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 gen erally assumed direct transfer mechanism. The argument is based on model ca lculations in which the system glycine-water is represented by a 1:6 superm olecule embedded in a dielectric continuum. Optimized geometries and vibrat ional frequencies are obtained at the Hartree-Fock level with a 6-31G* basi s 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 tra nsition state. At both levels the energetics are corrected by single-point quadratic configuration interaction calculations, including single and doub le substitutions with frozen-core inner-shell orbitals. Both models reprodu ce the observed endothermicity of the transfer better than models that use only a limited number of discrete water molecules without a continuum and m odels solely based on the continuum approximation. In the optimized structu res 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 compl ex, two of the other water molecules form hydrogen bonds with the amino hyd rogens, 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 mo dels implies that the mechanism of interconversion is concerted transfer of two protons along the amino-water-carboxyl bridge. The dynamics calculatio ns are performed with a multidimensional instanton model that includes solv ent reorganization. For both models the calculated transfer rate constants are about an order of magnitude larger than the observed rate constants, in dicating that the indirect mechanism can easily account for the observed dy namics. These results confirm the plausibility of the indirect mechanism of proton transfer via a water bridge in aqueous solutions of glycine. (C) 20 00 American Institute of Physics. [S0021-9606(00)51545-1].