Catalyzed peptide bond formation in the gas phase

The reactions between glycine and ammonia and the dimerization of glycine with and without Mg2+, Ni2+, Cu2+ and Zn2+ cations as catalysts have been studied as model reactions for peptide bond formation using the Becke3LYP functional with 6-311+G(d,p) and 6-31+G(d) basis sets. The B3LYP method was also used to characterize the 12 gas-phase complexes of neutral glycine, its amide and glycylglycine with Lewis acids Mg2+, Ni2+, Cu2+ and Zn2+, respectively. Enthalpies and Gibbs energies for each reaction have been calculated to determine the thermodynamics of the reactions investigated. A substantial decrease in the reaction enthalpies and Gibbs energies was found for glycine-ammonia and glycine-glycine reactions catalyzed by Mg2+, Ni2+, Cu2+ and Zn2+ ions compared with those of the uncatalyzed amide bond formation. The formation of a dipeptide is a more exothermic process than the creation of simple amide from glycine. The catalytic effect of the transition metal ions Ni2+ Cu2+ and Zn2+ is of similar strength and more pronounced than that of the Mg2+ cation. The basicity order of the bases investigated is : NH2CH2CO2H < NH2CH2CONH2 < NH2CH2CONHCH2CO2H. Interaction enthalpies and Gibbs energies of metal ion-base complexes increase as Mg2+ <Zn2+ Cu2+ <Ni2+.