Probing Enantiospecific Interactions at Chiral Solid−Liquid Interfaces

Langmuir 2003, 19, 785-792

785

Probing Enantiospecific Interactions at Chiral Solid-Liquid Interfaces by Absolute Configuration Modulation Infrared Spectroscopy Ronny Wirz, Thomas Bu¨rgi,* and Alfons Baiker Laboratory of Technical Chemistry, Swiss Federal Institute of Technology, ETH Ho¨ nggerberg, CH-8093 Zu¨ rich, Switzerland Received September 17, 2002. In Final Form: November 26, 2002 A method to selectively probe the different adsorption of enantiomers at chiral solid-liquid interfaces is presented, which combines attenuated total reflection infrared spectroscopy and modulation spectroscopy. The weak spectral changes upon adsorption of enantiomers at a chiral interface are followed in time, while periodically changing the absolute configuration of the admitted chiral molecule. A subsequent digital phase-sensitive data analysis reveals spectral differences arising due to the different diastereomeric interactions of the two enantiomers with the chiral interface. The main advantage of the method compared to conventional difference spectroscopy is the enhanced signal-to-noise ratio. The method is selective for differences in diastereomeric interactions of the enantiomers. Its potential is demonstrated by studying the adsorption of ethyl lactate on a chiral stationary phase, which is amylose tris[(S)-R-methylbenzylcarbamate] coated onto silica gel. D-Ethyl lactate interacts stronger with the chiral stationary phase. In particular the spectral shifts reveal a stronger N-H‚‚‚OdC hydrogen bonding interaction between amide group of the chiral stationary phase and the ester group of the ethyl lactate. The spectra also indicate that one of the three (S)-R-methylbenzylcarbamate side chains of the amylose derivative is predominantly involved in the interaction with the ethyl lactate. Furthermore, the experimental observations indicate that more than one interaction mode is populated at room temperature and that interaction with the ethyl lactate may induce a conformational change of the amide group of the chiral stationary phase.

Introduction Chiral interfaces are ubiquitous in nature and play an important role in technology, for example in separation processes.1 Intrinsically chiral metal surfaces2,3 and chiraly modified surfaces4-7 have also gained considerable interest for applications in the field of heterogeneous catalysis.8 Fundamental insight into processes occurring at such interfaces can benefit from techniques that give molecular level information on the interface on one hand and that selectively probe enantiospecificity on the other hand. The challenge for suitable experimental techniques is the combination of surface sensitivity with the selectivity to probe chirality. Many surface sensitive techniques can yield valuable information from chiral surfaces but do not probe selectively the chiral information. For example, adsorption of enantiomers on a chiral surface gives rise to diastereomeric interactions, which can be revealed by infrared spectroscopy.9 A disadvantage of such “nonspecific” methods is that the spectral differences of the adsorbed enantiomers are usually small compared to the absolute signal from either one of the enantiomers. * Corresponding author: E-mail: [email protected] Telephone: +41-1-632 22 67 Fax: +41-1-632 11 63. (1) Sheldon, R. A. Chirotechnology; Marcel Dekker: New York, 1993. (2) McFadden, C. F.; Cremer, P. S.; Gellman, A. J. Langmuir 1996, 12, 2483. (3) Attard, G. A. J. Phys. Chem. B 2001, 105, 3158. (4) Lorenzo, M. O.; Haq, S.; Bertrams, T.; Murray, P.; Raval, R.; Baddeley, C. J. J. Phys. Chem. B 1999, 103, 10661. (5) Lorenzo, M. O.; Baddeley, C. J.; Muryn, C.; Raval, R. Nature (London) 2000, 4004, 376. (6) Ferri, D.; Bu¨rgi, T. J. Am. Chem. Soc. 2001, 123, 12074. (7) Ferri, D.; Bu¨rgi, T.; Baiker, A. J. Phys. Chem. B 2001, 105, 3187. (8) Baiker, A.; Blaser, H. U. In Enantioselective Catalysts and Reactions. In Handbook of Heterogeneous Catalysis; Ertl, G., Kno¨zinger, H., Weitkamp, J., Eds.; VCH Publishers: Weinheim, Germany, 1997; Vol. 5, p 2422. (9) Gellman, A. G.; Horvath, J. D.; Buelow, M. T. J. Mol. Catal. A: Chem. 2001, 167, 3.

Furthermore, the small differences are buried in signals arising from nonspecifically adsorbed species. Nonlinear optical techniques, such as second harmonic generationcircular dichroism, are surface sensitive and may prove useful for studying chiral surfaces.10 Here we present a method that selectively enhances difference signals arising from diastereomeric interactions of enantiomers with chiral solid-liquid interfaces. We use attenuated total reflection (ATR)11 infrared spectroscopy to follow the adsorption of enantiomers at a chiral solid-liquid interface. Solutions of the two enantiomers are periodically admitted to the chiral solid surface in a flow-through cell. Time-resolved spectra are recorded and the signals subsequently demodulated by a digital phasesensitive data analysis. The resulting spectra selectively reveal the enantiospecificity of the interaction between chiral molecule and chiral interface. The potential of the method is demonstrated by investigating adsorption of ethyl lactate on a chiral stationary phase (CSP), which is used in HPL chromatography. There is currently considerable interest in a more fundamental understanding of the chiral recognition between chiral selector and selectand,12 which ultimately leads to separation of enantiomers. Absolute Configuration Modulation Infrared Spectroscopy Modulation spectroscopy is a sensitive technique for the investigation of reversible systems.13-16 The method (10) Kauranen, M.; Verbiest, T.; Maki, J. J.; Persoons, A. J. Chem. Phys. 1994, 101, 8193. (11) Harrick, N. J. Internal reflection spectroscopy; Interscience: New York, 1967. (12) Maier, N. M.; Schefzick, S.; Lombardo, G. M.; Feliz, M.; Rissanen, K.; Lindner, W.; Lipkowitz, K. B. J. Am. Chem. Soc. 2002, 124, 8611. (13) Mu¨ller, M.; Buchet, R.; Fringeli, U. P. J. Phys. Chem. 1996, 100, 10810.

10.1021/la026568y CCC: $25.00 © 2003 American Chemical Society Published on Web 01/01/2003

786

Langmuir, Vol. 19, No. 3, 2003

Wirz et al.

is based on the disturbance (stimulation) of the system under investigation by a periodic alteration of an external parameter, such as for example temperature,13 pressure, electric field, or concentration.16 The system will then respond periodically at the frequency of the stimulation. Here we use attenuated total reflection (ATR) infrared spectroscopy to follow the periodic changes of the system under investigation by collecting time-resolved infrared spectra. By a subsequent digital phase-sensitive data analysis according to eq 1, phase-resolved (demodulated) spectra are obtained from the set of time-resolved spectra. φkPSD

Ak

(ν˜ ) )

) dt ∫0TA(ν˜ ,t) sin(kωt + φPSD k

2 T

(1)

where k ) 1, 2, 3, ... (determines the demodulation frequency, i.e., fundamental, first harmonic...), T is the time of modulation period, φPSD is the phase angle (PSD: phase sensitive detection), ω is the modulation frequency, and A(ν˜ ,t) is the time-dependent absorbance at ν˜ (response signal). In case the system response is fast compared to the stimulation, the resulting demodulated spectra represent difference spectra between two states of the system. In case the system response is on the order of the stimulation period, phase lags between stimulation and response can be measured, which are connected to the kinetics of the system. Important features of the method, which are crucial for the following application, are as follows: (i) Only periodically changing signals show up in the demodulated spectra, whereas static signals cancel. (ii) The application of phase-sensitive data analysis results in high quality spectra, i.e., a large signal-to-noise ratio, compared to conventional difference spectra. We take advantage of these possibilities to investigate the different adsorption behavior of enantiomers on a chiral surface. The external parameter that is periodically altered is the absolute configuration of the chiral molecule (absolute configuration modulation), as schematically shown in Figure 1. Note that the concentration profile is not necessarily sinusoidal. In our case it resembles more a square wave pattern. This does however not change the shape of the resulting spectra. Signals arising from dissolved species are filtered out because the spectra of enantiomers are identical and do not change during modulation, assuming equal concentration (see point i above). Also, nonspecific interactions of the enantiomers with the surface are filtered out, because of the same reason. Only signals are detected that result directly from the different diastereomeric interactions of the CSP with either of the enantiomers. Hence, the received information is solely due to the changing absolute configuration of the adsorbate interacting with the chiral surface. The expected differences may be small, but these signals are enhanced by the phase-sensitive data analysis resulting in improved signal-to-noise ratio (see point ii above). Experimental Section Materials and Preparation of Chiral Film. The chiral films were prepared by dropping a slurry of a chiral stationary phase (CSP, Chiralpak AS from Chiral Technologies-Europe SARL) in CH2Cl2 on a Ge ATR-IR prism (50 × 20 × 2 mm, 45°, Harrick scientific corp.). Assuming refractive indices of 1.4 for the wet (14) Baurecht, D.; Fringeli, U. P. Rev. Sci. Instrum. 2001, 72, 3782. (15) Fringeli, U. P.; Baurecht, D.; Siam, M.; Reiter, G.; Schwarzott, M.; Bu¨rgi, T.; Bru¨esch, P. ATR spectroscopy of thin films. In Handbook of Thin Film Materials; Nalwa, H. S., Ed.; Academic Press: New York, 2001; Vol. 2, p 191. (16) Bu¨rgi, T.; Baiker, A. J. Phys. Chem. B 2002, 106, 10649.

Figure 1. Schematic representation of time-dependent concentration of individual enantiomers in an absolute configuration modulation experiment. The total concentration of EL remains constant (dotted line). The stimulation is sinusoidal in the depicted example, which is however not a necessary requirement. Scheme 1. Used Stationary Chiral Phase (CSP) and Adsorbate Molecules

film and 4.0 for Ge, a penetration depth dp of 0.64 µm (0.21 µm) at 1000 cm-1 (3000 cm-1) was calculated. The CSP is silica (20 µm) coated with amylose tris[(S)-R-methylbenzylcarbamate] as shown in Scheme 1. The prism was kept under a Petri dish while the CH2Cl2 evaporated and the procedure was repeated several times. Unnecessary CSP was removed again afterward, such that the area of the prism coated by the CSP matched the area of the cell. There was no loss of CSP detectable during the experiments. However, we noticed that the CSP did not adhere as well on the prism when the slurry was prepared with hexane solvent. (-)-Ethyl L-lactate (L-EL, Fluka, ∼99% purum) and (+)ethyl D-lactate (D-EL, Fluka, g99% puriss) were used as received. Hexane (Merck, Uvasol) was stored under molecular sieve (Chemie Uetikon AG, 4A-401, 2-3 mm). Ethyl propionate (Fluka, g 99% puriss) and 1-ethoxy-2-propanol (Acros, 90-95%) were used as received.

Probing Enantiospecific Interactions Experimental Setup and Data Acquisition. Infrared spectra were measured on a Bruker IFS 66/S FT-IR spectrometer equipped with a dedicated ATR-IR attachment (Optispec) and a liquid nitrogen cooled MCT detector. All spectra were recorded at a resolution of 4 cm-1. The CSP covered Ge prism was fixed within an in house built stainless steel flow cell.16 The gap between the polished steel surface of the cell and the IRE was 250 µm and defined by a 30 × 1 mm viton O-ring (Johannsen AG) fit into a precision electroeroded nut of the steel cell. The total volume of the cell is 0.077 mL. The flow-through cell was cooled by means of a thermostat and the measurements were performed at 20 °C. The flow of liquid over the sample was controlled by means of a peristaltic pump (ISMATEC Reglo 100) located behind the cell. Liquid was provided from two separate glass bubble tanks, where dry nitrogen gas (Pangas) was bubbled through the solutions to remove air. The flow from the two tanks was determined by a computer controlled pneumatically actuated three way Teflon valve (Parker PV-1-2324).16 Teflon tubing was used throughout. For transmission experiments a normal sample holder replaced the ATR-IR attachment. A variable path length IR cell (SPECAC) with KBr windows was used with a path length adjusted to 100 µm. Modulation Experiments. For the modulation experiments a flow rate of 0.9 mL/min was used. Hexane was allowed to flow first over the CSP until no variation in the spectrum could be detected. Then modulation was started. Liquids from the two bubble tanks were alternately admitted to the cell by switching the computer controlled valve within the data acquisition loop of the measurement program. The system was allowed reaching a quasi-stationary state during three full modulation periods. Data were then averaged over five modulation periods. Within one modulation period of 223.9 s, 60 spectra were recorded by co-adding 30 scans per spectrum. Demodulation was performed according to eq 1.14-16 Only spectra demodulated at the fundamental (k ) 1) are reported here. Before demodulation, the single beam spectra were transformed into absorbance spectra using the average of all single beam spectra as the background. It should however be noted that the result, i.e., the demodulated spectra, are independent of the choice of the reference spectrum. Because of the fast adsorption/desorption processes, no significant phase lags were observed between adsorbed and dissolved species. A series of experiments were typically performed in the following way: A first modulation experiment was performed by switching between hexane and a solution of (-)-ethyl L-lactate (L-EL; 1.8 mM). This type of experiment gives information about the adsorption of L-EL on the CSP. An analogous modulation experiment with the other enantiomer (hexane vs a solution of (+)-ethyl D-lactate; D-EL; 1.8 mM) was performed after cleaning the surface by flowing neat hexane over the CSP for about 5 min. Again a period of cleaning followed. Finally, a modulation experiment was performed between solutions of L-EL and D-EL (1.8 mM each) in hexane. As described in detail above this type of experiment selectively highlights differences in the interaction of the two enantiomers with the CSP. The CSP film on the ATR prism was freshly prepared for each series of experiment. In the following the solution, which was admitted first during modulation, will be mentioned first. Experiments were repeated under identical conditions at ethyl lactate concentrations of 0.5 and 3.6 mM. The sequence of the modulation experiments, i.e., D-EL first or L-EL first, was also investigated. Ethyl lactate can interact with the CSP in several ways. Hydrogen bonds can be formed with either the OH as a donor or the COOR group as an acceptor. The CSP itself can also interact as a H-acceptor by its COOR group and as a H-donor by its NH group. A double hydrogen-bonding interaction between chiral stationary phase and ethyl lactate is feasible, the acceptor/donor of the CSP interacting with the donor/acceptor of the adsorbate. To investigate the hydrogen-bonding interactions in more detail, modulation experiments were performed under the same conditions with two structurally similar molecules. One is ethyl propionate, where only H-acceptors are available and the other is a racemic mixture of 1-ethoxy-2-propanol (Scheme 1).

Results In Figure 2a, six time-resolved spectra of the modulation experiment hexane vs D-EL are displayed with a time

Langmuir, Vol. 19, No. 3, 2003 787

Figure 2. ATR spectra of the adsorption of (+)-ethyl lactate (D-EL) on Chiralpak AS chiral stationary phase (Scheme 1). (a) Six time-resolved spectra of a modulation experiment hexane vs D-EL (1.8 mM, modulation period T ) 223.9 s). The time between two consecutive spectra is 37.3 s. The reference spectrum was recorded while flowing neat hexane. (b) Demodulated spectra at phase angles φPSD ) 10 (lowest intensity), 20, 30, ..., 90° (highest intensity). The spectra were calculated from the data set shown in Figure 2a.

delay of 37.3 s in between. The corresponding demodulated spectra are presented in Figure 2b, starting with the spectra at φPSD ) 10° and going up to the spectra with φPSD ) 90° in steps of 10°. Note that the phase angle of the demodulated spectra was not corrected for the time the liquid needs to reach the cell. Absolute phase angles are however not of importance here. Figure 2 demonstrates that the demodulated spectra are of much better quality. Figure 3b shows the demodulated spectra of an analogous experiment but with L-EL instead of D-EL. Figure 3a shows the demodulated spectra of an experiment where the two enantiomers were modulated against each other; i.e., the parameter that is modulated is the absolute configuration of EL. The top traces in Figure 3a correspond to an experiment in the absence of the CSP on the clean Ge prism. No significant bands can be discerned, since the spectra of dissolved D- and L-EL are identical. The noise level in the displayed frequency range is about 3 × 10-5. In contrast, in the presence of the CSP, significant bands are observed, which arise due to the different diastereomeric interaction between CSP and the two enantiomers. The demodulated spectra of the experiments where the single enantiomers were modulated against the solvent show small differences, as a comparison between the spectra in Figures 2b and 3b reveals. These differences are confirmed in Figure 3a, namely an increase in intensity at 1254 cm-1 in the presence of D-EL. Also, there is a positive band formed at 1538 cm-1 and a negative band at 1500 cm-1 as soon as interaction with the adsorbate takes place. In the region of the CdO stretching vibrations

788

Langmuir, Vol. 19, No. 3, 2003

Figure 3. Demodulated ATR spectra at phase angles φPSD ) 10, 20, 30, ..., 90° of modulation experiments (a) L-EL vs D-EL (1.8 mM) and (b) hexane vs L-EL (1.8 mM). The top traces in part a were measured in the absence of CSP on the clean Ge ATR prism, whereas the lower traces in part a were measured in the presence of CSP under otherwise identical conditions. In all cases, the modulation period was 223.9 s.

at around 1700 cm-1, different signals can be observed. The negative band at 1749 cm-1 and the positive band at 1724 cm-1 is a result of the interaction of D-EL with the CSP. The corresponding band is found at 1728 cm-1 for L-EL. Free EL in hexane shows a band at 1740 cm-1. To check the consistency of the method, the results of three different modulation experiments are shown in Figure 4, traces a and b. The three experiments are as follows: modulation of (i) hexane vs L-EL, (ii) hexane vs D-EL, and (iii) L-EL vs D-EL. In all cases the concentration was 1.8 mM. Figure 4, trace a, shows a demodulated spectrum (φPSD ) 90°) of the experiment L-EL vs D-EL. Trace b shows the difference between the demodulated spectrum of the experiment hexane vs D-EL (φPSD ) 90°) and the corresponding spectrum of the experiment hexane vs L-EL (φPSD ) 90°). The two spectra, a and b match each other in an excellent way, so that the significance of the received results can be inferred. Small features in the spectra like the bipolar band around 1140 cm-1 and the weak structures between 1660 and 1710 cm-1 turn out to be significant. Traces c and d in Figure 4 show demodulated spectra of experiments D-EL vs L-EL at 0.5 mM (trace c) and 3.6 mM (trace d). Note that for these experiments D-EL was admitted first, in contrast to the experiment shown in trace a. Accordingly, the polarity of the bands changes (negative bands become positive and vice versa). Figure 5 shows demodulated spectra (φPSD ) 90°) of experiments where hexane was modulated against D- and L-EL, respectively, at different concentrations (0.5, 1.8, and 3.6 mM). The band intensities of the two spectra of L-EL at low concentration (0.5 and 1.8 mM) on the CSP (Figure 5d,e) match each other by a proportionality factor of about three, whereas this does not hold over the whole

Wirz et al.

Figure 4. Demodulated ATR spectra (T ) 223.9 s, φPSD ) 90°) of modulation experiments of D- and L-EL on the CSP: (a) L-EL vs D-EL (1.8 mM); (b) difference between the two demodulated spectra of hexane vs D-EL and hexane vs L-EL (1.8 mM each); (c) D-EL vs L-EL (0.5 mM); (d) D-EL vs L-EL (3.6 mM).

Figure 5. Demodulated ATR spectra (T ) 223.9 s, φPSD ) 90°) of modulation experiments of D- and L-EL on the CSP at different concentrations: (a) hexane vs D-EL (0.5 mM); (b) hexane vs D-EL (1.8 mM); (c) hexane vs D-EL (3.6 mM); (d) hexane vs L-EL (0.5 mM); (e) hexane vs L-EL (1.8 mM); (f) hexane vs L-EL (3.6 mM).

frequency range for the corresponding two spectra of D-EL (Figure 5a,b). Band intensities at 1749 (negative), 1539, around 1500 (negative), and 1254 cm-1 are larger than expected in the 0.5 mM spectrum when compared to the spectrum measured at 1.8 mM. Other signals at 1724 and 1134 cm-1 show the expected intensity proportionality.

Probing Enantiospecific Interactions

Figure 6. Demodulated ATR spectra (T ) 223.9 s, φPSD ) 90°) of modulation experiments of (a) hexane vs ethyl propionate (1.8 mM), (b) hexane vs racemic 1-ethoxy-2-propanol (1.8 mM), (c) L-EL vs D-EL (1.8 mM), and (d) hexane vs D-EL (1.8 mM).

Figure 5 shows that the observed bands tend to be stronger in the case of D-EL. By taking the band at 1539 cm-1, which is associated with the CSP, as a measure of the amount of adsorbed D- and L-EL, an intensity ratio of 1.5:1 is observed at 1.8 mM. This corresponds to a ∆∆G of adsorption of about 1 kJ/mol at RT. Using the carbonyl bands of adsorbed EL at 1724/1728 cm-1 a value of about 0.7 kJ/mol can be estimated. Figure 5 furthermore shows that there are some small, but significant band shifts when comparing the demodulated spectra for D- and L-EL. The band corresponding to the amide II vibration is found at slighly higher wavenumber in the presence of D-EL (1540 cm-1) than in the presence of L-EL (1536 cm-1). Also, the band between 1720 and 1730 cm-1, associated with adsorbed EL, is found at slightly lower wavenumber for D-EL (1724 cm-1) than for L-EL (1728 cm-1). Figure 6 shows demodulated (φPSD ) 90°) spectra of modulation experiments of (a) hexane vs ethyl propionate (1.8 mM), (b) hexane vs racemic 1-ethoxy-2-propanol (1.8 mM), (c) L-EL vs D-EL (1.8 mM), and (d) hexane vs D-EL (1.8 mM). The signals at 1254 cm-1, 1500, 1540, and 1749 cm-1 clearly show that 1-ethoxy-2-propanol has a larger effect on the CSP than ethyl propionate, likely due to the O-H group. In Figure 7 the transmission spectra of ethyl lactate, ethyl propionate, and 1-ethoxy-2-propanol in hexane are shown for comparison. A spectrum of the dry CSP is given in Figure 8. Also shown as an inset b is a spectrum of the CSP in the frequency range 1600-1800 cm-1 recorded in the presence of hexane. As the reference spectrum served the dry CSP. The CSP bands show up since in the presence of hexane the refractive index and hence the penetration depth is larger than in air. Three amide I signals are observed for the dry as well as the wet CSP, likely corresponding to the three chiral side chains connected to an amylose unit (Scheme 1). Interestingly, the band at highest frequency becomes more prominent with respect to the other two bands in the presence of hexane. Possibly the CdO group of one side chain is released from the surface resulting in

Langmuir, Vol. 19, No. 3, 2003 789

Figure 7. Transmission spectra of (a) ethyl propionate (44 mM), (b) 1-ethoxy-2-propanol (44 mM), and (c) (-)-ethyl L-lactate (L-EL, 44 mM) in hexane. The region around 1400 cm-1 marked with an asterisk is covered due to strong solvent absorption.

a tangling group in the presence of hexane. The three amide I signals of the CSP also show up as negative bands when EL is admitted, as can be seen for example in Figure 5. The highest frequency band at 1743 cm-1 gets weaker when D-EL is adsorbed, which leads to the negative bands in Figure 5. The effect is much weaker when L-EL is adsorbed. Because at the same time bands of adsorbed and dissolved D-EL arise at 1724 and 1740 cm-1, the maximum of the negative band shows up between 1747 and 1749 cm-1. The other two amide I bands of the CSP at 1691 and 1711 cm-1 are considerably weaker and overlapped by a broad band at 1660-1720 cm-1. Discussion General Considerations. The main objective of the present work is to demonstrate the advantages of absolute configuration modulation spectroscopy for the investigation of diastereomeric interactions at chiral solid-liquid interfaces. The most powerful features of the technique are the selectivity for diastereomeric interactions and the increase in sensitivity. An additional benefit emerges from the possible distinction between static and dynamic surface phenomena. The selectivity for diastereomeric interactions is best demonstrated in Figure 3a. In the top spectra, i.e., in the absence of CSP, no significant signals show up when modulating the absolute configuration of EL. In contrast, the different diastereomeric interactions of D- and L-EL with the CSP result in significant signals for the analogous experiments in the presence of CSP. Because enantiomers have the same spectrum, only species at the interface are detected and any contribution from dissolved enantiomers are filtered out, assuming equal concentrations. The increased sensitivity, which results in higher quality spectra, is obvious from Figure 2, where time-resolved and demodulated (phase-resolved) spectra are compared. As a consequence of these advantages information can be obtained, which would otherwise be obscured. For

790

Langmuir, Vol. 19, No. 3, 2003

Wirz et al.

Table 1. Assignments of the Infrared Spectra of Ethyl Lactate (EL), Chiral Stationary Phase (Scheme 1, CSP), and the Formed Complexc EL

CSP

obsd

lit.

assignment

1022 1039

1021a 1042a

ν (O-C2H5) δ (C-CH3)

1134

1135a

ν(C-OH)

1219

1229a

δ(O-H), ν(C-OH), δ(HOC-H)

observed

1061

1261

1740

1269a

1736b

CSP‚EL

assignment

obsd

assignment

ν(Si-O) ca. 1130 ca. 1147 1219 1220 1254

ν(C-OH), D-EL ν(C-OH), L-EL δ(O-H), ν(C-OH), δ(HOC-H) δ(N-H) amide III, negative δ(N-H) amide III, H-bridged

1497 1536 1540 ca. 1660-1720 1689 1707 1724 1728 1740 1749

δ(N-H) amide II, negative δ(N-H) amide II, H-bridged, L-EL δ(N-H) amide II, H-bridged, D-EL amide I, H bridged ν(N-CdO) amide I, negative ν(N-CdO) amide I, negative ν(CdO), D-EL ν(CdO), L-EL ν(CdO), dissolved EL ν(N-CdO) amide I, negative

δ(O-H) 1497 1539

δ(N-H) amide II δ(N-H) amide II, H-bridged

1695, 1691 1715, 1711

ν(N-CdO) amide I ν(N-CdO) amide I

1732, 1743

ν(N-CdO) amide I

ν(CdO)

a

Reference 20. b Reference 21. c The frequencies shown from literature were measured in CCl4, those observed were measured in hexane. Values in italic refer to the wet CSP.

Figure 8. ATR-IR spectrum of dry Chiralpak AS (CSP) on a Ge ATR prism. The sample was prepared as mentioned in the Experimental Section. Before measuring the spectrum, the prism was dried in a vacuum to remove residual CH2Cl2. As the reference served the clean Ge ATR prism. Adsorbed water from air humidity gives rise to the bands at 1649 cm-1 and above 3000 cm-1. Trace b of the inset shows an ATR spectrum of the wet CSP. As the reference spectrum served the dry CSP. The bands arise due to the increased refractive index and penetration depth in the presence of hexane. The spectrum is scaled by a factor of 1.5.

example, the feature in Figure 5 at around 1134 cm-1, associated with the C-O stretching vibration of EL, is a superposition of at least two bands. One is associated with dissolved EL and one with adsorbed EL. Inspection of spectra in Figure 5, which shows results of the experiments where hexane was modulated against solutions of D- and

L-EL, respectively, reveals no significant differences in intensity and band position at 1134 cm-1 between the two enantiomers. In contrast, the results of the absolute configuration modulation experiments in Figure 4, parts a and d, clearly show a weak bipolar band around 1140 cm-1 arising due to the different interaction of D- and L-EL with the CSP. The bipolar shape indicates that the corresponding band is found at higher (lower) wavenumber in the case of L-EL (D-EL). Assignment. The assignment of the main bands is summarized in Table 1. As can be seen in Figure 6, both the H-donor (1-ethoxy-2-propanol) and the H-acceptor group (ethyl propionate) of an adsorbate can interact with the surface, giving rise to several bands. The negative band at 1749 cm-1 is caused by a shift of an amide I type stretching vibration of the CSP due to interaction with the adsorbate. The negative band at 1749 cm-1 in Figure 6a is not that pronounced, because it is partly compensated by the CdO stretching vibration of ethyl propionate, as can be inferred from the transmission spectrum (Figure 7a). A CdO oscillator (amide I band) normally shifts to lower wavenumber due to hydrogen bonding. The broad band between 1660 and 1720 cm-1 is assigned to the amide I vibration of hydrogen-bonded CdO groups of the CSP. This band arises when the band at 1749 cm-1 becomes negative. This is most obvious from the spectrum of 1-ethoxy-2-propanol in Figure 6b). 1-Ethoxy-2-propanol itself does not contain a carbonyl group, and therefore, the signals around 1700 cm-1 are associated with the CSP. Superimposed on the broad band between 1660 and 1720 cm-1 are two sharp amide I bands. These bands are consistently weaker than the 1749 cm-1 band, but their intensities are correlated with the latter. We assign these features at 1689 and 1707 cm-1 and the one at 1749 cm-1 to the amide I bands of the three different side chains of the amylose derivative (Scheme 1). They match the bands of the CSP in hexane shown in Figure 8. The negative bands at 1220 and 1497 cm-1 (e.g., in Figures 5 and 6) are assigned to amide III and amide II vibrations (N-H bending), respectively, which are shifted up to 1254 and 1536 cm-1 (1540 cm-1), respectively, when interacting with L-EL (D-EL). In the case of EL adsorption,

Probing Enantiospecific Interactions

the band at 1220 cm-1 is partly covered by an EL band but it is clearly observed in the case of ethyl propionate adsorption (Figure 6b). The shift indicates hydrogenbonding interaction involving the N-H. Bands associated with EL are also observed. A comparison between Figures 5 and 7 shows that dissolved EL can be observed under the applied conditions but the bands associated with dissolved EL are weak. The carbonyl stretching vibration of dissolved EL arises at 1740 cm-1. Bands at 1724 and 1728 cm-1 are associated with adsorbed D- and L-EL, respectively. The shift to lower frequency with respect to dissolved EL is consistent with a hydrogenbonded CdO group. The bands at 1219 and 1261 cm-1 associated with dissolved EL (Figure 7) are relatively broad and bear O-H bending character as a normal-mode analysis shows. These vibrations are very sensitive (position and intensity) to hydrogen bonding. Compared to the C-O stretching vibration at 1134 cm-1 the intensity of the bands at 1219 and 1261 cm-1 becomes smaller (or the bands become considerably broader) when EL is adsorbed (compare Figures 5 and 7). This in turn indicated that the O-H group of EL is involved in hydrogen bonding. Interaction between EL and CSP. Figure 6, where the effect of ethyl propionate and 1-ethoxy-2-propanol on the CSP is compared, strongly indicates that a H-bond donor has a larger effect on the CSP than a H-bond acceptor. Several observations show that D-EL interacts stronger with the CSP than L-EL. The modulation experiments hexane vs D-EL and L-EL, respectively at different concentrations (Figure 5) consistently show that the spectral features are more intense when D-EL interacts with the CSP. This is fully confirmed by the absolute configuration modulation experiments in Figure 4. From the intensity ratios of bands associated with bonded L-/ D-EL (1728/1724 cm-1) a ∆∆G of about 0.7 kJ/mol can be estimated at room temperature. On the basis of the intensity of the amide II band of the CSP a ∆∆G of about 1.0 kJ/mol is calculated. Furthermore, there are small but significant shifts of the CSP amide II band of hydrogenbonded CdO and of the ester carbonyl band of EL when comparing D- with L-EL. The amide II and III band shift up in frequency upon hydrogen bonding from 1497 to about 1539 cm-1 and from about 1220 to about 1254 cm-1. The shift of the amide II band is larger by 4 cm-1 upon binding of D-EL compared to binding of L-EL. This strongly indicates that the N-H forms stronger hydrogen bonds to the D-EL. Also, the ester carbonyl vibration of EL shifts down in frequency when a hydrogen bond is formed involving the ester group. This shift is also larger for D-EL than for L-EL, which shows that the hydrogen bond toward the ester group is stronger for D-EL. To better understand the interaction of EL with the CSP we have performed density functional theory calculations using the hybrid functional B3PW9117 and a double-ζ version of Dunning’s correlation consistent basis sets (cc-pVDZ).18 Calculations were performed using GAUSSIAN98.19 We restricted the calculations to minimum energy searches and normal-mode analysis of EL and (1-phenyl-ethyl)-carbamic acid ethyl ester, which served as a model for the side chain of the amylose derivative, and some complexes between the two molecules. We want to stress that such calculations neglect the effect of the solid surface. Also, calculating a limited number of distinct structures for such a complex system (17) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (18) Woon, D. E.; Dunning, T. H. J. Chem. Phys. 1993, 98, 1358.

Langmuir, Vol. 19, No. 3, 2003 791

Figure 9. Feasible interaction modes between D- and L-EL and (1-phenyl-ethyl)-carbamic acid ethyl ester. The latter serves as model for the side chains of the amylose tris[(S)-R-methylbenzylcarbamate] (CSP in Scheme 1). The structures were minimized at the DFT B3PW91 level using a cc-pVDZ basis set. The complexes involving D-EL (b, d) are calculated to be 2.5-2.9 kJ/mol more stable than the corresponding complexes involving L-EL (a, c).

of floppy molecules cannot give a comprehensive picture. Nevertheless, the calculations for example show that the infrared spectrum of (1-phenyl-ethyl)-carbamic acid ethyl ester is sensitive to the conformation of the amide moiety H-N-CdO. Most prominently, the amide II and III bands are very strong for trans conformation of N-H and CdO groups. For cis conformation these bands are very weak but instead the CdO vibration (amide I) is much stronger and shifted higher up in energy with respect to trans conformation. Hence the calculations indicate that the observed changes in the amide II and III spectra are due to amide groups in trans conformation, which form hydrogen bonds with adsorbed EL. On the basis of the information that we have gained from the infrared spectra, namely involvement of the O-H and ester groups of EL and the N-H and CdO groups of the CSP, the structures in Figure 9 could serve as models for the interaction of the EL with the CSP. Consistent with the spectroscopic findings, the interaction complexes with D-EL shown in Figure 9b, d are calculated to be more stable than the corresponding L-EL complexes (Figure 9a,c) by ∆∆E ∼ 2.5-2.9 kJ/mol. (19) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.7; Gaussian, Inc.: Pittsburgh, PA, 1998. (20) Goulden, J. D. S. Spectrochim. Acta 1960, 16, 715. (21) Mori, N. Bull. Chem. Soc. Jpn. 1968, 41, 1871.

792

Langmuir, Vol. 19, No. 3, 2003

Several perceptions indicate that not one single interaction mode is responsible for our experimental observations. Inspection of the spectra in Figure 5 shows that the relative intensity of some signals changes with concentration. The most prominent effect can be observed for the negative band at 1749 cm-1, which is relatively pronounced at 0.5 mM concentration for D-EL but hardly increases when going to 1.8 mM (Figure 5a,b). In case only one interaction mode would prevail, the relative intensity of the signals from the surface are expected to be rather independent of concentration. As mentioned above the disappearance of the 1749 cm-1 band seems to be correlated with the appearance of a broad band at 16601720 cm-1; i.e., the band seems to shift down by several tenths of wavenumbers. This shift is rather large to be explained solely by hydrogen bonding. We therefore propose that a conformational change takes place involving the amide group, in addition to hydrogen bonding. This change is reversible, as the appearance of the 1749 cm-1 band in the modulation experiments shows. Possibly, it includes a conformational transition between cis and trans arrangement of the N-H and CdO groups. Also, the surface may play an important role in this change. The amide side chain of the amylose derivative associated with the 1743 cm-1 band may be bound to the surface and get free when contacted with EL, resulting in a tangling group. This hypothesis is supported by our observation that the 1749 cm-1 amide I band is almost absent in the case of the L-EL modulation experiments at low concentration (0.5 and 1.8 mM, Figure 5). The band becomes, however, more pronounced when the CSP is contacted before by D-EL. The latter can free part of the side chains, which are then also available for interaction with L-EL. We have also successfully applied absolute configuration modulation using other chiral stationary phases. The method seems generally applicable for the study of adsorption of enantiomers on chiral interfaces. Further improvement of the signal-to-noise ratio can be achieved by longer averaging (over more modulation periods), and by using ZnSe ATR elements (larger penetration depth). Conclusion Modulation spectroscopy in combination with FT-ATRIR is a valuable technique to investigate the different

Wirz et al.

adsorption of enantiomers at a chiral solid-liquid interface. In particular, monitoring spectral changes upon modulation of the absolute configuration of the chiral adsorbate, followed by a digital phase-sensitive data analysis, selectively highlights spectral differences due to the different diastereomeric interactions of the two enantiomers with the chiral interface. As an example the interaction of ethyl lactate with amylose tris[(S)-R-methylbenzylcarbamate] coated onto silica gel as the chiral stationary phase revealed that D-ethyl lactate is stronger adsorbed. From relative band intensities for adsorbed D- and L-ethyl lactate, a ∆∆G of about 0.7 kJ/mol was estimated. Spectral shifts showed that the amide groups of the chiral stationary phase served as hydrogen bond donor (N-H) and acceptor (CdO). The ester and O-H group of ethyl lactate in turn served as hydrogen acceptor and donor. The spectral shift of the N-H bending mode of the chiral stationary phase (amide II) and the CdO stretching mode of the lactate were larger for D-ethyl lactate than for L-ethyl lactate. This indicates that the N-H‚‚‚OdC hydrogen bonding interaction is stronger in the case of D-ethyl lactate. The spectra furthermore indicate that more than one interaction mode is populated, that one side chain of the amylose derivative is stronger involved in the chiral selection than the other two and that chiral selection may be accompanied by a conformational change of the amide group of the chiral stationary phase. Acknowledgment. Financial support of the Swiss National Science Foundation is gratefully acknowledged. We thank Prof. U. P. Fringeli, Institute of Physical Chemistry, University of Vienna, for helpful discussion on modulation spectroscopy and Dr. Dieter Baurecht, Institute of Physical Chemistry, University of Vienna, for making his demodulation program available to us. We also thank Chiral Technologies-Europe, Illkirch, France, for providing samples of chiral stationary phases. CSCS in Manno and ETH-Zurich are acknowledged for providing computing time. LA026568Y