Theoretical study of solvent effect on intramolecular proton transfer of glycine

The intramolecular proton transfer pathways for the passage from the neutral form of NH2-CH2-COOH (GN) to the zwitterionic form +NH3-CH2-COO- (GZ) of glycine hydrated by three water molecules are computed using DFT and ab initio methods at high levels of theory. The three water molecule cluster yields a zwitterion minimum of about the same energy as the neutral form. The transfer barrier and the GZ-GN energy difference are strongly sensitive to the correlation effects. The solvent effect on the unhydrated and the trihydrated proton transfer surfaces are treated using a continuum model. As modeled in water, the solvent stabilizes the zwitterionic cis conformation of glycine with regard to the neutral cis form. The free energy stabilization of GZ(cis) over the GN(cis) form is 5.4 kcal mol-1 for the solvated trihydrated complex compared to an experimental value of 7 kcal mol-1. Also computed is the small free energy barrier of 2.2 kcal mol-1 for the conversion of GN(cis) to GZ(cis). Rationalization of why this barrier persists at all levels of calculation is found in the fact that the solvent effect only becomes important when the structure is close to the zwitterionic configuration. (C) 2000 Elsevier Science B.V.