A Molecular Dynamics View on Hydrophilic Interaction

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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 Sergey M. Melnikov, Alexandra Hoeltzel, Andreas Seidel-Morgenstern, and Ulrich Tallarek J. Phys. Chem. C, Just Accepted Manuscript • DOI: 10.1021/acs.jpcc.6b03799 • Publication Date (Web): 26 May 2016 Downloaded from http://pubs.acs.org on June 5, 2016

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The Journal of Physical Chemistry

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 Sergey M. Melnikov,†,‡ Alexandra Höltzel,† Andreas Seidel-Morgenstern,‡ and Ulrich Tallarek†,* Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35032 Marburg, Germany, and Max-Planck-Institut für Dynamik komplexer technischer Systeme, Sandtorstrasse 1, 39106 Magdeburg, Germany

* Corresponding author. E-mail: [email protected] †

Philipps-Universität Marburg

‡

Max-Planck-Institut Magdeburg

ACS Paragon Plus Environment

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Abstract. In hydrophilic interaction chromatography solutes are retained in a water (W)-rich layer that forms upon equilibrating the polar stationary phase with an acetonitrile (ACN)-rich aqueous mobile phase. We study the properties of the W-rich layer at a polar-bonded phase, modeled by a planar silica surface carrying diol-functionalized ligands and residual OH groups at densities of 3.1 and 4.4 µmol/m2, respectively. Molecular dynamics simulations performed in a 10-nm slit pore containing between 30/70 and 2/98 (v/v) W/ACN show that a rigid, single layer of W molecules adsorbed directly at the silica surface is connected through an interstitial, single layer of W molecules with a ca. 0.8 nm-thick diffuse W layer associated with the polar groups at the flexible chain ends. Hydrophilic and hydrophobic elements are largely segregated in the diffuse W layer. Hydrophilic patches are formed by W clusters (groups of hydrogen-bond connected W molecules) and diol clusters (groups of typically 2‒4 directly connected diol chains), hydrophobic patches are formed by ACN molecules solvating hydrocarbon groups of the bonded phase. The W-rich layer at the diol-modified surface has lower translational mobility and can hold more excess W than the W-rich layer at an unmodified silica surface.


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1. Introduction In high performance liquid chromatography (HPLC) practice, hydrophilic interaction (liquid) chromatography (HILIC) has largely replaced traditional normal-phase chromatography as the standard separation technique for polar compounds.1 HILIC works with the polar stationary phases previously classified as “normal-phase columns”, but replaces the nonaqueous eluents used in normal-phase chromatography with an aqueous‒organic mobile phase, which is of great practical value. The HILIC mobile phase is compatible with electrospray mass spectrometry detection as well as with the conditions of reversed-phase liquid chromatography (RPLC), enabling sequential, orthogonal separations of complex samples by RPLC and HILIC (2D HPLC). Contrary to RPLC, the particulars of the aqueous‒organic mobile phase are essential to observe the HILIC effect, that is, for solute retention to set in: the mobile phase must contain a high fraction (≥70 vol %, but very often ≥90 vol %) of a polar, aprotic solvent (in practice nearly always acetonitrile (ACN)).2 When these conditions are met, the polar stationary phase accumulates water (W) molecules from the mobile phase during column equilibration (the column is said to take up W) to build up a W-rich layer between stationary and mobile phase. Except for bare (unmodified) silica, HILIC columns are polar-bonded phases, the hydrophilic equivalent of the hydrophobic bonded phases used in RPLC. Polar-bonded phases are prepared by chemically modifying the base material (usually silica) with (short) alkyl chains that carry one or more polar end groups.3 Polar-bonded phases have a better-defined stationary phase chemistry than the bare silica columns, which increases reproducibility and predictability of separations, as well as a larger variety of polar functionalities. The polar-bonded phases used in HILIC fall into three categories: neutral (i.e., uncharged: cyanopropyl, diol, amide), positively charged (amino), and zwitterionic.4 Judged by chemical similarity, the diol phase is the closest relative of bare


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silica among the polar-bonded phases. The uncharged bare-silica surface carries OH groups (in form of single, geminal, and vicinal silanol groups) and siloxane moieties, whereby the latter are not hydrophilic and do not contribute to the accumulation of W from the mobile phase.5,6 The diol phase, typically prepared from chemically attaching 3-(glycidoxypropyl)trimethoxysilane to the silica support followed by hydrolysis of the epoxy group, carries two OH groups and an ether moiety per chain (Figure 1).3

Figure 1. Chemical structure of the bonded-phase ligand. Atoms are color-coded as follows: Si ‒ yellow, O ‒ red, hydrocarbon elements (treated by the force field as united-atom groups) ‒ cyan, H ‒ white. Si0 and O0 belong to the silica surface; the position of Si0 defines Z = 0 nm. The close relation between diol phase and bare silica is also evident from the W uptake isotherms determined for various HILIC columns.7,8 According to these data, a diol phase can take up more W than bare silica, but less than amide, amino, and zwitterionic phases. On the other hand, diol columns are generally less retentive than bare-silica columns in HILIC,9 which shows that W uptake and retentivity are not necessarily proportional. A certain amount of dissociated surface OH groups, bestowing weak cation-exchange properties, cannot be avoided


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when working with bare-silica columns.4 These surface charges may be beneficial to analyte retention, but their amount and spatial distribution are beyond the chromatographer’s control, which affects the predictability and reproducibility of separations carried out on bare-silica columns. Solute retention in HILIC stems from partitioning and direct electrostatic interactions with the stationary phase.1,2,4 Partitioning means the distribution of a solute according to its hydrophilicity between the ACN-rich mobile phase and the W-rich layer at the stationary phase. Direct interactions between solute and stationary phase range in strength from weak (dipole‒dipole interactions and hydrogen bonding, sometimes referred to as weak adsorption) to moderate (interactions between charged solutes and uncharged functional groups of the stationary phase) to strong (ion exchange between charged solutes and charged functional groups of the stationary phase). In HPLC practice, solutes are more often than not charged because of electrospray mass spectrometric detection, so that weak and moderate interactions are always in place, whereas the extent to which strong interactions occur depends on the chemistry of the employed stationary phase. A diol phase under HILIC conditions is assumed to retain solutes by partitioning and by weak interactions with the uncharged functional groups of the bonded phase.4 Although the W-rich layer is often associated with the partitioning mechanism only, it is difficult to conceive how direct interactions between solutes and stationary phase could remain unaffected by the presence of a W-rich layer. Investigating the intricate details of the HILIC system is the realm of experimental chromatographers, who establish correlations between experimental conditions and solute retention and selectivity.1,2,4,9,10 Contrary to RPLC, small changes in experimental details can have comparatively large effects in HILIC separations, which is encouraging to those who pursue new separation strategies, but frustrating to those who


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wish to replicate the reproducibility and predictability of RPLC separations. If the properties of the W-rich layer are expressly considered in experimental HILIC studies, a more meaningful interpretation of the chromatographic data can be achieved.11 Understanding the W-rich layer, its composition, structure, mobility, and how these properties depend on solvent ratio and composition of the mobile phase as well as the surface chemistry of the stationary phase is key to understanding the HILIC system. By providing realistic pictures in molecular detail and probing solute motion at the nm-scale, molecular simulations have been invaluable to the understanding of chromatographic systems.12,13 Molecular simulations have contributed essentially to the theory of solute retention in RPLC systems, uncovering details unattainable by experimental methods alone.14‒24 Molecular simulations were also instrumental in elucidating the properties of the W-rich layer at a bare (unmodified) silica surface under HILIC conditions25‒28 and in examining the central role of the W-rich layer for solute retention.29‒31 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. In fact, the first layer of W molecules in contact with the surface is so rigidly structured and tightly adsorbed to the surface that it can be considered as an extenuation of the OH-group covered silica surface itself. This thin, rigid W layer is followed by a three-to-four times wider, diffuse W layer over whose extension composition, structure, and mobility of the bulk mobile phase are gradually recovered. The actual extension of the W-rich layer (in nm-distance from the hard surface) depends on the properties of the surface (its chemistry and curvature), but not on


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the W/ACN ratio, which influences only the amount of W molecules contained in the W-rich layer. The partitioning of hydrophilic solutes from the bulk mobile phase into the W-rich layer is driven by the difference in W content between these two environments and quantified as the ratio of the respective W mole fractions.29,30 The model of the W-rich layer established on the basis of MD simulations for the bare-silica surface cannot simply be transferred to a diol phase, because the latter system is more complex. The bare-silica system involves a solid‒liquid interface, the diol system additionally involves the interface between bonded phase and liquid. In the bare-silica system, OH groups are only found on the solid surface, whereas in the diol system, OH groups are also part of the bonded phase. Moreover, surface and bonded-phase OH groups are separated by alkyl chains, that is, by a hydrophobic element absent from the bare-silica system. (The combination of hydrophilic and hydrophobic elements renders the diol phase highly versatile: apart from normal-phase chromatography and HILIC, diol phases have been used for RPLC separations with highly aqueous mobile phases.) In this study we want to establish the properties of the W-rich layer associated with a diol phase to extend our understanding of the HILIC system from bare-silica columns to polarbonded phases. We model the diol phase through a planar (111) β-cristobalite SiO2 surface modified with 3-(2,3-dihydroxypropoxy)propyldimethylsilyl chains at a density of 3.1 µmol/m2, which leaves residual OH groups at a density of 4.5 µmol/m2 on the surface. (Only a fraction of the silica surface can be covered with diol chains for steric reasons.3) The (111) face of βcristobalite SiO2 has been shown to represent the properties of bare silica as a support structure for bonded phases32 as well as a hydrophilic surface under HILIC conditions.6 Bonded-phase coverage and ligand structure are those of real-life diol columns.3 We purposely did not cap a


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fraction of residual surface OH groups with trimethylsilyl groups, as this endcapping procedure (which is common practice with hydrophobic bonded phases for RPLC) is usually not applied to polar bonded phases intended for HILIC. MD simulations are carried out in a 10-nm slit pore containing W‒ACN mixtures at solvent ratios between 30/70 and 2/98 (v/v) W/ACN, which covers the range usually encountered in HILIC practice. The 10-nm slit-pore, representing a typical average pore diameter of real-life columns,3 ensures that we can observe the complete relaxation of surface and bonded-phase influences on the liquid and still have a sufficiently wide region where the liquid assumes the properties of a bulk mobile phase. We investigate the properties of the W-rich layer at the diol-modified silica surface, noting differences and similarities to the W-rich layer at an unmodified silica surface and paying close attention to the role of the bonded phase in the system.

2. Simulation details Simulation box. Figure 2 (top) shows our simulation box (4.048 x 5.28 x 10.93 nm), which contains a central three-layer slab of β-cristobalite SiO2 with the (111) face exposed to a solvent reservoir at each side. The diol phase was created by attaching 40 3-(2,3-dihydroxypropoxy)propyldimethylsilyl chains to surface O atoms (O0, cf. Figure 1) to realize a realistic bondedphase density of 3.1 µmol/m2, which left 56 single, isolated silanol groups on the surface (at a density of 4.4 µmol/m2). The diol chains were distributed quasi-uniformly on the surface; 50% of chains had one direct neighbour (i.e., a diol chain placed at the next grafting point on the surface), 25% of chains had two direct neighbors, 20% of chains had three direct neighbors, and 5% of chains had no direct neighbour (Figure 2, bottom). With the applied periodic boundary


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conditions the simulation box is equivalent to a 10-nm slit pore. The diameter of the slit pore is large enough to contain a sufficiently wide (6 nm) bulk liquid region.


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Figure 2. The simulation box (top, snapshot of the equilibrated system at 10/90 (v/v) W/ACN) and view onto the diol-modified silica surface (bottom). Atoms are color-coded as follows: Si ‒ yellow, O ‒ red, hydrocarbon elements ‒ cyan, H ‒ white, N ‒ blue. Silica structure and bonded phase are shown as sticks, residual surface OH groups and solvent molecules are shown as balls. Force-field parameters. For the Si, O, and H atoms of the silica surface (silanol and siloxane groups) we used the force-field parameters of Gulmen and Thompson.33 The motion of silica atoms was frozen during simulations except for the free rotation of H atoms. For an adequate representation of the liquid properties of W‒ACN mixtures,34 we used the simple point charge/extended (SPC/E) model for W35 and the united-atom version of the transferable potentials for phase equilibria (UA-TraPPE) force field for ACN (modelled as rigid, three-site molecules).36 UA-TraPPE force-field parameters were also used for all bonded-phase atoms.37‒39 Long-range electrostatic interactions were treated with the particle-mesh Ewald algorithm (with a real space cut-off of 1.2 nm). Non-bonded interactions were modelled with a 12−6 LennardJones potential and truncated at 1.2 nm. Lennard-Jones parameters for unlike interactions were calculated using the Lorentz‒Berthelot combination rule. Simulations. MD simulations were carried out with Gromacs 4.5.2.40 Individual simulation runs were conducted for a canonical NVT ensemble (constant number of particles N, simulation box volume V, and temperature T = 300 K). A Nosé‒Hoover thermostat with a coupling constant of 0.1 ps was used for temperature control. The equations of motion were integrated with a time step of 1.0 fs. Simulations were carried out for nominal solvent ratios of 30/70, 20/80, 15/85, 10/90, 05/95, and 02/98 (v/v) W/ACN. Four to five preliminary 60-ns simulation runs were performed to find the required number of W and ACN molecules (given in Table S1 in the


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Supporting Information) to reach the targeted nominal W/ACN ratio in the bulk liquid region of the system (at a distance of Z > 2 nm from the surface Si atoms).6,31 Productive simulation runs lasted 200 ns. Configurations of the trajectory were saved every 1 ps for data analysis. Analysis of hydrogen bonds. Hydrogen bonds (HBs) in the system (surface‒solvent, solvent‒ solvent, surface‒bonded phase, bonded phase‒bonded phase, and bonded phase‒solvent) were detected based on fulfilling three geometric criteria: i) distance between donor O atom and acceptor X atom (X = N, O) 0.45 nm indicate a minor conformation in which the middle segment of the chain backbone is approximately parallel to the surface. These chains are folded back to the silica surface; their fraction increases from 0.7% to 5% between 30/70 and 02/98 W/ACN, that is, backfolding is a mechanism by which the diol chains respond to a very low W supply in the bulk liquid. The contour distributions for the backbone atoms (Figure 4A) become more diffuse along the chain, reflecting increasing flexibility towards the chain terminus, which is also apparent in the spatial distribution of O2 (Figure 4B). The brightest spot in Figure 4B, at Z = 0.95 nm and RXY = 0.8 nm, indicates the preferred O2 location of chains that are 40° inclined to the surface normal. For chains with 15° inclination angle, surface distances between Z = 1.0 and 1.3 nm are observed for O2, which are related to the frequency of gauche defects in the last two dihedral angles of the chain (O1C4C5C6 and C4C5C6O2). For O2 to be found at Z = 1.0 nm, the probability that both edge dihedral angles have gauche defects is 61%, whereas for O2 at Z = 1.3 nm, the probability that both edge dihedrals are in the trans-conformation is 68%. Overall, the all-trans conformation is more often observed for diagonal (40° inclined) chains, so that the rather flexible distal OH


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group maintains a fairly constant surface distance regardless of the chain conformation. Figure 4C contains two distinct spots for the spatial distribution of O3, at Z = 1.05 nm and RXY = 0.2 nm for the 15° inclined chains and at Z = 0.9 nm and RXY = 0.6 nm for the 40° inclined chains, indicating that the proximal OH group essentially moves with the chain backbone. The minor conformation of backfolded chains appears in Figures 4B and 4C as a series of weaker spots at Z < 0.6 nm and RXY > 0.4 nm. Well-defined spots at Z = 0.27 nm in Figure 4B (RXY = 0.75 and 0.95 nm) and Figure 4C (RXY = 0.75 nm) reflect the position of O2 and O3 atoms, respectively, when engaged in HBs with residual surface OH groups (Figure S1 in the Supporting Information shows examples of backfolded chain conformations). Through formally substituting O1 with a methylene group, O3H2 with an H atom, and O2H1 with a methyl group (cf. Figure 1), the 3-(2,3-dihydroxypropoxy)propyldimethylsilyl ligand would become a dimethyloctylsilyl ligand, that is, a hydrophobic C8 phase as used in RPLC. Because diol phases are occasionally used for RPLC when working with highly aqueous mobile phases, a short comparison of the diol-phase conformation with that of a C8 phase under similar conditions may be of interest. We compare our diol phase (at a density of 3.1 µm/m2) with a C8 phase tethered at a density of 2.95 µm/m2 to the same planar silica support as used for the diol phase and equilibrated with a W‒ACN mobile phase in the studied W/ACN range.18 The diol phase exhibits a slightly higher degree of conformational order than the C8 phase, as indicated by a lower fraction of gauche defects, a ca. 0.1-nm longer chain extension, and a restriction to two major, distinct inclination angles rather than the broad range observed for the hydrophobic C8 chains. Other groups have observed a similar enhancement of conformational order for C18 phases when polar groups are embedded16,17 or attached to the chain ends.15,21


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3.2. Coordination of silica surface and bonded-phase polar groups Previous studies have shown the importance of surface coordination for the formation of the W-rich layer at the unmodified silica surface.6,29,31 There, coordination of surface OH groups can be regarded as the origin of the rigid W layer and attraction of further W molecules by the rigid W layer can be regarded as the origin of the diffuse W layer.29,31 Recently, solvent‒surface hydrogen bonding has also been shown to determine the solvent exchange at an unmodified silica surface in contact with methanol‒ACN mixtures (such as used in nonaqueous HILIC).45 We now take a look at the HB patterns exhibited by the polar groups of the present stationary phase, which comprises residual OH groups on the silica surface and the polar groups of the bonded phase (Table 1). Table 1. Number of hydrogen bonds (HBs) per functional group of the silica surface or bonded phase (cf. Figure 1). W/ACN

With W

With ACN

(v/v)

With the bonded phase

With the silica surface

Total

Number of HBs per surface OH group, HBOH 30/70

1.44

0.07

0.02

‒

1.53

10/90

1.32

0.10

0.05

‒

1.47

2/98

0.85

0.27

0.06

‒

1.18

Number of HBs per O1, HBO1 30/70

0.42

‒

0.08

‒

0.50

10/90

0.32

‒

0.08

‒

0.40

2/98

0.19

‒

0.11

‒

0.30


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Number of HBs per O2H1, HBO2H1 30/70

1.26

0.14

0.41

0.02

1.83

10/90

0.97

0.18

0.52

0.04

1.71

2/98

0.59

0.26

0.70

0.02

1.57

Number of HBs per O3H2, HBO3H2 30/70

1.18

0.14

0.49

‒

1.81

10/90

0.89

0.18

0.62

0.04

1.73

2/98

0.54

0.26

0.86

0.06

1.72

As expected, surface OH groups form HBs preferentially with W molecules (number of HBs per surface OH group HBOH = 1.44‒0.85 between 30/70 and 2/98 W/ACN), whereas HB formation with ACN molecules takes a secondary role (HBOH = 0.07‒0.27). HBs between silica surface and bonded phase are rare (HBOH ≤0.06), as they are only formed by chains in a backfolded conformation (≤5% of chains). The total number of HBs formed by the residual OH groups at the diol-modified silica surface (HBOH = 1.53‒1.18 between 30/70 and 2/98 W/ACN) is 1.2‒1.4 times lower than the values received for an unmodified silica surface of isolated, single silanol groups (HBOH = 1.84‒1.66).31 The lower overall HBOH stems from a lower number of HBs with W molecules (HBOH = 1.44‒0.85) compared with the unmodified silica surface (HBOH = 1.88‒1.66 between 30/70 and 2/98 W/ACN),31 that is, an OH group forms fewer HBs with W molecules when it is surrounded by grafted chains than when it is surrounded by other OH groups. The diol-modified surface is also more sensitive than the unmodified silica surface when it comes to coordination of surface OH groups at extremely low W fraction in the bulk liquid: between 30/70 and 2/98 W/ACN the contribution of W molecules falls from 88% to 75% compared with a decrease from 96% to 88% at the unmodified silica surface. The loss is partially


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compensated by ACN molecules, whose contribution to surface coordination rises from 7% to 27% between 30/70 and 2/98 W/ACN, compared with a rise from 8% to 22% at the unmodified surface.31 Increased ACN contribution to surface coordination at low W fraction in the bulk is probably facilitated by the hydrophobic moieties of the bonded phase. The increased participation of ACN plus the small contribution of backfolded diol chains to surface coordination (2% to 6% between 30/70 and 2/98 W/ACN) does not suffice to prevent the fraction of uncoordinated surface OH groups to rise from 8% to 15% between 30/70 and 2/98 W/ACN (see Table S3 in the Supporting Information for full data on surface coordination). Apart from HBs with the surface formed by the small fraction of backfolded chains, the diol chains form HBs with solvent molecules and with each other (Table 1). Chains inclined 40° to the surface normal are more often engaged in interchain HBs than chains with 15° inclination angle. The ether moiety of the bonded phase (O1) forms HBs with W molecules (number of HBs per O1 atom, HBO1 = 0.42‒0.19 between 30/70 and 2/98 W/ACN), but participates only to a small degree in interchain HBs (HBO1 = 0.08‒0.11). Bonded-phase OH groups form preferably HBs with W molecules, reaching 2.8‒3.1 times higher values than O1 and 1.1‒1.6 times lower values than the surface OH groups. The distal O2H1 group has a slightly higher number of HBs with W (HBO2H1 = 1.26‒0.59) than the proximal O3H2 group (HBO3H2 = 1.18‒0.54 between 30/70 and 2/98 W/ACN), but a lower number of interchain HBs (HBO2H1 = 0.41‒0.70 vs. HBO3H2 = 0.49‒0.86), which reflects the slightly different environments of the two OH groups. The total number of HBs formed in dependence of the W/ACN ratio is highly similar between the two bonded-phase OH groups (HBO2H1,total = 1.83‒1.57 and HBO3H2,total = 1.81‒1.72) and 1.2‒1.3 times higher than the total number of HBs formed by the surface OH groups (HBOH,total = 1.53‒ 1.18 between 30/70 and 2/98 W/ACN). Summarizing the contributions from the ether moiety


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and both OH groups, the number of interchain HBs per diol chain is HBchain = 0.98‒1.67 between 30/70 and 2/98 W/ACN, the number of bonded phase‒W HBs is HBchain = 2.86‒1.32, and the number of bonded phase‒ACN HBs is HBchain = 0.28‒0.52. These numbers show that the system responds to W-deprived conditions by increasing the number of interchain and bonded phase‒ ACN HBs. Interchain HBs are formed between direct neighbors as well as between more distantly grafted chains. All chains participate in interchain hydrogen bonding, but not all at the same time. Most chains (51‒45%) are connected to one other chain, very few chains (1‒3%) are connected to three chains. At 30/70 and 10/90 W/ACN, more chains are unconnected (39% and 29%, respectively) than connected to two chains (13% and 19%), whereas at 2/98 W/ACN, 35% of chains have two connections and only 17% of chains are unconnected. On average, a diol chain is directly connected to 0.76 and 0.92 chains at 30/70 and 10/90 W/ACN, respectively, and to 1.24 chains at 2/98 W/ACN (see Table S4 in the Supporting Information for full data).

3.3. Distribution, hydrogen bonding, and orientation of solvent molecules In this section we describe and explain how W and ACN molecules are arranged between silica surface and bulk liquid. Figure 5 shows the number density profiles calculated for the O atom of W and the N atom of ACN for nominal solvent ratios of 2/98, 5/95, 10/90, 15/85, 20/80, and 30/70 (v/v) W/ACN in the bulk region of the reservoirs (Z > 2 nm). Figure 6 reveals the contribution of HBs with the surface and bonded phase to each W peak by specifying the density of W molecules engaged in HBs with the surface and with ether moiety and OH groups of the bonded phase in the W density profile at 10/90 W/ACN. Table 2 lists the number of HBs per W molecule (HBW) that W molecules of a certain peak form with their different HB partners. These data, supplemented by information on solvent orientation and HB density (full data given by


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Page 22 of 48

Figures S2‒S4 in the Supporting Information), provide a detailed picture of the interplay between silica surface, bonded phase, and solvent molecules.

Figure 5. Solvent density profiles at W/ACN (v/v) ratios of 30/70, 20/80, 15/85, 10/90, 5/95, and 2/98 in the bulk region (Z > 2.0 nm). Profiles were calculated from the number density ρn of the O atom of W (blue) or the N atom of ACN (green). Peaks are labelled for reference. The W density profiles (Figure 5) contain four peaks: the first two peaks, at Z = 0.26 nm and at Z = 0.53 nm, are sharply defined and their density varies only little with the W/ACN ratio; the last two peaks, at Z = 0.83 nm and Z = 1.11‒1.25 nm (the peak maximum shifts toward the surface with increasing ACN fraction in the bulk liquid) are much broader and their density changes with the nominal W/ACN ratio. We know from previous work that the behavior of the first two W peaks indicates a strong influence of the hard silica surface,6,31 and we may assume that the behavior of the last two W peaks reflects an association with the more flexible bonded


22

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phase. The ACN profiles contain three maxima, at Z = 0.28, 0.53, and 0.76 nm, of whom the first two exhibit the surface-influence also observed for peaks (1) and (2) in the W density profiles.

Figure 6. W density profile at 10/90 (v/v) W/ACN broken down into specific HB interactions. Peak (3) is purposely marked. Blue, green, and red curves represent W molecules attached through HBs to surface OH groups, bonded-phase OH groups, and ether moiety, respectively; the cyan curve refers to unattached (to surface or bonded phase) W molecules. The dotted black curve is the sum of the green, red, and cyan curves and thus covers all W molecules apart from the surface layer. The solid black curve (sum of green and cyan curves) shows how the W density profile would look without the contribution from the ether moiety. Peak (1) in the W density profiles is built practically exclusively from surface-attached W molecules (Figure 6), which are strongly engaged in HBs with residual surface OH groups (HBW = 2.05). These W molecules are typically oriented with one OH-vector pointing towards an O atom of a surface OH group (the OH-vector forming an angle of about 110° with the surface normal); the other OH vector (almost parallel with the surface normal) points towards the bulk region, which allows surface-attached W molecules of peak (1) to form HBs with W and ACN molecules of the next layer (peaks (2)). W molecules of peak (2) act as HB acceptors to surfaceattached W molecules and thus orient their O atom to the surface, which leaves both H atoms free to form HBs with solvent molecules of peaks (3) and with ether moiety and OH groups of


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the bonded phase. While W molecules of peak (2) form most of their HBs with other W molecules (HBW = 1.82‒1.33 for W‒W HBs vs. HBW = 0.62‒1.11 for W‒bonded phase HBs between 30/70 and 2/98 W/ACN), Figure 6 shows that W molecules attached to O1 contribute nearly as much to the density of peak (2) as W molecules unattached to the bonded phase. ACN molecules of peaks (1) and (2) act as HB acceptors to surface OH groups and surface-bound W molecules, respectively, and thus point their N end to the surface. ACN molecules of peak (1) stand nearly perpendicular to the surface and are typically found in a “bridge” position between two equidistant surface OH groups. Table 2. Number of hydrogen bonds per W molecule (HBW) at peaks in the W density profiles (cf. Figure 5). W/ACN

With W

With ACN

(v/v)

With the bonded phase

With the silica surface

Total

Peak (1) 30/70

0.24

0.28

0.10

2.05

2.67

10/90

0.22

0.32

0.12

2.05

2.71

2/98

0.21

0.35

0.18

2.05

2.79

Peak (2) 30/70

1.82

0.36

0.62

‒

2.80

10/90

1.68

0.37

0.77

‒

2.82

2/98

1.33

0.21

1.11

‒

2.65

Peak (3) 30/70

1.70

0.30

0.99

‒

2.99

10/90

1.27

0.37

1.17

‒

2.81


24

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2/98

0.82

0.44

1.48

‒

2.74

Peak (4) 30/70

2.53

0.36

0.37

‒

3.26

10/90

1.95

0.56

0.50

‒

3.01

2/98

1.11

0.83

0.87

‒

2.81

Peak densities reflect the environment solvent molecules face at a particular distance from the surface. Peak (1) is much larger in the W than in the ACN profiles, because of the high affinity of residual surface OH groups for W molecules. Consequently, peak (1) is the largest peak in the W profiles and the smallest in the ACN profiles at all W/ACN ratios. Peak (2), however, is larger in the ACN than in the W profiles, because at this distance from the surface the hydrophobic environment created by the C1‒C3 segment of the bonded phase is more conducive to ACN than to W molecules. But what happens at the surface nonetheless influences the solvent densities at the level of peak (2). Between 30/70 and 2/98 W/ACN, the density of peak (1) decreases in the W profiles and increases in the ACN profiles. Partial substitution of surface-bound W by ACN molecules decreases the number of HB donors for ACN molecules at the level of peak (2) as well as the space available at this location (because the bulky methyl groups of ACN molecules occupy more space than W molecules). Consequently, peak (2) in the ACN density profiles decreases at increasing ACN fraction in the bulk. Peak (3) in the W density profiles is dominated by W molecules attached to the bonded phase, although unattached W molecules are present as well (Figure 6). Peak (3) contains the largest number of W‒bonded phase HBs in the system (HBW = 0.99‒1.48 between 30/70 and 2/98 W/ACN), whereas the number of W‒W HBs (HBW = 1.70‒0.82) is lower than observed for peak (2) and peak (4). Most often, W molecules of peak (3) are found with their dipole vector


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perpendicular to the surface normal, one OH vector pointing to the surface, the other to the bulk liquid. Figure 6 shows that while ether moiety and bonded-phase OH groups contribute to a similar degree to the density of peak (3), the ether moiety is responsible for the existence of peak (3) as a distinct feature in the W density profiles. ACN molecules of peak (3), whose width compared to the narrow shape of the surface-influenced peaks (1) and (2) already indicates a structural change, form the familiar double layer arrangement observed for ACN molecules near a silica surface.46‒49 ACN molecules of peak (3) are arranged so that N atoms are located in the middle and methyl groups at the edges of the double layer. ACN molecules of the layer closer to the surface point their methyl group in surface direction in response to the hydrophobic environment created by the Si(CH3)2 groups of the bonded phase and the methyl groups of the surface-attached ACN molecules (peak (1) in the ACN density profiles); ACN molecules of the layer closer to the bulk liquid point their N atom in surface direction to act as HB acceptors to W molecules of peak (2). Together, ACN molecules of peak (2) and peak (3) solvate hydrophobic moieties of the bonded phase. Over the extension of peak (4) in the W density profiles, ACN molecules ascend to their bulk liquid density. W molecules of peak (4) show no preference for molecular orientation, but are characterized by W‒W and W‒bonded phase HBs (HBW = 2.53‒1.11 and 0.37‒0.87, respectively, between 30/70 and 2/98 W/ACN). The surface side of peak (4) is dominated by HBs between W and bonded-phase OH groups, whereas the bulk side of peak (4) is dominated by W‒W HBs (Figure 6). Next to the immediate surface region, peak (4) contains the maximum HB density in the system (HB density profiles are shown in Figure S4 in the Supporting Information). At Z = 1.05 nm, the HB density has a local maximum to which W‒bonded phase and W‒W HBs contribute. The maximum HB density in W‒W HBs coincides with the density


26

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maximum of peak (4). That the maximum W density (away from the surface) and the maximum W‒W HB density in the system are located just where the W-rich layer transitions into the bulk liquid had already been observed with a bare-silica surface.29 Then, the formation of the diffuse W layer was attributed to the ability of surface-bound W molecules to attract more W molecules from the mobile phase. Figure 6 shows that this principle also holds for the diol-modified silica surface: W molecules attached to the polar groups of the bonded phase attract and bind more W molecules from the bulk liquid, raising the local W density above the level in the mobile phase. The data shown in Figures 5 and 6 allow us to assign the peaks in the W density profiles to specific parts of the W-rich layer: Peak (1) constitutes the rigid W layer, peaks (3) and (4) form inner and outer part of the diffuse W layer, respectively, and the small peak (2) is an interstitial layer that connects the surface-bound W molecules of peak (1) with the bonded-phase associated W molecules of peaks (3) and (4) and thus fulfils the important role of linking rigid and diffuse part of the W-rich layer.

3.4. Structure of the diffuse W layer In the preceding section we have shown that the diffuse W layer at the diol-modified silica surface is not built upon the rigid W layer, but around the polar groups of the flexible bonded phase. Consequently, the bonded-phase moieties present at this distance from the surface, polar as well as hydrocarbon groups, are an integral part of the diffuse W layer. In this section we will show by snapshots (Figure 7) how bonded-phase groups and solvent molecules are distributed in the diffuse W layer. Figures 7A and 7B show the XY-locations of W and bonded-phase O atoms and of ACN and bonded-phase C atoms, respectively, in the inner diffuse W layer (i.e., peak (3) in the W density profiles) collected over a 1-ns period. According to the contour plots of Figure


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4, the bonded-phase atoms are moderately flexible within the interval of Z = 0.75‒0.9 nm, and so Figures 7A and 7B show the bonded-phase atoms concentrated in certain places. W molecules appear for the most part near the bonded-phase O atoms (O1, O2, and O3 may all turn up at Z = 0.75‒0.9 nm, but the O atom of the proximal OH group (O3) has the highest probability to be in this interval, cf. Figure 4), whereas ACN molecules occupy the space between bonded-phase hydrocarbon groups (C4, C5, and C6, cf. Figure 4A) that is vacated by the hydrophilic elements.


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Figure 7. Snapshots visualizing the XY-distribution of bonded-phase and solvent atoms in the diffuse W layer at 5/95 (v/v) W/ACN. The silica structure is shown in the background. (A) O atom locations from the bonded phase (grey) and W molecules (red) at Z = 0.75‒0.9 nm (inner diffuse W layer, peak (3) in the W density profiles), (B) C atom locations from the bonded phase (cyan) and ACN molecules (central C atom, blue) at Z = 0.7‒0.85 nm. (C) O atom locations from


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the bonded phase (grey) and W molecules (red) at Z = 1.0‒1.36 nm (outer diffuse W layer, peak (4) in the W density profiles). The atom locations shown in (A), (B), and (C) were collected from a 1-ns trajectory with a 30-ps time step. (D) Instant configuration showing the arrangement of bonded-phase OH groups (grey) and W molecules (O ‒ red, H ‒ white) in the outer diffuse W layer. The outer diffuse W layer also exhibits the pattern of W molecules staying close to bondedphase O atoms and leaving space unoccupied, as Figure 7C shows for the interval Z = 1.0‒1.36 nm (i.e., peak (4) in the W density profiles). Figure 7C contains more O atom locations than Figure 7A, because W density and chain flexibility are higher at the level of peak (4) than peak (3). Bonded-phase O atoms from both OH groups may be present, with a higher probability for the O2 atoms from the flexible distal OH group (cf. Figure 4), whereas only a few bonded-phase hydrocarbon groups (C5 and C6, cf. Figure 4A) are found at Z = 1.0‒1.36 nm. The space left mostly free of W molecules and bonded-phase OH groups is then filled by ACN molecules, which recover most of their bulk density over this interval. According to Figures 7A‒7C, the diffuse W layer is segregated into hydrophilic and hydrophobic patches. From a visual inspection of trajectories, the patch size can be roughly estimated as ~1 nm. Key to this segregation is extensive hydrogen bonding between the hydrophilic elements: W molecules of peaks (3) and (4) are either directly attached to polar groups of the bonded phase or connected through HBs to bonded-phase attached W molecules, and the polar groups of the bonded phase themselves are connected through interchain HBs. An instant configuration of the system taken at the level of peak (4) provides a closer look at the arrangement of the hydrophilic elements in the diffuse W layer (Figure 7D). W molecules and bonded-phase OH groups are not randomly gathered together, but tend to be grouped into W and


30

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diol clusters, respectively. We used W‒W and interchain HB connections, respectively, as the criterion to determine the average size of W and diol clusters in the outer diffuse W layer. The average number of molecules per W cluster decreases from 6.08 at 30/70 W/ACN to 3.93 at 10/90 W/ACN to 2.65 at 2/98 W/ACN; the average number of diol chains per cluster increases from 2.58 at 30/70 W/ACN to 2.77 at 10/90 W/ACN to 3.23 at 2/98 W/ACN. Most diol clusters consist of two chains (61‒38% between 30/70 and 2/98 W/ACN), but three chains also occur frequently (27‒24%). Diol clusters of four chains are more often found when W is scarce (24% at 2/98 W/ACN) than at 30/70 or 10/90 W/ACN (10‒11%). Diol clusters of up to seven chains are observed, though with very low frequency (see Table S5 in the Supporting Information). Overall, a diol cluster typically contains between 2 and 4 chains. Diol chains leave or join a cluster when interchain HBs are redistributed (after 10‒100 ns). W clusters form and dissolve at a ca. 10-times faster rate (1‒10 ns) than diol clusters, while individual W molecules in a cluster are exchanged after only ~10 ps.

3.5. W surface excess adsorption W uptake under HILIC conditions is the common property of all stationary phases used for HILIC. Figure 8 compares the W excess adsorption isotherms of the diol-modified and the unmodified silica surface. W surface excess adsorption isotherms were calculated on a volume basis (rather than on a molar basis as in our previous study6), because experimental isotherms are usually derived by frontal analysis measuring retention volumes.5 From a W volume fraction of 5% onward, the diol phase has higher W excess adsorption values than the unmodified silica surface. Our simulated data thus recover the experimental observation that a diol column takes up more W than a bare-silica column.7,8


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Figure 8. Areal-reduced W surface excess adsorption isotherm, calculated on a volume basis, for the diol-modified (red) and the unmodified silica surface (blue). An increased W uptake of the investigate diol phase is expected from its 1.4-times higher OH group density compared with an unmodified silica surface. Figure 8 shows that the diol-modified surface can hold more excess W than the unmodified silica surface, but not as much as expected from its enhanced OH density. When considering the W uptake of a column, the structural properties of the W-rich layer must be taken into account. The presence of grafted hydrophobic chains reduces the accessibility of residual surface OH groups and decreases the density of the rigid W layer compared with that at the unmodified surface (by a factor of ~2.5 according to the surface peak maxima in the respective W density profiles, cf. 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. Structural differences between the two systems also explain why at extremely low W fraction the unmodified silica surface holds more excess W than the diol phase. As we have already seen, the diol phase copes with W deprivation in ways that are not available to the unmodified silica


32

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surface: by increasing the ACN contribution to surface coordination, which is facilitated by the environment created by the hydrophobic alkyl chains, as well as by increasing interchain hydrogen bonding and backfolding of diol chains to the surface.

3.6. Translational mobility of solvent molecules and diol chains Mobility of individual solvent molecules. Parallel diffusion coefficients 1∥ and residence timesτ were calculated for the solvent density peaks of Figure 5 to judge the solvent mobility in XY- and Z-directions at different distances from the surface (Table 3). Table 3. Translational mobility of solvent molecules at characteristic points in the solvent density profiles (cf. Figure 5). W/ACN

Peak (2)

Peak (3)

ACN

1∥

τ

1∥

τ

(10-5 cm2s-1)

(ps)

(10-5 cm2s-1)

(ps)

30/70

0.01±0.004

3000

0.01±0.001

1600

10/90

0.01±0.005

3200

0.01±0.004

2100

2/98

0.01±0.001

3550

0.01±0.003

2350

30/70

0.14±0.04

73

0.11±0.02

43

10/90

0.09±0.02

127

0.10±0.03

46

2/98

0.09±0.02

163

0.11±0.02

48

30/70

0.29±0.06

11

0.25±0.01

9

10/90

0.25±0.07

12

0.26±0.07

10

2/98

0.17±0.13

14

0.35±0.07

12

(v/v)

Peak (1)

W


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Peak (4)a

Bulk

a

Page 34 of 48

30/70

0.65±0.03

8.5

0.67±0.04

7

10/90

0.53±0.02

9

0.76±0.05

6

2/98

0.44±0.09

11

0.96±0.15

5

30/70

1.77±0.06

4.5

2.22±0.06

4.5

10/90

2.18±0.13

4

3.07±0.06

3.5

2/98

3.37±0.28

3.5

3.63±0.10

3.5

Mobility of ACN molecules is given at the location of peak (4) in the W density profiles.

The data in Table 3 reflect a general picture that has become familiar from previous studies of unmodified silica surfaces in contact with pure solvent or solvent mixtures. Solvent mobility decreases from the bulk liquid to the surface, taking a drastic leap close to the surface. Generally, the horizontal and vertical mobility of W molecules decreases with the nominal ACN fraction, while the opposite applies to ACN molecules. This dynamic response to a changing W/ACN ratio in the bulk liquid reflects that the availability of a certain solvent in the system influences the mobility of this solvent. At 2/98 (v/v) W/ACN, for example, the probability for replacing a W molecule close to the surface with a W molecule from the bulk reservoir is very low. Surfaceattached molecules (peaks (1) in the W and ACN density profiles) have a very low, practically frozen mobility, and this rigidity is transmitted to some extent to the next layer of solvent molecules (peaks (2)). Solvent molecules of peak (1) do not move continuously along the surface, just oscillate around an equilibrium position. Vertical exchange with solvent molecules from other layers takes a relatively long time (τ = 1.6‒3.55 ns), and horizontal exchange is only undertaken by a few W molecules (3‒5%) that jump to vacant positions nearby. Solvent molecules of peaks (2) behave quite similar as those of the surface layer, but their XY-oscillations cover a bit more space and their vertical exchange rate is much higher, as evidenced by the


34

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residence times (τ = 43‒163 ps). Solvent mobility in peaks (3) and (4) is restricted compared to the bulk liquid, but remains much higher than in the surface-influenced peaks (1) and (2). Horizontal mobility of solvent molecules is 6‒20 times lower in peak (3) and 3‒8 times lower in peak (4) compared with the bulk, whereas vertical exchange in these peaks is only decreased by a factor of 2‒4.

Figure 9. Mobility of individual W molecules in XY- (top) and Z-directions (bottom) at 10/90 (v/v) W/ACN. Blue, green, and red color indicates W molecules of peaks (1), (2), and (4), respectively, in the W density profiles (cf. Figure 5). Shown are trajectories with a 3-ps time step for time intervals during which a W molecule remained part of its designated density peak. Figure 9 contrasts the mobility of a W molecule in the outer diffuse W layer with the severely restricted mobility in rigid and interstitial W layer by following the movement of individual W


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molecules of peaks (1), (2), and (4) for the whole time interval during which a molecule remains part of its assigned density peak. A surface-bound W molecule of peak (1) oscillates in a very limited space interval around its initial XY-position (∆X = ≤0.05 nm in both directions, ∆Y = ±0.1 nm) for as long as 3 ns. A W molecule of peak (2), which has a bit more leeway in Y-direction than a W molecule of peak (1), keeps its distance to the surface for 180 ps, during which time interval a W molecule of peak (4) has moved away from its initial position by as much as 0.8 nm in X- and Y-direction. The movement trajectories in Figure 9 demonstrate the characteristic mobility differences between rigid, interstitial, and diffuse W layer well. A comparison with mobility data calculated for an unmodified silica surface at 10/90 (v/v) W/ACN (cf. Tables 4 and 6 in ref. 31) reveals that solvent molecules of the rigid W layer have much higher residence times and lower parallel diffusion coefficients at the diol-modified silica surface, which is expected from the restricted space at the surface due to chain grafting. W molecules of the diffuse W layer have also lower parallel diffusion coefficients at the diolmodified surface. Considering that the diffuse W layer is built by polar groups at the flexible chain ends (as opposed to being directly attached to the rigid W layer as at the unmodified silica surface), the “stiffening effect” of the bonded phase seems remarkable. Mobility of diol chains. The mobility of the diol chains is discussed in reference to their conformation (Section 3.1.). Figure 4 had already shown that the bonded-phase atoms sample various locations in the system, and that the mobility of an atom depends on its position along the chain, with the frequency of trans‒gauche transitions increasing towards the chain end. The chain elements up to C5 move slowly and more or less as an entity; the flexible, terminal segment of the chain (C6, O2, and H1) moves noticeably faster. Parallel diffusion coefficients


36

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calculated for O2 are in the order of 1∥ ≈ 0.1 x 10-5 cm2s-1, that is, about 3‒5 times smaller than observed for solvent molecules at Z ≈ 1 nm.

Figure 10. Translational mobility of individual O2 atoms of the bonded phase in XY- (top, relative to grafting points) and Z-directions (bottom) at 10/90 (v/v) W/ACN. Shown are 200-ns trajectories with a 30-ps time step. Colors mark identical time intervals in top and bottom panels. Panels A and C contain only typical conformations (upright chains), panels B and D include a minor chain conformation (chain folds back to the surface). Figure 10 gives an impression of the mobility of the terminal chain segment by showing O2 movement trajectories for two different chains. The panels on the left side of Figure 10 represent the majority of diol chains, which do not fold back to the surface during the whole 200-ns observation interval. At the start of the observation interval, the diol chain is inclined 40° to the


37


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surface normal; O2 keeps an average surface distance of Z ≈ 0.9 nm and moves in a region reaching from ∆X = ‒0.6 to 0 nm and from ∆Y = 0.2 to 0.8 nm around the chain grafting point (blue trajectories in Figures 10A and 10C). After 70 ns, the diol chain changes its inclination angle to 15° and O2 increases its average surface distance slightly to Z ≈ 1.0 nm. In this erect state of the chain, which is held for 95 ns, O2 covers a territory of ∆X = ‒0.5 to 0.5 nm and ∆Y = ‒0.6 to 0.6 nm around the chain grafting point (green trajectories in Figures 10A and 10C). During this time interval, the Z-coordinate changes with a higher amplitude (more gauche defects) than observed for the starting conformation. Finally, the chain returns to the 40° inclination angle, but bends to the other side, where O2 moves within ∆X = ‒0.2 to 0.6 nm and

∆Y = ‒0.8 to 0 nm around the chain grafting point (red trajectories in Figure 10A and 10C). The panels on the right side of Figure 10 represent the minor fraction of diol chains (3% at 10/90 (v/v) W/ACN) that eventually fold back to the surface during the 200-ns observation interval. At the beginning, the chain is in a typical conformation with 40° inclination to the surface normal, and O2 has a distance of Z = 0.8 nm to the surface. After 20 ns, the chains stretch themselves to the all-trans conformation, increasing the surface distance of O2 to Z = 1.2 nm (blue trajectories in Figures 10B and 10D), before at t = 25 ns, the chain suddenly folds back to the surface and O2 drops down to Z = 0.25 nm, where it stays ‒ apart from a short period at Z = 0.6 nm (during which the HB with the surface is released, but the chain remains backfolded) ‒ for the next 35 ns (green trajectories in Figures 10B and 10D). In the backfolded state of the chain, O2 has noticeably less freedom of movement in XY-direction than when then chain is upright. Figure 10B shows that O2 covers only a small region of ∆X = ‒0.8 to ‒0.4 nm and ∆Y = ‒0.2 to 0.2 nm around the chain grafting point, restrained by HBs with the surface OH groups. At t = 60 ns, O2 breaks its HB with the surface and the chain recovers an upright conformation, which it holds for


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the rest of the observation interval (red trajectories in Figures 10B and 10D). During this 140-ns long interval, the chain conformation goes through inclination angles of 15° and 40° and O2 covers a wide territory (∆X = ‒0.7 to 0.8 nm and ∆Y = ‒0.6 to +0.7 nm) around the chain grafting point.

4. Conclusions With the rise of HILIC, diol columns, once introduced to overcome the unpredictable surface chemistry of bare-silica columns, have found renewed interest and application due to their ability to take up W under HILIC conditions and presumably build up a solute-retaining W-rich layer. The details and implications of a W-rich layer formed with a flexible and not fully hydrophilic bonded phase as opposed to a hard, hydroxylated silica surface were, however, not considered until now. Our MD study has shown how the bonded phase influences the properties of the Wrich layer at every level. The grafted diol chains interrupt the rigid W layer at the silica surface, yielding an ensemble of individual W molecules firmly attached to residual surface OH groups as opposed to the closed W structure observed at the unmodified silica surface. The rather weak rigid W layer at the diol-modified silica surface would not suffice to build up a diffuse W layer, which instead is built by the polar groups of the bonded phase. An interstitial W layer connects rigid and diffuse part of the W layer through an axial HB network. Rigid and interstitial W layer together support the diol chains in a rather upright, extended conformation. In the diffuse W layer, hydrophilic and hydrophobic elements are largely segregated. Hydrophilic patches formed by W molecules and bonded-phase polar groups are held together by W‒W, W‒bonded phase, and interchain HBs. In the hydrophilic patches, clusters of HB-connected W molecules appear


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next to clusters of typically 2‒4 directly connected diol chains. The space between hydrophilic patches is filled by ACN molecules solvating bonded-phase hydrocarbon groups. Our results have further shown that, compared with an unmodified silica surface, the W-rich layer at the diol-modified surface can hold more excess W (confirming experimental data) and has lower translational mobility. High W density and low translational mobility are the retaining forces for hydrophilic solutes in the diffuse W layer. Additionally, the observed penchant of the diol chains for HB formation strongly suggests that hydrophilic solutes in the W-rich layer attach themselves to the diol chains through HBs, a retention mechanism that has been supposed (but not proven) by chromatographers for a long time. Judged by W density, translational mobility, and the capacity for HB formation, the diol-modified surface should be more retentive than the unmodified silica surface. Yet, in chromatographic practice diol columns are (for most analytes) less retentive than bare-silica columns. Three possible causes come to mind that could account for the higher retentivity of bare-silica columns: adsorption of solutes by weak electrostatic forces on the solid silica surface (when no bonded phase is present, solutes would presumably approach the silica surface and find sufficient room and contact area there), a higher W density arising from the presence of residual surface charges, and electrostatic attraction of solutes by residual surface charges. Whereas these causes cannot be distinguished in chromatographic experiments, they could be evaluated separately by future dedicated simulations including solute molecules.


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ASSOCIATED CONTENT Supporting Information. Number of W and ACN molecules used in final simulation runs (Table S1). Fraction of gauche defects among dihedral angles of the bonded-phase chains (Table S2). Fraction of surface OH groups hydrogen-bonded to solvent molecules and diol chains (Table S3). Distribution of hydrogen-bond connections between diol chains (Table S4). Distribution of diol chains into clusters (Table S5). Examples of backfolded chain conformations (Figure S1). Orientation of W and ACN molecules at peaks in the respective density profiles (Figures S2 and S3). HB density profiles (Figure S4). This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author * Corresponding author. Phone: +49-(0)6421-28-25727; Fax: +49-(0)6421-28-27065; E-mail: [email protected] Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. ACKNOWLEDGMENT This work was supported by the Deutsche Forschungsgemeinschaft DFG (Bonn, Germany) under grant TA 268/7–1.


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ABBREVIATIONS W, water; ACN, acetonitrile; HB, hydrogen bond; HPLC, high performance liquid chromatography; HILIC, hydrophilic interaction (liquid) chromatography; RPLC, reversedphase liquid chromatography.

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A Molecular Dynamics View on Hydrophilic Interaction

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