of this complex and of complexes with fewer water molecules, one of the water molecules always bridges the two functional groups. In the 1:6 complex, two of the other water molecules form hydrogen bonds with the amino hydrogens, two others with the carboxyl oxygens, and the sixth water molecule forms a bridge between the two water molecules attached to the amino group. The interaction of this supermolecule with the bulk solvent is treated by means of the Onsager model. The transition state calculated with the two models implies that the mechanism of interconversion is concerted transfer of two protons along the amino-water-carboxyl bridge. The dynamics calculations are performed with a multidimensional instanton model that includes solvent reorganization. For both models the calculated transfer rate constants are about an order of magnitude larger than the observed rate constants, indicating that the indirect mechanism can easily account for the observed dynamics. These results confirm the plausibility of the indirect mechanism of proton transfer via a water bridge in aqueous solutions of glycine. (C) 2000 American Institute of Physics. [S0021-9606(00)51545-1].