Structure and Dynamics of Water near the Interface with Oligo

F. Goujon , C. Bonal , B. Limoges and P. Malfreyt. The Journal of ... Modelling and Simulation in Materials Science and Engineering 2014 22 (4), 04501...
0 downloads 0 Views 379KB Size
Download PDF
8508

Langmuir 2007, 23, 8508-8514

Structure and Dynamics of Water near the Interface with Oligo(ethylene oxide) Self-Assembled Monolayers Ahmed E. Ismail,* Gary S. Grest, and Mark J. Stevens Sandia National Laboratories, Albuquerque, New Mexico 87185-1395 ReceiVed March 21, 2007. In Final Form: May 30, 2007 We performed molecular dynamics simulations of the oligo(ethylene oxide) (OEO) self-assembled monolayers in water to determine the nature of the systems’ interfacial structure and dynamics. The density profiles, hydrogen bonding, and water dynamics are calculated as a function of the area per molecule A of OEO. At the highest coverages, the interface is hydrophobic, and a density drop is found at the interface. The interfacial region becomes more like bulk water as A increases. The OEO and water become progressively more mixed, and hydrogen bonding increases within the interfacial region. Water mobility is slower within the interfacial region, but not substantially. The implications of our results on the resistance of OEO SAMs to protein adsorption are discussed. Our principal result is that as A increases the increasingly waterlike interfacial region provides a more protein-resistant surface. This finding supports recent experimental measurements that protein resistance is maximal for less than full coverage on Au.

1. Introduction The structure and dynamics of water at interfaces are fundamental to a broad range of physical phenomena, such as the selfassembly of amphiphiles, protein folding, and surface wetting.1-4 The presence or lack of hydrogen bonding at an interface, particularly near a surface, determines whether the interface is hydrophilic or hydrophobic, which in turn determines many of the interfacial properties.1,5-8 Determining the interfacial structure and dynamics of any system is difficult, not least because of the need to separate the bulk and interfacial signals. Significant developments in experimental techniques have recently advanced the ability to measure the structure and dynamics at or near an interface.6,8-12 Simulations of water interfaces, which can easily separate the interface from the bulk, have also provided new insight.13-16 Measurement of interfacial properties can be enhanced by the ability to control the interfacial structure. Self-assembled monolayers (SAMs) provide a versatile means to have an atomically controlled surface structure and to vary the chemical nature of the interface easily. In particular, the number of hydroxyls at the surface can be controlled through SAM mixtures of different * Corresponding author. E-mail: [email protected]. (1) Israelachvili, J.; Wennerstro¨m, H. Nature (London) 1996, 379, 219. (2) Hummer, G.; Garde, S.; Garcı´a, A. E.; Paulaitis, M.; Pratt, L. J. Phys. Chem. B 1998, 102, 10469. (3) Netz, R. Curr. Opin Colloid Interface Sci. 2004, 9, 192. (4) Hopkins, A. J.; McFearin, C. L.; Richmond, Geraldine, L. Curr. Opin. Solid State Mater. Sci. 2005, 9, 19. (5) Ulman, A.; Evans, S.; Shnidman, Y.; Sharma, R.; Eilers, J. AdV. Colloid Interface Sci. 1991, 39, 175. (6) Scatena, L. F.; Richmond, G. Science 2001, 292, 908. (7) Lum, K.; Chandler, D.; Weeks, J. J. Phys. Chem. B 1999, 103, 4570. (8) Jensen, T. R.; Jensen, M. O.; Reitzel, N.; Balashev, K.; Peters, G.; Kjaer, K.; Bjornholm, T. Phys. ReV. Lett. 2003, 90, 086101. (9) Ostroverkhov, V.; Waychunas, G. A.; Shen, Y. R. Phys. ReV. Lett. 2005, 94, 046102. (10) McGuire, J. A.; Shen, Y. R. Science 2006, 313, 1945. (11) Tarbuck, T.; Ota, S. T.; Richmond, G. J. Am. Chem. Soc. 2006, 128, 14519. (12) Briscoe, W.; Titmuss, S.; Tiberg, F.; Thomas, R.; McGillivray, D.; Klein, J. Nature (London) 2006, 444, 191. (13) Lee, S.; Rossky, P. J. Chem. Phys. 1994, 100, 3334. (14) Wallqvist, A.; Berne, B. J. Phys. Chem. 1995, 99, 2893. (15) Wensink, E. J. W.; Hoffmann, A. C.; Apol, M. E. F.; Berendsen, H. J. C. Langmuir 2000, 16, 7392. (16) Wang, R. Y.; Himmelhaus, M.; Fick, J.; Herrwerth, S.; Eck, W.; Grunze, M. J. Chem. Phys. 2005, 122, 164702.

terminal groups.5 In this manner, the surface chemistry can be varied from wetting to nonwetting by water. Self-assembled monolayers of oligo(ethylene oxide) (OEO) are an interesting, special case. OEO itself is a special molecule in multiple respects. It is hydrophilic, although its backbone is two-thirds hydrocarbon. Besides the usual all-trans conformation, there is a helical conformation that is an energy minimum. The spacing between the O atoms in the backbone is such that a water molecule can hydrogen bond to successive O atoms. Adding to or subtracting from the backbone a C atom between successive O atoms ruins these features. OEO SAMs possess another important feature: they are a standard surface that resists protein adsorption.17 Because proteins contain monomers that are hydrophobic, hydrophilic, and charged (both positively and negatively), they adsorb to most surfaces. Proteins can change their conformation so that the appropriate monomers that preferentially bind to a given surface are exposed to the surface so that the whole protein adsorbs. Although there is an understanding of how poly(ethylene oxide) brushes are protein resistant based on the entropic interactions of polymers,18,19 this mechanism does not apply to the short molecules in the OEO SAM; the protein resistance of the OEO SAM is not fully understood. Presumably, the nature of the water interface with an OEO SAM is critical in determining the protein resistance and may give insight into the general nature of water interfaces. An intriguing experimental result is that methyl-terminated OEO SAMs on Ag are not protein resistant, even though they have the same wetting angles as the SAMs on Au.20 Ag has a smaller lattice spacing, resulting in the area per chain for the OEO chains being smaller than on Au. This tight packing forces the OEO chains to be in all-trans conformations. More recently, Vanderah et al.21 showed that the protein resistance on Au is maximal at about two-thirds coverage, not full coverage. Herrwerth et al. had previously noted a dependence on packing density.22 These results imply that there is something significant (17) Prime, K. L.; Whitesides, G. M. Science 1991, 252, 1164. (18) Szleifer, I. Biophys. J. 1997, 72, 595. (19) Szleifer, I. Curr. Opin. Solid State Mater. Sci. 1997, 2, 337. (20) Harder, P.; Grunze, M.; Dahint, R.; Whitesides, G. M.; Laibinis, P. E. J. Phys. Chem. B 1998, 102, 426. (21) Vanderah, D. J.; La, H.; Naff, J.; Silin, V.; Rubinson, K. A. J. Am. Chem. Soc. 2004, 126, 13639. (22) Herrweth, S.; Eck, W.; Reinhardt, S.; Grunze, M. J. Am. Chem. Soc. 2003, 125, 9359.

10.1021/la700829r CCC: $37.00 © 2007 American Chemical Society Published on Web 07/10/2007

Structure and Dynamics of Water near OEO Interfaces

about the area per molecule and its effect on the interfacial structure and dynamics. Almost a decade ago, the question was, “is it polyethylene oxide or water that imparts and controls fouling resistance?”23 This echos the discussions of hydration and structured water that have been occurring for a long time.1 Here we present results of molecular dynamics (MD) simulations of OEO SAMs in water to examine these issues. Inspired by the work of Vanderah et al.,21 we performed simulations to examine the interfacial structure and dynamics of water as a function of OEO SAM coverage. We analyze the nature of hydrogen bonding and water dynamics in the interfacial region. We show that the hydrogen bonding within the interfacial region becomes more like that of bulk water as the SAM coverage descreases. We find that both the OEO conformation and the water play important roles in the structure and dynamics of the interface. The protein-surface interaction is determined by the interfacial structural and dynamics. An interface that is increasingly more like bulk water is more resistant to protein adsorption, as found in recent experiments.21 There have been a number of experimental investigations into the structure and dynamics of water near the interface with SAMs. Schwendel et al. measured the interfacial structure of ethylene glycol SAMs with both hydroxyl and methyl termination using neutron reflectivity.24 For the methyl-terminated SAMs, an unexpectedly thick layer (∼4 nm) of reduced water density was measured at the SAM-water interface. They note the possibility that air bubbles could be the source of this thick layer. For hydroxyl-terminated SAMs, the water density at the interface is within a few percent of the bulk water density, which is consistent with expectations. More recent neutron reflectivity measurements of octadecyl-trichlorosilane (OTS) SAMs find a smaller thickness (8-11 Å) of reduced water density at the interface for untreated water (naturally aerated D2O).25 They also examined the effect of degassing and found that the thickness decreases to between 5 and 6 Å. Jensen et al. measured the water interface with paraffin wax using X-ray reflectivity and found a density drop extending less than 15 Å into the bulk water.8 The integrated density deficit is about 1 water molecule per 25-30 Å2. Recent synchrotron X-ray reflectivity measurements of the interface between water and OTS SAMs find a depletion layer that is only about 4 Å thick.26,27 In both sets of experiments, they determine that the density profile is not a result of nanobubbles. Several simulation studies of OEO SAMs in water have been performed. Pertsin et al. used Monte Carlo simulations to examine the molecular structure within the SAMs on both Au and Ag substrates with and without water.28,29 A higher degree of water penetration and OEO disorder in the SAMs on Au than on Ag was found. Zheng et al. studied water near the surface of mixed monolayers of S(CH2)4(OCH2CH2)4OH and S(CH2)4OH, also varying the area per OEO end group.30,31 They calculated density profiles and examined the hydrogen bonding of the water and OEO molecules. They also included a lyzozyme protein in the (23) Morra, M. J. Biomater. Sci. Polym. Ed. 2000, 11, 547. (24) Schwendel, D.; Hayashi, T.; Dahint, R.; Pertsin, A.; Grunze, M.; Stoltz, R.; Schreiber, F. Langmuir 2003, 19, 2284. (25) Doshi, D.; Watkins, E.; Israelachvili, J.; Majewski, J. Proc. Nat. Acad. Sci. U.S.A. 2005, 102, 9458. (26) Poynor, A.; Hong, L.; Robinson, I.; Granick, S. Phys. ReV. Lett. 2006, 97, 266101. (27) Mezger, M.; Reichert, H.; Schoder, S.; Okasinski, J.; Schroder, H.; Dosch, H.; Palms, D.; Ralston, J.; Honkimaki, V. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 18401. (28) Pertsin, A. J.; Grunze, M. Langmuir 2000, 16, 8829. (29) Pertsin, A. J.; Hayashi, T.; Grunze, M. J. Phys. Chem. B 2002, 106, 12274. (30) Zheng, J.; Li, L.; Chen, S.; Jiang, S. Langmuir 2004, 20, 8931. (31) Zheng, J.; Li, L.; Tsao, H.-K.; Sheng, Y.-J.; Chen, S.; Jiang, S. Biophys. J. 2005, 89, 158.

Langmuir, Vol. 23, No. 16, 2007 8509

simulations and examined protein-surface interactions. They calculated force-distance curves between a protein and OEO SAMs (and others).31 They claim that a “tightly bound” water layer just above the interface is responsible for the large repulsive protein-surface force. Whereas we find similar interfacial structure, our analysis of the dynamics is in disagreement with the water being “tightly bound.” The rest of the article is organized as follows. We briefly outline the structure of the systems analyzed and describe our molecular dynamics (MD) simulations in the following section. We present results for the interfacial structure and dynamics in section 3. In section 4, we compare and contrast the data at low and high coverages. The implications for protein resistance are also discussed, and comparison with earlier simulations is made. We summarize our findings in section 5.

2. Simulation Method 2.1. Systems. We have studied a number of water-OEO monolayer systems. The OEO molecules, HSCH2(CH2CH2O)6CH3, consist of six ethylene oxide units with methyl termination and a short alkanethiol end-group bonded to a substrate of either Au or Ag atoms.21 In each case, the substrate was defined as a 10 × 10 array of bonding sites organized as a c(4 × 2) superlattice, following experimental and simulation observations.32-35 The lattice parameters for gold and silver are aAu ) 5.0 Å and aAg ) 4.67 Å.36 We define the xy plane to be the plane in which the sulfur atoms are fixed and the z axis to be perpendicular to the substrate, with the sulfur atoms located on the z ) 0 plane. The key quantity determining the interfacial structure of the OEO SAM-water system is the area per molecule, A. On the Au substrate, the minimum area per site is 21 Å2, and for Ag, the minimum area is 19 Å2.36 Whereas the deposition of alkanethiols can achieve the maximum packing, OEO SAMs generally do not. On Au, the maximum observed complete OEO coverage occurs at roughly A ) 27 Å2.20-22 On Ag, the densest observed coverage is 21 Å2, which corresponds to the minimum area occupied by an all-trans OEO chain.36 We simulated the following values of A: 21, 24, 27, 36, and 54 Å2. The 21 and 24 Å2 systems were simulated only on the Ag substrate because the Au substrate does not accommodate these coverages; the 36 and 54 Å2 systems were simulated only on the Au substrate. The 27 Å2 system was simulated with both Au and Ag substrates; however, we report data only for the Au substrate because the results obtained for the Ag substrate were equivalent within the simulation error. The 36 Å2 system corresponds to the minimum in the protein adsorption data of Vanderah et al.21 Figure 1 shows images of the interface for two values of A. To achieve a given area per molecule for each simulation, sites on the substrate were randomly chosen to be occupied, with the total number of occupied sites determined by the desired value of A. Experimentally, the variable coverage is achieved by controlling the deposition time. A random placement of chains should yield a good representation of the experimental structure.37 Furthermore, the fact that the simulations with different lattice spacing but the same A yield the same results suggests that A is the dominant quantity and that the binding sites of the chains are at best secondary in importance. (32) Poirier, G. E.; Tarlov, M. J. Langmuir 1994, 10, 2853. (33) Bhatia, R.; Garrison, B. J. Langmuir 1997, 13, 4038. (34) Zhang, L.; Goddard, W. A., III.; Jiang, S. J. Chem. Phys. 2002, 117, 7342. (35) Love, J. C.; Estroff, L. A.; K., K. J.; Nuzzo, R. G.; Whitesides, G. M. Chem. ReV. 2005, 105, 1103. (36) Wang, R. L. C.; Kreuzer, H. J.; Grunze, M. J. Phys. Chem. B 1997, 101, 9767. (37) Rundqvist, J.; Hoh, J. H.; Haviland, D. B. Langmuir 2005, 21, 2981.

8510 Langmuir, Vol. 23, No. 16, 2007

Ismail et al.

Figure 2. Total density profile of a system for different values of A (top). In the bottom plot, the density of OEO oxide chains (---) and water (-) are shown separately. (z > 30 Å not shown to focus on the interfacial region.) Profiles are shown for the following values of A: 54 Å2 (b), 36 Å2 (9), 27 Å2 ((), 24 Å2 (O), and 21 Å2 (0). In the top plot, the points mark the minimum at the interface (if it exists); in the bottom plot, the points mark the intersection of the two curves.

Figure 1. Penetration of water (van der Waals representation) into the OEO monolayer (CPK representation) for A ) 36 Å2 on Au (top) and A ) 21 Å2 on Ag (bottom) systems. The images show the xz plane and only waters within the OEO layer. For the top image Lx ) 50 Å, and for the bottom image, Lx ) 46.7 Å.

2.2. Simulation Method. Molecular dynamics (MD) simulations were performed in the NVT ensemble using the LAMMPS simulation package.38 All calculations were carried out using the revised OEO-water force field of Smith and co-workers,39 which includes cross terms for the OEO-water interactions as well as a hydrogen bonding term for interactions between the oxygens of the OEO chains and the hydrogens in the water molecules. The TIP4P water model of Jorgensen et al.40 is used in these simulations. The Au and Ag substrate dynamics are not explicitly treated; the substrate lattice is instead used to define the bonding sites of the OEO molecules. The sulfur atoms were fixed in position; Lennard-Jones interactions for the sulfur atoms were modeled using the OPLS force field.41 The cutoff for the van der Waals potentials and the real-space part of the electrostatic potential were set to 10 Å. Electrostatic interactions were calculated using the particle-particle particlemesh (PPPM) technique of Hockney and Eastwood,42 with a rms accuracy of 10-4. The bond lengths and bond angles of the water molecules were constrained using the SHAKE technique.43 Following experimental observations,35 the Au-S-C bond angles were likewise constrained with SHAKE at an angle of 120°. A Lennard-Jones 9-3 wall was placed approximately 20 Å above (38) Plimpton, S. J. J. Comput. Phys. 1995, 117, 1. See also website at lammps.sandia.gov (39) Smith, G. D.; Borodin, O.; Bedrov, D. J. Comput. Chem. 2002, 23, 1480. (40) Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. J. Chem. Phys. 1983, 79, 926. (41) Jorgensen, W. L.; Maxwell, D. L.; Tirado-Rives, J. J. Am. Chem. Soc. 1996, 118, 11236. (42) Hockney, R. W.; Eastwood, J. W. Computer Simulation Using Particles; Adam Hilger-IOP: Bristol, U.K., 1988. (43) Ryckaert, J.-P.; Ciccotti, G.; Berendsen, H. J. C. J. Comput. Phys. 1977, 23, 327.

the top of the water layer to prevent particles from crossing over the periodic boundary in the z direction. In each simulation, the initial state of the OEO monolayer has the chains in an all-trans conformation with a tilt angle of 30°, corresponding to experimental observations on Ag.35 A 50-Å-thick layer of 3555 water molecules was placed above the OEO monolayers on Au substrates, and a 60-Å-thick layer of 3586 water molecules was placed above the Ag substrates. The water was first equilibrated at 300 K in a box with the same lateral dimensions as for the monolayer. The equations of motion were integrated using the Verlet algorithm; the average temperature was maintained at 300 K using a Nose´-Hoover thermostat with a relaxation time of 500 fs. Each simulation was performed for at least 2.5 ns with a time step of ∆t ) 1 fs. The various systems were allowed to equilibrate for 1 ns, and data from the remaining simulation time of at least 1.5 ns for each system were used to compute the various properties reported.

3. Results 3.1. Structure. For grafted systems, the density profiles parallel to the substrate are a basic characterization of the system structure. In particular, the density profiles plotted in Figure 2 show the degree of mixing between the water and the OEO SAMs as a function of SAM coverage. For the densest coverage, A ) 21 Å2, a sharp interface exists between the SAM and the water with little penetration of the water into the SAM. At this A, the OEO profile shows some oscillations due to the degree of ordering that occurs in a densely packed SAM. The bottom image of Figure 1 shows a snapshot of the system at A ) 21 Å2. Only the (few) waters within the SAM volume and near the interface are shown. The high degree of order can be seen by looking at the red O atoms in the OEO chains. They are found in distinct layers corresponding to density oscillations in the density profile at this A. As A increases from 21 to 27 Å2, there is increasing overlap of the water profile with the OEO profile. The hydrophilic character of OEO results in mixing of the water and the OEO. One measure of the overlap is the ratio of the position at which the water density equals the OEO density to the maximum extent of the OEO density (Figure 2). At A ) 21 Å2, this ratio is 0.89, which shows that the water density is dropping quickly at the interface. For the lowest OEO coverage of A ) 54 Å2, the ratio

Structure and Dynamics of Water near OEO Interfaces

Figure 3. Dihedral angle distributions P(φ) for the O-C-C-O (-) and C-C-O-C (---) dihedrals for the A ) 36 Å2 system and the O-C-C-O distribution for the A ) 21 Å2 system (‚‚‚). The C-C-O-C is not shown for A ) 21 Å2 because it is almost identical to the solid curve.

decreases to 0.46. Thus, as the OEO coverage decreases, water molecules occupy the free volume made available by the absence of the OEO chains. The images in Figure 1 demonstrate the contrast in the amount of water in the monolayer as a function of the area per chain. The dense packing of the chains for A ) 21 Å2 leaves little free volume for water molecules to diffuse into the monolayer. There are on average 493 water molecules adsorbed at A ) 36 Å2, but there are only 90 water molecules adsorbed at A ) 21 Å2, most of which are at the position of the terminal group of the SAM. Besides allowing the water to mix within the SAM, the lower coverage allows the OEO chains to move. As coverage decreases, the OEO chains on average become more compact, which lowers the free energy by increasing the entropy. The more compact chains result in the OEO density decreasing with increasing z. The OEO density near the substrate decreases only a small amount at larger A because some chains bend over to occupy the vacant sites, exposing hydrophilic oxygens to water and lowering the energy as a result. To determine the conformations of the OEO molecules, we calculated the probability distributions for the dihedral angles along the backbone of the OEO chains. There are two distinct atom sequences along the backbone: O-C-C-O and C-CO-C (or C-O-C-C, which is equivalent); each sequence corresponds to a different dihedral potential function. The distributions were obtained by measuring the dihedral angles every 2.5 ps during the 1.5 ns total simulation time. Distributions for the individual dihedrals are averaged together with others of the same type. The distributions are normalized such that the integral of the distribution in radians from 0 to 2π is 1. In Figure 3, distributions are plotted for the O-C-C-O and C-C-O-C dihedrals for the A ) 36 and 21 Å2 systems. The initial configurations for all dihedral angles were assigned to be exclusively trans. After equilibration, the C-C-O-C dihedral distribution at A ) 36 Å2 has a resolvable gauche peak, with the trans peak being about 2.5 times greater. This distribution is the same as at A ) 21 Å2. However, the O-C-C-O distribution changes significantly. At A ) 21 Å2, as shown in Figure 3, the O-CC-O distribution has a main trans peak and monotonically decreasing tails on either side without a resolvable gauche peak. At A ) 36 Å2, the O-C-C-O dihedral distribution is very broad, and the gauche peaks are the same height as the trans peak. These results are consistent with the picture that at lower values of A the chains are confined by packing to be predominantly all-trans.

Langmuir, Vol. 23, No. 16, 2007 8511

Figure 4. Oxygen density as a function of distance z from the substrate surface. The plot shows only the region near the interface to highlight the details of the interfacial structure. Labels are the same as in Figure 2.

As A increases, the gauche conformations in O-C-C-O become more likely, and the chains become more flexible dynamically. Because hydrogen bonding can involve the oxygens in both the water and the OEO molecules, it is also useful to plot the total oxygen density profile, as shown in Figure 4. Provided that the volume is accessible to water molecules, the plot gives the hydrogen bond acceptor density. For small values of A, the O density drops sharply at the water-OEO interface, which is a result of the sharp interface seen in the separate OEO and water density profiles. At A ) 21 Å2, there are strong oscillations in the O density profile within the SAM volume corresponding to the oscillations in the OEO density profile. For the lower-coverage monolayers, the oxygen density at the interface increases as A increases. Part of this is due to the smaller thickness of the OEO SAM (cf. Figure 2) and the concomitant water at lower z, but there is also significant water penetration within the SAM. For A g 27 Å2, the oscillations in the O density weaken and disappear. This indicates that the chain conformations deviate substantially from an all-trans conformation. The hydrophilic nature of PEO is due to the hydrogen bonding capability of the O atom in each subunit. We can explicitly determine the hydrogen bond network from the geometry of the configurations. A hydrogen bond was considered to have been formed between a water molecule and an OEO chain or between two water molecules if the distance between the hydrogen on the water molecule and the oxygen atom on either an OEO chain or another water molecule is less than 3.0 Å and if θOHO > 150°, where θOHO is the bond angle formed by the three atoms.44 The number of hydrogen bonds was calculated as a function of height within the monolayer, and the resulting hydrogen bond density profiles are shown in Figure 5. At A ) 21 and 24 Å2, hydrogen bonding involving the O in OEO occurs only in a narrow region a few angstroms wide at the interface between OEO and water. From the density data, we know that this interface is sharp. Together with the sharp interface, the geometry strongly limits the water molecules’ ability to form hydrogen bonds with the O in OEO. For larger values of A, the number of hydrogen bonds increases at each z with increasing A. A simple and convenient way to quantify the hydrogen bonding within the SAM is to examine the position z1/2 where the number of hydrogen bonds is half the bulk value. At the highest coverage A ) 21 Å2, z1/2 ) 25 Å, which is basically at the top of the SAM. At lower coverages (44) Lommerse, J. P. M.; Price, S. L.; Taylor, R. J. Comput. Chem. 1997, 18, 757.

8512 Langmuir, Vol. 23, No. 16, 2007

Figure 5. Hydrogen bond density as a function of distance from the substrate. Labels are the same as in Figure 2.

(A ) 36 and 54 Å2), the hydrogen bond network extends into the SAM: z1/2 ) 11 and 18 Å, respectively. These positions are almost equal to the positions where the OEO and water densities are equal (Figure 2). The overall structural picture is one of increasing water mixing and hydrogen bonding within the PEO SAM as the coverage decreases. 3.2. Dynamics. Having characterized the structure of the system, we now consider its dynamics. We are especially interested in the effect of the OEO SAM on the water dynamics. In particular, we want to determine how mobile the waters are within the SAM and near the interface. Ideally, one would calculate the diffusion constant for water in a slab volume parallel to the substrate at selected z positions and compare it to bulk water diffusion. However, because individual water molecules might, and in the present case do, diffuse from one slab to another, the diffusion constant could be calculated only for the time within a slab, which might be insufficient and, in any case, would be a 2D diffusion constant that cannot be compared to the standard 3D constant. The first issue to be determined is whether the water is mobile within the SAM, particularly at large A. For this purpose, we calculated the mean-square displacement 〈r2(t)〉 as a function of the initial position of the water molecules in an equilibrated configuration. The plot of the mean-square displacement in Figure 6 shows that the water molecules are mobile, independent of the starting position, at A ) 36 Å2. The water molecules starting near the substrate move the least, as expected, because of confinement effects. However, these waters still move a substantial distance (>40 Å) within 1 ns, and the difference with waters starting outside the SAM volume is not large. Thus, the waters within the SAM volume are not significantly different from the bulk water molecules with respect to their mobility. To better characterize the time it takes for water molecules within the interfacial region to move some distance, we divided the system into slabs of thickness ∆z ) 5 Å parallel to the substrate. For each slab, we identify the water molecules in the slab at the starting time and then determine the number of these molecules that remain in the slab as a function of time. Figure 7 shows a semilog plot of this data for the A ) 36 Å2 system. The waters in the two slabs furthest from the substrate have identical distribution functions; they both exhibit bulk behavior. The next closest slab (20 Å < z < 25 Å) shows an increase in residence times. The density profile of the OEO SAM at A ) 36 Å2 extends to about 21 Å (Figure 2), thus waters in contact with the outermost part of the SAM are slightly slowed down. For water just 5 Å away from the SAM, residence times are unaffected. This is

Ismail et al.

Figure 6. Mean-square displacement (〈r2〉) versus time for water molecules in the A ) 36 Å2 system. Profiles are shown for water molecules as a function of zinit: 5 Å e zinit < 10 Å (b), 10 Å e zinit < 15 Å (9), 15 Å e zinit < 20 Å ((), 20 Å e zinit < 25 Å (2), 25 Å e zinit < 30 Å (O), and 30 Å e zinit < 35 Å (0).

Figure 7. Residence fraction of water molecules within slabs parallel to the substrate as a function of time in the A ) 36 Å2 system. The plot is semilog, and the lines are least-square fits to the data. From right to left, the profiles are shown for water molecules as a function of the water’s initial position zinit; labels are the same as in Figure 6. The water density equals the OEO density at z ) 16.7 Å (Figure 2).

consistent with the standard picture of liquid dynamics at a solid interface, in which the first layer or two of liquid can have a slower diffusion rate as a result of interaction with the substrate. For waters initially within the OEO SAM volume (z < 20 Å), the residence time profiles for the three closest slabs show progressively slower water diffusion as z decreases. Because the available free volume for water decreases with z and the water must diffuse around the larger and slower OEO molecules, water diffusion should be slower at smaller z. A linear plot of the data in Figure 7 (not shown) shows that by t ) 125 ps all of the water molecules have moved to a neighboring slab, which is consistent with the mean-square displacement data. We can calculate the relaxation time from the distributions by fitting the data to an exponential and relating the slope to the relaxtion time. For z > 25 Å, the relaxation time is 6.5 ps; for the slab closest to the substrate, the relaxation time increases to 24.4 ps. Thus, the water dynamics is slower, as expected, but only by a factor of 4.

4. Discussion In all of the quantities calculated, the changes as a function of coverage are gradual. Whereas the transition between the high

Structure and Dynamics of Water near OEO Interfaces

and low coverages studied is continuous, the differences between the two are rather stark and exhibit important qualitative changes. For this reason, we now compare and contrast the interfacial structure and dynamics at the interfaces for the densest coverage (A ) 21 Å2) and for two-thirds coverage (A ) 36 Å2). This examination will emphasize that the OEO SAM plays as important a role in the interface as does the water. For the densest coverage, the interfacial region is very narrow. There is very little penetration of water into the SAM,28 and mixing of the water and SAM is confined to the terminal region of the SAM. In agreement with recent experimental data8,26,27 and earlier calculations7,8 on hydrophobic interfaces, there is a density drop at the interface. Because of the dense packing of the chains, there is little mobility of the chains. The OEO SAM presents a stiff, hydrophobic surface to the water. This agrees with the wetting angle measurements of Harder et al.20 The structure at about two-thirds coverage is very different. The interfacial region is relatively wide. Water penetrates well into the SAM, and the water and OEO molecules mix. A significant amount of hydrogen bonding occurs in the interfacial region. There is no density drop in the interface, and the interfacial region is basically hydrophilic. The dynamics at the interface is also very different. Because of the low coverage, there is much room for the water in the interfacial region and OEO molecules to move. The water diffuses freely into and out of the region. The OEO molecules have torsional mobility and are flexible. This flexibility and the water dynamics yield a dynamic hydrogen bonding network in the interface that is similar to that of bulk water. The contrast between the two coverages is rather stark, suggesting that the interfaces have very different characters. Part of the motivation of this work is the study by Vanderah et al.,21 which showed a coverage dependence of the protein resistance of OEO SAMs on Au. We can view the protein as a probe of the interface: whether a protein absorbs gives information about the interface. Our simulation results make it easier to understand both the protein interaction and the SAM protein resistance as a function of coverage. As noted in the Introduction, the protein resistance of OEO SAMs is not understood, although much is known about these systems. The interfacial structure and dynamics determined by the simulations reveals a different picture than what has previously been considered. The focus of previous work has tended to be on the water.30,31,36 Our results suggest that the packing and flexibility of the SAM are also important factors.1,22,23 We now compare the free-energy contributions for a protein absorbing at the two coverages using experimental data and our simulation data. We consider the contributions of the various terms to the free energy in light of the results from this work. While the present work does not calculate all of these terms, the insight provided suggests a basic understanding of the protein resistance mechanism that we suggest here, which will be studied in detail in future work. We note that protein adsorption requires one of two situations: (1) at least partial unfolding of the protein and multiple (weak) binding sites to the surface, which sum to yield a large binding energy or (2) a local, very strong binding site on the protein surface that binds to the surface. For the case of interest here, only situation 1 is relevant. Consider a protein adsorbing to a hydrophobic, methylterminated solid surface, such as OEO on Ag at A ) 21 Å2. As the protein diffuses to the surface, it sees a hydrophobic surface. The surface is rather inflexible and impenetrable by the protein’s residues. Thus, the protein sees almost exclusively the terminal end of the SAM. In addition, the density drop at the interface provides some space for the protein to occupy. The protein

Langmuir, Vol. 23, No. 16, 2007 8513

unfolds, exposing its hydrophobic core to the surface. This increases the protein entropy because a (partially) unfolded protein has more conformations than a folded one. In addition, the energy is lowered as the hydrophobic groups in the protein and the surface are matched, reducing the number of unfavorable waterprotein and water-surface interactions. The hydrophilic protein residues are exposed to water (i.e., the protein becomes a surfactant). Each of these contributions is a decrease or a neutral change in the free energy, so the free energy decreases for protein adsorption and thus the protein adsorbs. The protein interaction with the OEO SAM surface at A ) 36 Å2 is very different. As the protein diffuses to contact, it sees a hydrophilic surface. There is no gain in free energy from the protein unfolding to expose its hydrophobic core to the surface. The protein interfacial energy is minimized with the protein remaining folded because the interfacial region is hydrophilic. The protein can penetrate the interfacial region to some extent because the region is flexible, but there are no specific sites to which the protein can strongly bind. The generic hydrogenbonding environment appears much like water, maintaining the solubility of the protein. As the protein diffuses deeper, the steric repulsion of the collective packing of the SAM molecules limits the penetration. If the coverage were to be too low and the Au substrate were exposed, then the protein could adsorb to the Au, which is seen experimentally.21 However, as long as the coverage is large enough for the OEO to cover the Au, the protein will see only the hydrophilic interfacial region. The free-energy difference between the bulk protein and adsorbed protein is positive, and thus the protein does not adsorb. The flexibility of the interface is a key factor in protein resistance. The mixing of the water with the interface requires that the OEO molecules not be densely packed.28 On Ag, the dense packing produces a methyl-terminated hydrophobic surface. As the packing density decreases, more water is at the interface, and the OEO SAMs can have conformations that expose their O atoms. The layer of methyl groups disperses over a larger volume and does not dominate the interaction with water or a protein. As A changes, the interface changes continuously. The protein adsorption data on Au is continuous, with adsorption decreasing at full coverage to reach a minimum at about two-thirds coverage and then rising again near 50% coverage.21 We note that the OEO molecular structure and dynamics affect the maximal area per molecule that can be achieved. Whereas ideally coverages in the range of 19-21 Å2 may be possible for OEO, measured values are larger (A ) 27 Å2 on Au).20 Because OEO has conformations other than all-trans that are favored, the packing of the monolayer as it forms is limited. The length of the ethylene oxide segment thus can have a strong influence on packing. Helical conformers require sufficiently long segments. Thus, short segments will be able to pack densely, but segments with six monomers will not. Longer segments will start to have polymeric structure, which will also limit the packing and bring in other contributions to the free energy. The effect of molecular structure on packing in the SAM plays an important role in determining A and consequently in the surface’s protein resistance.22,45 A suggested source of protein resistance is that the water layer directly above the interface has unusual physical properties, leading to enhanced resistance.30,31,36 These ideas appear to be similar to “structured water” ideas refuted in the past.1 Whereas we find that the water dynamics at the interface is different from that of the bulk, we do not find that the water is substantially (45) Kane, R.; Deschatelets, P.; Whitesides, G. Langmuir 2003, 19, 2388.

8514 Langmuir, Vol. 23, No. 16, 2007

different, and it does not present a barrier to protein adsorption. In fact, we find the opposite: water is sufficiently mobile within the interface, and the interface appears to be bulk-like. With respect to the issue of simulating protein adsorption, the (partial) unfolding of the protein has been neglected. Previous simulations have treated only the interaction between a soluble, folded protein and the OEO SAM.30,31 This is by necessity as a result of simulations of protein adsorption being severely limited because protein unfolding (even partial) is outside the capability of standard MD simulations, requiring time scales greater than 1 µs. Thus, at best, one can just obtain the “colloidal” interaction between a folded protein and the surface. Unfortunately, this interaction does not determine whether a protein will adsorb because it neglects essential dynamics that alters the proteinsurface interaction. A repulsive interaction is not an indicator of resistance to adsorption. Consider, for example, the case of two lipid bilayers coming into contact with each other. Their interaction is repulsive,46 yet vesicles will fuse spontaneously (on time scales that are long for simulation) because the fused structure has a lower free energy. The repulsion presents a barrier for fusion but does not prevent fusion. Similarly, repulsive protein-surface interactions are not indicative of protein resistance to adsorption. (46) Lis, L. J.; McAlister, M.; Fuller, N.; Rand, R. P.; Parsegian, V. A. Biophys. J. 1982, 37, 657.

Ismail et al.

5. Conclusions Our principal finding is that as the surface area per molecule of OEO increases, the environment in the SAM volume becomes more waterlike as a result of the mixing with water, the mobile dynamics of the mixed water, the participation of O atoms in the OEO chains in the hydrogen bond network, and the increased flexbility of the OEO chains. Each of these factors increases with decreasing OEO coverage. There is a significant change in all of these factors between the highest and lowest coverages studied. At high coverages that occur on Ag substrates, the methylterminated OEO SAM presents a hydrophobic surface that mixes well with water, forms few hydrogen bonds, and is a stiff monolayer. With respect to the protein resistance of OEO SAMs, these differences in interfacial structure and dynamics yield the difference in protein adsorption that was recently measured. The high-coverage case has protein adsorption because it presents a hydrophobic interface, which the protein can unfold and adsorb onto. At lower coverages, the interface is more waterlike and the protein interacts with the interface much as it interacts with water. The protein remains folded and freely moves between the surface and the bulk. Acknowledgment. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under contract no. DE-AC04-94AL85000. LA700829R