Solutes at the liquid:liquid phase boundary—Solubility and solvent conformational response alter interfacial microsolvation Yasaman Ghadar, Payal Parmar, Alex C. Samuels, and Aurora E. Clark
Citation: J. Chem. Phys. 142, 104707 (2015); doi: 10.1063/1.4914142 View online: http://dx.doi.org/10.1063/1.4914142 View Table of Contents: http://aip.scitation.org/toc/jcp/142/10 Published by the American Institute of Physics
THE JOURNAL OF CHEMICAL PHYSICS 142, 104707 (2015)
Solutes at the liquid:liquid phase boundary—Solubility and solvent conformational response alter interfacial microsolvation Yasaman Ghadar,a) Payal Parmar, Alex C. Samuels, and Aurora E. Clarka) Department of Chemistry and the Materials Science and Engineering, Washington State University, Pullman, Washington 99164, USA
(Received 4 November 2014; accepted 23 February 2015; published online 13 March 2015) A detailed understanding of solvent structure and dynamics at liquid:liquid interfaces is a necessary precursor for control and manipulation of these phase boundaries. Experimentally, amphiphilic solutes are often used to alter transport properties across water:organic interfaces; however, a fundamental model for the mechanism of this action has not been determined. This work compares the solvation profiles of ampiphilic solutes that traverse the phase boundary in binary water:n-hexane, and the individual microsolvation processes for interfacial water and hexane molecules therein. Microsolvation is defined as the rare event where one solvent molecule temporarily penetrates the co-solvent phases and is fully solvated therein. The solutes tri-butyl phosphate (TBP), hydrogen di-butyl phosphate, and di-hydrogen mono-butyl phosphate have been examined as they exhibit a systematic increase in aqueous solubility and selectively partition to the interfacial region at the infinite dilution limit. The relationship between adopted configurations of the solute, orientation of the solvent, and the ability of the solute to enhance microsolvation, specifically the ability of n-hexane to penetrate the aqueous phase, is demonstrated within a 20 Å radius of TBP. C 2015 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4914142]
I. INTRODUCTION
Immiscible liquid:liquid interfaces mediate numerous physical processes (e.g., phase transfer catalysis, solvent extraction, and drug delivery).1 Probing the nature of liquid:liquid interfaces in terms of their structure and dynamics is important to understand the underlying mechanisms involved in their formation and how to ultimately control their physicochemical properties. The water:alkane interface represents a simple model and quintessential system to study and develop theories about immiscible liquid:liquid and biological water membrane interfaces.2 In this context, both experimental methods such as x-ray and neutron scattering,3 optical ellipsometry,4 vibrational sum frequency spectroscopy,5–8 x-ray reflectivity,9 and molecular simulations have helped to quantify the density profile, interfacial tension and thickness, and aqueous dipole moment profiles of many water:alkane systems, including water:n-hexane.10–16 While these fundamental studies have helped to understand the physics associated with interfacial properties, the manipulation of those characteristics remains an active area of research. Experimentally, amphiphilic solutes which contain a hydrophobic tail and hydrophilic head are often used to alter the properties of water:organic interfaces in a variety of industrial scenarios, for example, within the detergent industry and in solvent extraction.17,18 Very little is understood about the mechanisms by which ampiphilic solutes perturb these interfaces, particularly at the molecular level. a)Authors to whom correspondence should be addressed. Electronic ad-
dresses: [email protected] and [email protected] 0021-9606/2015/142(10)/104707/9/$30.00
To investigate this issue, the molecular solvation of three ampiphilic solutes with the common names tri-butyl phosphate (TBP), hydrogen di-butyl phosphate (HDBP), and di-hydrogen mono-butyl phosphate (H2MBP) has been examined within the interfacial region of biphasic water:nhexane. These solutes exhibit the same hydrophilic phosphate head group while their hydrophobic tail is altered through varying number of alkyl chains, which alters their aqueous solubility. The solubility of TBP in water is 1.58 mM at 25 ◦C,19 HDBP in water is 82 mM,19,20 and H2MBP is completely miscible in water and acidic media.19–21 Closely related to solubility is the distribution ratio, D, of a solute across the aqueous:organic phase boundary, defined as [concentration of solute]org/[concentration of solute]aq in mol/L. Here, the concentration dependent D values for TBP, HDBP, and H2MBP in water:n-hexane are 2170, 13, and 0.74, respectively,19,21,22 when the solute concentrations in the organic phase are 3.43 M for TBP, 0.63 M for HDBP, and 0.40 M in the case of H2MBP. While these bulk properties reflect the general tendency of the solute to partition to a specific phase, they do not indicate what effect the solute has upon the interface when the solute traverses the phase boundary. Solvation within this unique region of space will involve both water23 and n-hexane about the solute and on the ns timescale of a classical molecular dynamics (MD) simulation, the influence of these solutes upon the interfacial properties may be large. Herein, the partitioning of a single TBP, HDBP, and H2MBP in water:n-hexane has been examined using MD. Changes in the conformation of the solute as it traverses either side of the phase boundary have been monitored and the effect of the solute upon the
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FIG. 1. Molecular structures of (a) TBP, (b) HDBP, and (c) H2MBP.
individual microsolvation processes of water and n-hexane has been investigated. Microsolvation is defined as the rare event where one solvent molecule temporarily penetrates the adjoining phases and is completely solvated by the co-solvent. It is presumed that microsolvation is related to the concept of permeability of the interface, and thus, a quantification of microsolvation events may aid future understanding of how ampiphilic solutes alter phase transfer.
II. COMPUTATIONAL METHODS A. Molecular models
Pair-wise additive models represent the potential energy of the system, with intermolecular pair potentials being taken as the sum of all pair potentials between interaction sites within the molecules. The organic molecules n-hexane, TBP, HDBP, and H2MBP have been described by the AMBER-99 force field (Figure 1),24,25 while charges for the atoms on organophosphorus solutes have been obtained from Khomami et al.26 Water was described using a modified rigid TIP3P/Ew water potential.27 All simulations were performed using the LAMMPS software (version 14Feb 2012),28 with the Verlet algorithm29 and a 1 fs timestep. Ewald summation used a 11 Å cutoff with a 1 × 10−6 tolerance threshold. Tables S1 and S2 in supplementary material54 present the bonded and non-bonded potentials utilized. B. Simulation details
Four simulation boxes (L x = L y = 40 Å, L z = 80 Å) were constructed using the Packmol program30 that represents the binary water:n-hexane system with initial configurations having either no solute or a single TBP, HDBP, or H2MBP placed within 5 Å of the interface and the phosphoryl O-atom pointed toward the n-hexane layer (Figure 2). Three-dimensional periodic boundary conditions were employed. The water portion of the biphasic system contained 2731 molecules, while 293 n-hexanes were present. The liquids were brought to mechanical and thermal equilibrium at 298 K using the NVT ensemble of Nose31 and Hoover,32 followed by a series of NPT simulations, until a pressure of 1 atm was reached.33,34 The systems were run in NPT for at least a ns followed by a ns of simulation in the NVE ensemble to
verify the system temperature and pressure. Production runs for every system consisted of 1 ns of an NVE simulation with capture of the trajectories every 25 fs, leading to a total of 40 k snapshots for data analysis for 1 ns of the production run. C. Data analysis
The data were analyzed using a graph theoretical, or network, approach implemented in the ChemNetworks software package.35 The emphasis of this work is to examine the local interfacial organization about a solute as its aqueous solubility is systematically altered. This includes examination of the solute solvation environment, the ability of the solute to alter the microsolvation of individual water and n-hexane molecules, and the mechanisms by which the solute can drag solvents in their respective immiscible phases (i.e., water into n-hexane and vice versa). The molecular simulation data are first converted into a star graph of the intermolecular interactions that define the first solvation shell about a reference molecule. Three specific star graphs have been defined by either the solute–water, solute–n-hexane, or the water–n-hexane interactions. The geometric criteria employed to define the intermolecular interactions are presented in Table I and are generally based upon the position of the first minima in the radial distribution functions (RDFs) presented in Figure S1 in the supplementary material.54 In the case of the water–n-hexane interactions, a geometric criterion of r < 4.3 Å between the Ow and Hh was utilized, which is slightly larger than the minimum of the two body potential energy surface for the interaction of the water Oatom, Ow, with alkane H-atoms, Hh.36 Using these criteria, the weighted average number of interactions was approximately
FIG. 2. Initial configuration of the simulation box, wherein the phosphoryl O-atom of the solute is pointed toward the interfacial region, with R being –CH2CH2CH2CH3 (butyl group) and R′ is either a butyl group or H-atom as in Figure 1.
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TABLE I. Geometric criteria used to define edges between molecular vertices in the intermolecular star graphs that define first solvation shells about a reference molecule. These distances are based upon the first minima in the radial distribution function between each pair of atoms. Atom labels provided in Figure S2 in the supplementary material, with O∗ being the alcoholic O-atom of the phosphate head of the solute.54 Interaction Cutoff (in Å)
Hw–OP
Hw–OC
Hw–OP
Hh–O∗
Hw–O∗
C,H–C,H
OP–Hh
Hh–O∗
Ow–HC
2.5
3.5
3.5
3.5
3.5
7.0
4.3
4.3
3.5
that of the integrated RDF for pairwise interactions of interest (Figure S1 in the supplementary material54). Here, the solvation environment is defined solely by the composition of the 1st solvation shell. The distribution of solvation environments about each solute was normalized according to the total number of different solvation environments observed. Thus, out of all possible solvation environments, the percentage of one, two, three, four, and so on, number of solvent molecules in the first solvation shell was determined. For example, the percentage observation for a solvation environment with a single solvent in the 1st shell (X1) would be determined according to N=40000
%X1 =
i=1 N=40000 i=1
(X1)i × 100,
(1)
(X1 + X2 + X3 + X4 + · · ·)i
where the sum is over all snapshots and the XN’s represent the different solvation environment with N edges between the solute and all solvent in the 1st solvation shell star graph. These first solvation shell star graphs were studied in different layers, or distances, relative to the interface due to the changes in partitioning of the solutes associated with their aqueous solubility. The simulation box, shown in Figure 2, has a total length in the z-dimension of 80 Å, beginning at z = 0. Therein, the interfacial region was identified using the position of the Gibbs dividing surface, which was obtained from the nhexane density profile and is labeled as z0, the position in the z-axis where the n-hexane density is half the bulk density (0.327 g/cm3).37 Figure 3 presents the density profiles of nhexane for all systems, highlighting their similarity. Amongst the four simulation boxes, the Gibbs dividing surface was found to be 40 Å ± 2, and thus, z0 = 40 Å was used as the point of reference for defining four layers, each 4 Å wide, that fully spanned the interfacial region (Figure 3). The two layers on either side of the phase boundary are labelled Aaq and Aorg while Baq and Borg represent the next layer 4 Å farther into the aqueous and organic phases, respectively. As shown in Figure 3, layer Aaq exists between 40 and 44 Å, Baq is between 44 and 48 Å, layer Aorg is between 36 and 40 Å, and Borg is between 32 and 36 Å. The presence of the solute within each layer was ascertained based upon the coordinates of the P-atom of the organophosphorus solute, which enables detailed tracking of the solute position throughout the simulation. The persistence of the solute in each layer was determined by counting the number of consecutive snapshots that the P-atom existed in each layer, and then taking the weighted average. The solvation environment about the solute was then examined, wherein it
is noted that the relative size of the first solvation shell will be influenced by the number of potential solute–solvent interaction points. TBP contains 52 total interaction points, HDBP has 31, and H2MBP has 19. A star graph was then constructed wherein the entire solute molecule was considered a vertex, with a single edge between the solute and solvent molecular vertices being present upon satisfaction the geometric criterion outlined in Table I. Using these graphs at every snapshot in the simulation, the potential mechanism wherein the solute “drags” n-hexane or water across the interface was investigated along with the ability of the solute to alter the partial solvation and microsolvation of n-hexane and water in the vicinity of the solute and beyond the 1st solvation shell. As the solute and co-solvent molecules dynamically move at the interface, partial solvation of one solvent by another is inevitable and fairly common. In prior work, we have demonstrated that in water:n-hexane interfaces, individual n-pentane molecules may be partially solvated by up to 18 H2O during the dynamic motion of the n-pentane at the interface. Similarly, individual H2O molecules may interact with up to 5 npentane molecules and still be partially solvated by other water molecules. In contrast to partial solvation, microsolvation is the rare event wherein the individual molecules of the immiscible liquids become completely solvated by the cosolvent in the interfacial region.36 Based upon our current
FIG. 3. Density profile of n-hexane in water:n-hexane in the absence and presence of a single TBP, HDBP, or H2MBP solute. The layers relative to the interface are illustrated and labeled with the Gibbs dividing surface, z 0 at 40 Å.
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study, microsolvation of water by n-hexane will occur when at least 6 n-hexane molecules surround an individual water, whereas microsolvation of n-hexane by water will require at least 20 H2O in the first solvation shell. The surface tension of the interface was calculated using the capillary wave method, following the procedure of Senapati and Berkowitz,38 where the density profile of water (ρ w ) and alkane (ρa ) is fitted to Eqs. (2) and (3), respectively, z − z0,w ), (2) ρw(z) = 0.5ρw − 0.5ρwerf( √ 2wc z − z0,a ρa(z) = 0.5ρa − 0.5ρaerf( √ ). (3) 2wc In Eqs. (2) and (3), z0,w and z0,a represent the Gibbs dividing surface for the water or n-hexane, respectively. The width due to thermal fluctuations is wc while the intrinsic width w0 is |z0, w − z0,a | and the total width is w. The three terms are related by w 2 = wc 2 + w02. After finding the value of wc , one can find the value of γe due to the capillary wave and thermal fluctuations using39 w2c =
Lx kBT ln( ), 2πγe lb
(4)
where L x is the total length in the x = y direction and l b is the bulk correlation length (on the order of the molecular length). In this work, we have estimated the value of l b as the cut off distance of 11 Å.38,39 The orientational order parameter of n-hexane was also examined so as to understand any impact of the solute upon the orientation of interfacial n-hexane molecules. The order parameter for n-hexane is defined as
Sz = 0.5(3 cos θ2 − 1), (5) where θ is the angle between the interface normal (the zaxis) and a vector that represents the local orientation and conformation of n-hexane.40 For each n-hexane, a vector is defined that bisects C-atoms that are two bond lengths apart, which results in four such vectors per n-hexane molecule. If an n-hexane is in the all trans conformation, these vectors are all parallel, as in Figure 4. Within Eq. (5), the average angle that each of the four vectors makes with the z-axis of the simulation box (the interface normal) over all molecules and all time is determined. The z-dependent profile of Sz is plotted in Figure 4, wherein a value of 1 signifies an average orientation of all vectors perpendicular to the interface normal (the z-axis), which correlates to a parallel arrangement of n-hexane relative to the xy-plane (the interfacial plane). An Sz value of −0.5 denotes an average orientation parallel to the interface normal (the z-axis), which corresponds to a perpendicular arrangement of n-hexane relative to the xy-plane (the interfacial plane). A value of Sz = 0 indicates a completely random orientation.41 D. Potential of mean force (PMF)
Potential of mean force calculations were used to investigate the relationship between the relative solubility of each solute in water and n-hexane with the associated energy of traversing the interface. Each solute was dragged from an
FIG. 4. The orientational order parameter S z of n-hexane with respect to the angle θ made with the z-axis (interface normal).
initial position ∼20 Å from the interface in the organic phase to a distance of ∼20 Å from the interface in the aqueous phase, leading to a total reaction path of 40 Å. An umbrellasampling scheme was used to calculate the unbiased free energy A(ξ) along the reaction coordinate.42–44 Umbrella sampled windows were then combined with the umbrella integration method.43–45 A harmonic biasing potential was used with a force constant of 0.5 kcal/mol Å2 to drag the solute within 0.2 Å intervals and 0.5 ns of equilibration.
III. RESULTS AND DISCUSSION
The system was first examined with respect to known trends in solute partitioning and average interfacial properties so as to confirm the quality of the force fields employed and consistency with experimentally known interfacial behavior of ampiphilic solutes. The PMF for the transport of each solute across the phase boundary was initially studied.46,47 As presented in Figure 5, it is first noted that the minima in the PMF are located at the interfacial region for all solutes herein, and thus, it is reasonable to have initial configurations of the MD simulation wherein the solute is partitioned at the interface. The observed PMFs of the individual solutes also reflect the relative solubility and distribution coefficients observed in prior experimental studies,19,21 and are good indications of the quality of the force fields employed. Namely, the energy required for TBP to be transported from n-hexane into the aqueous phase is much higher than for HDBP, which is in turn higher than for H2MBP, respectively. This complements the relative solubility of the three solutes in water which is 1.58 mM at 25 ◦C for TBP, 82 mM for HDBP, while H2MBP is completely miscible in water.19–21 In the fully equilibrated systems, the persistence of the solute on either side of the phase boundary is also correlated with the relative solubility. As observed in Table II, the solute TBP (which is the least soluble in the aqueous phase) is likely to be found with the phosphate head within the immediate interfacial region of the organic phase, Aorg, 67% of the time,
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J. Chem. Phys. 142, 104707 (2015) TABLE III. Persistence (in ps) of the head group of each solute within the 4 Å layers on either of the water:n-hexane phase boundary (Figure 3).
TBP HDBP H2MBP
FIG. 5. Potential of mean force for each solute migration across the water: n-hexane interfaces in kcal/mol.
and persisting in that region for 3 ps (Table III). Thirty percent of the time, the TBP head group exists within the immediate interfacial region of the aqueous phase, Aaq, where it persists for 1 ps. As the experimental aqueous solubility of the solute increases,19,21 the solute head groups are observed to spend more of their time in the Aaq region. In the case of HDBP, 37% of the time its head group resides in Aorg and 62% of the time it is observed in the Aaq layer. The H2MBP head group spends 15% in the Aorg and 84% in the Aaq layer. Complete aqueous solvation of the three solutes, characterized by migration of the solute into bulk water and solvation shells that consist of ∼50 H2O about TBP, and ∼30 H2O about HDBP and H2MBP is incredibly rare, occurring in only 1% of the total simulation time. Thus, during the entire simulation, the solutes preferentially partition to the interfacial region, in accordance with the PMF profile, and they diffuse primarily within the Baq to Borg regions (or the 8 Å on either side of the phase boundary). The presence of the ampiphilic solute in the interfacial region can alter the average physical characteristics of the interface, namely, interfacial tension and width. Table IV presents the interfacial tension of the neat liquid interface which is 45.24 dyn/cm, in good agreement with prior theoretical work (43.9 dyn/cm)41 and the previously reported underestimation relative to experiment.50,51 Introduction of a single TBP or HDBP to the interface increases the interfacial tension, while the presence of H2MBP slightly decreases it. The interfacial width (wc ), which is calculated from the fit TABLE II. Percent observation of the head group of each solute within the 4 Å layers on either side of the water:n-hexane phase boundary (Figure 3).
TBP HDBP H2MBP
Borg (%)
Aorg (%)
Aaq (%)
Baq (%)
2 0 ...
67 37 15
30 62 84
... 0 2
Borg
Aorg
Aaq
Baq
1 0 ...
3 1 1
1 2 5
... 0 1
interfacial tension data using Eq. (4), necessarily decreases as the tension increases. These data at the infinite dilution limit do not agree with the general experimental observations that ampiphilic solutes decrease interfacial tension in oil:water biphasic systems; however, experimental studies are generally undertaken at much higher solute concentration. Prior studies with sodium dodecyl sulfate (SDS) decreased the interfacial tension from 50 to 13 dyn/cm as the concentration of SDS was increased from 0.000 001 M to 0.01 M in biphasic water:nhexane.48 While beyond the scope of current work, we have examined the interfacial tension in equilibrated systems that have 0.54 M (using 21 solutes) and 1.1 M (using 42 solutes) concentration of TBP, HDBP, and H2MBP and observed the anticipated decrease in interfacial tension with increasing ampiphilic solute concentration. Thus, the perturbations in interfacial tension caused by ampiphilic solutes appear to be concentration dependent and at infinite dilution may not behave in the same manner as when higher concentrations are utilized. In the case of the phosphonic acid solutes, this may be due to the known aggregation phenomena of the solutes at higher concentrations,19,23 though this is beyond the scope of the current study. The perturbations in the average interfacial characteristics caused by the presence of the ampiphilic solutes likely derive from complex changes in the molecular scale solvation properties at the interface itself. While the solute migrates between both layers immediately on either side of the interface, the first solvation shell of the solute will likely contain both water and n-hexane. The entire first solvation shell of each solute has thus been decomposed into the partially solvating aqueous and nhexane portions. If the distribution of water about each solute is first considered, several interesting features are observed as the phosphate head of the solute migrates between Aorg and Aaq (Figure 6). When the phosphate head exists on the organic side of the interface, each solute has a fairly large number of water molecules in the first solvation shell about entire molecule, and the hydration number correlates with the relative aqueous solubility. Representative snapshots that highlight the aqueous solvation are presented in Figure S3 in the supplementary TABLE IV. Calculated interfacial tension values and interfacial thickness (w c ) in the presence and absence of a single TBP, HDBP, and H2MBP at the water:n-hexane interface. System
Interfacial tension (dyn/cm)
Interfacial thickness (Å)
Neat interface TBP HDBP H2MBP
45.24 (43.941 and 50.049,50) 50.05 51.52 44.51
1.37 1.30 1.28 1.48
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material,54 wherein the partial aqueous solvation of the alkyl groups, in addition to the head group, is illustrated. Thus, when the more hydrophilic H2MBP exists on the organic side of the interfacial region, it has a significantly higher percentage distribution of solvating waters in comparison to the more hydrophobic TBP. Consider that when the phosphate head of the H2MBP is in Aorg, there are 13 waters in the first solvation shell 16% of the time, while that solvation environment is only observed 6% of the time in the case of TBP (Figure 6(a)). The generally large number of waters in the first solvation shell for all solutes when their phosphate head is in organic side of the interface (Aorg) may be attributed to several features. Recall that the interface exhibits the common interfacial phenomenon of capillary waves and is thus not a flat surface.51 Though the position of the Gibbs dividing surface is somewhat removed from the actual monolayer of water contacting nhexane, the Aorg layer may sometimes exist within the aqueous side of the phase boundary at different points along the 2D interfacial surface. Second, the alkyl groups of the solutes may adopt configurations wherein they interact with water, irrespective of the location of the phosphate head (vide infra). As expected, when the phosphate head of the solute travels
FIG. 6. Distributions of water molecules in the 1st solvation shell about individual solutes in (a) the Aorg layer and (b) in the Aaq layers at 298 K. The average number of solvating water is presented as ⟨nH2O⟩. These distributions are about the whole molecule and have been determined based on Table I distance thresholds. The position of TBP, HDBP, and H2MBP has been determined by the position of the head group.
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across the interface and to the aqueous phase, the average number of solvating water, ⟨nH2O⟩, increases, however, it is only by the addition of a few H2O molecules. This is not surprising, given the small distance travelled by the solute and the fact that a large portion of alkyl groups can still exist in the n-hexane even when the phosphate head is in Aaq. If the n-hexane solvation environment about the solute is then considered, a slightly larger number of n-hexane is observed to solvate TBP relative to the other solutes. For example, ∼14% of the time, TBP is solvated by 7 n-hexane molecules, while less than ∼1% of the time, HDBP and H2MBP are solvated by 5 n-hexane molecules in the Aorg layer. Yet the number of solvating n-hexane molecules on average changes very little when the phosphate head of each solute migrates into Aaq (Figure 7). The qualitative picture that emerges regarding the three solutes is that the most likely solvation environment in the interfacial region consists of a large amount of water molecules in the first solvation shell, with a comparably small number of n-hexanes around the alkyl groups, and that this solvation environment is stable for motions of the solute within the 8 Å region that encompasses Aaq and Aorg. The organization of both the aqueous and organic components of the first solvation shell about each solute does reveal interesting differences across the series studied. The distribution of solvating waters in the first solvation shell about TBP is Gaussian when the phosphate head of
FIG. 7. Distribution of n-hexane molecules in the 1st solvation shell about individual solutes in (a) the Aorg layer and (b) the Aaq layer at 298 K. These distributions are about the whole molecule and have been determined based on Table I distance thresholds. The position of TBP, HDBP, and H2MBP has been determined by the position of the head group.
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TBP is in Aorg. This indicates only a few preferred solvation shell environments and thus a generally organized aqueous solvation structure. In contrast, a more random distribution (non-Gaussian) of aqueous environments is observed when the hydrophilic head of TBP is in Aaq. Interestingly, the aqueous solvation environment about HDBP and H2MBP in the interfacial region indicates a Gaussian like distribution of solvation environments in both Aaq and Aorg layers, and is indicative of a consistently organized aqueous solvation shell. These data indicate that TBP has a unique organization of water in the 1st solvation shell relative to HDBP and H2MBP and that this organization changes upon migration of the phosphate head from Aorg to Aaq, implying a conformational change within this solute as the phosphate head migrates across the phase boundary (vide infra). Given these complex solvation features about the solutes, it becomes pertinent to investigate the corresponding organization of water and n-hexane that are beyond the immediate solvation environment of the solute, and upon the individual dynamic processes of each co-solvent. Of the three solutes, only TBP is observed to significantly alter the orientation of one co-solvent, namely, n-hexane. As presented in Figure 8, the orientation order parameter in the neat liquid interface indicates that the n-hexanes’ solvent molecules have significant populations that are parallel with respect to the interface, in agreement with prior studies;14,52 however, in the presence of TBP, a statistically significant number of interfacial n-hexane molecules orient perpendicular to the interfacial plane (Figure 4) in a statistically significant manner. Commensurate with the change in orientation of n-hexane in the presence of TBP is an alteration of the individual microsolvation processes that represent the ability of n-hexane to temporarily penetrate the aqueous phase. Star graphs that represent the 1st solvation shell about every n-hexane were constructed in three regions about the solute: Region (I) within
10 Å of the head group of the solute, Region (II) between 10 and 20 Å of the head group of the solute, and Region (III) greater than 20 Å from the head group of the solute. As illustrated in Figure 9, n-hexane molecules in the 1st solvation shell (Region I) are dragged into the aqueous phase during the dynamic motion of the solute at the interface, thus leading to large amount of water solvating n-hexane. This works both ways, however, as water can also easily penetrate n-hexane when the solutes migrate from Aaq to Aorg (Figure S6 in the supplementary material54). These phenomena are observed for all solutes, and thus, all solutes are able to drag solvent molecules in their 1st solvation shells from one phase to the other. Yet out of all the solutes, TBP uniquely alters the microsolvation of n-hexane beyond the 1st solvation shell, specifically region II between 10 and 20 Å of the head group of the solute, and to a smaller extent region III (beyond 20 Å). Figure 10 presents the microsolvation of C6H14 and H2O in Region (II) for different solutes. To highlight the changes in microsolvation relative to the neat interface, the normalized values of solvation have been subtracted from the neat liquid interface. In this context, positive values present an increase in the solvation probability from its neat liquid interface and negative values mean a decrease relative to the neat liquid interface. Recall that microsolvation is characterized by more than 20 H2O in the first solvation shell, while partial solvation has nH2O < 20. It is apparent that only TBP increases the microsolvation of n-hexane in water while the effect of HDBP and H2MBP is very small. The ability of TBP to alter microsolvation of n-hexane beyond the first solvation shell may be related to several aforementioned features; first, the implied change in conformation of TBP as it traverses the phase boundary indicated by the significant perturbation in the solvating water configurations illustrated in Figure 6; second, the vertical orientation that TBP appears to induce within n-hexane in the interfacial region. To further examine these features, the TBP conformation and solvation environments were explicitly examined along
FIG. 8. Orientational order parameter, S z , of n-hexane in water:n-hexane, with the Gibbs dividing surface labeled as z 0. A value of S z of 1 indicates n-hexane parallel to the interface, while a value of −0.5 indicates a perpendicular orientation relative to the xy-plane.
FIG. 9. Microsolvation of n-hexane by water at the interface and within three regions about TBP, where Region (I) is less than 10 Å from the phosphate head P-atom, Region (II) is between 10 and 20 Å, and Region (III) is beyond 20 Å.
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FIG. 11. Change in solvation environment of TBP as it traverses the interface from z = 25 Å to z = 52 Å.
FIG. 10. Partial and microsolvation of (a) n-hexane by water and (b) interfacial water by n-hexane in the presence of different solutes in Region (II) between 10 and 20 Å from the phosphate head.
the PMF reaction coordinate. As observed in Figure 11, when in the phosphate head of TBP is deep in the bulk organic solvent, two of the three alkyl chains of TBP are bunched together. However, as the phosphate head traverses the phase boundary and becomes solvated by water, a major conformational change occurs such that each alkyl chain spreads away from each other to form an overall “Y” configuration. The conformational change is further clarified in Figure S4 in the supplementary material54 wherein the explicit solvent molecules have been removed. Upon changing conformation, one alkyl group remains embedded in the organic phase at z = 40 Å while the other two alkyl chains become fully solvated by water. At this point on the PMF, some n-hexane molecules directly solvating TBP become partially solvated by water, in Region I about the solute. Concurrently, the second and third solvation n-hexane molecules which adopt a perpendicular alignment relative to the interfacial plane in response to the change in TBP configuration also find it easier to penetrate the aqueous phase, which increases the microsolvation processes of n-hexane in Region II. Further along the PMF, at z = 52 Å as the solute fully penetrates the aqueous phase, the n-hexane molecules that are dragged into the aqueous phase through their association with the solute become apparent. While the ability of TBP to enhance n-hexane concentration in the aqueous phase has been observed in experimental and theoretical work, the specific mechanism of how this
occurs has not been previously discussed.19,53 In total, these data indicate that the presence of even a single solute can disturb the likelihood of microsolvation events within the interfacial region; however, this phenomenon appears to be correlated with the ability of the solute to induce orientational changes in the organic phase and perhaps changes in the conformation of the solute as it traverses the phase boundary. It is presumed that microsolvation processes are related to the concept of permeability of the interface and if so, these observations may provide a basis for future understanding of how ampiphilic solutes alter phase transfer.
IV. CONCLUSION
The combination of graph theoretical and configurational analyses of TBP, HDBP, and H2MBP at the water:n-hexane interface reveals that the systematic change in aqueous solubility has a distinct impact upon the local interfacial dynamics and structural arrangement of the interface. All three of the solutes examined drag solvating hexane and water molecules across the interface during the dynamical motion of the solute between the aqueous and organic phase. However, only TBP influences the individual microsolvation processes of n-hexane and water at a distance far from the solute, between 10 and 20 Å away. This may be attributed to a change in the orientation of n-hexane molecules from a parallel arrangement in the neat water:n-hexane interface, to a perpendicular arrangement in the presence of TBP, which may alter the kinetic ease of microsolvation of n-hexane in water and vice versa. A distinct conformational change in the alkyl groups of TBP is also observed that may be related to the n-hexane orientation or microsolvation probability. ACKNOWLEDGMENTS
This work was supported by a grant from Department of Energy, Basic Energy Sciences Heavy Element program (DE-SC0001815). This research used resources of the Oak Ridge Leadership Computing Facility located in the Oak Ridge National Laboratory, which is supported by the Office
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of Science within the Department of Energy under Contract No. DE-AC05-00OR22725. The authors wish to thank Dr. Johannes Kästner for providing the umbrella integration sampling software program. 1K.
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Citation: J. Chem. Phys. 142, 104707 (2015); doi: 10.1063/1.4914142 View online: http://dx.doi.org/10.1063/1.4914142 View Table of Contents: http://aip.scitation.org/toc/jcp/142/10 Published by the American Institute of Physics
THE JOURNAL OF CHEMICAL PHYSICS 142, 104707 (2015)
Solutes at the liquid:liquid phase boundary—Solubility and solvent conformational response alter interfacial microsolvation Yasaman Ghadar,a) Payal Parmar, Alex C. Samuels, and Aurora E. Clarka) Department of Chemistry and the Materials Science and Engineering, Washington State University, Pullman, Washington 99164, USA
(Received 4 November 2014; accepted 23 February 2015; published online 13 March 2015) A detailed understanding of solvent structure and dynamics at liquid:liquid interfaces is a necessary precursor for control and manipulation of these phase boundaries. Experimentally, amphiphilic solutes are often used to alter transport properties across water:organic interfaces; however, a fundamental model for the mechanism of this action has not been determined. This work compares the solvation profiles of ampiphilic solutes that traverse the phase boundary in binary water:n-hexane, and the individual microsolvation processes for interfacial water and hexane molecules therein. Microsolvation is defined as the rare event where one solvent molecule temporarily penetrates the co-solvent phases and is fully solvated therein. The solutes tri-butyl phosphate (TBP), hydrogen di-butyl phosphate, and di-hydrogen mono-butyl phosphate have been examined as they exhibit a systematic increase in aqueous solubility and selectively partition to the interfacial region at the infinite dilution limit. The relationship between adopted configurations of the solute, orientation of the solvent, and the ability of the solute to enhance microsolvation, specifically the ability of n-hexane to penetrate the aqueous phase, is demonstrated within a 20 Å radius of TBP. C 2015 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4914142]
I. INTRODUCTION
Immiscible liquid:liquid interfaces mediate numerous physical processes (e.g., phase transfer catalysis, solvent extraction, and drug delivery).1 Probing the nature of liquid:liquid interfaces in terms of their structure and dynamics is important to understand the underlying mechanisms involved in their formation and how to ultimately control their physicochemical properties. The water:alkane interface represents a simple model and quintessential system to study and develop theories about immiscible liquid:liquid and biological water membrane interfaces.2 In this context, both experimental methods such as x-ray and neutron scattering,3 optical ellipsometry,4 vibrational sum frequency spectroscopy,5–8 x-ray reflectivity,9 and molecular simulations have helped to quantify the density profile, interfacial tension and thickness, and aqueous dipole moment profiles of many water:alkane systems, including water:n-hexane.10–16 While these fundamental studies have helped to understand the physics associated with interfacial properties, the manipulation of those characteristics remains an active area of research. Experimentally, amphiphilic solutes which contain a hydrophobic tail and hydrophilic head are often used to alter the properties of water:organic interfaces in a variety of industrial scenarios, for example, within the detergent industry and in solvent extraction.17,18 Very little is understood about the mechanisms by which ampiphilic solutes perturb these interfaces, particularly at the molecular level. a)Authors to whom correspondence should be addressed. Electronic ad-
dresses: [email protected] and [email protected] 0021-9606/2015/142(10)/104707/9/$30.00
To investigate this issue, the molecular solvation of three ampiphilic solutes with the common names tri-butyl phosphate (TBP), hydrogen di-butyl phosphate (HDBP), and di-hydrogen mono-butyl phosphate (H2MBP) has been examined within the interfacial region of biphasic water:nhexane. These solutes exhibit the same hydrophilic phosphate head group while their hydrophobic tail is altered through varying number of alkyl chains, which alters their aqueous solubility. The solubility of TBP in water is 1.58 mM at 25 ◦C,19 HDBP in water is 82 mM,19,20 and H2MBP is completely miscible in water and acidic media.19–21 Closely related to solubility is the distribution ratio, D, of a solute across the aqueous:organic phase boundary, defined as [concentration of solute]org/[concentration of solute]aq in mol/L. Here, the concentration dependent D values for TBP, HDBP, and H2MBP in water:n-hexane are 2170, 13, and 0.74, respectively,19,21,22 when the solute concentrations in the organic phase are 3.43 M for TBP, 0.63 M for HDBP, and 0.40 M in the case of H2MBP. While these bulk properties reflect the general tendency of the solute to partition to a specific phase, they do not indicate what effect the solute has upon the interface when the solute traverses the phase boundary. Solvation within this unique region of space will involve both water23 and n-hexane about the solute and on the ns timescale of a classical molecular dynamics (MD) simulation, the influence of these solutes upon the interfacial properties may be large. Herein, the partitioning of a single TBP, HDBP, and H2MBP in water:n-hexane has been examined using MD. Changes in the conformation of the solute as it traverses either side of the phase boundary have been monitored and the effect of the solute upon the
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FIG. 1. Molecular structures of (a) TBP, (b) HDBP, and (c) H2MBP.
individual microsolvation processes of water and n-hexane has been investigated. Microsolvation is defined as the rare event where one solvent molecule temporarily penetrates the adjoining phases and is completely solvated by the co-solvent. It is presumed that microsolvation is related to the concept of permeability of the interface, and thus, a quantification of microsolvation events may aid future understanding of how ampiphilic solutes alter phase transfer.
II. COMPUTATIONAL METHODS A. Molecular models
Pair-wise additive models represent the potential energy of the system, with intermolecular pair potentials being taken as the sum of all pair potentials between interaction sites within the molecules. The organic molecules n-hexane, TBP, HDBP, and H2MBP have been described by the AMBER-99 force field (Figure 1),24,25 while charges for the atoms on organophosphorus solutes have been obtained from Khomami et al.26 Water was described using a modified rigid TIP3P/Ew water potential.27 All simulations were performed using the LAMMPS software (version 14Feb 2012),28 with the Verlet algorithm29 and a 1 fs timestep. Ewald summation used a 11 Å cutoff with a 1 × 10−6 tolerance threshold. Tables S1 and S2 in supplementary material54 present the bonded and non-bonded potentials utilized. B. Simulation details
Four simulation boxes (L x = L y = 40 Å, L z = 80 Å) were constructed using the Packmol program30 that represents the binary water:n-hexane system with initial configurations having either no solute or a single TBP, HDBP, or H2MBP placed within 5 Å of the interface and the phosphoryl O-atom pointed toward the n-hexane layer (Figure 2). Three-dimensional periodic boundary conditions were employed. The water portion of the biphasic system contained 2731 molecules, while 293 n-hexanes were present. The liquids were brought to mechanical and thermal equilibrium at 298 K using the NVT ensemble of Nose31 and Hoover,32 followed by a series of NPT simulations, until a pressure of 1 atm was reached.33,34 The systems were run in NPT for at least a ns followed by a ns of simulation in the NVE ensemble to
verify the system temperature and pressure. Production runs for every system consisted of 1 ns of an NVE simulation with capture of the trajectories every 25 fs, leading to a total of 40 k snapshots for data analysis for 1 ns of the production run. C. Data analysis
The data were analyzed using a graph theoretical, or network, approach implemented in the ChemNetworks software package.35 The emphasis of this work is to examine the local interfacial organization about a solute as its aqueous solubility is systematically altered. This includes examination of the solute solvation environment, the ability of the solute to alter the microsolvation of individual water and n-hexane molecules, and the mechanisms by which the solute can drag solvents in their respective immiscible phases (i.e., water into n-hexane and vice versa). The molecular simulation data are first converted into a star graph of the intermolecular interactions that define the first solvation shell about a reference molecule. Three specific star graphs have been defined by either the solute–water, solute–n-hexane, or the water–n-hexane interactions. The geometric criteria employed to define the intermolecular interactions are presented in Table I and are generally based upon the position of the first minima in the radial distribution functions (RDFs) presented in Figure S1 in the supplementary material.54 In the case of the water–n-hexane interactions, a geometric criterion of r < 4.3 Å between the Ow and Hh was utilized, which is slightly larger than the minimum of the two body potential energy surface for the interaction of the water Oatom, Ow, with alkane H-atoms, Hh.36 Using these criteria, the weighted average number of interactions was approximately
FIG. 2. Initial configuration of the simulation box, wherein the phosphoryl O-atom of the solute is pointed toward the interfacial region, with R being –CH2CH2CH2CH3 (butyl group) and R′ is either a butyl group or H-atom as in Figure 1.
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TABLE I. Geometric criteria used to define edges between molecular vertices in the intermolecular star graphs that define first solvation shells about a reference molecule. These distances are based upon the first minima in the radial distribution function between each pair of atoms. Atom labels provided in Figure S2 in the supplementary material, with O∗ being the alcoholic O-atom of the phosphate head of the solute.54 Interaction Cutoff (in Å)
Hw–OP
Hw–OC
Hw–OP
Hh–O∗
Hw–O∗
C,H–C,H
OP–Hh
Hh–O∗
Ow–HC
2.5
3.5
3.5
3.5
3.5
7.0
4.3
4.3
3.5
that of the integrated RDF for pairwise interactions of interest (Figure S1 in the supplementary material54). Here, the solvation environment is defined solely by the composition of the 1st solvation shell. The distribution of solvation environments about each solute was normalized according to the total number of different solvation environments observed. Thus, out of all possible solvation environments, the percentage of one, two, three, four, and so on, number of solvent molecules in the first solvation shell was determined. For example, the percentage observation for a solvation environment with a single solvent in the 1st shell (X1) would be determined according to N=40000
%X1 =
i=1 N=40000 i=1
(X1)i × 100,
(1)
(X1 + X2 + X3 + X4 + · · ·)i
where the sum is over all snapshots and the XN’s represent the different solvation environment with N edges between the solute and all solvent in the 1st solvation shell star graph. These first solvation shell star graphs were studied in different layers, or distances, relative to the interface due to the changes in partitioning of the solutes associated with their aqueous solubility. The simulation box, shown in Figure 2, has a total length in the z-dimension of 80 Å, beginning at z = 0. Therein, the interfacial region was identified using the position of the Gibbs dividing surface, which was obtained from the nhexane density profile and is labeled as z0, the position in the z-axis where the n-hexane density is half the bulk density (0.327 g/cm3).37 Figure 3 presents the density profiles of nhexane for all systems, highlighting their similarity. Amongst the four simulation boxes, the Gibbs dividing surface was found to be 40 Å ± 2, and thus, z0 = 40 Å was used as the point of reference for defining four layers, each 4 Å wide, that fully spanned the interfacial region (Figure 3). The two layers on either side of the phase boundary are labelled Aaq and Aorg while Baq and Borg represent the next layer 4 Å farther into the aqueous and organic phases, respectively. As shown in Figure 3, layer Aaq exists between 40 and 44 Å, Baq is between 44 and 48 Å, layer Aorg is between 36 and 40 Å, and Borg is between 32 and 36 Å. The presence of the solute within each layer was ascertained based upon the coordinates of the P-atom of the organophosphorus solute, which enables detailed tracking of the solute position throughout the simulation. The persistence of the solute in each layer was determined by counting the number of consecutive snapshots that the P-atom existed in each layer, and then taking the weighted average. The solvation environment about the solute was then examined, wherein it
is noted that the relative size of the first solvation shell will be influenced by the number of potential solute–solvent interaction points. TBP contains 52 total interaction points, HDBP has 31, and H2MBP has 19. A star graph was then constructed wherein the entire solute molecule was considered a vertex, with a single edge between the solute and solvent molecular vertices being present upon satisfaction the geometric criterion outlined in Table I. Using these graphs at every snapshot in the simulation, the potential mechanism wherein the solute “drags” n-hexane or water across the interface was investigated along with the ability of the solute to alter the partial solvation and microsolvation of n-hexane and water in the vicinity of the solute and beyond the 1st solvation shell. As the solute and co-solvent molecules dynamically move at the interface, partial solvation of one solvent by another is inevitable and fairly common. In prior work, we have demonstrated that in water:n-hexane interfaces, individual n-pentane molecules may be partially solvated by up to 18 H2O during the dynamic motion of the n-pentane at the interface. Similarly, individual H2O molecules may interact with up to 5 npentane molecules and still be partially solvated by other water molecules. In contrast to partial solvation, microsolvation is the rare event wherein the individual molecules of the immiscible liquids become completely solvated by the cosolvent in the interfacial region.36 Based upon our current
FIG. 3. Density profile of n-hexane in water:n-hexane in the absence and presence of a single TBP, HDBP, or H2MBP solute. The layers relative to the interface are illustrated and labeled with the Gibbs dividing surface, z 0 at 40 Å.
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study, microsolvation of water by n-hexane will occur when at least 6 n-hexane molecules surround an individual water, whereas microsolvation of n-hexane by water will require at least 20 H2O in the first solvation shell. The surface tension of the interface was calculated using the capillary wave method, following the procedure of Senapati and Berkowitz,38 where the density profile of water (ρ w ) and alkane (ρa ) is fitted to Eqs. (2) and (3), respectively, z − z0,w ), (2) ρw(z) = 0.5ρw − 0.5ρwerf( √ 2wc z − z0,a ρa(z) = 0.5ρa − 0.5ρaerf( √ ). (3) 2wc In Eqs. (2) and (3), z0,w and z0,a represent the Gibbs dividing surface for the water or n-hexane, respectively. The width due to thermal fluctuations is wc while the intrinsic width w0 is |z0, w − z0,a | and the total width is w. The three terms are related by w 2 = wc 2 + w02. After finding the value of wc , one can find the value of γe due to the capillary wave and thermal fluctuations using39 w2c =
Lx kBT ln( ), 2πγe lb
(4)
where L x is the total length in the x = y direction and l b is the bulk correlation length (on the order of the molecular length). In this work, we have estimated the value of l b as the cut off distance of 11 Å.38,39 The orientational order parameter of n-hexane was also examined so as to understand any impact of the solute upon the orientation of interfacial n-hexane molecules. The order parameter for n-hexane is defined as
Sz = 0.5(3 cos θ2 − 1), (5) where θ is the angle between the interface normal (the zaxis) and a vector that represents the local orientation and conformation of n-hexane.40 For each n-hexane, a vector is defined that bisects C-atoms that are two bond lengths apart, which results in four such vectors per n-hexane molecule. If an n-hexane is in the all trans conformation, these vectors are all parallel, as in Figure 4. Within Eq. (5), the average angle that each of the four vectors makes with the z-axis of the simulation box (the interface normal) over all molecules and all time is determined. The z-dependent profile of Sz is plotted in Figure 4, wherein a value of 1 signifies an average orientation of all vectors perpendicular to the interface normal (the z-axis), which correlates to a parallel arrangement of n-hexane relative to the xy-plane (the interfacial plane). An Sz value of −0.5 denotes an average orientation parallel to the interface normal (the z-axis), which corresponds to a perpendicular arrangement of n-hexane relative to the xy-plane (the interfacial plane). A value of Sz = 0 indicates a completely random orientation.41 D. Potential of mean force (PMF)
Potential of mean force calculations were used to investigate the relationship between the relative solubility of each solute in water and n-hexane with the associated energy of traversing the interface. Each solute was dragged from an
FIG. 4. The orientational order parameter S z of n-hexane with respect to the angle θ made with the z-axis (interface normal).
initial position ∼20 Å from the interface in the organic phase to a distance of ∼20 Å from the interface in the aqueous phase, leading to a total reaction path of 40 Å. An umbrellasampling scheme was used to calculate the unbiased free energy A(ξ) along the reaction coordinate.42–44 Umbrella sampled windows were then combined with the umbrella integration method.43–45 A harmonic biasing potential was used with a force constant of 0.5 kcal/mol Å2 to drag the solute within 0.2 Å intervals and 0.5 ns of equilibration.
III. RESULTS AND DISCUSSION
The system was first examined with respect to known trends in solute partitioning and average interfacial properties so as to confirm the quality of the force fields employed and consistency with experimentally known interfacial behavior of ampiphilic solutes. The PMF for the transport of each solute across the phase boundary was initially studied.46,47 As presented in Figure 5, it is first noted that the minima in the PMF are located at the interfacial region for all solutes herein, and thus, it is reasonable to have initial configurations of the MD simulation wherein the solute is partitioned at the interface. The observed PMFs of the individual solutes also reflect the relative solubility and distribution coefficients observed in prior experimental studies,19,21 and are good indications of the quality of the force fields employed. Namely, the energy required for TBP to be transported from n-hexane into the aqueous phase is much higher than for HDBP, which is in turn higher than for H2MBP, respectively. This complements the relative solubility of the three solutes in water which is 1.58 mM at 25 ◦C for TBP, 82 mM for HDBP, while H2MBP is completely miscible in water.19–21 In the fully equilibrated systems, the persistence of the solute on either side of the phase boundary is also correlated with the relative solubility. As observed in Table II, the solute TBP (which is the least soluble in the aqueous phase) is likely to be found with the phosphate head within the immediate interfacial region of the organic phase, Aorg, 67% of the time,
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J. Chem. Phys. 142, 104707 (2015) TABLE III. Persistence (in ps) of the head group of each solute within the 4 Å layers on either of the water:n-hexane phase boundary (Figure 3).
TBP HDBP H2MBP
FIG. 5. Potential of mean force for each solute migration across the water: n-hexane interfaces in kcal/mol.
and persisting in that region for 3 ps (Table III). Thirty percent of the time, the TBP head group exists within the immediate interfacial region of the aqueous phase, Aaq, where it persists for 1 ps. As the experimental aqueous solubility of the solute increases,19,21 the solute head groups are observed to spend more of their time in the Aaq region. In the case of HDBP, 37% of the time its head group resides in Aorg and 62% of the time it is observed in the Aaq layer. The H2MBP head group spends 15% in the Aorg and 84% in the Aaq layer. Complete aqueous solvation of the three solutes, characterized by migration of the solute into bulk water and solvation shells that consist of ∼50 H2O about TBP, and ∼30 H2O about HDBP and H2MBP is incredibly rare, occurring in only 1% of the total simulation time. Thus, during the entire simulation, the solutes preferentially partition to the interfacial region, in accordance with the PMF profile, and they diffuse primarily within the Baq to Borg regions (or the 8 Å on either side of the phase boundary). The presence of the ampiphilic solute in the interfacial region can alter the average physical characteristics of the interface, namely, interfacial tension and width. Table IV presents the interfacial tension of the neat liquid interface which is 45.24 dyn/cm, in good agreement with prior theoretical work (43.9 dyn/cm)41 and the previously reported underestimation relative to experiment.50,51 Introduction of a single TBP or HDBP to the interface increases the interfacial tension, while the presence of H2MBP slightly decreases it. The interfacial width (wc ), which is calculated from the fit TABLE II. Percent observation of the head group of each solute within the 4 Å layers on either side of the water:n-hexane phase boundary (Figure 3).
TBP HDBP H2MBP
Borg (%)
Aorg (%)
Aaq (%)
Baq (%)
2 0 ...
67 37 15
30 62 84
... 0 2
Borg
Aorg
Aaq
Baq
1 0 ...
3 1 1
1 2 5
... 0 1
interfacial tension data using Eq. (4), necessarily decreases as the tension increases. These data at the infinite dilution limit do not agree with the general experimental observations that ampiphilic solutes decrease interfacial tension in oil:water biphasic systems; however, experimental studies are generally undertaken at much higher solute concentration. Prior studies with sodium dodecyl sulfate (SDS) decreased the interfacial tension from 50 to 13 dyn/cm as the concentration of SDS was increased from 0.000 001 M to 0.01 M in biphasic water:nhexane.48 While beyond the scope of current work, we have examined the interfacial tension in equilibrated systems that have 0.54 M (using 21 solutes) and 1.1 M (using 42 solutes) concentration of TBP, HDBP, and H2MBP and observed the anticipated decrease in interfacial tension with increasing ampiphilic solute concentration. Thus, the perturbations in interfacial tension caused by ampiphilic solutes appear to be concentration dependent and at infinite dilution may not behave in the same manner as when higher concentrations are utilized. In the case of the phosphonic acid solutes, this may be due to the known aggregation phenomena of the solutes at higher concentrations,19,23 though this is beyond the scope of the current study. The perturbations in the average interfacial characteristics caused by the presence of the ampiphilic solutes likely derive from complex changes in the molecular scale solvation properties at the interface itself. While the solute migrates between both layers immediately on either side of the interface, the first solvation shell of the solute will likely contain both water and n-hexane. The entire first solvation shell of each solute has thus been decomposed into the partially solvating aqueous and nhexane portions. If the distribution of water about each solute is first considered, several interesting features are observed as the phosphate head of the solute migrates between Aorg and Aaq (Figure 6). When the phosphate head exists on the organic side of the interface, each solute has a fairly large number of water molecules in the first solvation shell about entire molecule, and the hydration number correlates with the relative aqueous solubility. Representative snapshots that highlight the aqueous solvation are presented in Figure S3 in the supplementary TABLE IV. Calculated interfacial tension values and interfacial thickness (w c ) in the presence and absence of a single TBP, HDBP, and H2MBP at the water:n-hexane interface. System
Interfacial tension (dyn/cm)
Interfacial thickness (Å)
Neat interface TBP HDBP H2MBP
45.24 (43.941 and 50.049,50) 50.05 51.52 44.51
1.37 1.30 1.28 1.48
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material,54 wherein the partial aqueous solvation of the alkyl groups, in addition to the head group, is illustrated. Thus, when the more hydrophilic H2MBP exists on the organic side of the interfacial region, it has a significantly higher percentage distribution of solvating waters in comparison to the more hydrophobic TBP. Consider that when the phosphate head of the H2MBP is in Aorg, there are 13 waters in the first solvation shell 16% of the time, while that solvation environment is only observed 6% of the time in the case of TBP (Figure 6(a)). The generally large number of waters in the first solvation shell for all solutes when their phosphate head is in organic side of the interface (Aorg) may be attributed to several features. Recall that the interface exhibits the common interfacial phenomenon of capillary waves and is thus not a flat surface.51 Though the position of the Gibbs dividing surface is somewhat removed from the actual monolayer of water contacting nhexane, the Aorg layer may sometimes exist within the aqueous side of the phase boundary at different points along the 2D interfacial surface. Second, the alkyl groups of the solutes may adopt configurations wherein they interact with water, irrespective of the location of the phosphate head (vide infra). As expected, when the phosphate head of the solute travels
FIG. 6. Distributions of water molecules in the 1st solvation shell about individual solutes in (a) the Aorg layer and (b) in the Aaq layers at 298 K. The average number of solvating water is presented as ⟨nH2O⟩. These distributions are about the whole molecule and have been determined based on Table I distance thresholds. The position of TBP, HDBP, and H2MBP has been determined by the position of the head group.
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across the interface and to the aqueous phase, the average number of solvating water, ⟨nH2O⟩, increases, however, it is only by the addition of a few H2O molecules. This is not surprising, given the small distance travelled by the solute and the fact that a large portion of alkyl groups can still exist in the n-hexane even when the phosphate head is in Aaq. If the n-hexane solvation environment about the solute is then considered, a slightly larger number of n-hexane is observed to solvate TBP relative to the other solutes. For example, ∼14% of the time, TBP is solvated by 7 n-hexane molecules, while less than ∼1% of the time, HDBP and H2MBP are solvated by 5 n-hexane molecules in the Aorg layer. Yet the number of solvating n-hexane molecules on average changes very little when the phosphate head of each solute migrates into Aaq (Figure 7). The qualitative picture that emerges regarding the three solutes is that the most likely solvation environment in the interfacial region consists of a large amount of water molecules in the first solvation shell, with a comparably small number of n-hexanes around the alkyl groups, and that this solvation environment is stable for motions of the solute within the 8 Å region that encompasses Aaq and Aorg. The organization of both the aqueous and organic components of the first solvation shell about each solute does reveal interesting differences across the series studied. The distribution of solvating waters in the first solvation shell about TBP is Gaussian when the phosphate head of
FIG. 7. Distribution of n-hexane molecules in the 1st solvation shell about individual solutes in (a) the Aorg layer and (b) the Aaq layer at 298 K. These distributions are about the whole molecule and have been determined based on Table I distance thresholds. The position of TBP, HDBP, and H2MBP has been determined by the position of the head group.
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TBP is in Aorg. This indicates only a few preferred solvation shell environments and thus a generally organized aqueous solvation structure. In contrast, a more random distribution (non-Gaussian) of aqueous environments is observed when the hydrophilic head of TBP is in Aaq. Interestingly, the aqueous solvation environment about HDBP and H2MBP in the interfacial region indicates a Gaussian like distribution of solvation environments in both Aaq and Aorg layers, and is indicative of a consistently organized aqueous solvation shell. These data indicate that TBP has a unique organization of water in the 1st solvation shell relative to HDBP and H2MBP and that this organization changes upon migration of the phosphate head from Aorg to Aaq, implying a conformational change within this solute as the phosphate head migrates across the phase boundary (vide infra). Given these complex solvation features about the solutes, it becomes pertinent to investigate the corresponding organization of water and n-hexane that are beyond the immediate solvation environment of the solute, and upon the individual dynamic processes of each co-solvent. Of the three solutes, only TBP is observed to significantly alter the orientation of one co-solvent, namely, n-hexane. As presented in Figure 8, the orientation order parameter in the neat liquid interface indicates that the n-hexanes’ solvent molecules have significant populations that are parallel with respect to the interface, in agreement with prior studies;14,52 however, in the presence of TBP, a statistically significant number of interfacial n-hexane molecules orient perpendicular to the interfacial plane (Figure 4) in a statistically significant manner. Commensurate with the change in orientation of n-hexane in the presence of TBP is an alteration of the individual microsolvation processes that represent the ability of n-hexane to temporarily penetrate the aqueous phase. Star graphs that represent the 1st solvation shell about every n-hexane were constructed in three regions about the solute: Region (I) within
10 Å of the head group of the solute, Region (II) between 10 and 20 Å of the head group of the solute, and Region (III) greater than 20 Å from the head group of the solute. As illustrated in Figure 9, n-hexane molecules in the 1st solvation shell (Region I) are dragged into the aqueous phase during the dynamic motion of the solute at the interface, thus leading to large amount of water solvating n-hexane. This works both ways, however, as water can also easily penetrate n-hexane when the solutes migrate from Aaq to Aorg (Figure S6 in the supplementary material54). These phenomena are observed for all solutes, and thus, all solutes are able to drag solvent molecules in their 1st solvation shells from one phase to the other. Yet out of all the solutes, TBP uniquely alters the microsolvation of n-hexane beyond the 1st solvation shell, specifically region II between 10 and 20 Å of the head group of the solute, and to a smaller extent region III (beyond 20 Å). Figure 10 presents the microsolvation of C6H14 and H2O in Region (II) for different solutes. To highlight the changes in microsolvation relative to the neat interface, the normalized values of solvation have been subtracted from the neat liquid interface. In this context, positive values present an increase in the solvation probability from its neat liquid interface and negative values mean a decrease relative to the neat liquid interface. Recall that microsolvation is characterized by more than 20 H2O in the first solvation shell, while partial solvation has nH2O < 20. It is apparent that only TBP increases the microsolvation of n-hexane in water while the effect of HDBP and H2MBP is very small. The ability of TBP to alter microsolvation of n-hexane beyond the first solvation shell may be related to several aforementioned features; first, the implied change in conformation of TBP as it traverses the phase boundary indicated by the significant perturbation in the solvating water configurations illustrated in Figure 6; second, the vertical orientation that TBP appears to induce within n-hexane in the interfacial region. To further examine these features, the TBP conformation and solvation environments were explicitly examined along
FIG. 8. Orientational order parameter, S z , of n-hexane in water:n-hexane, with the Gibbs dividing surface labeled as z 0. A value of S z of 1 indicates n-hexane parallel to the interface, while a value of −0.5 indicates a perpendicular orientation relative to the xy-plane.
FIG. 9. Microsolvation of n-hexane by water at the interface and within three regions about TBP, where Region (I) is less than 10 Å from the phosphate head P-atom, Region (II) is between 10 and 20 Å, and Region (III) is beyond 20 Å.
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FIG. 11. Change in solvation environment of TBP as it traverses the interface from z = 25 Å to z = 52 Å.
FIG. 10. Partial and microsolvation of (a) n-hexane by water and (b) interfacial water by n-hexane in the presence of different solutes in Region (II) between 10 and 20 Å from the phosphate head.
the PMF reaction coordinate. As observed in Figure 11, when in the phosphate head of TBP is deep in the bulk organic solvent, two of the three alkyl chains of TBP are bunched together. However, as the phosphate head traverses the phase boundary and becomes solvated by water, a major conformational change occurs such that each alkyl chain spreads away from each other to form an overall “Y” configuration. The conformational change is further clarified in Figure S4 in the supplementary material54 wherein the explicit solvent molecules have been removed. Upon changing conformation, one alkyl group remains embedded in the organic phase at z = 40 Å while the other two alkyl chains become fully solvated by water. At this point on the PMF, some n-hexane molecules directly solvating TBP become partially solvated by water, in Region I about the solute. Concurrently, the second and third solvation n-hexane molecules which adopt a perpendicular alignment relative to the interfacial plane in response to the change in TBP configuration also find it easier to penetrate the aqueous phase, which increases the microsolvation processes of n-hexane in Region II. Further along the PMF, at z = 52 Å as the solute fully penetrates the aqueous phase, the n-hexane molecules that are dragged into the aqueous phase through their association with the solute become apparent. While the ability of TBP to enhance n-hexane concentration in the aqueous phase has been observed in experimental and theoretical work, the specific mechanism of how this
occurs has not been previously discussed.19,53 In total, these data indicate that the presence of even a single solute can disturb the likelihood of microsolvation events within the interfacial region; however, this phenomenon appears to be correlated with the ability of the solute to induce orientational changes in the organic phase and perhaps changes in the conformation of the solute as it traverses the phase boundary. It is presumed that microsolvation processes are related to the concept of permeability of the interface and if so, these observations may provide a basis for future understanding of how ampiphilic solutes alter phase transfer.
IV. CONCLUSION
The combination of graph theoretical and configurational analyses of TBP, HDBP, and H2MBP at the water:n-hexane interface reveals that the systematic change in aqueous solubility has a distinct impact upon the local interfacial dynamics and structural arrangement of the interface. All three of the solutes examined drag solvating hexane and water molecules across the interface during the dynamical motion of the solute between the aqueous and organic phase. However, only TBP influences the individual microsolvation processes of n-hexane and water at a distance far from the solute, between 10 and 20 Å away. This may be attributed to a change in the orientation of n-hexane molecules from a parallel arrangement in the neat water:n-hexane interface, to a perpendicular arrangement in the presence of TBP, which may alter the kinetic ease of microsolvation of n-hexane in water and vice versa. A distinct conformational change in the alkyl groups of TBP is also observed that may be related to the n-hexane orientation or microsolvation probability. ACKNOWLEDGMENTS
This work was supported by a grant from Department of Energy, Basic Energy Sciences Heavy Element program (DE-SC0001815). This research used resources of the Oak Ridge Leadership Computing Facility located in the Oak Ridge National Laboratory, which is supported by the Office
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of Science within the Department of Energy under Contract No. DE-AC05-00OR22725. The authors wish to thank Dr. Johannes Kästner for providing the umbrella integration sampling software program. 1K.
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