Theoretical study of solvent effect on intramolecular proton transfer of glycine

The intramolecular proton transfer pathways for the passage from the neutra l 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 ini tio methods at high levels of theory. The three water molecule cluster yiel ds a zwitterion minimum of about the same energy as the neutral form. The t ransfer barrier and the GZ-GN energy difference are strongly sensitive to t he correlation effects. The solvent effect on the unhydrated and the trihydrated proton transfer su rfaces are treated using a continuum model. As modeled in water, the solven t stabilizes the zwitterionic cis conformation of glycine with regard to th e neutral cis form. The free energy stabilization of GZ(cis) over the GN(ci s) form is 5.4 kcal mol(-1) for the solvated trihydrated complex compared t o 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 t he structure is close to the zwitterionic configuration. (C) 2000 Elsevier Science B.V. All rights reserved.