(55f) The Effect of Monovalent Cations on the Structure and Dynamics of Multimodal Chromatographic Surfaces

While multimodal (MM) chromatography is a promising approach for purifying proteins, the lack of fundamental understanding of selectivity limits its use in the biopharmaceutical industry. This is in part because while ion-surface interactions have been well studied for simple charged and hydrophobic surfaces, they are poorly understood for multimodal surfaces. Therefore, to understand multimodal chromatography at the molecular level, it is necessary to characterize multimodal ligand-salt interactions in the context of a chromatography surface. Here, we study the interactions between simple monovalent cations and two commonly used, structurally similar multimodal chromatography ligands, the Capto Ligand and Nuvia cPrime, immobilized on the surface. On the Capto Ligand surface, ion presence and type play a key role in modulating the formation of phenyl ring and carboxylate clusters. The flexible linkage attaching the Capto Ligand to the SAM surface allowed multiple ligands to form interactions with the small cations, while large cations interacted less strongly. Thus, smaller cations resulted in more ordering on the surface and lower ion diffusivities, while larger cations resulted in less ordering and higher ion diffusivities. In contrast, due to the rigid attachment of Nuvia cPrime to the SAM surfaces, the cations bound less strongly and had much smaller effect on ligand clustering or ordering. Additionally, ions in the presence of the Nuvia cPrime surface had generally greater diffusivities than those in the presence of the Capto Ligand. Overall, the interaction of cations with the multimodal ligands leads to unique configurations on the SAM that likely contribute to differential behavior in biological separations.