Investigation of chloromethane complexes of cryptophane-A analogue with butoxy groups using ¹³C NMR in the solid state and solution along with single crystal X-ray diffraction.

Host-guest complexes between cryptophane-A analogue with butoxy groups (cryptophane-But) and chloromethanes (chloroform, dichloromethane) were investigated in the solid state by means of magic-angle spinning (13)C NMR spectroscopy. The separated local fields method with (13)C-(1)H dipolar recoupling was used to determine the residual dipolar coupling for the guest molecules encaged in the host cavity. In the case of chloroform guest, the residual dipolar interaction was estimated to be about 19 kHz, consistent with a strongly restricted mobility of the guest in the cavity, while no residual interaction was observed for encaged dichloromethane. In order to rationalize this unexpected result, we performed single crystal X-ray diffraction studies, which confirmed that both guest molecules indeed were present inside the cryptophane cavity, with a certain level of disorder. To improve the insight in the dynamics, we performed a (13)C NMR spin-lattice relaxation study for the dichloromethane guest in solution. The system was characterized by chemical exchange, which was slow on the chemical shift time scale but fast with respect to the relaxation rates. Despite these disadvantageous conditions, we demonstrated that the data could be analyzed and that the results were consistent with an isotropic reorientation of dichloromethane within the cryptophane cavity.

Introduction

Cryptophanes are cage‐like compounds consisting of two equivalent cyclotribenzylene caps, often carrying substituents on the phenyl rings and connected by flexible –O‐(CH2)n‐O‐linkers. The first cryptophane synthesized by Collet et al. in 19811, 2 was an anti‐isomer, carrying one methoxy group on each phenyl ring with three caps, often carrying (n = 2) linkers and was called cryptophane‐A. Cryptophanes can act as molecular hosts, forming inclusion complexes with small organic molecules (such as chloromethanes),3, 4 as well as with xenon atoms.5 The chemistry of cryptophanes has been reviewed a few years ago.6 The cryptophane‐A analogue with butoxy substituents instead of methoxy groups – called cryptophane‐But – was prepared by Brotin et al.7, 8 The structure of cryptophane‐But is shown in Fig. 1. We have recently reported a study of the chloromethane complexes of cryptophane‐A and cryptophane‐But using a variety of liquid‐state NMR techniques.9 Here, we extend this work by studying cryptophane‐But complexes with dichloromethane and chloroform in the solid state, using 13C NMR and single‐crystal X‐ray diffraction (XRD). We thereby exploit the fact that cryptophane‐But is readily prepared in the crystalline form. Solid cryptophane complexes with chloromethane guests have previously been studied using XRD by the Collet group,10, 11 by our laboratory12 and by Taratula and co‐workers.13 Solid‐state investigations of chloromethane@cryptophane systems, using the deuteron NMR12 and 13C NMR14 have also been reported.

Figure 1

Schematic structure of cryptophane‐But.

In this paper, we report solid‐state 13C cross‐polarization (CP) magic‐angle spinning (MAS) NMR spectra for CH2Cl2 and CHCl3 complexed by cryptophane‐But, where two‐dimensional MAS spectra obtained using the separated local fields (SLF) method inform about the motionally averaged 13C‐1H dipolar couplings.15 Because the results turned out to deviate from our expectations, we also gained complementary information from single crystal XRD studies of both complexes, as well as 13C NMR relaxation experiments in solution for CH2Cl2@cryptophane‐But.

Experimental

Materials

Cryptophane‐But was synthesized following the method of Brotin et al.7, 8 13C‐labelled chloroform and dichloromethane, as well as the deuterated solvent, 1,1,2,2‐tetrachloroethane‐d, were obtained from Cambridge Isotope Laboratory, while non‐labelled chloroform and dichloromethane were purchased from Sigma‐Aldrich (St. Louis, Mo, USA).

Sample preparations and methods

Solid‐state NMR

For the solid‐state NMR experiments, two powder samples were prepared by dissolving cryptophane‐But in a mixture containing a 1 :10 ratio of 13C‐labelled and natural abundance chloroform or dichloromethane. The two mixtures were left to evaporate at room temperature over 2 days. The crystals obtained were then ground and packed in 4 mm zirconia pencil rotors that were spun at a 9.00 kHz MAS frequency throughout all NMR experiments.

The solid‐state experiments were performed at 9.4 T (−400.07 MHz 1H Larmor frequency) using a Bruker Avance‐III spectrometer (Rheinstetten, Baden‐Württemberg, Germany). All experimentation on CHCl3@cryptophane‐But and CH2Cl2@cryptophane‐But was carried out at temperatures of 268 and 238 K, respectively. In the case of CH2Cl2@cryptophane‐But, additional experiments were also carried out at a lower temperature of 203 K (not shown); no significant differences were observed at the two temperatures. All NMR experimentation started with a ramped16 CP pulse block, using 13C and H nutation frequencies of 50 ± 5 and 59 kHz, respectively, contact intervals of 5.0 ms (CHCl3@cryptophane‐But) and 2.5 ms (CH2Cl2@cryptophane‐But) and relaxation delays of 5 s throughout. The 90° proton pulse prior to CP operated at 83 kHz. High‐power decoupling at 83 kHz using the two pulse phase modulation (TPPM) scheme17 (τ p = 5.8 µs and Δφ = 15°) was used during the NMR signal acquisitions in both 1D and 2D NMR measurements. Chemical shifts are referenced externally to neat tetramethylsilane.

The 2D SLF recoupling experiments utilized the constant‐time protocol of ref. 18 and the symmetry‐based pulse sequence18, 19 for reintroducing the heteronuclear 13C‐1H interactions. It is based on a repeating pair of 180° pulses, 18070180−70 (where each subscript denotes the rf phase in degrees) that demands a 1H nutation frequency of exactly 9 times the MAS rate,18, 19 i.e. 81 kHz for the present experimentation. The 2D NMR acquisitions involved 4994 t 2 increments and 40 (CHCl3@cryptophane‐But) and 80 (CH2Cl2@cryptophane‐But) t 1‐increments, with the respective dwell times Δt 2 = 20.0 µs and Δt 1 = 37.04 µs (the latter implying that t 1 was sampled after completion of six 1800‐pulse pairs of the repeating scheme); this provided spectral windows of 50 and 27 kHz along the direct and indirect spectral dimensions, respectively. The 2D data sets were zero‐filled to 512(t 1) × 8192(t 2) time points and apodized by 250 Hz Gaussian (t 1) and 20 Hz Lorentzian (t 2) full width at half maximum broadening before 2DFT of the s(t 1, t 2) data set. A cosine Fourier transform was used in the indirect dimension. The 1H rf carrier frequency was set at the middle of the proton spectrum (5 ppm), while that of 13C was at 77 and 51 ppm for CHCl3 and CH2Cl2, respectively. The 180° 13C pulse for chemical shift‐refocussing that appears at the centre of the constant time interval T = 4.4 ms operated at 90 kHz. The remaining of T not involving pulsing decoupled the heteronuclear interactions by a CW field at 85 kHz (see ref. 18). The total number of scans per t 1 value was 40 for CHCl3@cryptophane‐But and 80 for CH2Cl2@cryptophane‐But.

Numerically, exact simulations of the heteronuclear recoupling segment of the 2D SLF experiment on CHCl3@cryptophane‐But assumed an isolated 13CH group in the presence of the recoupling sequence. The calculations included all relevant experimental parameters (MAS rate, rf pulses and 13C‐1H interaction) and employed 500 Hz full width at half maximum Lorentzian line broadening. All numerical procedures followed those outlined in detail in our previous work.4

X‐ray diffraction

Crystals for the XRD measurements were obtained by dissolving the cryptophane‐But in chloroform or dichloromethane at near‐critical concentrations. The single crystals were obtained from a slow controlled solvent evaporation and, once selected, were directly covered with epoxy glue to prevent them from deterioration during the diffraction experiments.

Single crystal XRD experiments were performed on an Oxford Diffraction Xcalibur3 (Oxford Instruments, Oxford, UK) diffractometer equipped with a graphite monochromator. The data were collected at room temperature using Mo Kα radiation (λ = 0.71073 Å). Absorption correction and data reduction were performed with the software CrysAlis red which was also employed for the analytical absorption correction.20 The structure solution was carried out with SIR9721 and the refinement with SHELXL22 in the WinGX23 environment.

Direct methods (SIR97) yielded reasonable atomic positions for the cryptophane. Severe structural disorder was found to be present in the butoxy groups. Thus, the C—C distances to the nearest and the next nearest neighbour were restricted to 1.54 and 2.52 Å, respectively, in order to obtain regular carbon chains having C—C—C bond angles close to 110°. The butoxy groups were found to occupy two almost equally populated positions. Minor disorder was also observed in the carbon atoms belonging to the linkers.

The atomic positions for the guest molecules were located in the difference Fourier map. Both dichloromethane and chloroform were disordered over several positions. The distances of the guest molecules were restrained (C‐Cl: 1.7 Å) to obtain a reasonable molecular geometry. All occupancies for the disordered guest positions were refined to fully occupy the host cavity.

Hydrogen atom positions were generated in expected positions and refined using the default parameters in SHELXL. No hydrogen atoms were assigned to the guest molecules. Non‐hydrogen atoms were refined anisotropically, except for the carbon atom in the guest chloroform that was refined isotropically.

The crystal data and selected details of the reduction and refinement calculations are summarized in Table 1. The structures were drawn with the program diamond.24 The electron density maps were calculated in WinGX23 and displayed in vesta.25

Table 1

Crystal data and structure refinement parameters

Empirical formula	C72H90O12 · CHCl3	C72H90O12 · CH2Cl2
Formula weight (g/mol)	1265.80	1230.35
Temperature (K)	293	293
Wavelength (Å)	0.71073	0.71073
Crystal system	Trigonal	Trigonal
Space group	R‐3c (No. 167)	R‐3c (No. 167)
a (Å)	17.2579(9)	17.2060(7)
b (Å)	17.2579(9)	17.2060(7)
c (Å)	40.398(2)	40.4426(16)
α (°)	90	90
β (°)	90	90
γ (°)	120	120
Volume (Å3)	10420.0(9)	10368.8(7)
Z	6	6
Densitycalc. (g cm−3)	1.210	1.183
Absorption coefficient (mm−1)	0.191	0.153
F(000)	4050	3948
Crystal colour	Colourless	Colourless
Crystal habit	Block	Block
Crystal size (mm3)	0.188 × 0.169 × 0.088	0.445 × 0.288 × 0.169
Theta range for data collection (°)	3.39–28.82	3.40–27.72
Index ranges	−23 ≤ h ≤ 10	−22 ≤ h ≤ 22
	−6 ≤ k ≤ 22	−21 ≤ k ≤ 21
	−54 ≤ l ≤ 50	−52 ≤ l ≤ 52
Reflections collected / unique	7325/2686 (R int = 0.043)	20569/2526 (R int = 0.040)
Reflections [I > 2sigma(I)]	1284	1598
Data/restraints/parameters	1284/16/194	1598/19/208
Goodness‐of‐fit on F 2	0.998	1.170
Final R indicesa	R 1 = 0.0760	R 1 = 0.0793
[I > 2sigma(I)]	wR 2 = 0.1649	wR 2 = 0.1658
R indices (all data)	R 1 = 0.1628	R 1 = 0.1309
	wR 2 = 0.2104	wR 2 = 0.1867
Largest diff. peak and hole (eÅ−3)	0.18 and −0.13	0.13 and −0.12

R 1 = ∑‖F o| – |F c‖/∑|F o|; wR 2 = {∑[w(F o 2–F c 2)2]/∑[w(F o 2)2]}1/2

Solution‐state NMR

Cryptophane‐But was dipped into non‐labelled dichloromethane, and the solvent was then let to evaporate. This process was repeated three times to remove undesirable products that potentially formed during synthesis. For this work, a sample containing 11 mM cryptophane‐But and 13 mM CH2Cl2 in 1,1,2,2‐tetrachloroethane‐d was used. This sample corresponds to specimen number 4 in the earlier work from our laboratory.9

The liquid‐state experiments were run on a Bruker Avance spectrometer operating at 14.1 T with a 5 mm TXI probehead. Temperature calibration (±1 K) was performed by using a resistance detector made of copper wire dipped into silicon oil contained in a 5 mm tube.

The spin‐lattice relaxation time T 1 of dichloromethane@cryptophane‐But was measured by a series of 2D inversion‐recovery 1H‐13C HSQC experiments26 using a double INEPT transfer27 (with a delay equal to 1/4J  = 1.4 ms for CH2Cl2) and sensitivity improvement.28 The number of real data points acquired was 128 in the t dimension (13C) and 2048 in the t dimension with a spectral width of 10 ppm in the 1H dimension and 100 ppm in the 13C dimension. Echo‐antiecho acquisition29 was used for frequency‐sign discrimination in the ν 1 dimension. For these experiments, 32 scans and a recycle delay of 3 s were used. The T 1 determination was based on the acquisition of 12 spectra with inversion‐recovery delays ranging from 5 ms to 3 s.

Data were processed with the Bruker Topspin software. Linear prediction was applied in the indirect dimension, followed by apodization with a squared‐cosine‐bell function.

Results and discussion

Solid‐state NMR

Figure 2 shows the 13C CPMAS spectra recorded from the (a) CHCl3@cryptophane‐But and (b) CH2Cl2@cryptophane‐But samples, both revealing NMR signals from the guest molecules assuming encaged as well as interstitial positions. In an alternative interpretation, one could consider the ‘interstitial’ signal as arising from chloromethane adsorbed on the surface of the crystals. The 13C chemical shifts of the encaged guests accord very well with those obtained by solution NMR (not shown). This observation is in agreement with our earlier work.4, 14

Figure 2

13C cross‐polarization magic‐angle spinning spectra recorded at 9.4 T and a magic‐angle spinning frequency of 9.0 kHz from powders of (a) CHCl3@cryptophane‐But and (b) CH2Cl2@cryptophane‐But at temperatures of 268 and 238 K, respectively. The resonances from ‘interstitial’ and ‘encaged’ guest molecules are marked; the remaining atom numbers correspond to those of Fig. 1.

Figure 3 displays the respective 2D SLF 13C NMR spectra. Each CH moiety exhibiting a significant residual heteronuclear contact produces a ‘split lineshape’ along the horizontal spectral dimension, with the splitting reflecting the size of the recoupled dipolar 13C‐1H interaction(s).18 The 2D NMR spectrum from CHCl3@cryptophane‐But is shown in Fig. 3a (left panel), together with slices (right panel) revealing the recoupled 13C NMR peak‐shapes observed from the interstitial and encaged CHCl3 molecules. While the former signal is narrow, that associated with the encaged molecules reveals the three‐peak pattern expected from a 13C‐1H moiety with a significant residual dipolar interaction.19 The accompanying best‐fit numerical simulation (red trace) reproduces well the experimental splitting of 5.46 kHz between the outer peaks when using a dipolar coupling constant of |b C‐H| = 19.0 kHz. The C—H bond length in chloroform is reported as 107.3 pm from the microwave spectrum,30 which translates into a rigid dipolar coupling constant of 24.0 kHz. The ratio of 0.792 between the motionally averaged residual dipolar coupling and its rigid counterpart is equivalent with an order parameter for the encaged molecule, the square of which can be compared with the generalized order parameter squared from relaxation data in solution (see succeeding discussions). For interstitial chloroform, we observe an essentially fully averaged dipolar interaction. These observations accord overall with earlier reports on chloroform encaged in a larger host, cryptophane‐E (with three linkers with n = 3), |b C‐H| = 19.0 kHz,14 as well as with relaxation measurements in solution.31, 32, 33, 34 For the ‘interstitial’ (here perhaps adsorbed) site, the earlier study14 displayed a sizable splitting not observed here. Indeed, the presence of the butoxy chains in the cryptophane makes the system to crystallize differently, thereby affecting the motions of the chloroform molecules.

Figure 3

(Left panel) 13C spectra recorded by the 2D separated local field NMR protocol from powders of (a) CHCl3@cryptophane‐But and (b) CH2Cl2@cryptophane‐But. The 2D NMR spectra are presented such that the various 13C resonances from host/guest molecules are resolved along the vertical (ν 2) spectral dimension, while its horizontal (ν 1) counterpart comprises information about the recoupled 1H‐13C dipolar interactions. (right panel) Selected slices along the ν 1 dimension at the as‐indicated 13C sites, including each ‘interstitial’ and ‘encaged’ guest molecule. The red traces represent numerically simulated peak shapes used to extract the value of the motionally averaged dipolar interactions. The relatively intense centre peak of each recoupled peak shape is an undesirable feature of the experiment, but it does not compromise the dipolar coupling‐estimates (see ref. 18 for further discussions). The lowest 2D contour level is set at about 5% of the maximum 2D peak amplitude in each spectrum.

Contrary to the case of chloroform, the 2D SLF NMR spectrum observed from CH2Cl2@cryptophane‐But [Fig. 3(b)] manifests no dipolar splittings of guest molecules, with an estimated upper limit |b C—H| < 3 kHz of the residual dipolar coupling that could pass undetected. The interstitial molecules gave a very similar result. This suggests that their motions are isotropic and thereby make the dipolar interaction to vanish. The same result was obtained from a 2D SLF experiment performed at a lower temperature of 203 K (not shown). We also note that significant recoupling effects are observed for the CH2 aliphatic linkers of the cryptophane‐But host (Fig. 3), evidencing a successful operation of the heteronuclear recoupling, as further illustrated for the 1″ 13CH2 groups in each respective 2D NMR spectrum (Supporting information). We have previously observed low residual dipolar couplings of 3.3 kHz (in the solid state) and 3.2 ± 0.3 kHz (from NMR relaxation in solution) for dichloromethane encaged in cryptophane‐E, with its fairly large cavity.14 In the case of CH2Cl2@cryptophane‐A, we measured the residual coupling of 14.2 ± 0.9 kHz, while intermediate values were reported for cryptophanes with linkers of mixed lengths (n = 2 and n = 3).4 From that study, we concluded that the restricted mobility of the dichloromethane molecule in a cryptophane cavity becomes more confined when the size of the cavity is reduced. Neglecting the substituents on the phenyl groups, the cavity of cryptophane‐But should be identical to that of cryptophane‐A, except for perhaps a different distribution of the linker conformations (see succeeding dicussions). This might result in a somewhat larger cavity. In any case, the vanishing dipolar interaction of CH2Cl2 in cryptophane‐But is unexpected.

Single crystal X‐ray diffraction

In order to rationalize the unexpected finding of a vanishing 13C‐1H interaction in the case of dichloromethane guest, we performed single crystal XRD experiments on the cryptophane‐But complexes of chloroform and dichloromethane. Both systems crystallize in the trigonal space group R‐3c. As expected, the cryptophane cages were found to be isostructural with substantial disorder present in the butoxy chains. As mentioned previously, the ‐O‐(CH2)2‐O‐ linkers are slightly disordered but the dominant conformation is trans. The orientation of the guest molecules within the cryptophane cavity is shown in Fig. 4. In both cases, the chlorine atoms are oriented towards the opening of the cavity, whereas the carbon atoms are located close to the −3 rotation axis.

Figure 4

X‐ray structures of CHCl3@cryptophane‐But (left) and CH2Cl2@cryptophane‐But (right). The blue ellipsoids refer to the butoxy groups.

For CHCl3@cryptophane‐But, the chloroform molecule was found to be disordered over four positions. For CH2Cl2@cryptophane‐But, dichloromethane molecules occupy 12 distinct positions. The reason for the larger number of disordered positions for CH2Cl2 is its smaller size and the lack of a threefold rotation axis. The disorder of the guest molecules can also be observed from the electron density maps shown in the Supporting information. By superimposing the structural model, it is evident that the refined atom positions agree with what is observed from the electron density maps, while the electron density was insignificant in the rest of the cavity.

We could not identify any interstitially located guests, which can be explained either by structural disorder at these locations, or as a corroboration of the alternative interpretation of the NMR data in terms of chloromethanes adsorbed on the crystal surfaces. It is perhaps possible to interpret the XRD‐derived structures as indicative of a slightly lower ordering of encaged dichloromethane guests compared with those of chloroform, but the XRD data as such cannot explain the vanishing residual dipolar coupling for the former system.

NMR relaxation in the liquid state

The XRD‐derived structures provide a structural average but give no information on possible dynamic disorder, i.e. disorder because of molecular motions. On the other hand, the molecular motions can be sensitively probed by 13C NMR relaxation measurements. In our recent solution NMR study of cryptophane‐But complexes over a wide temperature range,9 we found that the CH2Cl2@cryptophane‐But system exhibited slow exchange (on the chemical shift time scale) of the guest between the encaged site and the free site in solution. However, the exchange was fast enough to have a strong effect on the spin‐lattice relaxation measurements of the two sites, not investigated further in that study. We return to this issue here.

To probe the mobility of dichloromethane within the host cavity, the longitudinal relaxation of the free and the bound guest was investigated by using a series of 2D heteronuclear HSQC‐type experiments.26 The results are shown in Fig. 5. The results of Fig. 5 reveal that the spin‐lattice relaxation curves for the free (left) and the bound (right) sites show a bi‐exponential behaviour because of chemical exchange.35 In order to determine the relaxation and the exchange rates, the time‐dependence of the longitudinal magnetization has to be treated according to the Bloch–McConnell equations.36, 37, 38 For a two‐site chemically exchanging system, the evolution of the longitudinal magnetization for the free and the bound sites Mz and Mz can be expressed as39 where and correspond to the equilibrium magnetizations, and the respective longitudinal relaxation rates in the absence of exchange, while k is the rate constant for the transition from free to bound sites (with k representing that of the reversed process). The solutions to these coupled equations are as follows: with and

Figure 5

Result of the HSQC‐type inversion‐recovery experiments and the bi‐exponential fitting for the free (left) and the bound (right) relaxation curves. The dashed lines represent the two exponentials.

Λ1, Λ2, Λ3 and Λ4 are the amplitudes of the exponentials; their expressions are given elsewhere.39

Before fitting the parameters of Eqns (3), (4), (5), (6) to the experimental data, two assumptions are made: (1) the free site relaxation rate (R 1  = 0.17 s−1) is fixed at the value obtained from an independent experiment on a dilute CH2Cl2 sample in the tetrachloroethane solvent without cryptophane. (2) The value of the ratio between the two exchange rates k /k  = p /p  = 4.5 is taken from our earlier work9 at 245 K, where p = 0.82 and p = 0.18 are the relative populations of the bound and free site, respectively. The fitting of the T 1 relaxation curves was achieved by a nonlinear least‐squares analysis using the Simplex algorithm and Matlab software.40 The parameters and k were optimized. The errors on the optimized values were obtained from 500 Monte Carlo iterations by considering an error of 5% on the experimental data and an error of 20% on the assumed ratio k /k . The results are shown in Table 2 and in Fig. 5.

Table 2

Optimized parameters from the fitting of the T 1 relaxation curves

	Relaxation rates (s−1)	Exchange rates (s−1)
Free site	R1f=0.17	k fb = 12 ± 5
Bound site	R1b=1.2±0.2	k bf = 2.6 ± 1.1

The two exponential decay rates, λ 1 and λ 2, given by Eqns (5) and (6) with the parameters from Table 2 are −1.0 and −15.0. The former number is very close to the population‐averaged relaxation rate:38 while the latter is similar to the sum of the two exchange rates. Thus, we may conclude that the results conform to the limit of exchange being slow on the chemical shift time scale but much faster than relaxation.

From the relaxation results, we can obtain some information concerning the re‐orientational dynamics of dichloromethane within the host cavity by using the Lipari–Szabo ‘model‐free’ approach.41 According to this model, the spectral density is with where τ is a rotational correlation time characterizing the isotropic global rotational diffusion, τ loc is a local correlation time, and S 2 is the generalized order parameter squared describing the spatial restrictions of the internal motions.

From the NMR solid‐state experiments, we found that the motion of dichloromethane within the cryptophane‐But cavity is completely unrestricted, i.e. isotropic. This result leads then to S 2 = 0 so that the spectral density becomes

Considering the expression of the relaxation rate in the case of dominant dipolar interactions,33 with N  = 2 being the number of protons attached to the 13C nucleus and the dipole–dipole coupling constant. Assuming that r = 107.3 pm and using the previously derived value of found in the previous discussions, the correlation time associated with the motion of the bound CH2Cl2 within the cavity is estimated to be around 30 ps, which is in reasonable agreement with the values found earlier for the same guest in other cryptophane cavities.4 This result from solution‐state NMR is thus consistent with that obtained in the solid state.

Concluding remarks

Estimated residual dipolar 13C‐1H interactions for chloroform and dichloromethane encaged within cryptophane‐But cavity by solid‐state 2D SLF 13C NMR revealed a relatively large dipolar coupling constant (b|C‐H| = 19.0 kHz) in the case of chloroform guest, while the dipole–dipole interaction for dichloromethane guest were fully averaged out. Noteworthy, the present 2D SLF experimentation involved a significantly lower 13C isotopic enrichment than those utilized in our previous cryptophane studies: The present experiments are readily performed at a natural abundance level of 13C at a modest field of 9.4 T, as may be appreciated from the sufficient NMR data quality of all 13C signals from cryptophane‐But in Fig. 3. Although not targeted in the present study, all sets of heteronuclear contacts of the host molecules are readily extracted from the 2D spectra.

Because the solid‐state NMR result for the dichloromethane guest is unexpected, we utilized single crystal XRD to unambiguously confirm the occurrence of the dichloromethane guests within the cryptophane‐But cavity. Moreover, XRD revealed the presence of static or dynamic disorder of the encaged guests. To further characterize the CH2Cl2 dynamics inside the host, we reported a 13C relaxation study in the solution. The system is characterized by exchange rates between free and encaged guest molecules that are slow on the chemical shift time scale but fast compared with the 13C spin‐lattice relaxation. This complicates the analysis of the detailed guest dynamics. Nevertheless, we found that the solution‐state relaxation data are consistent with a fast and isotropic reorientation of the CH2Cl2 molecule within the cryptophane‐But cavity.

Supporting info item

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