Molecular-dynamic modelling of the adsorption of optical isomers of leucine on the chiral supramolecular surface of γ-glycine

Abstract

To establish the mechanism for the chiral recognition of a surface with supramolecular chirality, we conducted molecular- dynamic simulation of the adsorption of leucine enantiomers on a fragment of a γ-glycine crystal. Simulations were conducted using the GROMACS software package with the GROMOS96 54a7 force field. Simulation of D- and L-leucine sorption was performed in an NVT ensemble with a modified Berendsen thermostat (V-rescale). Before that, the systems were subjected to energy minimisation and NVT and NPT equilibration for 200 ps at 300 K. To uniformly distribute adsorbate molecules on the surface of a glycine crystal monolayer, we used an annealing protocol at 433 K with gradual cooling to 230 K. To prevent glycine molecules from changing their geometry during the simulation, they were “frozen” to 0 K, and the simulation time was 20 ns. To exclude interactions of adsorbate molecules with the reverse side of the crystal layer, we used periodic boundary conditions only in the x and y directions. Simulations of 20, 40, 60, and 80 molecules of leucine enantimers were performed on a fragment of a γ-glycine crystal with a size of 147 molecules and a graphene surface of 12x6 nm. The Coulomb and Lennard-Jones energies of intermolecular interactions of glycine-leucine, leucine-leucine, and graphene-leucine were calculated. When 20 leucine molecules were adsorbed on the surface of γ-glycine with upward-directed COO^– groups, the degree of covering the glycine surface was θ≈0.44. At this degree of covering, there were no distinctive differences in the Coulomb and Lennard-Jones energies of glycine-leucine interactions between the enantiomers of leucine. However, with the adsorption of 40 leucine molecules (θ≈0.88), the Coulomb energy of interactions of leucine enantiomers with the glycine surface differed by 168.0 kJ/mol and the Lennard-Jones energy differed by 15.1 kJ/mol. Over the course of adsorption of 60 leucine molecules (θ≈1.32), a significant difference was observed in the Coulomb energy (∆ E_CoulGly-Leu=664.1 kJ/mol) and the Lennard-Jones energy (∆ E_LJGly-Leu=194.5 kJ/mol) of glycine-leucine interactions. Over the course of adsorption of 80 leucine molecules (θ≈1.76), there was a difference in glycine-leucine interactions (∆ E_CoulGly-Leu=116.7 kJ/mol, ∆ E_LJGly-Leu=105.4 kJ/mol). Over the course of adsorption of leucine (θ≈0.44) on the surface of γ-glycine with upward-directed NH₃⁺ groups, a significant difference was observed in the energies of glycine-leucine interactions already with the adsorption of 20 molecules (θ≈0.44, ∆ E_CoulGly-Leu=420.0 kJ/mol). Over the course of adsorption of 40 leucine molecules (θ≈0.88) ∆ E_CoulGly-Leu=624.4 kJ/mol, ∆ E_LJGly-Leu=71.5 kJ/mol. Over the course of adsorption of 60 leucine molecules (θ≈1.32) ∆ E_CoulGly-Leu=304.4 kJ/mol, ∆ E_LJGly-Leu=59.1 kJ/mol. Over the course of adsorption of 80 leucine molecules (θ≈1.76) there was a difference in glycine-leucine interactions ∆ E_CoulGly-Leu=384.8 kJ/mol., ∆ E_LJGly-Leu=122.2 kJ/mol.

Thus, based on the results of molecular-dynamic modelling, it was established that the selected form of the γ-glycine crystal demonstrated enantiselectivity similar to the previously studied cytosine. When modelling adsorption on different sides of γ-glycine, we observed chiral selectivity in relation to L-leucine. It was found that the sides with different functional groups showed enantioselectivity in different ranges of surface covering. This phenomenon will allow achieving greater enantioselectivity of the γ-glycine surface in the future by blocking the side with carboxyl groups.