and Intermolecular Hydrogen Bonding - American Chemical Society

Ind. Eng. Chem. Res. 2000, 39, 463-472

463

Competition between Intra- and Intermolecular Hydrogen Bonding: Effect on para/ortho Adsorptive Selectivity for Substituted Phenols Amy Jo Glemza,† Kristy L. Mardis,‡ Asiya A. Chaudhry,† Michael K. Gilson,‡ and Gregory F. Payne*,†,§ Department of Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, Center for Advanced Research in Biotechnology, National Institute of Standards and Technology, 9600 Gudelsky Drive, Rockville, Maryland 20850, and Center for Agricultural Biotechnology, University of Maryland Biotechnology Institute, 6138 Plant Sciences Building, College Park, Maryland 20742

This study examines the molecular basis for para/ortho selectivity in the adsorption of two phenol derivatives from a nonpolar solvent onto an acrylic ester sorbent. Experimental results show that p-methyl hydroxybenzoate (p-MHB) and p-hydroxyacetophenone (p-HAP) adsorb with a 400-fold higher affinity than their ortho isomers. The adsorption results are interpreted using infrared spectroscopy, free energy calculations, and ab initio calculations using the small molecule ethyl propionate (EP) as an analogue of the hydrogen bond accepting site of the acrylic ester sorbent. Free energy calculations show that p-MHB and p-HAP bind to EP primarily via an intermolecular hydrogen bond to the carbonyl oxygen of EP. In contrast, o-MHB and o-HAP possess strong intramolecular hydrogen bonds that are retained upon complexation with EP. As a consequence, complexation between the ortho isomers and EP involves not intermolecular hydrogen bonding but other, weaker interactions. Although the free energy calculations reveal the mechanism for para/ortho selectivity, they do not reproduce the magnitude of these selectivities because of an underestimation of the para isomer binding affinities. Ab initio calculations suggest that part of this underestimation is due to a failure of the force field to adequately account for substituent effects. Overall, the results from this study indicate that competing intramolecular hydrogen-bonding interactions prevent intermolecular (i.e., adsorptive) hydrogen bonding for the ortho isomers and account, at least in part, for the observed para/ ortho selectivity. Introduction Hydrogen bonding substantially affects phase equilibrium and there is considerable current interest in relating microscopic hydrogen-bonding behavior to macroscopic phase behavior.1-8 In particular, hydrogen bonding can be an important mechanism in the adsorption of polar compounds from nonpolar phases onto polar surfaces.9-11 If hydrogen-bonding adsorptive interactions can be understood at the molecular level, then it should be possible to better exploit these interactions to confer selectivity in adsorptive separations. Indeed, hydrogen bonding is well-recognized for its ability to confer selectivity to interactions in biological and supramolecular systems.12-15 To understand how hydrogen bonding can be exploited for adsorptive separations, we have been examining the adsorption of various solutes from a nonpolar solvent onto an acrylic ester sorbent (XAD-7, Rohm and Haas) as illustrated in Figure 1. The carbonyl oxygens of the acrylic ester sorbent are strong hydrogen-bond acceptors and earlier studies provided phenomenological evidence that hydrogen bonding is the primary mechanism for the adsorption of solutes capable of hydrogenbond donation to these sites.16,17 Unfortunately, it is * To whom correspondence should be addressed. Phone: 301-405-8389.Fax: 301-314-9075.E-mail: [email protected]. † University of Maryland Baltimore County. ‡ National Institute of Standards and Technology. § University of Maryland Biotechnology Institute.

difficult to obtain direct mechanistic information on adsorptive hydrogen bonding because the spectroscopic and computational methods that provide such information are not readily applied to the study of adsorption from solution. One approach to overcome this difficulty is to use a small-molecule analogue of the sorbent surface and to apply spectroscopic and computational methods to study binding between the solute and the small molecule analogue.18-21 We have used ethyl propionate (EP) as a hexane-soluble analogue of the acrylic ester surface. The validity of this small-molecule analogue was investigated for a series of phenolic solutes. We observed a correlation between the affinity of a solute for the acrylic ester sorbent and the infrared (IR) frequency shift (∆νOH) for the solute:EP hydrogenbonded complex.22 This correlation suggests that EP is a good analogue for the adsorptive hydrogen-bonding mechanism. More recently, we have examined hydrogen bonding for the adsorptive separation of the para and ortho isomers of methoxyphenol onto the acrylic ester sorbent.23 We found that p-methoxyphenol is preferentially adsorbed from hexane with separation factors (Rpara-ortho) exceeding 15. IR studies indicated the following: (i) o-methoxyphenol exists in hexane solutions primarily as an intramolecularly hydrogen-bonded species; (ii) p-methoxyphenol forms a strong intermolecular hydrogen bond with EP; and (iii) intermolecular hydrogen bonding between o-methoxyphenol and EP is considerably less favorable. On the basis of these results, we

10.1021/ie990594i CCC: $19.00 © 2000 American Chemical Society Published on Web 01/15/2000

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Ind. Eng. Chem. Res., Vol. 39, No. 2, 2000

Figure 1. Competition between intra- and intermolecular hydrogen bonding for o-methoxyphenol in a hexane solvent. The upper path illustrates the two-centered intermolecular hydrogen-bonding mechanism initially proposed based on adsorption and IR results.23 The lower path illustrates the three-centered hydrogen-bonding mechanism proposed from subsequent molecular modeling studies.24 The hatched area represents the acrylic ester sorbent while the bolded section represents the soluble analogue of the sorbent, ethyl propionate (EP), which was used in IR and molecular modeling studies.

envisioned that the adsorption of o-methoxyphenol required the breakage of the intramolecular hydrogen bond and the formation of a two-centered intermolecular hydrogen bond, as illustrated by the upper path in Figure 1. We reasoned that this competition between intramolecular and intermolecular hydrogen bonding suppresses the adsorption of o-methoxyphenol and leads to the preferential adsorption of its para isomer. Molecular mechanics calculations24 largely support this interpretation, although they suggest that the intramolecular hydrogen bond of o-methoxyphenol is not broken during adsorption and that intra- and intermolecular hydrogen bonding can occur simultaneously. This mechanism is illustrated by the lower path in Figure 1. Quantum mechanical calculations also indicate that the location of the OH stretching peak in the IR spectrum would be similar for the two-centered and three-centered hydrogen bonds, which implies that our IR results cannot discriminate between the two possibilities in Figure 1. The present studies were initiated to determine whether our observations on the competition between intramolecular and intermolecular hydrogen bonding could be generalized to other isomer systems. We therefore studied the ortho and para isomers of methyl hydroxybenzoate (MHB) and hydroxyacetophenone (HAP). Berthelot and co-workers25,26 reported that, in a nonpolar solvent, o-MHB (I) and o-HAP (II) form six-

membered intramolecular hydrogen-bonded rings as shown below, and that these six-membered rings are

more stable than the five-membered rings formed by o-methoxyphenol (III). If strong intramolecular hydrogen bonds are formed for o-MHB and o-HAP, then we expect adsorption of these isomers onto the acrylic ester sorbent to be suppressed relative to their para isomers. Moreover, this suppression is expected to be greater than that of o-methoxyphenol and thus we expect greater para/ortho selectivities for the MHB and HAP isomers. The present study uses a combination of modeling and experiment to test these expectations, and to develop a deeper understanding of the role of intramolecular hydrogen bonding on para/ortho selectivity. Computational Procedures Molecular Mechanics. Free energy calculations were used to determine the lowest energy conformations for the ortho and para isomers of MHB and HAP in hexane and to estimate the adsorptive binding equilibrium for each of the isomers. For binding calculations, the small molecule ethyl propionate (EP) was used in place of the solid acrylic ester sorbent. Previous spectroscopic and modeling studies indicate that the ester group of EP provides a reasonable analogue to the hydrogen bond accepting site of the acrylic ester sorbent.22-24 Table 1 outlines the molecular modeling procedure used to compute the binding constants (KB) and binding free energies (∆G°Β) for the MHB:EP and HAP:EP complexes. Further details of the modeling are reported elsewhere.24 Equation 1 shows the relationship between KB and ∆G°Β, while eq 2 relates ∆G°Β to the standard chemical potentials of the free and complexed species. Equation 3 is the classical statistical thermodynamic relationship between the chemical potential and atomiclevel interactions.27,28 In eq 3, C0 is the standard

Ind. Eng. Chem. Res., Vol. 39, No. 2, 2000 465 Table 1. Model Equations °

binding constant binding free energy change chemical potential of species xa

KB ) e(-∆GB/RT) ° ∆G°B ) µS:EP - µ°S - µ°EP 8π2 µ°x ) -RT ln Z C°σ

configuration integral

Z)

potential energy solvation energy solvation energy approximation approximate configuration integral of energy well i approximate chemical potential of energy well i from Monte Carlo integration corrected chemical potential of energy well i chemical potential as sum over all N energy wells

∫e

(1) (2)

( )

-(U(r)+∆Gsolv(r))/RT

all

(3)

dr

(4)

U(r) ) Ubond(b) + Uangle(θ) + Udihedral(O) + Uelec(r) + UvdW(r) ∆Gsolv(r) ) ∆GNP(r) + ∆Gelec(r) ∆Gsolv,app(r) ) ∆Gelec,GB(r) ) Zapp i

∫e

-(U(r)+∆Gsolv,app(r))/RT

i

µ°i )

)

dr

8π app Z C°σ c NP + ∆G (ri) + ∆Gelec,FD(ri) - ∆Gelec,GB(ri)

µapp ) -RT ln i µapp i

(

2

(5) (6) (7) (8) (9) (10)

N

µ°x

) -RT ln(

∑e

-µi°/RT

)

(11)

i)1

a

Species x refers to the solute (S), ethyl propionate (EP), or solute:EP complex (S:EP).

Table 2. Atomic Charge Parametersa Used in Molecular Modeling Studies chemical group

atom

charge (electrons)b

aromatic -C-O-H

-C-O-H -C-H -CdO dC-C-H dO dC-O-C-H

0.11 -0.54 0.43 -0.115 0.115 0.00 -0.52 0.52 -0.27 0.09 -0.52 0.63 -0.34 -0.14 0.09

aromatic -C-H aromatic -C-CdO OdC-CH3

OdC-O-CH3

a Charges assigned from CHARMm 26.29 × 10-19 C.

b

One electron ) 1.602

concentration (1 mol/L), σ is the symmetry number of the molecule, and Z is the configuration integral.28 It should be noted that P0V contributions to the chemical potential are omitted because they are expected to be negligible under the conditions studied,28 and a mass factor has not been included in our calculation because it will cancel when determining ∆G°Β. As shown in eq 4, the Boltzmann factor in the configuration integral includes two energy contributions: the gas-phase potential energy U(r) and the solvation energy ∆Gsolv(r). Both energy terms depend on r, the set of internal coordinates that specify conformation. The gas-phase potential energy for each molecular conformation is computed using eq 5 which consists of bonding and nonbonding terms. The bonding interactions account for energies associated with bond stretching (Ubond(b)), bond bending (Uangle(θ)), and bond rotation (Udihedral(O)). The nonbonding interactions account for electrostatic (Uelec(r)) and van der Waals (UvdW(r)) interactions. Equation 5 was evaluated using the CHARMm2629 force field with the all hydrogen representation. Table 2 shows the charges assigned to all atoms. The EP force constants and charges were taken from the ethyl acetate parameters included in the September 1998 release.30 The MHB and HAP force constants and charges were taken from CHARMm 26. The solvation energy is evaluated by considering a two-step solvation process as suggested by eq 6. The first

step is the formation of a Lennard-Jones cavity in the solvent to accommodate the solute. The nonpolar energy associated with this first step is designated ∆GNP(r). The nonpolar term (∆GNP(r)) is approximated as being linearly related to the solvent-accessible surface area with a coefficient of -69.87 J/(mol Å2) and an offset of -20.46 kJ/mol as obtained through a fit of recent experimental data.31 While the physical reason for this large offset is unknown, it is similar to offsets determined for other nonpolar solvents.32 Because it is applied to both ortho and para isomers, it has no effect on the relative binding affinities discussed here. Because calculation of ∆GNP(r) for each conformation is computationally intensive, this term is omitted in evaluating the configuration integral and then accounted for in a later stage of the calculation. The second solvation step is the electrostatic charging of the atomic partial charges within the cavity, and the energy associated with this step is designated ∆Gelec(r). The most accurate method for evaluating ∆Gelec(r) is to numerically solve the Poisson equation using a detailed finite difference method.33,34 However, such a calculation is too computationally intensive for analysis of each conformation that must be sampled in evaluating the configuration integral of eq 8. Therefore, ∆Gelec(r) is evaluated using a computationally rapid generalized Born (GB) approximation35,36 in which the effective Born radius of each atom is computed via a charge-induced dipole interaction term.37 Again, corrections between the finite difference Poisson approach (∆Gelec,FD(r)) and the generalized Born approach (∆Gelec,GB(r)) are made at a later stage of the calculations. The solvent dielectric constant is set to that of hexane, 1.89. The cavity radius of each atom is set to the average of the solvent probe radius and the atom’s van der Waals radius from the CHARMm force field. The probe radius of hexane is taken to be 2.0 Å. Equation 8 is evaluated using the Mining Minima38 algorithm which is implemented in a local version of UHBD.39 This algorithm finds energy wells, maps out the extent of these energy wells (i.e., the well’s depth and width), and performs the integration of eq 8 for the various conformations associated with each energy well. Integration of eq 8 for the ith energy well yields Zapp i . The approximate chemical potential for the ith energy well (µapp i ) is calculated from eq 9. The “app” in eqs 8 and 9 indicates the use of the approximate solvation

466


energy of eq 7. The chemical potential for the ith energy well (µ°i ) is then determined from eq 10 which shows is corrected for the approximations used for that µapp i evaluating the solvation energy. For the nonpolar term, the solvent accessible area is calculated only for the minimum energy conformation for each well (i.e., all conformations within an energy well were assumed to have the same solvent-accessible surface area). Corrections for the generalized Born approximation of ∆Gelec,GB(r) were also performed as indicated in eq 10. For this correction, a reference electrostatic solvation energy was calculated using a detailed finite difference solution to the Poisson equation (∆Gelec,FD(r)). This calculation was only performed for the minimum energy conformation for each energy well (i.e., it was assumed that the correction was the same for each conformation within an energy well). The electrostatic solvation energy calculated from the generalized Born approximation, ∆Gelec,GB(ri), was then subtracted from ∆Gelec,FD(ri) and this difference (∆Gelec,FD(ri) - ∆Gelec,GB(ri)) was used as a correction for all conformations within the potential energy well. Finally, the chemical potential of species “x” is approximated as a sum of the free energy contributions from the N individual energy wells as shown in eq 11.32 Quantum Mechanics. Ab initio calculations were used to estimate the strength of the intramolecular hydrogen bond for o-MHB, o-HAP, and o-methoxyphenol, and to consider substituent effects on hydrogen bonding. Gas-phase potential energies were calculated using GAMESS40 at the restricted Hartree-Fock level with the 6-G31(d,p) basis set and MP2 corrections. Experimental Methods and Data Analysis The ortho and para isomers of hydroxyacetophenone (HAP) and methyl hydroxybenzoate (MHB) were obtained from Aldrich (Milwaukee, WI). The sorbent was Rohm and Haas XAD-7, an acrylic ester macroporous polymer with a specific surface area reported by the supplier (Sigma Chemical Co.) to be ≈450 m2/g. The sorbent was sequentially washed with water, methanol, acetone, and hexane and vacuum-dried prior to use. Adsorption. Adsorption studies were conducted by equilibrating known amounts of sorbent with hexane solutions containing a single solute. The equilibrated concentration (C) for each single solute was obtained by measuring the absorbance using UV-visible spectrophotometry (Spectronic Genesys 2). The adsorbed amount of solute (q) was determined by calculating the difference between the initial (Cinit) and equilibrated concentration of solute in hexane by

q)

(Cinit - C)V M

(12)

where V is the volume of hexane and M is the mass of the sorbent. Ideally, comparisons between modeling and experiment would be based on the equilibrium binding constants. Such a comparison would require an experimental determination of the adsorption equilibrium constant, K:

[AdsorbedSolute] K) [DissolvedSolute][AvailableBindingSites]

(13)

Determination of K requires information on qmax, the

total number of adsorption sites per gram of sorbent, but assessing qmax can be problematic both experimentally and conceptually. Determination of qmax from elemental analysis of the sorbent requires an assumption that all carbonyl sites are equally accessible for adsorption, while determination of qmax from adsorption studies is ambiguous for systems in which multilayer adsorption is possible. For p-MHB and p-HAP adsorption, the formation of an intermolecular hydrogen bond is expected to “consume” one carbonyl site on the sorbent surface. However, adsorbed MHB and HAP also have carbonyl groups that could serve as secondary adsorption sites for multilayer adsorption. In addition to complexities in determining qmax, it is not clear if, or how much, K varies as a function of surface coverage due either to geometric heterogeneities of the sorbent or steric effects imposed by occupation of neighboring surface sites. To avoid such complexities in previous studies, we focused on the low-concentration regime where the isotherm was linear and we correlated our data in terms of the adsorption affinity (q/C) and not the equilibrium constant (K).16,17,22-24 From eq 13, it can be seen that (q/C) in the linear region of the isotherm simplifies to

q ) Kqmax C

(14)

where qmax is the adsorption capacity (mmol/g). Thus, in the low-concentration region, the parameters K and qmax can be evaluated as a single, lumped parameter. The ortho isomers adsorbed onto the acrylic ester sorbent with low affinities. As a result, there was no difficulty confining studies to the linear region of the isotherms. The adsorption affinity (q/C) for the ortho isomers was thus determined from the slope of the best fit line passing through the origin. The isotherms for the para isomers were observed to be nonlinear. The reason for this nonlinearity was not studied but could result because the high-adsorption affinities lead to high fractional coverages, even at low solution-phase concentrations (i.e., adsorption approaches saturation even at low solution-phase concentrations). Alternatively, isotherm curvature could result if the para isomers undergo solution-phase self-association interactions (i.e., dimerization) that compete with adsorption. To evaluate the adsorption affinity (q/C) at the low solute concentration regime (i.e., to evaluate Kqmax), the experimental data for para isomer adsorption was first fit to a Langmuir adsorption model:

q)

qmaxC 1 +C K

(15)

The Langmuir model was selected because it is a simple two-parameter model widely used for fitting adsorption data, and it provided a reasonable fit for the adsorption of the para isomers. From this fit, K and qmax were calculated, and the affinity in the low-concentration regime was determined by

qmax q ) Kqmax ) lim C Cf0 1 +C K

(16)

For p-MHB, adsorption data were collected at five different temperatures and the Langmuir model was fit

Ind. Eng. Chem. Res., Vol. 39, No. 2, 2000 467

affinity than its ortho isomer. The para/ortho adsorptive selectivity, defined as the ratio of affinities ((q/C)para/ (q/C)ortho), exceeds 400 for both the MHB and HAP isomer systems. As shown in Table 3, these adsorptive selectivities are an order of magnitude higher than that previously observed for the methoxyphenol isomers. These observed para/ortho selectivities are consistent with the expectation that the adsorption of o-MHB and o-HAP would be suppressed relative to their para isomers and that this suppression would be greater than that of o-methoxyphenol. However, Table 3 shows that the increased para/ortho selectivities for MHB and HAP result primarily from the increased adsorption of their para isomers and to a lesser extent from the suppression in the adsorption of their ortho isomers. This is illustrated by considering the 20-fold increased para/ortho selectivity of HAP adsorption relative to methoxyphenol:

SelectivityRatio )

[ ][ ] (Cq ) (Cq )

p-HAP

o-HAP

(/ Cq ) (Cq )

p-Methoxy

)

o-Methoxy

460/19 ≈ 20

This 20-fold increase results from a 10-fold higher affinity for adsorption of the para isomer and only a 2-fold reduction in affinity for o-HAP adsorption:

SelectivityRatio ) Figure 2. Adsorption of ortho and para isomers from hexane onto the acrylic ester sorbent for (a) methyl hydroxybenzoate (MHB) and (b) hydroxyacetophenone (HAP). The adsorption affinities (q/ C) are reported in units of (mmol adsorbed per g of sorbent)/(mmol dissolved per L of solution). Adsorption temperature was 25 °C.

assuming qmax to be independent of temperature. From this fit, qmax for p-MHB was calculated to be 0.20 mmol/ g. Adsorption of p-HAP was studied at 25 °C and the fitted value of qmax for this temperature was determined to be 0.43 mmol/g. The adsorption enthalpies (∆H°) for the MHB isomers were also estimated from the temperature dependence of the adsorption affinities:

∂ ln K ∂ ln Kqmax ∆H° ) )R ∂(1/T) ∂(1/T)

(17)

Spectroscopy. In the Fourier transform infrared (FTIR) spectroscopy studies, MHB and HAP spectra were obtained using a Nicolet Instrument Corporation 5DXC FTIR spectrometer. The spectrometer has a resolution of 4 cm-1, and the spectral data was obtained using KBr windows and a 0.762-mm spacer. Because of C-H stretching interference by hexane in one of the spectral regions of interest (3000-3200 cm-1) and low solubility of the para isomers, we used an alternative nonpolar solvent, carbon tetrachloride, to obtain all spectra. Signal-to-noise ratios were enhanced by averaging the spectra over 32 scans. Results and Discussion Adsorption Measurements. The adsorption isotherms for o-MHB and p-MHB are shown in Figure 2a and demonstrate that the para isomer has a much higher adsorption affinity than o-MHB. Similarly, Figure 2b shows that p-HAP has a much higher adsorption

[ ][ ] (Cq ) (Cq )

p-HAP

p-Methoxy

(Cq ) (Cq )

o-Methoxy

)

o-HAP

13 × 1.9 ≈ 20

The increased affinity for p-MHB and p-HAP adsorption may result in part from the electron-withdrawing characteristics of their substituents which are expected to enhance their hydrogen-bonding abilities relative to that of p-methoxyphenol.22 Additionally, the affinity of p-MHB and p-HAP adsorption may be enhanced if their polar substituents can interact favorably with the sorbent at the same time as their hydroxyl groups form an intermolecular hydrogen bond. Indeed, previous studies indicate that solutes that cannot hydrogen bond can nonetheless adsorb onto the acrylic ester sorbent through polar interactions.17 However, there is insufficient information about the sorbent surface geometry to assess whether a single solute could interact with multiple sites simultaneously. For completeness the adsorption equilibria for the MHB isomers were measured over a range of temperatures and the adsorption enthalpies were determined as described in the Methods section. Figure 3a shows the linear isotherms for o-MHB and ∆H° for adsorption of this isomer was calculated to be -21 kJ/mol. Figure 3b shows the experimental data and the fitted Langmuir isotherms for p-MHB adsorption. The enthalpy estimated for p-MHB adsorption is -49 kJ/mol, which is considerably more negative than ∆H° for o-MHB adsorption. This observation is similar to the previous observation that p-methoxyphenol adsorbs with a more negative enthalpy than its ortho isomer.23 Intramolecular Hydrogen Bonding. To confirm that the ortho isomers of MHB and HAP form an intramolecular hydrogen bond, we obtained infrared spectra for each of the isomer systems in carbon tetrachloride. As shown in Figure 4a, the spectrum for

468


Table 3. Comparison of Adsorption with Computed Binding methyl hydroxybenzoate (MHB) (q/C)para (q/C)ortho (q/C)para/(q/C)ortho KB,para KB,ortho KB,para/KB,ortho a

hydroxy-acetophenone (HAP)

Experimentally Observed Binding with Acrylic Ester Sorbent 5.7 9.7 0.013 0.021 440 460 Computed Binding with Ethyl Propionate 76 64 3.4 5.2 22 12

methoxyphenola 0.75 0.039 19 39 2.8 14

Observed binding from ref 23 and computed binding from ref 24.

Figure 3. Adsorption isotherms at various temperatures for (a) o-methyl hydroxybenzoate (MHB) and (b) p-MHB. Solid lines represent the best fit straight lines for o-MHB and the best fit to a Langmuir model for p-MHB (qmax ) 0.20 mmol/g). Adsorption enthalpies were estimated from the temperature dependence of the adsorption equilibria.

p-MHB has a peak at 3602 cm-1 which is assigned to OH stretching for a non-hydrogen-bonded species. The spectrum for o-MHB does not have a peak in the 3600cm-1 region, but it has a broader peak at a considerably lower frequency of 3197 cm-1 which is consistent with an intramolecular hydrogen-bonded species. The IR results for the HAP isomers, shown in Figure 4b, are similar to those obtained for MHB. The para isomer has a peak at 3600 cm-1 which is indicative of a nonhydrogen-bonded OH stretch, while the ortho isomer spectrum lacks this peak, instead displaying a broad peak near 3100 cm-1. These results are in agreement with those of Berthelot and co-workers25,26 and indicate that the ortho isomers of MHB and HAP exist primarily as intramolecular hydrogen-bonded species. Intramolecular hydrogen bonding for o-MHB and o-HAP was further supported by molecular modeling. Specifically, the minimum energy conformations obtained by the

Figure 4. Infrared spectra of (a) o-MHB and p-MHB and (b) o-HAP and p-HAP. All spectra were collected at 22 °C using isomer concentrations of 12 mM in carbon tetrachloride.

Mining Minima algorithm indicate that both ortho isomers prefer to form an intramolecular hydrogen bond in nonpolar solvents. To test our expectation that the intramolecular hydrogen bond strength is greater for o-MHB and o-HAP than for o-methoxyphenol, we used ab initio methods to compute the difference in potential energy between the cis and trans conformations (see structures below)

of each of the ortho isomers. Only the cis conformations can form intramolecular hydrogen bonds, so these energy differences are measures of the strength of the intramolecular hydrogen bond.41 For the trans conformation, calculations were done with the R substituents


Figure 5. Minimum energy conformations for the p-MHB:EP and p-HAP:EP complexes. The dashed lines indicate intermolecular hydrogen bonds between each isomer’s hydroxyl hydrogen and EP’s carbonyl oxygen.

in both of their possible rotomer positions, and the reported hydrogen bond energies are based upon the most stable of these two trans conformations. The ∆E’s ()Ecis - Etrans) obtained from these quantum calculations for o-methoxyphenol, o-HAP, and o-MHB are -21, -32, and -44 kJ/mol, respectively. These calculations indicate that o-HAP and o-MHB form considerably stronger intramolecular hydrogen bonds than o-methoxyphenol. Molecular Modeling: Mechanism of Binding to Ethyl Propionate (EP). To examine the mechanism of adsorptive binding, we identified the minimum energy conformations of the MHB and HAP isomers bound to ethyl propionate (EP), the soluble analogue of the sorbent. In the lowest energy conformations for the p-MHB:EP and p-HAP:EP complexes (Figure 5), the hydroxyl hydrogen of the para isomers forms an intermolecular hydrogen bond with the carbonyl oxygen of EP. The intermolecular hydrogen bond distances for these minimum energy complexes are 1.76 and 1.77 Å for p-MHB:EP and p-HAP:EP, respectively. The intermolecular bond angles (i.e., OH‚‚‚O angle) are 174° for the p-MHB:EP complex and 171° for the p-HAP:EP complex. These distances and angles are consistent with the formation of moderately strong intermolecular hydrogen bonds.42 To further assess the role of hydrogen bonding in the p-isomer:EP complexes, we examined the energy wells that had been identified by the Mining Minima algorithm (see ref 38 for details of the Mining Minima algorithm). The chemical potential associated with the ° ) was computed ith energy well of the complex (µi,S:EP using eq 10 in Table 1. The stability of the ith energy well was then determined as the difference between ° and the chemical potentials of the uncomplexed µi,S:EP species (µ°S and µ°EP) where µ°S and µ°EP were determined from eq 11 in Table 1. Figure 6a shows the stabilities ° - (µ°S + µ°EP), as a for the various energy wells, µi,S:EP function of the hydrogen bond distance (i.e., the distance

Figure 6. Stability of various energy wells for p-MHB:EP and o-MHB:EP complexation. (a) Stability as a function of intermolecular hydrogen bond distance between the isomer’s hydroxyl hydrogen and the carbonyl oxygen of EP (OH...O). (b) Stability as a function of intermolecular hydrogen bond angle (OH...O). Stabil° - (µ°S + µ°EP)]. ity of the ith energy well is calculated as [µi,S:EP

between the hydroxyl hydrogen of the para isomer and the carbonyl oxygen of EP) for the minimum energy conformation of each energy well. It is evident that the majority of the low-energy conformations for the pMHB:EP complexes have intermolecular hydrogen bonds with bond distances less than 2.0 Å. The OH‚‚‚O angles for the same low-energy conformations are shown in Figure 6b. All of the intermolecular hydrogen bonds in the p-MHB:EP complexes are nearly linear, with an average OH‚‚‚O angle of 170°. Data for p-HAP:EP complexation were not shown for reasons of clarity but the results were similar to those for p-MHB:EP complexation. The above results indicate that the dominant binding mechanism for the p-isomer:EP complexation is the formation of an intermolecular hydrogen bond between the hydroxyl hydrogen of the para isomers and the carbonyl oxygen of EP. Free energy calculations were also used to examine hydrogen-bonding interactions for the ortho isomers. Figure 7 shows the minimum energy conformations for o-MHB:EP and o-HAP:EP complexes. Here, the intramolecular hydrogen bonds for both ortho isomers are retained upon complexation with EP. Moreover, complexation with EP has almost no effect on the geometry of these intramolecular hydrogen bonds. Neither of the minimum energy conformations of the ortho isomer:EP complexes have an intermolecular hydrogen bond. The computed distances between the ortho isomers’ hydroxyl hydrogen and the carbonyl oxygen of EP exceed 4.4 Å for both the o-isomer:EP complexes while the computed

470


Figure 7. Minimum energy conformations for the o-MHB:EP and o-HAP:EP complexes. The dashed lines indicate intramolecular hydrogen bonds between each isomer’s hydroxyl hydrogen and carbonyl oxygen.

OH‚‚‚O angles are both about 95°. In fact, in none of the energy wells examined did o-isomer:EP complexes form intermolecular hydrogen bonds. Figure 6a shows the stability of various o-MHB:EP energy wells as a function of the intermolecular hydrogen bond distance. For all of these low-energy conformations, the distance between the hydroxyl hydrogen and the carbonyl oxygen of the EP exceeds 3 Å which is too long for hydrogen bonding. In addition, the OH‚‚‚O (intermolecular) hydrogen bond angles for the o-MHB:EP complexes shown in Figure 6b are all less than 115° which is smaller than the range of 155°-180° typically associated with intermolecular hydrogen bonding. Again, o-HAP:EP data is not shown but the results are similar to those for o-MHB:EP. In summary, molecular modeling supports the conclusion that intramolecular hydrogen bonding of the ortho isomers competes with and suppresses intermolecular hydrogen bonding with EP. Table 3 shows the computed binding constants (KB) for complexes of the various isomers with EP. The calculations indicate that the para isomers bind more favorably than their ortho isomers. As discussed, this para/ortho selectivity results from the ability of para isomers to form strong intermolecular hydrogen bonds while intramolecular hydrogen bonding of the ortho isomers prevents intermolecular hydrogen bonding. Comparison of Adsorption and Modeling: Evaluation of EP as a Sorbent Analogue. The calculations

in the previous section examined the binding of the substituted phenols to ethyl propionate (EP). EP is believed to be a good analogue for the hydrogen-bonding site of the sorbent because it contains an ester group. In addition, EP contains nonpolar groups similar to those in the sorbent. Thus, it is of interest to compare relative values of the computed binding constants (KB) for phenol:EP complexes with observed adsorption affinities (q/C) for the phenols to the sorbent. As mentioned, the para-substituted phenols are calculated to bind more tightly to EP than the ortho isomers. This is in agreement with the observed para/ortho adsorption selectivities. However, the calculated para/ortho selectivity for EP is much smaller than the observed adsorption selectivity for MHB and HAP. This difference is largely traceable to differences in the para isomer binding affinities for EP compared to the sorbent. Table 3 shows that the observed affinities for p-MHB and p-HAP adsorption are about 10 times greater than that for p-methoxyphenol adsorption. However, the computed KB’s for the para isomer EP complexes vary by less than a factor of 2. One source for discrepancies between experiment and calculations could be an inadequate treatment of substituent effects on the hydroxyl force field parameters.22 For all three phenols in this study, we used the hydroxyl force field parameters for phenol. This is despite the greater electron-withdrawing nature of a carbonyl group which is expected to endow p-HAP and p-MHB with greater hydrogen-bond-donating abilities than p-methoxyphenol. Ab initio calculations, which account for substituent effects, show that a hydrogen bond between p-HAP and the carbonyl oxygen of formaldehyde is 2.5 kJ/mol stronger than a hydrogen bond between pmethoxyphenol and formaldehyde. Thus, the failure to include substituent effects contributes, at least in part, to the discrepancy between observed adsorption and computed EP binding. Another possible cause of the disagreement between the experimental and computational affinities for paraisomer binding may be the limitations of EP as an analogue for the acrylic ester sorbent. Previous studies have shown that EP is a reasonable analogue for the sorbent’s hydrogen-bond-accepting site.22-24 However, it is possible that the para substituent of an adsorbed phenolic may interact with the sorbent surface in ways that are not possible to simulate using a single EP molecule. It is impossible to further assess this possibility due to the lack of a detailed understanding of the sorbent surface geometry. A final cause for the discrepancies between observed and calculated para/ortho selectivities could be that EP is not an adequate analogue for weak, non-hydrogenbonding interactions. Because intramolecular hydrogen bonding of o-MHB and o-HAP appears to completely prevent intermolecular hydrogen bonding with the sorbent, then adsorption of these ortho isomers appears to result from non-hydrogen-bonding interactions. EP has not been adequately tested to determine its ability to serve as an analogue for low-energy, non-hydrogenbonding interaction mechanisms. Conclusions This study has investigated the mechanism of adsorption of para and ortho isomers of MHB and HAP from a nonpolar solvent onto the acrylic ester sorbent, XAD7. Conformational studies indicate that for both p-MHB


and p-HAP, hydrogen bonding is the predominant interaction mechanism for complexation with ethyl propionate (EP) and thus, by analogy, with the chemically similar acrylic ester sorbent. However, this mechanism is not available for binding of the ortho isomers because o-MHB and o-HAP form strong intramolecular hydrogen bonds. Free energy calculations indicate that these intramolecular hydrogen bonds are retained upon complexation with EP, and that none of the low-energy conformations of o-MHB:EP and o-HAP:EP form intermolecular hydrogen bonds. Additionally, free energy calculations with the EP analogue correctly predict high para/ortho selectivities for MHB and HAP binding, although the magnitudes of these selectivities differ somewhat from experiment. Thus, the results from modeling and experiment show a high para/ortho selectivity for MHB and HAP binding which can be explained, at least in part, by a competition between inter- and intramolecular hydrogen bonding for the ortho isomers. Acknowledgment This work was supported by the National Institute of Standards and Technology, the United States Department of Agriculture (Grant 98-35504-6357), and the National Science Foundation (CTS-9531812). K.L.M. was supported by a National Research Council Research Associateship. Certain commercial equipment and materials are identified in this paper to specify the methods adequately. Such identification does not imply recommendation or endorsement by the National Institutes of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. Literature Cited (1) Tamada, J. A.; King, C. J. Extraction of Carboxylic Acids with Amine Extractants. 2. Chemical Interactions and Interpretation of Data. Ind. Eng. Chem. Res. 1990, 29, 1327. (2) Wolbach, J. P.; Sandler, S. I. Thermodynamics of Hydrogen Bonding from Molecular Orbital Theory: 1. Water. AIChE J. 1997, 43, 1589. (3) Wolbach, J. P.; Sandler, S. I. Thermodynamics of Hydrogen Bonding from Molecular Orbital Theory: 1. Organics. AIChE J. 1997, 43, 1597. (4) Wolbach, J. P.; Sandler, S. I. Using Molecular Orbital Calculations to Describe the Phase Behavior of Hydrogen-Bonding Fluids. Ind. Eng. Chem. Res. 1997, 36, 4041. (5) Wolbach, J. P.; Sandler, S. I. Using Molecular Orbital Calculations to Describe the Phase Behavior of Cross-associating Mixtures. Ind. Eng. Chem. Res. 1998, 37, 2917. (6) Sum, A. K.; Sandler, S. I. A Novel Approach to Phase Equilibria Predictions Using Ab Initio Methods. Ind. Eng. Chem. Res. 1999, 38, 2849. (7) Brinkley, R. L.; Gupta, R. B. Intra- and Intermolecular Hydrogen Bonding of 2-Methoxyethanol and 2-Butoxyethanol in n-Hexane. Ind. Eng. Chem. Res. 1998, 37, 4823. (8) Hancu, D.; Beckman, E. J. Production of Hydrogen Peroxide in Liquid CO2. 1. Design, Synthesis, and Phase Behavior of CO2Miscible Anthraquinones. Ind. Eng. Chem. Res. 1999, 38, 2824. (9) Stoeckli, F.; Huguenin, D. Water Adsorption in Active Carbon Characterized by Adsorption and Immersion Techniques. J. Chem. Soc., Faraday Trans. 1992, 88, 737. (10) Muller, E. A.; Rull, L. F.; Vega, L. F.; Gubbins, K. E. Adsorption of Water on Activated Carbons: Molecular Simulation Study. J. Phys. Chem. 1996, 100, 1189. (11) Natal-Santiago, M. A.; Hill, J. M.; Dumesic, J. A. Studies of the Adsorption of Acetaldehyde, Methyl Acetate, Ethyl Acetate, and Methyl Trifluoroacetate on Silica. J. Mol. Catal. A. Chem. 1999, 140, 199.

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Received for review August 6, 1999 Revised manuscript received November 15, 1999 Accepted November 21, 1999 IE990594I

and Intermolecular Hydrogen Bonding - American Chemical Society

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