Ion-exchange chromatography and multimodal ion-exchange chromatography are widely used for the separation of small molecules, peptides and proteins. Salts generally attenuate the electrostatic interactions between charged moieties of solutes and those of resins through electrostatic screening. However, little is known about how salts affect the interaction between the uncharged moieties of the solutes, such as aromatic moieties, and the charged moieties of the resins. In this study, we used alkyl gallates as model aromatic solutes to investigate the interaction mechanism of aromatic moieties with multimodal and conventional ion-exchange resins. Interestingly, alkyl gallates retained by these resins were readily eluted from the columns by the addition of 0.01–1 M NaCl, even though the alkyl gallates used contained no charged group. Molecular dynamics (MD) simulations were performed to understand the mechanism of these interactions. The MD simulation with a conventional force field showed that 1 M NaCl enhances the binding of an alkyl gallate molecule to the ligand, which contradicts the experimental results. Thus, we modified the force field to express a cation–π interaction between sodium ions and aromatic moieties, which successfully reproduced the experimental results at 1 M, suggesting that the cation–π interaction between sodium ions and aromatic moieties plays a crucial role in reducing the binding affinity of alkyl gallates for the ligands. These results provide new information indicating that aromatic moieties, including the aromatic residues of proteins and nucleobases of nucleic acids, favorably interact with multimodal and conventional ion-exchange resins and that cations, such as sodium ions, contribute to attenuating the binding of aromatic moieties to the ligands.

离子交换色谱法和多峰离子交换色谱法被广泛用于小分子，肽和蛋白质的分离。盐通常通过静电筛选减弱溶质的带电部分与树脂的带电部分之间的静电相互作用。然而，关于盐如何影响溶质的不带电部分（例如芳族部分）与树脂的带电部分之间的相互作用的了解甚少。在这项研究中，我们使用烷基没食子酸酯作为模型芳族溶质，以研究芳族部分与多峰和常规离子交换树脂的相互作用机理。有趣的是，即使所用的没食子酸烷基酯不包含带电基团，这些树脂保留的没食子酸烷基酯也可以通过添加0.01-1 M NaCl轻松地从色谱柱上洗脱下来。进行分子动力学（MD）模拟以了解这些相互作用的机理。使用常规力场的MD模拟显示1 M NaCl增强了没食子酸烷基酯分子与配体的结合，这与实验结果相矛盾。因此，我们修改了力场以表达钠离子与芳族基团之间的阳离子-π相互作用，从而成功地再现了1 M时的实验结果，表明钠离子与芳族基团之间的阳离子-π相互作用在还原过程中起着至关重要的作用。没食子酸烷基酯对配体的结合亲和力。这些结果提供了新的信息，表明芳香族部分，包括蛋白质的芳香族残基和核酸的核碱基，