Quantitative In Silico Analysis of Ion Exchange from Chromatography to Protein

Abstract

Molecular interaction forces are based on solubility factors. Coulombic force is the strongest, followed by the Lewis acid‐base interaction, including hydrogen bonding and charge‐transfer effects, and van der Waals forces. Steric hindrance affects the molecular interaction. The individual interaction force can be studied using chromatography. The main interaction force in reversed‐phase liquid chromatography is the van der Waals force. The main interaction force in normal phase liquid chromatography is the Lewis acid-base interaction, including hydrogen bonding, and that in ion exchange liquid chromatography is the Coulombic force. Enantiomer separation is achieved by the combination of these molecular interaction forces with steric hindrance as the molecular recognition of proteins. Previously, the retention mechanism in reversed‐phase liquid chromatography was demonstrated using quantitative in silico analysis of chromatographic data of various compounds, such as phenolic compounds, aromatic acids, and acidic and basic drugs.1 The retention mechanism of ion exchange liquid chromatography was then quantitatively analyzed in silico. Carboxyl and guanidino phases were selected for studying the basic molecular recognition mechanism of proteins, and the selective molecular recognition of d‐amino acid oxidase was quantitatively analyzed in silico. The main molecular interaction was the Coulombic force, and the enantioselectivity was affected by the steric hindrance of the surrounding amino acid residues.