J. Phys. Chem. B 2000, 104, 4735-4744
4735
Intramolecular versus Intermolecular Hydrogen Bonding in the Adsorption of Aromatic Alcohols onto an Acrylic Ester Sorbent Kristy L. Mardis,† Brian J. Brune,‡ Prashanth Vishwanath,‡ Binyam Giorgis,† Gregory F. Payne,‡ and Michael K. Gilson*,† Center for AdVanced Research in Biotechnology, National Institute of Standards and Technology, 9600 Gudelsky DriVe, RockVille, Maryland 20850, Department of Chemical and Biochemical Engineering and Center for Agricultural Biotechnology, UniVersity of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250 ReceiVed: October 5, 1999
Intramolecular hydrogen bonds influence intermolecular binding in adsorption and molecular recognition, but the interplay between intra- and intermolecular hydrogen bonding is poorly understood. In this study, a series of four aromatic alcohols, 2-phenylethanol, 3-phenyl-1-propanol, 2-phenoxyethanol, and 3-phenoxy1-propanol, are examined to determine the effect of intramolecular hydrogen bond formation on the binding to ethyl propionate (EP), an analogue of an acrylic ester separation resin. A combination of infrared spectroscopy, molecular modeling, and ab initio calculations are used to investigate the conformational preferences of the alcohols and the alcohol:EP complexes in hexane. Without EP, 2-phenylethanol and 2-phenoxyethanol prefer intramolecularly hydrogen-bonded conformations, whereas 3-phenyl-1-propanol overwhelmingly favors a conformer without an intramolecular hydrogen bond. For 3-phenoxy-1-propanol, there is a smaller preference for conformers without an intramolecular hydrogen bond. These results agree qualitatively with the experimentally measured IR spectra. The conformational preferences are explained by examining the energy components of low-energy conformers. Electrostatic interactions favor the intramolecularly hydrogen-bonded species, whereas the dihedral energy term and entropic term favor conformers without an intramolecular hydrogen bond. The balance determines the most stable conformer. The calculations predict that all four alcohols bind EP weakly compared with para-methoxyphenol. This ranking is in good agreement with experimental adsorption measurements. The small calculated ∆G° values of ≈ -0.9 to -2.4 kJ/mol for the alcohols is explained in terms of hydrogen bond donating ability, entropy, and the competition between inter- and intramolecular hydrogen bonds.
Introduction The competition between inter- and strong intramolecular hydrogen bonds influences the mechanism of a wide variety of processes: protein folding,1 reversible CO2 absorption to amino alcohols,2,3 binding of cyclitols to synthetic molecular receptors,4 and the adsorption of oxygenated aromatic compounds (OAC) by acrylic ester sorbents.5-7 In molecular recognition, intramolecular hydrogen bonds diminish the intermolecular binding constants. In principle, this competition can be exploited to enhance binding selectivities. This study aims to develop insight into the competition between inter- and intramolecular hydrogen bonds in systems where relatively weak intramolecular hydrogen bonds are expected. In previous work,5-7 we used a combined molecular modeling/experimental approach to investigate how competition between intra- and intermolecular hydrogen bonding affects the adsorption of OACs onto an acrylic ester sorbent. A variety of OACs could be recovered from plant extracts or lignin wastes if separation operations were available for isolating individual components from the complex mixtures. This would permit plant phenols to become a useful source of specialty chemicals. * To whom correspondence should be addressed. E-mail: gilson@umbi. umd.edu. † National Institutes of Standards and Technology. ‡ University of Maryland Baltimore County.
However, while adsorption offers potential for such separations, the molecular level interactions that confer selectivity are not completely understood. We have shown that the para isomers of three substituted phenols (methoxyphenol, methyl hydroxybenzoate, and hydroxyacetophenone) adsorb onto the acrylic ester resin from hexane primarily through an intermolecular hydrogen bond formed between the phenolic hydroxyl hydrogen and the sorbent’s carbonyl oxygen. For the ortho isomers of these phenols, however, an intramolecular hydrogen bond competes with the intermolecular hydrogen bond, diminishing the adsorption to the acrylic ester resin. For these three OACs, the competition between intra- and intermolecular hydrogen bonding could be used to adsorb regioselectively the para isomers from ortho/para mixtures. In all three of the previously studied systems, the ortho isomers have little conformational freedom, because the donating and accepting groups are in close proximity and are constrained energetically to lie in the plane of the ring. Additionally, the donating group is a phenolic hydroxyl, a good donating group. Thus, these structures form strong intramolecular hydrogen bonds. Compounds with more flexibility and weaker donating groups also form intramolecular hydrogen bonds.8-10 However, it is unclear whether these presumably weaker bonds can suppress adsorption. In this work, we examine the competition between weak
10.1021/jp993531m CCC: $19.00 © 2000 American Chemical Society Published on Web 04/21/2000
4736 J. Phys. Chem. B, Vol. 104, No. 19, 2000
Figure 1. Structures of the four aromatic alcohols studied in this work.
Figure 2. Partial structure of the acrylic ester sorbent XAD-7. The circled P refers to additional polymer units connecting at these points. The area inside the dashed outline corresponds to EP, the small molecule analogue used in modeling and IR studies.
intramolecular hydrogen bonding and intermolecular (i.e., adsorptive) hydrogen bonding. Specifically, we study four aromatic alcohols shown in Figure 1: 2-phenylethanol (PE), 3-phenyl-1-propanol (PP), 2-phenoxyethanol (POE), and 3-phenoxy-1-propanol (POP). All are able to form weak intramolecular hydrogen bonds. The effect of the intramolecular hydrogen bonding on intermolecular hydrogen bonding is evaluated by calculating the binding affinities of the four alcohols to ethyl propionate (EP), an analogue of the intermolecular hydrogen bonding site of the acrylic ester resin, XAD-7 (Rohm and Haas) shown in Figure 2.11 The validity of using EP as an analogue for the resin has been tested for a series of phenols.12 A correlation between the affinity of the phenol for the acrylic ester sorbent and the IR frequency shift (∆νOH) for the solute:EP complex was observed for hydrogen-bonded complexes. The IR frequency shift to lower wavenumbers upon complexation with EP is consistent with the formation of an intermolecular hydrogen bond between the phenol and EP. The correlation between the ∆νOH value and the adsorption affinity of the phenol for the acrylic ester sorbent suggests that EP is a good model for the adsorptive hydrogenbonding mechanism. This correlation can only be directly established in the absence of intramolecular hydrogen bonding. The ability of intramolecular hydrogen bonding to compete with and suppress adsorption is expected to depend on at least three factors. First, it depends on the nature of the intramolecular hydrogen bond acceptor, with a stronger acceptor leading to a stronger intramolecular bond. For the phenyl alcohols (PE and PP) the aromatic π electrons serve as weak hydrogen bond acceptors.8 For the phenoxy alcohols (POE and POP), the ether oxygen is the hydrogen bond accepting site.10,13,14 Second, the geometry of the bonded conformer affects the strength of the intramolecular hydrogen bond. For compounds with little conformational flexibility, such as ortho-substituted phenols, intramolecular hydrogen bonding is generally favorable when planar, five- or six-membered rings are formed, with sixmembered ring structures being the more stable.15,16 Likewise, for a series of flexible N-(p-nitrophenyl)alkylenediamines, it has been reported that intramolecular hydrogen bonds do form, and that the strongest bond occurs for the molecule that is able to
Mardis et al. form a six-membered ring.17 The molecules in the present study all form either a five- or six-membered ring when in an intramolecularly hydrogen-bonded conformer. Finally, we expect the stability of the intramolecularly hydrogen-bonded species to depend on the entropic cost associated with restricting the intervening dihedral angles. For a flexible chain, an intramolecular hydrogen bond that requires the formation of a six-membered ring has a greater entropic cost than the formation of a five-membered ring because of the additional degrees of freedom that must be constrained. The interplay of these three factors makes it difficult to predict the relative populations of intramolecularly hydrogen-bonded species and thus their effect on intermolecular binding affinities. This study uses molecular modeling, ab initio calculations, and IR to evaluate the contributions of all three factors to the stability of the intramolecular hydrogen bond. Next, the binding free energies of the alcohol:EP complexes are calculated using a novel molecular modeling technique that efficiently identifies the stable conformers of a molecule or complex and uses these conformations as the basis for free-energy calculations.18 These binding free energies are compared with those of substituted phenols to elucidate the roles of entropy, hydrogen bond donating ability, and intramolecular hydrogen bonding on adsorptive bonding. Finally, the calculated alcohol:EP binding affinities are compared with experimental adsorption binding affinities of the alcohols onto the acrylic ester resin. Methods 1. Experimental. a. Materials. The acrylic ester sorbent (Rohm and Haas Amberlite XAD-7), with a reported specific surface area of 450 m2/g, was purchased from Sigma Chemical Company (St. Louis, MO). Before use, the sorbent was washed sequentially with water, methanol, acetone, and hexane and dried in a vacuum oven overnight. The solvents (OPTIMA grade) were purchased from Fisher Scientific (Pittsburgh, PA). The solutes 2-phenylethanol and 2-phenoxyethanol were purchased from Sigma Chemical, and 3-phenyl-1-propanol (98%) and 3-phenoxy-1-propanol (97%) were purchased from Acros Chemical (Pittsburgh, PA). Ethyl propionate, the soluble analogue of the acrylic ester sorbent, was purchased from Aldrich (Milwaukee, WI). All chemicals were used without further purification. b. Procedures. Adsorption studies were performed by contacting a predetermined amount of sorbent with a hexane solution containing solute of a known initial concentration (C0). After 2 days of equilbriation, the solute concentration (C) was determined by UV spectrophotometry using a Spectronic Genesys 20 spectrophotometer (Milton Roy Co., Rochester, NY). The amount of solute adsorbed per unit mass of sorbent (q) was determined from the difference between the initial and equilibrium solute concentrations by the following equation:
q)
(C0 - C) V M
(1)
where V is the volume of solution and M is the mass of the sorbent. Adsorption affinities (q/C) are calculated from the slopes of the linear region of the adsorption isotherms. Adsorption enthalpies were determined from the temperature dependence of the adsorption affinities by means of a van’t Hoff plot of ln(q/C) vs 1/T. Uncertainties in the enthalpies (95% confidence level) were estimated using the uncertainties in the best fit lines of the van’t Hoff plot.
Intra- vs Intermolecular H Bonds in Adsorption
J. Phys. Chem. B, Vol. 104, No. 19, 2000 4737
IR spectra were collected for each of the alcohols in the presence and absence of EP. In the absence of EP, spectra were analyzed qualitatively to determine solute conformations in hexane solutions. In the presence of EP, IR spectra were used to demonstrate intermolecular hydrogen bonding between the alcohol and EP. In these cases, the spectrum of EP was subtracted from spectra of the alcohol:EP mixture. Spectra were collected (32 scans per spectrum) using a Nicolet Instrument Corporation (Madison, WI) 5DXC FTIR Spectrometer with a resolution of 4 cm-1. The IR chamber was purged with N2 before and during sampling to eliminate interference from CO2 and H2O. The IR cell used in these experiments had KBr windows and a 0.152-cm Teflon spacer. To determine peak areas, the IR spectra were deconvoluted using PeakFit 4.0 (SPSS Inc., Chicago, IL). The peaks were fit to the Voigt function in a manner analogous to that described by Brinkly and Gupta.10 2. Free-Energy Calculations. a. Theory. As described in previous work,6,7 free-energy calculations are used to calculate the standard free energy of binding, ∆G°b, of an alcohol (A) to EP and to determine the lowest-energy conformations of the free species and bound complexes. The standard free energy of binding can be written as:19
∆G°b ) -RT ln
ZA:EP 8π2σA:EP + RT ln ZAZEP C° σA σEP
(2)
where R is the gas constant; T is the temperature; C° is the standard concentration; σA:EP, σA, σEP are symmetry numbers; and ZA:EP, ZA, and ZEP are the configuration integrals of the complex, the alcohol, and EP, respectively. In eq 2 a factor of P°V h is omitted because it is very small at the standard temperature and pressure.19 The configuration integrals have the form:19
Z)
∫ e-β(U(r)+W(r)) dr
(3)
where β ) 1/kT and the Boltzmann factor is given as a function of U(r) and W(r), the gas-phase potential energy and the solvation energy, respectively. For the isolated molecules, the integral is calculated over r, the full range of internal coordinates. For the complex, the configuration integral also extends over the six rotational and translational degrees of freedom of the alcohol molecule with respect to the EP molecule.20 b. Algorithm. Evaluation of eq 3 was performed by the Mining Minima (MM) method which has been described previously.18 The MM method uses the predominant states approximation21 that the free energy is dominated by a small number of lowenergy states. The free energy, or more properly the chemical potential, can therefore be computed from the contributions Gj of a finite number N of energy wells j: N
G° ) -RT ln(
e-G /RT) ∑ j)1 j
(4)
The algorithm proceeds by finding a minimum energy conformation, mapping out the extent of the potential energy well around this structure, and calculating the configuration integral for that well by Monte Carlo integration of the Boltzmann factor. The configuration integral is then approximated as the sum of the contributions of individual energy wells. New energy wells are included in the sum until for five successive minima either (a) contributions to the free energy drop to a fractional change of
