Evaluation of Aqueous and Nonaqueous Binary Solvent Mixtures as Mobile Phase Alternatives to Water–Acetonitrile Mixtures for Hydrophilic Interaction Liquid Chromatography by Molecular Dynamics Simulations

Abstract

The retentive principle of hydrophilic interaction liquid chromatography (HILIC) with a water (W)−acetonitrile (ACN) mobile phase (MP) and a hydrophilic stationary phase is the formation of a W-rich layer with a rigid and diffuse part in the immediate and extended surface region, respectively. Through molecular dynamics simulations of the adsorption of W−acetone (Ace), W−methanol (MeOH), and MeOH−ACN mixtures to a hydrophilic silica surface, we evaluate their MP potential for aqueous and nonaqueous HILIC. We analyze solvent and hydrogen-bond density profiles, solvent−surface coordination, as well as local solvent orientation, mobility, and composition. Our data show that W−Ace mixtures closely mimic the behavior of W− ACN mixtures, whereas W−MeOH mixtures fail as HILIC MP because the similar affinity of the silica surface for W and MeOH prevents preferential adsorption of W. MeOH−ACN mixtures form a rigid MeOH layer that reverses the surface polarity and prohibits formation of a diffuse MeOH layer in the extended surface region. Generally, a rigid layer at a hydrophilic surface is formed by binary mixtures whose solvents have sufficiently different hydrogen-bonding abilities, and a diffuse layer is formed when the rigid layer maintains hydrophilic properties.

A Molecular Dynamics View on Hydrophilic Interaction Chromatography with Polar-Bonded Phases: Properties of the Water-Rich Layer at a Silica Surface Modified with Diol-Functionalized Alkyl Chains

“…Figure 5 in this work and Figure 2A in ref. 31). It could also be argued that the persistence of hydrogen bonding between the diol chains decreases their potential to attract W molecules, so that the diffuse W layer does not hold as much excess W than possible based on OH density, although the contribution of the ether moiety may somewhat mitigate this effect.…”

“…14-24 Molecular simulations were also instrumental in elucidating the properties of the W-rich layer at a bare (unmodified) silica surface under HILIC conditions [25][26][27][28] and in examining the central role of the W-rich layer for solute retention. [29][30][31] Molecular dynamics (MD) simulations show the W-rich layer as a closed "barrier" between the solid silica surface and the bulk mobile phase, which means that to interact directly with the functional groups of the bare-silica surface, a solute must first partition into and then cross the W-rich layer. In doing so, solute motion is expected to slow down as the W-rich layer becomes increasingly more structured and rigid towards the silica surface.…”

“…6,31 Productive simulation runs lasted 200 ns. Configurations of the trajectory were saved every 1 ps for data analysis.…”

Single‐Molecule and Ensemble Diffusivities in Individual Nanopores with Spatially Dependent Mobility

“…In recent years, MD simulations have become ap owerful tool in the analysis of diffusion processes for both solventa nd solute molecules in confined systems. [33][34][35][36][37][38][39][40] For example, the RPLC characteristics were elucidated from MD simulations [39,[41][42][43][44][45] and Monte Carlo computations, particularly by Siepmannand co-workers. [46] Using MD simulations,single-molecule and ensembled iffusivities can be directly recorded in the same nanopore used as am odel geometry with full flexibility on the chemical-surface modification, pore size, and choice of the solute molecules.…”

“…(This phenomenons hould not be confused with the microheterogeneity that is also observedi n water/ACN( W/ACN) mixtures in the absence of any confinement due to the amphiphilic character of acetonitrile. [53] )A ll these effects can be analyzed in detail by using MD simulations, [38][39][40][49][50][51][52] and the solute molecules can be accurately traced individually through all mobility regions. This allows ac omplete pore-level molecular exchange to be achieved and, thus, allows the long-time behavioro fD pore to be monitored.…”