Anal. Chem. 1997, 69, 1000-1005
Mass-Sensitive Solvent Vapor Detection with Calix[4]resorcinarenes: Tuning Sensitivity and Predicting Sensor Effects Franz L. Dickert,* Uwe P. A. Ba 1 umler, and Helen Stathopulos
Institute of Analytical Chemistry, University of Vienna, Wa¨ hringer Strasse 38, A-1090 Vienna, Austria
Preorganized calix[4]resorcinarenes forming vaselike cavities are tested with respect to their chemical sensing capabilities as coatings on mass-sensitive devices. A synthetically modified vaselike host molecule with a definite cavity morphology forms densely packed layers for measurements with a SAW oscillator. In contrast to this detection of surface phenomena with ultrathin layers, QCM resonators require bulky microporous coatings with a high vapor permeability. Thus, short response times are attained even for layers using bulk effects, which are necessary to compensate the smaller sensitivity of the QCM. A 3-fold substitution of a basic calix[4]resorcinarene cavity with 2,3-dichloroquinoxaline provides a one-sideopened structure forming a molecular entrance for the easy access of analyte molecules. In combination with aliphatic spacers, this material fulfills the required demands of high sensitivity and short response times, and the detection of solvents in the gas phase to 2.5 ppm is realized. The sensor effects of the established coatings are correlated to host-guest stabilization enthalpies which were calculated by force field methods. An improved thermodynamic model that considers entropies of condensation is tested successfully for the prediction of the sensor behavior. Supramolecular materials featuring molecular recognition of analyte molecules combined with mass-sensitive devices provide a promising field for the monitoring of gaseous analytes.1-3 The total mass of the sensor layer increases if the host molecules incorporate solvent molecules from the gas phase. This change of mass can be detected accurately by mass-sensitive devices, such as the quartz crystal microbalance (QCM) or the surface acoustic wave (SAW) oscillator, via resonance frequency shifts due to host-guest complex formation. In this way, low-cost equipment highly capable of gas phase monitoring is designed. The applicability of receptors for enzyme analogue analyte recognition based on calix[4]resorcinarene host molecules in mono- or multilayers for mass-sensitive devices was already proven in principle.4-6 Preliminary measurements with calix[4](1) Dickert, F. L.; Haunschild, A. Adv. Mater. 1993, 5, 887-895. (2) Dickert, F. L.; Bauer, P. A. Adv. Mater. 1991, 3, 436-438. (3) Dickert, F. L.; Bruckdorfer, T.; Feigl, H.; Haunschild, A.; Kuschow, V.; Obermeier, E.; Bulst, W.-E.; Knauer, U.; Mages, G. Sens. Actuators B 1993, 13-14, 297-301. (4) Dickert, F. L.; Ba¨umler, U. P. A.; Zwissler, G. K. Synth. Met. 1993, 61 1-2, 47-52. (5) Nelli, P.; Dalcanale, E.; Faglia, G.; Sberveglieri, G.; Soncini, P. Sens. Actuators B 1993, 13-14, 302-304.
1000 Analytical Chemistry, Vol. 69, No. 6, March 15, 1997
resorcinarene sensor materials revealed the property of the basic host cavity 1a to form host-guest complexes for chemical sensing. Furthermore, the molecular structure of cavitand 1a could be modified to tune density and porosity of the coating to the special requirements of SAW and QCM devices.4 This could be realized on the one hand by using various aldehydes to create different basic calix[4]resorcinarene cavities with variable spacers, such as alkyl chains or alkyl thiolates for self-assembling on gold surfaces7,8 and on the other hand via bridging of two resorcine molecules of the cavitand by forming cyclic ethers. Sensitivity and selectivity of the host molecules could be varied within a large range in this way. Figure 1 gives an overview of the calix[4]resorcinarenes investigated and their schematic structures. As described earlier, 2a, which takes a stable vaselike conformation at room temperature,9 was found to be an efficient coating material for the SAW oscillator in ultrathin layers. By the application of long aliphatic spacers, the porous coating material 2b for QCMs is created, which exhibits drastically reduced response times if the sensitive layer is within a limit of up to 60 nm. Compared to the flat bowl-shaped host 1b, the elongation of the cavity in 2a and 2b results in an enhanced host-guest interaction at the inner surface of the host molecule. An increasing sensitivity for chlorinated solvents was achieved, which was confirmed by force field calculations. Stabilization enthalpies are nearly doubled in going from cavitands to vases. For the further improvement of sensor properties, the host materials 2c and 3 were synthesized and their sensing capabilities investigated. 3, in which only three quinoxalines bridge the almost vaselike cavity, was prepared for use as a QCM coating material. With the last position left unsubstituted, a host molecule is generated, flexible and adaptive to various guest molecules. The partially open structure facilitates the fast inclusion and desorption of the guest molecule, and in combination with the aliphatic substituents, short response times even in thick layers using bulk effects could be found. Coatings for SAW devices, which mainly react on surface phenomena, have to combine both the sufficient molecular package and the porosity for unhindered analyte diffusion. This was achieved by substituting the alkyl chains with 4-methylphenyl spacers to preserve the conformationally well-defined structure of the host molecule 2c and to reduce SAW response times to some minutes. (6) Schierbaum, K.-D.; Weiss, T.; Thoden van Velzen, E. U.; Engbersen, J. F. J.; Reinhoudt, D. N.; Go ¨pel, W. Science 1994, 265, 1413-1415. (7) Thoden van Velzen, E. U.; Engbersen, J. F. J.; de Lange, P. J.; Mahy, J. W. G.; Reinhoudt, D. N. J. Am. Chem. Soc. 1995, 117, 6853-6862. (8) Davis, F.; Stirling, C. J. M. J. Am. Chem. Soc. 1995, 117, 10385-10386. (9) Moran, J. R.; Karback, S.; Cram, D. J. J. Am. Chem. Soc. 1982, 104, 5826. S0003-2700(96)00585-9 CCC: $14.00
© 1997 American Chemical Society
Figure 1. Investigated molecular cavities: structure and schematic morphology. 1a, 2a: R ) CH3. 1b, 2b: R ) (CH2)8CH3. 1c, 2c: R ) C6H4CH3. 1d, 3: R ) (CH2)10CH3.
Furthermore, we present improved considerations for the estimation of sensing capabilities of calix[4]resorcinarenes, based on the combination of thermodynamic data and experimental measurements. EXPERIMENTAL SECTION Chemicals. 1a, 1b, 1c, 1d, 2a, 2b, and 3 were prepared according to literature.10-12 Compound 2c was prepared according to ref 7 with 1c as starting material and an 1:3 ratio of 1c and 2,3-dichloroquinoxaline. Dimethyl sulfoxide (DMSO) was distilled under nitrogen. For verification of the molecular structures, proton NMR spectra were recorded on a JEOL JNM-GX 270 FT NMR spectrometer. 2b: 1H NMR (CDCl3, room temperature) δ 0.88 (t, 12H, CH3), 1.28 (br s, 48H, CH2), 1.42 (br s, 8H, CH2), 2.25 (dd, 8H, CH2), 5.54 (t, 4H, CH2CH), 7.18 (s, 4H, ArH), 7.44 (m AA′BB′, 8H, QuinH) 7.78 (m AA′BB′, 8H, Quin-H) 8.12 (s, 4H, ArH). 2c: 1H NMR (CDCl3, room temperature) δ 2.30 (s, 12H, ArCH3), 6.95 (s, 4H, ArCH), 7.06 (d, 8H, ArH), 7.14 (d, 8H, ArH), 7.34 (s, 4H, ArH), 7.48 (m AA′BB′, 8H, Quin-H) 7.82 (m AA′BB′, 8H, Quin-H) 8.38 (s, 4H, ArH). (10) Moran, J. R.; Ericson, J. R.; Dalcanale, E.; Bryant, J. A.; Knobler, C. B.; Cram, D. J. J. Am. Chem. Soc. 1991, 113, 5707-5714. (11) Dalcanale, E.; Constantini, G.; Sonicini, P. J. Inclusion Phenom. 1992, 13, 87-92. (12) Tunstad, L. M.; Tucker, J. A.; Dalcanale, E.; Weiser, J.; Bryant, J. A.; Sherman, J. C.; Helgeson, R. C.; Knobler, C. B.; Cram, D. J. J. Org. Chem. 1989, 54, 1305-1312.
3: 1H NMR (CDCl3, room temperature) δ 0.85 (t, 12H, CH3), 1.3 (br s, 64H, (CH2)8CH3), 1.55 (s, 8H, CH2), 2.22 (br s, 8H, CHCH2), 4.27 (t, 1H, CH2CH), 5.52 (m, 3H, CH2CH), 7.08 (s, 2H), 7.13 (s, 2H) 7.27 (s, 2H), 7.48 (m, 6H, 2OH), 7.67 (dd, 2H), 7.82 (m, 2H), 7.94(dd, 2H), 8.22 (s, 2H). The 3-fold quinoxaline substitution in 3 was confirmed by the ratio of the methylene bridging protons of 3H + 1H:4H in 3:2b and by the ratio of the sum of the quinoxaline protons in 2b and 3. Force Field Calculations. The starting geometries of isolated host and guest structures and of host-guest complexes were constructed by the HyperChem 4.0 molecular graphics/modeling package. The Cartesian coordinates of the output files were converted afterward by a self-made software, generating inputs for the molecular modeling program MM3 by Allinger.13-15 The MM3 force field was used for final optimizations, performed on a HP 715/80 work station. The host-guest stabilization energies were calculated as the difference between the heat of formation of the complex and the sum of the heats of formation of the isolated compounds. Measurements. Membranes for SAW experiments were prepared by spin coating directly on the device with a 200 mg/L chloroformic solution of the sensitive material after hydrophobizing the quartz surface with (dimethylamino)trimethylsilane. The same solutions were applied to double spreading host molecules by solvent evaporation to the QCMs, which were coated with nonadecanethiol as an adhesion promoter by dipping into the pure liquid. The thickness of the coatings was determined according to calibration curves. For this purpose, the devices were coated with solutions of a solid paraffin or the respective sensor material and the frequency was plotted vs the mass load. For heights exceeding 40 nm, these findings could be confirmed with a filmthickness measuring unit (Tencor alpha-step 200) by determining the step between a coated and uncoated part of the target. The QCM measurements were performed with a 10 MHz AT-cut quartz with gold electrodes (5.5 mm in diameter), operating in the thickness shear mode. The 433 MHz SAW resonators consist of an ST-cut quartz wafer with aluminum electrodes. Responses were measured with a Keithley 775A frequency counter in a resolution of (0.1 Hz in the case of the 10 MHz QCM and with a HP 5385A frequency counter in a resolution of (1 Hz in the case of the 433 MHz SAW devices. The resulting frequency data were transferred via an IEC bus to a computer. The sensor elements were exposed to a stream of air with defined amounts of humidity and organic solvent, as generated by an automatic gas mixing apparatus. Both gas chamber and gas mixing apparatus were temperature controlled. RESULTS AND DISCUSSION Coating Materials for the SAW Oscillator. For the QCM and the SAW devices, a bulk effect of the rigid sensor material 2a could be proved, indicating a direct relationship between sensor response and layer height. With increasing coating thickness up to 100 nm, a sluggish time behavior with response times of ∼10 min is observed. 2b and 3 should be more suitable, showing a dispersed structure due to their spacer groups. For (13) Allinger, N. L.; Yuh, Y. H.; Lii, J.-H. J. Am. Chem. Soc. 1989, 111, 85518565. (14) Lii, J.-H.; Allinger, N. L. J. Am. Chem. Soc. 1989, 111, 8576-8582. (15) Allinger, N. L.; Schmitz, L. R.; Motoc, I.; Bender, C.; Labanowski, J. K. J. Am. Chem. Soc. 1992, 114, 2880-2883.
Analytical Chemistry, Vol. 69, No. 6, March 15, 1997
1001
Figure 2. Sensor response of a 433 MHz SAW oscillator with a 30 nm layer of 2c, exposed to an increasing concentration of tetrachloroethylene in 10 ppm steps (20% RH, 20 °C).
the SAW, these soft materials, however, yield an anomalously strong damping and phase shift behavior and therefore no improved signal to noise ratio is observed in comparison to QCM findings. A suitable molecule with enhanced sensing capabilities is 2c, which has the same vaselike cavity as the host 2b, but additionally unflexible 4-methylphenyl spacers to create a compact but sufficiently porous coating material. As confirmed by molecular modeling, the highly defined conformational structure of this receptor molecule is not influenced by spacers and has almost no possibility to change its geometry without a correlated movement of other parts of the molecule as well. Quinoxaline substituents and the 4-methylphenyl spacers affect each other when the geometry of the molecule is changed, which results in sterical hindrance and a very unflexible structure. Figure 2 shows a time scan of a SAW oscillator with a resonance frequency of 433 MHz, covered with a 30 nm layer of 2c. The response times are in the range of a few seconds, and a signal to noise ratio is achieved that allows the detection of tetrachloroethylene in 10 ppm steps. If this coating is applied to a QCM oscillator, the sensor response to 10 ppm is buried within the noise. The QCM sensor answer reveals a sensitivity less by a factor of ∼5 in comparison to SAW data. The response amplitude usually shows a nearly quadratic dependence on the resonance frequency. The improvement in the signal to noise ratio is of course less and depends on the layer homogeneity, too. The gain of sensitivity observed in going from a QCM to a high-frequency SAW oscillator is unexpectedly low, which may be due to changes of the elastic properties16 of 2c under vapor exposition. The linearity of the SAW sensor characteristic of 2c favors it as a material for sensor arrays and pattern recognition by linear methods. The stability and linearity of the sensor signal is valid not only for low analyte concentrations but for higher ones as well. Experimentally this could be proved for tetrachloroethylene concentrations in the range of 0-500 ppm. The modification of 2a with the 4-methylphenyl groups provides an efficient coating material for SAW devices, because a rigid host structure is preserved that forms microporous layers. (16) Ballantine, D. S., Jr.; Wohltjen, H. Anal. Chem. 1989, 61, 704A-715A.
1002 Analytical Chemistry, Vol. 69, No. 6, March 15, 1997
Figure 3. Sensor response of a 10 MHz QCM coated with 120 nm layers of 3 on both gold electrodes, exposed to an increasing concentration of tetrachloroethylene in 2.5 ppm steps (20% RH, 20 °C).
Coating Materials for the QCM. A further improvement of the sensor properties of the vaselike cavitand 2b could be realized by 3, in which three substituents protrude from the basic cavity. Two hydroxyl groups of the molecule do not react with quinoxaline so that a molecular entrance is left and fast kinetics of inclusion and desorption of the guest molecules are guaranteed. In Figure 3, the frequency shift during exposition to an increasing tetrachloroethylene concentration in 2.5 ppm steps is visualized, measured with a 10 MHz QCM coated with a 120 nm layer of 3 on each gold electrode. This provides the highly sensitive detection of chlorinated or aromatic solvents such as tetrachloroethylene or toluene down to a few ppm. Both rise and recovery times last only several seconds. The lack of water cross sensitivity is advantageous, too, as presented in Figure 4, because the remaining hydroxyl groups are shielded. Sensitivities of Different Host Molecules. The development of sensor arrays requires layers yielding linearly independent sensor characteristics. This can be achieved if host molecules are combined with different functional groups or the cavity size is varied.17,18 Figure 5a compares the sensitivity of five calix[4]resorcinarene host molecules to some chlorinated solvents. The sensor effects are characterized by the degree of filling at an analyte concentration of 1000 ppm, that is, the molar ratio of absorbed analyte to host molecules. 3 has the highest sensitivity toward almost all solvents; 2c possesses a better affinity to CH2Cl2, because here in addition to the vaselike cavity a smaller one, formed by the 4-methylphenyl spacers, exists that engulfs dichloromethane but is too narrow for the larger homologues. Moreover, the cavity of 2c is hindered in adapting its size to larger guest molecules, because the repulsion of the 4-methylphenyl groups prevents the necessary enlarging of the cavity. This leads (17) Dickert, F. L.; Schuster, O. Adv. Mater. 1993, 5, 826-829. (18) Dickert, F. L.; Reif, H.; Reif, M. Fresenius J. Anal. Chem. 1995, 352, 620624.
Figure 6. MM3-optimized host-guest complexes of 1a and 2a with p-xylene.
Figure 4. Sensor characteristics for the frequency difference between a 10 MHz QCM coated with 36 nm layers of 3 on both gold electrodes and a reference quartz (20 °C).
Figure 5. Degrees of filling (in %) at c(solvent) ) 1000 ppm for the host molecules 1b, 2a, 2b, 2c, and 3 (0% RH, 20 °C).
to the lowest sensitivity to tetrachloroethylene and CCl4, because these guests are not completely engulfed and only weak attractive interactions between host and guest molecules can be established. The increased sensitivity of 2a and 2b for chlorinated solvents
compared to 1b is explained by the larger surface of contact for the vaselike molecules. The aromatic guests m-xylene and p-xylene show similar sensor effects for 1b, slight differences for 3, 2b, and 2c, and the best differentiation is observed for 2a (see Figure 5b). As demonstrated in Figure 6, cavitand 1a, which forms the same hollow as 1b, is not able to engulf the isomer xylenes completely and therefore no significant separation is possible. In contrast to this behavior, p-xylene fits excellently into the interior of 2a and can be discrimined from m-xylene. Benzene is preferred to cyclohexane by the same ranking as p-xylene to m-xylene for all host molecules investigated. The increased sensitivity toward toluene elucidates the importance of σ-π interactions of the toluene methyl group with the aromatic quinoxaline substituents in combination with the π-π interactions. Figure 5c presents the sensor effects of some solvents able to form hydrogen bonds. Since the host molecules 1b and 3 have eight and two hydroxyl groups, respectively, they reveal a high affinity to solvents such as butanol or pyridine. The extraordinary sensitivity resulting from host-guest interactions of molecules able to form hydrogen bonds proves the almost superior strength of this specific donor-acceptor interaction. In the case of pyridine, the filling factor indicates the binding of more than one analyte molecule per host 1b and 3. The sensitivity of the host molecules toward humidity can be reduced or eliminated by a high fraction of aromatic or aliphatic components in the host molecule, even if two hydroxyl groups are not substituted. Analytes with a large fraction of aromatic or aliphatic moieties and an additional hydrogen bond ability still develop good access to the host molecule and show high sensitivities. Force Field calculations (MM3). Computational chemistry favorably supports the prediction of the sensitivity of novel supramolecular compounds, provided that stabilization enthalpies and sensor effects are correlated.19-21 As described earlier, this is true for calix[4]resorcinarene derivatives and other host molecules, because the inclusion phenomena are of an intracavitative nature.22 The expression for the equilibrium constant K can be derived from the chemical potential of the analyte (A) being equal in the gas phase (g) and in the sensor layer (s) [µg(A) ) (19) Dickert, F. L.; Haunschild, A.; Maune, V. Sens. Actuators B 1993, 12, 169173. (20) Dickert, F. L.; Haunschild, A.; Reif, M.; Bulst, W.-E. Adv. Mater. 1993, 5, 277-279. (21) Dickert, F. L.; Schuster, O. Microchim. Acta 1995, 119, 55-62. (22) Dickert, F. L.; Haunschild, A.; Kuschow, V.; Reif, M.; Stathopulos, H. Anal. Chem. 1996, 68, 1058-1061.
Analytical Chemistry, Vol. 69, No. 6, March 15, 1997
1003
Figure 7. Correlation of the equilibrium constant K of solvent incorporation of 1b and the MM3-calculated stabilization energies ∆H° of the respective host-guest complex (regression coefficient r2 ) 0.666).
Figure 8. Correlation of the equilibrium constant K of solvent incorporation of 3 and the MM3-calculated stabilization energies ∆H° of the respective host-guest complex (regression coefficient r2 ) 0.667).
µs(A), eq 1, mole fraction x of analyte A in the gas and solid phase].
(µ°(A) + RT ln x)g ) (µ°(A) + RT ln x)s
(1)
[HA] K ) p° [H]0pA
(2)
For the equilibrium constant K, the expression in eq 2 is obtained with the normal pressure p°, the partial vapor pressure pA of the analyte, and the ratio of [HA] (host analyte complex) and [H]0 (overall host molecules), which is equal to the mole fraction xs in eq 1. The experimentally determined equilibrium constant K for the host-guest complexation is described by the parameters ∆H° and ∆S° in eq 3. The logarithm of K is plotted vs the MM3
ln K ) -
∆H° ∆S° + RT R
(3)
complexation enthalpy ∆H° as a first attempt to predict sensor effects. According to Figure 7 and Figure 8 this behavior is fulfilled for both coatings 2c and 3, and the model can be used for a qualitative interpretation of the frequency change during analyte exposition. Here, in analogy to isokinetic phenomena, the entropy of the complexation process either may be linearly dependent on the stabilization enthalpy or proves to be constant. For theoretical modeling of the complex formation, however, the loss of entropy that accompanies every host-guest complexation has to be taken into consideration, according to eq 3. As visualized in Figure 9, the prediction of sensor behavior can be formulated more precisely for the rigid vase structure 2a, as represented by the regression coefficients r2 ) 0.997 and r2 ) 0.963 instead of a regression coefficient of r2 ) 0.751 for the mere ∆H° correlation. In this improved model, the way of incorporation into this narrow vaselike cavity is more intimately dependent on the shape and functionality of the analyte. Therefore, entropic terms are used additionally to enthalpic effects and the loss of disorder during analyte inclusion is considered. For an ideal case 1004 Analytical Chemistry, Vol. 69, No. 6, March 15, 1997
Figure 9. Correlation of the equilibrium constant K of solvent incorporation of 2b and the MM3-calculated stabilization energies ∆H° (b) (regression coefficient r2 ) 0.751) and the free enthalpies ∆G° using entropies of condensation (2) of the respective host-guest complex [group 1, regression coefficient r2 ) 0.997; group 2, regression coefficient r2 ) 0.963 (CHCl3 omitted)].
where host-guest interactions are similar to those in the corresponding pure phase of the solvent, the inclusion of the analyte could be described as a condensation out of the gaseous phase. Thus, for an estimation, we compare sensor effects, expressed by the equilibrium constant, to Gibbs enthalpies, which were calculated by stabilization energies, and the entropies of condensation for every solvent. In this way, a separation into two groups appears, as given in Figure 9, indicating two different states of complexation. For the spacious m- and p-xylene, which stick in the upper narrowing region of the cavity, as well as for pyridine and 1-butanol, which develop extraordinarily strong dipole-dipole or hydrogen-bonding interactions to the inner surface of the cavity, the entropic loss during encircling is larger than that of the smaller and low functionalized analytes forming the second group. While the analytes of group 2 adopt a flexible orientation and seem to behave as in the liquid phase, the molecules of group 1 suffer from a larger decrease of disorder. In those host-guest complexes the analytes are supposed to realize a pseudocrystalline
state. The behavior of chloroform in group 2 can be explained as due to its special orientation in the host-guest complex. The spacious chlorine atoms hinder the formation of a strong hydrogen bond to the host molecule, resulting in a quite flexible complexation. Altogether, this extended model not only gives aid for the prediction of the sensor response of rigid host-guest structures but can also estimate the mechanism of incorporation.
the accessibility to the host, turning a formerly densely packed structure into fluffy fast-responding coating materials. Molecular modeling facilitates the search for supramolecular materials that form efficient host-guest inclusions. The refinement of this thermodynamic model by terms of entropy further improves the possibilities to predict sensitive capabilities in the forefield of synthesis.
CONCLUSIONS The derivatization of calix[4]resorcinarenes allows the design of sensitive host molecules that meet the high demands of chemical sensing. Sensitivities and kinetics were promoted by increasing the hydrophobic inner contact surface of the cavity and
Received for review June 13, 1996. Accepted December 20, 1996.X AC9605859 X
Abstract published in Advance ACS Abstracts, February 1, 1997.
Analytical Chemistry, Vol. 69, No. 6, March 15, 1997
1005
