Analysis of guest binary mixtures by tert-butylcalix[6]arene using host memory of previously bound guests†

Goulnaz D. Safina ^a, Marat A. Ziganshin ^a, Aidar T. Gubaidullin ^b and Valery V. Gorbatchuk *^a
aKazan Federal University, A.M. Butlerov Institute of Chemistry, Kremlevskaya, 18, 420008 Kazan, Russia. E-mail: Valery.Gorbatchuk@ksu.ru; Fax: +7 843 2337416; Tel: +7 843 2337309
^bA.E. Arbuzov Institute of Organic and Physical Chemistry, Akad. Arbuzova 8, 420088 Kazan, Russia

First published on 14th December 2012

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Introduction

A search of new experimental approaches giving molecular recognition of small neutral molecules is of major importance for a number of applications including medical diagnostics and odor detection.^1,2 A usual key-to-lock recognition scheme requires a substrate (guest) to have at least two specifically oriented functional groups capable of H-bonding or donor–acceptor interaction with receptor (host) having complementary structure.^3,4 The substrate, which fits to such lock, is preferentially bound. However, only moderate selectivity is observed in many cases, especially in mixtures, which is a true test of molecular recognition.^5,6 Partial improvement can be reached by using receptor arrays.⁷ Still, this approach gives poor results for recognition of relatively inert compounds.

To reach higher selectivity, clathrate-forming hosts, like calixarenes, were tried, which offer a variety of possibilities.³ Being a little more selective than rubbery polymers,³ crystalline receptors have problems with guest-binding irreversibility, host thermal history^8,9 and mutual influence of the guests in a mixture on each others’ binding.^10–12 This makes their preferential binding ability not good enough for recognition purposes. So, some other properties of calixarenes may be used. Thus, two-step formation of clathrates gives a genuine molecular recognition of benzene in mixtures with its close homologues just by number and position of guest-binding steps in sensor experiment.¹³

Another promising property of some calixarenes is their ability for induced polymorphism.^14,15 If this polymorphism is induced by a previously bound guest, it may be very selective^16–19 being equivalent to host memory of a particular guest compound eliminated from host–guest clathrate. After clathrate decomposition, tert-butylcalix[6]arene,¹⁶ adamantylcalix[4]arene¹⁸ and some thiacalix[4]arene derivatives^17,19 can form loose metastable polymorphs, Fig. 1a, which parameters (enthalpy and temperature of exothermic collapse) strongly depend on the guest molecular structure. Thus, an eliminated guest leaves its image, or imprint, in the guest-free host phase. The written memory can be read in a DSC experiment. Only few guests can be remembered in such a way, while most others do not induce any memory, Fig. 1b.

In the present work, the applicability of this memory-based approach was studied for binary mixtures of guests with close molecular structure. One of two guests in each studied mixture can be remembered by studied host, tert-butylcalix[6]arene (1), after formation and decomposition of single clathrate, while the other one does not have such property, Fig. 1. With the potential ability of both guests entering the same clathrate crystal, Fig. 1c, the problem is to find, which trait is dominant: that of remembered guest or of non-remembered one? Such mutual influence creates a possibility for detection of compounds in mixtures, with the host keeping an image not only of a target guest but also of its concentration in the presence of other guests. This can give a new principle of molecular recognition of a substrate without an ordinary key-to-lock mechanism and preferential binding.

Experimental section

Materials

tert-Butylcalix[6]arene (1) purchased from Fluka (No. 19723) was purified from nonvolatile impurities using multiple recrystallization from toluene, and from volatile impurities by heating in vacuum of 100 Pa during 30 min at 230 °C and then for 6 h at 200 °C. This gives a thermally stable form of host 1 (α-phase).¹⁶ The purity of the calixarene 1 powder was checked as described elsewhere.¹⁸ Purified guests²⁰ had at least 99.5% purity.

The samples of mixed clathrates (7–17 mg) were prepared in the aluminum crucibles (40 μl) by the saturation of calixarene 1 powder (α-phase) with vapors created by a large excess of binary liquid mixtures of volatile compounds (100 μl). Equilibration was performed in hermetically sealed vials of 15 ml for 72 h at 298 K. In this equilibration process, liquid mixture remained mostly unevaporated, and its composition did not essentially changed due to evaporation and binding. Also single clathrates of calixarene 1 with benzene, cyclohexane, carbon tetrachloride and chloroform were prepared by the saturation of host with guest vapors at relative vapor pressure of P/P₀ = 1, as described elsewhere.¹⁸ Here, P is partial vapor pressure of guest, and P₀ is its saturated vapor pressure.

Methods

Simultaneous thermogravimetry and differential scanning calorimetry (TG/DSC) combined with evolved gas analysis by mass spectrometry (MS) were performed for clathrate samples using thermoanalyzer STA 449 C Jupiter (Netzsch) coupled with quadrupole mass-spectrometer QMS 403 C Aeolos as described elsewhere.¹⁸

The TG/DSC/MS experiment for these samples began after 15–20 min of their equilibration in argon flow (75 ml min⁻¹) inside the oven of thermoanalyzer at room temperature. In each experiment, the temperature rate was 10 K min⁻¹. Compositions of mixed and intermediate clathrates were calculated by comparison of mass loss and peak area ratios on the thermogravimetric curve and ion thermogram, respectively, on the first and second steps of guests elimination. The guest contents values were determined with 2% error but no less than 0.02 mol of guest per 1 mol of host. The error of the enthalpy determination for polymorphic and pseudopolymorphic transitions is 1 kJ·mol⁻¹ for host 1.

All powder X-ray diffraction data (XRPD) were collected on Bruker D8 Advance diffractometer equipped with Vantec linear PSD, using Cu Kα radiation (40 kV, 40 mA). Room temperature data were collected in the Bragg–Brentano mode with a flat-plate sample. The samples of host 1 clathrates with cyclohexane and most clathrates with c-C₆H₁₂–C₆H₆ mixtures were lightly grounded and loaded into a standard sample holder. Other clathrate samples were studied on the flat silicon plate. X-ray patterns were recorded in the 2θ range in 0.008° steps, with a step time of 0.5 s.

Thermodynamic activity P/P₀ of benzene dissolved in polyethyleneglycol PEG-400 was determined by headspace GC analysis as described elsewhere.²¹

Results and discussion

To study the concentration effect of guest mixture on the properties of host saturation products, α-phase of calixarene 1 was equilibrated with headspace of binary liquids: CCl₄ (1)/CHCl₃ (2) and C₆H₆ (1)/c-C₆H₁₂ (2). In each mixture, host 1 can remember only component (1) after its elimination from clathrate.¹⁶

The saturation products were studied using simultaneous TG/DSC/MS analysis. The most representative TG and DSC curves from these experiments are shown separately in Fig. 2 and 3. Full data are given in ESI.† The obtained parameters of the studied systems are given in Tables 1 and 2, including the composition of clathrates S, mass loss Δm in each step of clathrate decomposition, enthalpy of the second guest elimination step, ΔH, and enthalpy of polymorphic transition, ΔH_col.

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Both enthalpies are given per 1 mole of host. End points of the first decomposition step and temperatures of DTG-peaks are given in ESI.†

Each studied pair of guests has a concentration range, where their saturation product with 1 has two exothermic peaks in DSC curve: at T_col = 186 ± 3 and 253 ± 3 °C for C₆H₆/c-C₆H₁₂, and at T_col = 193 ± 3 and 249 ± 3 °C for CCl₄–CHCl₃ mixture, Fig. 3. This range of liquid concentration is 0–22 vol% of c-C₆H₁₂ in C₆H₆ and 0–8 vol% CHCl₃ in CCl₄. The second exothermic peak on each DSC curve is not analyzed here being too small for quantitative estimations (−1/−4 kJ·mol⁻¹, ESI†). Besides, the enthalpy of the first guest elimination step is not considered in the present work, because of the big error of determination.

Once temperatures of host collapse, T_col, do not depend significantly on the guest mixture composition, Fig. 3, the values T_col may be used for qualitative recognition of benzene or tetrachloromethane. Other guests remembered by 1 have the higher T_col values.¹⁶

The enthalpy of the first exothermic peak of host collapse, ΔH_col, changes with concentration of saturating mixtures, φ (vol%), in a sigmoidal way, Fig. 4. This shape of ΔH_col concentration dependence is similar to the sigmoidal shape of vapor sorption isotherms by calixarenes and other clathrate forming hosts,^{13,16,18,21–23} which indicates a phase transition of clathrate formation. Respectively, one can conclude the presence of two solid phases near the half-wave points of the plots on Fig. 4.

The enthalpy of the second guest elimination step, ΔH, may have a more complex dependence on the concentration of saturating mixtures. First, ΔH values increase with the increase of component (2) contents but in a wider concentration range than ΔH_col value does. Then, for the C₆H₆–c-C₆H₁₂ mixture, no significant change of ΔH value takes place, while for the CCl₄–CHCl₃ mixture, a decrease of this value is observed, Fig. 4. So, the analysis of ΔH_col concentration dependence is a simpler problem.

The shape of TG curves obtained complies with the conclusion made above on the phase transition. Below the concentrations of saturating mixtures, corresponding to the half-wave points of ΔH_colvs. φ plots, Fig. 4, the saturation products have the coinciding initial parts of TG curves, Fig. 2, which are differing only by the end points of the first guest elimination step (ESI†). Above φ values of these half-wave points, TG curves have coinciding parts corresponding to the second step of guest loss. So, below the half-wave concentration, the saturation product behaves as a clathrate with component (1), benzene or tetrachloromethane. Above this point, a behavior similar to that of clathrate with component (2), cyclohexane or chloroform is observed.

To check if this phase transition is really caused by component (2) additive, not by decrease of component (1) activity, we studied a product of host 1 saturation by excess of benzene vapor at relative vapor pressure P/P₀ = 0.79 and 298 K. This P/P₀ value corresponds to benzene activity in its liquid mixture with 24 vol% of c-C₆H₁₂, which is the end point of phase transition range, Fig. 4, Table 1. Benzene activity coefficient in this mixture is γ = 1.²⁴ In this alternative experiment, host 1 powder was equilibrated with vapor of benzene solution in PEG-400, and then benzene activity in the equilibrated system was determined using headspace GC analysis. Thermogram of thus prepared sample is given in Fig. 5.

The TG and DSC curves of this sample indicate that it does not differ much from a single-guest clathrate of benzene. A high negative enthalpy of host collapse (ΔH_col = −32 kJ·mol⁻¹) is observed which is only 11% lower than that of saturated clathrate. Besides, the TG curve shows a one-step guest removal from 1·2.92C₆H₆ clathrate, which also indicates a complete host saturation. So, the change in sample properties at variation of saturating mixture concentration within the phase transition range is caused not by reduction of guest (1) activity, but by the presence by unremembered guest (2). So, the concentration dependence of host collapse enthalpy may be used for quantitative estimation of guest contents in the analyzed mixture.

Another problem is the nature of phases, participating in phase transition near a half-wave point on Fig. 4. To make clear whether these phases are mixed clathrates, not the mechanical mixtures of two single clathrates, the thermal behavior of the next two clathrate samples was compared. The first one was a mechanical mixture of two single clathrates prepared separately by saturation of 1 (α-phase) with pure vapors of chloroform and tetrachloromethane. This sample contains 53% (w/w) of 1·3.80CCl₄ and 47% of 1·1.18CHCl₃. The second sample was prepared by saturation of host 1 (α-phase) with vapor mixture of chloroform and tetrachloromethane created by 20 vol% solution of CHCl₃ in CCl₄. This mixture gives nearly the same guest ratio in solid host phase after equilibration as in the first sample. The results of thermal analysis for these samples are shown in Fig. 6. Thermograms of pure clathrates of 1 with CCl₄ and CHCl₃ are given in ESI.†

These data, Fig. 6, perform a non-equivalence of the studied samples. The mechanical mixture of clathrates shows an independent release of guests, and each resulting thermogram is close to a simple sum of thermograms for pure single guest clathrates from separate experiments, Fig. 6a. Exothermic peak on DSC curve (ΔH = −18 kJ·mol⁻¹) is near a half of that for pure 1·3.80CCl₄ clathrate, Table 2. Additive thermal behavior was also observed for mechanical mixture of 1·2.86C₆H₆ and 1·1.81c-C₆H₁₂ clathrates, ESI.†

The thermogram of the second sample prepared by host 1 saturation with CCl₄–CHCl₃ vapor mixture, Fig. 6b, is essentially different from those of mechanical mixture, Fig. 6a. The host memory for tetrachloromethane is completely absent in the second sample according to the DSC curve, which performs the absence of exothermic transition. The TG curve resembles that of pure 1·1.18CHCl₃ clathrate, ESI,† where the most amount of guest is evolved with DTG peak at 230 °C. Ion thermograms and TG curve indicate simultaneous release of both guests in two steps. The first step is at 105 °C, which is lower than those of single clathrates with both guests. The most of tetrachloromethane leaves the product of 1 saturation with guest mixture at 237 °C, Fig. 6b, which corresponds to the main decomposition step of single clathrate with chloroform 1·1.18CHCl₃, ESI.† So, this mixed clathrate sample behaves as a single phase having no significant traces of single clathrate with CCl₄.

A specific nature of this mixed clathrate is confirmed by its X-ray powder diffractogram, Fig. 7a, sample 2, which is closer to that of single 1·1.18CHCl₃ clathrate, sample 1, and is essentially different from diffractogram of single-guest clathrate 1·3.80CCl₄, sample 4, despite the mixed clathrate contains more tetrachloromethane than chloroform, Table 2. Besides, diffractograms of samples 1 and 2 also have some noticeable distinctions at 2θ = 5° and in the range from 16 to 19°. The sample 3, prepared by saturation of 1 with mixture of 6 vol% CHCl₃ in CCl₄, has a large reflex at 2θ = 5.2°, which is observed for mixed clathrate 2, but not for single clathrates (sample 1 and 4). So, formation of mixed clathrates with CCl₄/CHCl₃ mixture gives at least one new phase, not coinciding with phases of corresponding single clathrates. This conclusion is in agreement with non-monotonous change of shape both of DSC and TG curves at the variation of guests’ ratio in their mixture, Fig. 2b and 3b.

The packing of mixed clathrates of host 1 changes more monotonously with variation of guest ratio in C₆H₆–c-C₆H₁₂ saturating mixture, Fig. 7b. The samples 3 and 4 prepared by saturation of 1 with mixtures having cyclohexane contents ≥15 vol% are practically isomorphous to the single clathrate 1·1.81c-C₆H₁₂, sample 5. The sample 2 prepared by saturation of host 1 with mixture of 10 vol% c-C₆H₁₂ in benzene gives mixed clathrate phase having packing very close to that of single clathrate 1·2.86C₆H₆, sample 1. So, the formation of only 2 clathrate phases may be concluded for this ternary system.

The dependence of guest mixture composition Z in saturation product on guest contents X in saturating binary mixtures indicates a moderate selectivity of 1 for cyclohexane in its mixture with benzene, and a low selectivity for CCl₄/CHCl₃ pair, Fig. 8. The values Z and X are guest molar fraction in a mixture bound by host and in initial binary liquid, respectively. The observed selectivity is not much different from that of other clathrate-forming hosts studied elsewhere.^25–29

Comparison of concentration dependencies of ΔH_col and Z(CHCl₃) values on the concentration of chloroform in the saturating binary liquid given in Fig. 4b and 8b, respectively, performs the possibility of molecular recognition of binary mixture even without preferential host–guest binding.

However, the obtained ion thermograms show a strong mutual influence of bound guests on their release parameters. This is a change of guest distribution between clathrate decomposition steps depending on the composition of the saturating mixture, Tables 1 and 2. In each studied system, both bound guests are released simultaneously in one or two steps, despite essential difference in elimination temperatures observed for respective single-guest clathrates. Within the transition range 5–22 vol% of c-C₆H₁₂ (2) in C₆H₆ (1) and 2–20 vol% of CHCl₃ (2) in CCl₄ (1), each ion thermogram has 2 peaks at temperatures, corresponding to the main decomposition steps of single clathrates with components of each mixture, ESI.†

Above and below the transition range, both bound guests are released by scenarios, which were set up by single clathrates with components (2) and (1), respectively. For example, at cyclohexane concentrations in benzene ≤16 vol%, most of bound benzene leaves clathrate at the first step with a peak at 129 °C, Fig. 9a, corresponding to the peak of its release from the single clathrate, Fig. 2a, ESI.† Below 12 vol% of c-C₆H₁₂ in this saturating mixture, also most cyclohexane is eliminated at this step, Table 1. At the 24 vol% and higher concentrations, cyclohexane becomes a major component in solid phase, Table 1, and both guests are simultaneously released in one step at much higher temperature of 230 °C, Fig. 9b, which corresponds to a second step of cyclohexane elimination from its pure clathrate with 1, Fig. 2a, ESI.† So, the sample prepared using this guest mixture may be considered as homogeneous enough, which is in agreement with the XRPD data described above, Fig. 7.

The samples prepared by saturation of 1 with CCl₄ (1) + CHCl₃ (2) mixture have even more cooperative dependence of their thermal behavior on the presence of component (2), chloroform. Already 8 vol% of chloroform in the initial saturating mixture is enough to move a significant amount of bound tetrachloromethane, 0.72 mol per mol host 1, to the second decomposition step at 222 °C, which corresponds to DTG peak of 1·1.18CHCl₃ single clathrate (230 °C), Fig. 9c, ESI.†

However, in this sample, only 0.05 mol of CHCl₃ leaves clathrate on the second step. Moreover, for chloroform contents in saturating mixture of 20 vol%, this guest and tetrachloromethane are mutually exchanged by their steps of elimination from mixed clathrate, Fig. 6b. Most of tetrachloromethane leaves this clathrate at higher temperature of 237 °C, while most of chloroform is released at the first step with DTG peak at 105 °C. So, by heating this sample to 205 °C, one may prepare 1·0.88CCl₄·0.07CHCl₃ clathrate, losing tetrachloromethane on 80 °C above the point of this guest release from its single clathrate with 1. In this case, the temperature of remembered guest elimination is defined by unremembered guest, most of which had gone already at lower temperature.

Conclusions

An ability of tert-butylcalix[6]arene to remember selectively previously bound guests can be effectively used for molecular recognition of such compounds in binary mixtures of guests, where the second guest is not remembered but still plays an active role wiping the host memory of the first one. This property may be used for quantitative estimation of mixture composition even in the absence of preferential binding of its components.

While the guest release from tert-butylcalix[6]arene saturated by a mixture of 2 guests gives up to 4 pseudopolymorphic and polymorphic transitions, such behavior may be used also to increase the stability of guest encapsulation by host. The complex mutual influence of 2 bound guests on their release points may cause the formation of an intermediate clathrate with a given guest where only a small additive of the second guest is present. The thermal stability of such clathrate was found to be much higher than that formed by saturation of host with pure guest.

Acknowledgements

This work was supported by Russian Foundation for Basic Research (grant no. 11-03-01215-a) and the Russian Ministry of Science and Education (State Contract no. 16.552.11.7008).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c2ob27164h

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