A COMPARISON OF THE STEREOISOMERIC PENTA-COORDINATED PHOSPHORUS INTERMEDIATES FORMED FROM 19 DIMETHOXYL N-PHOSPHORYL AMINO ACIDS BY DFT CALCULATIONS

N-phosphoryl amino acids (PAAs) are important species in the origin of life that self-catalyze and self-assemble into polypeptides and polynucleotides under mild conditions. Both experimental and theoretical studies have shown that a penta-coordinated phosphorus intermolecular mixed carboxylic-phosphoric anhydride (IMCPA) is formed as the common intermediate in these reactions. In this work, the mechanism for the formation of stereoisomeric IMCPAs from PAAs is investigated using density functional theory (DFT) calculations at the B3LYP/6-311+G(d,p) theoretical level. The molecular structures of the cis- and the trans-IMCPAs, as well as the transition states of the two stereochemical reaction pathways, were characterized in detail. The results showed that the hydroxyl groups of PAAs were situated in favorable positions for attacking the phosphorus atom from two sides of the phosphoryl group, resulting in the formation of the cis-IMCPA and the trans-IMCPA, respectively. The trans-isomers were predicted to be more likely to undergo a further reaction involving an ester exchange on the phosphorus than the cis-isomers. By comparing the relative energies of the IMCPAs and the activation energies, the trans-IMCPAs were computed to be more stable than the cis-IMCPAs, but the energy barriers for the formation of the trans- and the cis-isomers were similar. This work is expected to shed light on the stereochemical effect involved in the chemical evolution of biomolecules.