Bivalent cation binding effect on formation of the peptide bond

The reactions between formic acid (or glycine) and ammonia, without and with Mg2+, Ni2+ and Cu2+ cations as catalysts, have been studied as model reactions for peptide bond formation using the Becke3LYP functional and 6-311+G(d,p) basis set of DFT theory. Enthalpies and free energies for the stationary points of each reaction have been calculated to determine the thermodynamics of reactions investigated. A substantial decrease in reaction enthalpies and free energies was found for formic acid-ammonia and glycine-ammonia reactions catalysed by Mg2+, Ni2+ and Cu2+ ions compared with those of the uncatalysed amide bond formation. The catalytic effect of the transition metal ions Ni2+ and Cu2+ is of similar strength and more pronounced than that of the Mg2+ cation.