π-Hydrogen Bonding in Liquid Water

π-Hydrogen Bonding in Liquid Water ABSTRACT: We report the experimental observation and quantitation of π-hydrogen bond formation between liquid water and benzene using Raman multivariate curve resolution (Raman-MCR) combined with quantum and classical (cluster and liquid) calculations. Our results establish that π-hydrogen bonds between liquid water and benzene are weaker and more flexible (have a more positive enthalpy and entropy) than bulk water hydrogen bonds. We further establish that such bonds also form between water and other aromatics, including the amino acid phenylalanine, thus implying their common occurrence at hydrated biological interfaces. SECTION: Kinetics, Spectroscopy T he biologically ubiquitous OH 3 3 3 O and NH 3 3 3 O bonds are members of a much larger class of hydrogen-mediated AH 3 3 3 B interactions, all of which may reasonably be called hydrogen bonds.1 Among the more unusual members of this class is the π-hydrogen bond (πHB) AH 3 3 3 ϕ where ϕ represents an aromatic ring and A may be a N, O, or C atom.1,2 Such bonds have previously been well characterized in cold (matrix and gas phase) clusters3
9 and the interiors of native proteins,10,11 but not at protein surfaces in liquid water. Here we report the experimental observation of the quintessential πHB between liquid water and benzene (as well as other aromatics), and quantify the corresponding πHB probability, flexibility, and dynamic equilibrium between the benzene
water πHB and water
water hydrogen bond (wHB). Our results imply that πHB formation is likely to be common at biological interfaces, and thus may well participate in various binding, recognition, and signaling processes. Early evidence of πHB formation was obtained from vibrational spectroscopic studies of liquid benzene containing a trace amount of dissolved water.1,12 These seminal studies were followed by many others, including detailed investigations both under ambient conditions13 and at high pressure and temperature,14
17 as well as in low temperature benzene
water clusters.3
6 However, an aqueous solution containing benzene is quite different from any of the above systems, in that liquid water wHB formation provides an energetically and statistically competitive alternative to πHB formation. Previous experiments have found that πHBs are far more flexible than OH 3 3 3 O hydrogen bonds. For example, highresolution rotational and vibrational spectra of the πHB in benzene
H2O, benzene
HOD, and benzene
NH3 dimers indicate that the formation of a πHB leaves water (or ammonia) remarkably free to rotate.4
9 Moreover, recent time-resolved infrared studies of the πHB between phenol and benzene (as well as other aromatics) confirm that the OH group may readily reorient and translate parallel to the aromatic plane even in systems with substantially different πHB strengths.18
20 Our results reveal that benzene
water OH 3 3 3 ϕ configurations in liquid water are also more flexible (have greater entropy) than water
water OH 3 3 3 O structures. A substantial number of prior theoretical investigations have focused on characterizing the interaction between benzene and water. These include quantum calculations of benzene
(H2O)n clusters containing between n = 1 and n = 10 water molecules,4,21
23 as well as both classical24,25 and quantum mechanical26,27 molecular dynamics simulations of benzene in liquid water. Although all of these studies suggest that a πHB may form between water and benzene, detailed predictions obtained using different theoretical methods are not entirely consistent with each other, particularly with regard to πHB strengths, probabilities, and structural distribution functions. Here we employ a recently developed experimental strategy that combines ultralow-noise Raman scattering measurements and multivariate curve resolution (Raman-MCR)28 to obtain a solute-correlated (SC) spectrum that reveals OH vibrational features arising from benzene’s hydration-shell. The same Raman-MCR method has previously been used to discover dangling water OH bonds around dissolved saturated hydrocarbon Figure 1. Aqueous solutions containing dissolved aromatic (and alkane) groups reveal vibrational peaks assigned to water πHB (and dangling) OH groups. (A) The total Raman scattering spectrum of a dilute (∼22 mM) solution of benzene in water (dashed blue curve) looks virtually identical to that of bulk water. The resulting Raman-MCR SC spectrum (red curve) reveals a small, relatively narrow peak at ∼3610 cm
1 assigned to a πHB between benzene and liquid water (expanded in the insert). (B) The latter πHB peak is similar to that observed in the SC spectrum of phenol in water (red curve, expanded in the insert) and is about 50 cm
1 red-shifted with respect to the dangling OH peak that appears in the SC spectrum of cyclohexanol in water (green curve). The full SC spectrum of phenol in water is given in the Supporting Information (Figure S3). (alkane) groups, as well as to provide preliminary evidence of the formation of a πHB between water and benzyl alcohol.29 Extending these results to benzene in water poses formidable challenges because the low aqueous solubility of benzene (∼20 mM) means that the πHB OH vibrational peak of interest is more than 1000 times smaller than the broad overlying bulk water OH stretch band. Thus, Raman spectra of benzene in water must be obtained with a signal-to-noise ratio of at least 10,000:1. Figure 1A shows such a Raman spectrum and the relatively narrow blue-shifted OH peak at ∼3610 cm
1 that appears in the resulting SC spectrum of benzene in water (obtained as further described in the Supporting Information). Our assignment of the ∼3610 cm
1 peak to water molecules in the benzene hydration shell is supported in part by our isotopic studies of C6D6 in H2O, and C6H6 in D2O, which confirm that the above peak only appears when benzene is present and is not a vibrational combination band of benzene, but rather arises from the interaction between water and benzene (see Supporting Information for details). Our assignment of the ∼3610 cm
1 peak to a πHB is further supported by the results shown in Figure 1B, which reveal that a similar peak appears in the SC spectrum of phenol (C6H5OH) dissolved in water, and is redshifted by ∼50 cm
1 with respect to the dangling (free) OH peak (at ∼3660 cm
1) that appears in the SC spectrum of cyclohexanol (C6H11OH).29 Note that the latter red-shift is similar to the ∼60 cm
1 red-shift of a πHB with respect to a free OH previously observed in both benzene
water clusters and liquid benzene containing a trace amount of water.1,12,30 Moreover, the much larger intensity of the SC peaks of benzene and phenol, Figure 2. Temperature dependent measurements are used to obtain the enthalpy difference between πHB and wHB structures in liquid water. (A) The temperature dependence of the benzene
water πHB peak reveals a slight broadening and blue-shift with increasing temperature. These πHB peaks are all normalized by dividing the SC spectra by the area of the benzene ring breathing peak at ∼992 cm
1, thus assuring that the areas of the πHB peaks are proportional to nπHB. (B) The temperature dependence of the πHB peak areas are used to obtain the corresponding average number of πHBs between water and either benzene (C6H6) or deuterated benzene (C6D6), both of which imply that ΔH ∼ 7 ( 2 kJ/mol for the conversion of a wHB to a πHB structure (see text for details). relative to the dangling OH peak in the SC spectrum of cyclohexanol (see Figure 1B), clearly implicates the role of aromaticity in giving rise to the ∼3610 cm
1 peak. We have further verified that a virtually identical πHB peak appears in the SC spectrum of aqueous phenylalanine (see Supporting Information). Thus, there is little doubt that the observed peak at ∼3610 cm
1 arises from a πHB between liquid water and benzene as well as other aromatic solutes. Figure 2A shows how the benzene
water πHB peak depends on temperature. The areas of these πHB peaks, combined with those arising from benzene and bulk water, may be used to determine the average number nπHB of πHBs formed between liquid water and a dissolved benzene molecule (as further described below, and in the Supporting Information). In order to improve the accuracy of the resulting nπHB values, we have made use of the fact that the OH Raman scattering cross section of OH 3 3 3 O is predicted to be ∼1.21 times larger than that of OH 3 3 3 ϕ (obtained using ab initio MP2/aug0 -cc-pVTZ level calculations of the OH Raman cross sections in H2O
H2O and C6H6
H2O dimers, as further described in the Supporting Information). The resulting average number of πHBs between benzene and liquid water nπHB is ∼0.64 ( 0.12 at 20 °C, and increases mildly with temperature from ∼0.51 ( 0.12 (at 0 °C) to ∼0.83 ( 0.12 (at 50 °C). The above experimental results are in reasonable agreement with the predicted value of nπHB ∼ 1.1 ( 0.03, which we have obtained from classical simulations of benzene in liquid water (with OPLS-AA/TIP4P potentials, and OH vibrational frequency predictions obtained from a semiempirical Stark-shift correlation, as further described in the Supporting Information). The fact that the predicted value of nπHB is larger than the experimental value is consistent with the fact that such classical simulations are known to be overstructured, and thus overestimate πHB probabilities, when compared to higher level quantum calculations26 (as further discussed below, as well as in the Supporting Information). Both the simulation and experimental results agree in indicating that increasing temperature produces a slight increase in both the mean frequency and width of the πHB peak. More specifically, while our experimental results indicate a frequency increase of ∼10 cm
1 (from ∼3603 ( 1 cm
1 to ∼3613 ( 1 cm
1) and a full-width-at-half-maximum (fwhm) increase of ∼17 cm
1 (from ∼61 ( 4 cm
1 to ∼78 ( 4 cm
1) over a 0 to 50 °C temperature range, the simulations predict frequency and width increases of ∼25 cm
1 and ∼10 cm
1, respectively, over the same temperature range (see Supporting Information for further details). The temperature dependence of the experimental πHB peak areas may be used to obtain a quantitative estimate of the enthalpy difference ΔH between a benzene
water πHB configuration and an average wHB in liquid water, as shown in Figure 2B. More specifically, the Gibbs
Helmholtz relation implies that ΔH =
R[∂ lnK/∂(1/T)]p where K = [πHB]/ [wHB] is the ratio of the πHB and wHB concentration in a benzene
water solution (of fixed benzene concentration), and R ∼ 8.3 J/(K mol) is the gas constant. Since [πHB] µ nπHB and [wHB] µ [H2O], we expect that ln K = ln(nπHB/[H2O]) + C (where C is a temperature-independent constant) and thus ΔH =
R{∂ ln(nπHB/[H2O])/∂(1/T)}p ∼ 7 ( 2 kJ/mol, as shown in Figure 2B. A similar analysis of the temperature-dependent SC spectra of phenol in water yields ΔH ∼ 3 ( 2 kJ/mol. Although the above ΔH values have significant uncertainty, repeated measurements as well as alternative analysis procedures invariably produce positive experimental ΔH values of similar magnitude, which implies that a πHB is weaker than a wHB in liquid water. The positive signs of the above ΔH values are consistent with previous experimental and theoretical benzene
water cluster results. For example, fragmentation threshold studies imply that a benzene
water dimer is slightly more weakly bound (by about 10
20%) than a water
water dimer.2,31 Moreover, hybrid quantum-classical effective fragment potential (EFP) calculations of benzene
water clusters imply that replacement of one water molecule by benzene in water clusters with 4
8 water molecules leads to an intermolecular binding energy change of +7.5 ( 2.5 kJ/mol.22 Note that the latter energy difference is remarkably similar to our experimental ΔH result for the enthalpy difference between πHB and wHB configurations in liquid water (see Figure 2B). Additional information regarding the thermodynamics of πHB formation may be obtained by focusing on a single water molecule situated nearest to the center of the benzene ring. Such a water molecule may be assumed to either form a πHB to benzene HOH 3 3 3 C6H6 (with a probability of p), or not H2O C6H6 (with a probability of 1
p). This simplified two-state description assumes that each of the OH groups on such a nearest neighbor water molecule either form a πHB to benzene or a wHB to another water. Thus, the transformation of a HOH 3 3 3 C6H6 structure to a H2O C6H6 structure involves exchanging one πHB for one wHB. The ratio of the probabilities of finding the system in the latter two configurations, k = p/(1
p) = nπHB/(2
nπHB), represents the equilibrium constant for the H2O C6H6 f HOH 3 3 3 C6H6 transformation. Note that the second of the above equalities is obtained by identifying p = nπHB/2 as the probability that a water molecule closest to one side of the benzene ring will form a πHB. The equilibrium constant k may be used to estimate the free energy ΔG and entropy ΔS of the H2O C6H6 f HOH 3 3 3 C6H6 process. For example, at 20 °C nπHB∼ 0.64, so p ∼ 0.32 and k ∼ 0.32/(1
0.32) ∼ 0.47, which implies that ΔG =
RT ln(0.47) ≈ +2 kJ/mol. This experimental free energy is in remarkably good agreement with value of ΔG ≈ +3 kJ/mol inferred from the benzene
water πHB potential of mean force, obtained from our classical molecular dynamics simulations (as further described in the Supporting Information). The experimental ΔG, combined with the fact that ΔH > 2 kJ/mol, clearly implies that ΔS = (ΔH
ΔG)/T > 0. This conclusion is also consistent with the value of ΔS obtained from the temperature derivative of ΔG, ΔS =
(∂ΔG/∂T)p = R[∂(Tlnk)]/ ∂T]p ≈ + 30 J/(K mol). The positive sign of ΔS indicates that HOH 3 3 3 C6H6 (πHB) configurations have a larger entropy than H2O C6H6 (non-πHB) configurations. In other words, the water molecule nearest to benzene’s center of mass has a greater conformational flexibility when one of its two OH groups forms a πHB than it does when both of its OH groups form a wHB. Our experimental results imply that the conversion of a wHB to a πHB in liquid water is entropically favored (ΔS > 0) but enthalpically disfavored (ΔH > 0). The observed entropy increase is consistent with previous observations of the remarkably high orientational freedom of a πHB in benzene
water clusters6 as well as phenol dissolved liquid benzene.20 We have further found that, in spite of the fact that a πHB is somewhat weaker than a wHB (and the statistically greater number of potential wHB partners), approximately one πHB is formed between liquid water and each dissolved benzene molecule, as well as between water and other aromatic solutes including phenylalanine. The observed ubiquity of πHB formation in liquid water implies that such bonds are undoubtedly common at biological interfaces containing aromatic amino acids, nucleic acids, or metabolites, and thus πHB formation may well prove to play an important role in biological binding, recognition, and signaling processes. ’ REFERENCES (1) Pimentel, G. C.; McClellan, A. L. The Hydrogen Bond. W. H. Freeman: San Francisco, CA, 1960. (2) Zwier, T. S. The Spectroscopy of Solvation in Hydrogen-Bonded Aromatic Clusters. Annu. Rev. Phys. Chem. 1996, 47, 205–241. (3) Engdahl, A.; Nelander, B. A Matrix-Isolation Study of the Benzene Water Interaction. J. Phys. Chem. 1985, 89, 2860–2864. (4) Suzuki, S.; Green, P. G.; Bumgarner, R. E.; Dasgupta, S.; Goddard, W. A.; Blake, G. A. Benzene Forms Hydrogen-Bonds with Water. Science 1992, 257, 942–944. (6) Pribble, R. N.; Garrett, A. W.; Haber, K.; Zwier, T. S. Resonant Ion-Dip Infrared-Spectroscopy of Benzene
H2O and Benzene
HOD. J. Chem. Phys. 1995, 103, 531–544. (7) Gruenloh, C. J.; Carney, J. R.; Arrington, C. A.; Zwier, T. S.; Fredericks, S. Y.; Jordan, K. D. Infrared Spectrum of a Molecular Ice Cube: The S4 and D2d Water Octamers in Benzene
(Water)8. Science 1997, 276, 1678–1681. (8) Gruenloh, C. J.; Carney, J. R.; Hagemeister, F. C.; Zwier, T. S.; Wood, J. T.; Jordan, K. D. Resonant Ion-Dip Infrared Spectroscopy of Benzene
(Water)9: Expanding the Cube. J. Chem. Phys. 2000, 113, 2290–2303. (9) Rodham, D. A.; Suzuki, S.; Suenram, R. D.; Lovas, F. J.; Dasgupta, S.; Goddard, W. A.; Blake, G. A. Hydrogen-Bonding in the Benzene Ammonia Dimer. Nature 1993, 362, 735–737. (10) Steiner, T.; Koellner, G. Hydrogen Bonds with π-Acceptors in Proteins: Frequencies and Role in Stabilizing Local 3d Structures. J. Mol. Biol. 2001, 305, 535–557. (11) Chakrabarti, P.; Bhattacharyya, R. Geometry of Nonbonded Interactions Involving Planar Groups in Proteins. Prog. Biophys. Mol. Biol. 2007, 95, 83–137. (12) Greinacher, E.; Luttke, W.; Mecke, R. Infrarotspektroskopische Untersuchungen an Wasser, Gelost in Organischen Losungsmitteln. Z. Elektrochem. 1955, 59, 23–31. (13) Besnard, M.; Danten, Y.; Tassaing, T. Dynamics of Solitary Water in Benzene and Hexafluorobenzene: An Infrared and Raman Study. J. Chem. Phys. 2000, 113, 3741–3748. (14) Tassaing, T. A Vibrational Spectroscopic Study of Water Confined in Benzene from Ambient Conditions up to High Temperature and Pressure. Vib. Spectrosc. 2000, 24, 15–28. (15) Furutaka, S.; Ikawa, S. Hydrogen Bonding of Water with Aromatic Hydrocarbons at High Temperature and Pressure. J. Chem. Phys. 1998, 108, 5159–5160. (16) Furutaka, S.; Kondo, H.; Ikawa, S. Infrared Spectroscopic Study of Water
Aromatic Hydrocarbon Mixtures at High Temperatures and Pressures. Bull. Chem. Soc. Jpn. 2001, 74, 1775–1788. (17) Furutaka, S.; Ikawa, S. π-Hydrogen Bonding between Water and Aromatic Hydrocarbons at High Temperatures and Pressures. J. Chem. Phys. 2002, 117, 751–755. (18) Zheng, J. R.; Kwak, K.; Asbury, J.; Chen, X.; Piletic, I. R.; Fayer, M. D. Ultrafast Dynamics of Solute
Solvent Complexation Observed at Thermal Equilibrium in Real Time. Science 2005, 309, 1338–1343. (19) Rosenfeld, D. E.; Kwak, K.; Gengeliczki, Z.; Fayer, M. D. Hydrogen Bond Migration between Molecular Sites Observed with Ultrafast 2D IR Chemical Exchange Spectroscopy. J. Phys. Chem. B 2010, 114, 2383–2389. (20) Rosenfeld, D. E.; Gengeliczki, Z.; Fayer, M. D. Solvent Control of the Soft Angular Potential in Hydroxyl
π Hydrogen Bonds: Inertial Orientational Dynamics. J. Phys. Chem. B 2009, 113, 13300–13307. (21) Feller, D. Strength of the Benzene
Water Hydrogen Bond. J. Phys. Chem. A 1999, 103, 7558–7561. (22) Slipchenko, L. V.; Gordon, M. S. Water
Benzene Interactions: An Effective Fragment Potential and Correlated Quantum Chemistry Study. J. Phys. Chem. A 2009, 113, 2092–2102. (23) Prakash, M.; Samy, K. G.; Subramanian, V. Benzene
Water (BZWn (n = 1
10)) Clusters. J. Phys. Chem. A 2009, 113, 13845–13852. (24) Raschke, T. M.; Levitt, M. Nonpolar Solutes Enhance Water Structure within Hydration Shells While Reducing Interactions between Them. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 6777–6782. (25) Schravendijk, P.; van der Vegt, N. F. A. From Hydrophobic to Hydrophilic Solvation: An Application to Hydration of Benzene. J. Chem. Theory Comput. 2005, 1, 643–652. (26) Allesch, M.; Lightstone, F. C.; Schwegler, E.; Galli, G. First Principles and Classical Molecular Dynamics Simulations of Solvated Benzene. J. Chem. Phys. 2008, 128. (27) Allesch, M.; Schwegler, E.; Galli, G. Structure of Hydrophobic Hydration of Benzene and Hexafluorobenzene from First Principles. J. Phys. Chem. B 2007, 111, 1081–1089. (28) Perera, P.; Wyche, M.; Loethen, Y.; Ben-Amotz, D. SoluteInduced Perturbations of Solvent-Shell Molecules Observed Using Multivariate Raman Curve Resolution. J. Am. Chem. Soc. 2008, 130, 4576–4579. (29) Perera, P. N.; Fega, K. R.; Lawrence, C.; Sundstrom, E. J.; Tomlinson-Phillips, J.; Ben-Amotz, D. Observation of Water Dangling OH Bonds around Dissolved Nonpolar Groups. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 12230–12234. (30) Pribble, R. N.; Zwier, T. S. Size-Specific Infrared-Spectra of Benzene-(H2O)n Clusters (n = 1 through 7): Evidence for Noncyclic (H2O)n Structures. Science 1994, 265, 75–79. (31) Mons, M.; Dimicoli, I.; Piuzzi, F. Gas Phase Hydrogen-Bonded Complexes of Aromatic Molecules: Photoionization and Energetics. Int. Rev. Phys. Chem. 2002, 21, 101–135.