Introduction

Since decades, calixarenes act as attractive building units for supramolecular systems as they can be obtained easily and offer a huge range of possible modifications [1]. They consist of a hydrophobic cavity capable of binding small molecules and a hydrophilic lower rim, which after adequate functionalization is suitable for the complexation of ionic guest molecules. These facts result in a broad variety of applications in the field of ion sensing and reversible guest inclusion as well as for objects of biomimetics [2]. Another reactive site, giving rise to lateral substitution, involves the bridging methylene units which, however, has much less been taken into consideration for making calixarenes useful [3–6]. Even studies of the inclusion properties of simple laterally monosubstituted calix[4]arenes in the solid state are rather rare [7–9] although we recently reported the conformational behaviour of such monoalkyl substituted calix[4]arenes [10] and of a carboxy functionalized analogue [11] both in crystalline state and in solution. Here, we describe crystal structures of the unsolvated laterally ethyl substituted tetra-tert-butyltetramethoxycalix[4]arene 1 and its solvated inclusion compounds with tetrahydrofuran (THF) (1a) and dichloromethane (1c), and comparatively discuss these structures including also the known structures of the inclusion complexes of 1 with chloroform (1b) [10] and of the basic laterally non-substituted parent calixarene 2 with THF (2a) [12] (Fig. 1). A detailed study of structure and molecular similarity by means of isostructural and molecular isometricity calculations [13, 14] is performed in order to make the conclusions with regard to solvent and lateral substitution effects sound.

Fig. 1
figure 1

Chemical structures of the compounds studied in this article with denotation of the aromatic rings

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Experimental

The title calixarene, 2-ethyl-tetra-tert-butyltetramethoxycalix[4]arene (1), was prepared as described in our recent article [10] and following the references therein.

X-ray structure determination

Single crystals of 1, 1a and 1c suitable for X-ray diffraction were obtained by slow evaporation of solutions of the calixarene 1 in acetonitrile/MeOH (1:1), THF/MeOH/Et2O (1:2:2) and CH2Cl2/ethanol (1:1), respectively. The diffraction data were collected on a Bruker APEX II diffractometer with MoKα radiation (λ = 0.71073 Å) using ω- and φ-scans. Reflections were collected for background, Lorentz and polarization effects. Preliminary structure models were derived by application of direct methods and were refined by full-matrix least squares calculation based on F 2 for all reflections [15]. All hydrogen atoms were included in the models in calculated positions and were refined as constrained to bonding atoms. Crystal data and details of the structure determination and refinement can be found in Table 1.

Table 1 Crystal data and selected details of the data collection and refinement calculations of compounds 1a, 1c and 1
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Isostructural and isometricity calculations

The cell similarity index (π) has been calculated as π = [(a + b + c)/(a′ + b′ + c′) − 1], where a, b, c, and a′, b′, c′ are the orthogonalized lattice parameters of the compared crystals [14]. In the event of great similarity of the two unit cells, the value of π is close to zero [16]. For the calculation of the isostructurality index [I(s)], the distance differences between the crystal coordinates of identical non-H atoms within the same section of the related structures were used [14], taking into account both the differences in the geometry of the molecules and the positional differences caused by rotation and translation. The molecular isometricity calculations [I(m)]were carried out by least-squares fitting of the positions occupied by the identical heavy atoms of the two related molecules [13].

Results and discussion

While the solvent-free laterally ethyl substituted tetra-tert-butyltetramethoxy-calix[4]arene 1 (Fig. 1) shows the monoclinic P21/n space group, its three solvate structures with THF (1a), CHCl3 (1b) [10] and CH2Cl2 (1c) (Fig. 2) crystallise in the same orthorhombic space group Pca21. The THF solvated laterally non-substituted tetra-tert-butyltetramethoxycalix[4]arene 2a [12] has the same space group as the laterally substituted calixarene 1 in unsolvated form. The calixarene inclusion structure 2a differs from all the other presented structures involving 1 in Z′. There are two crystallographically independent host and guest molecules in the asymmetric unit of 2a (their 2a1/2a2 conformations are rather different; the calculated molecular isometricity index I m [13, 14] for the 40 non-hydrogen atoms of the calix[4]arene frame without the tert-butyl substituents is 92.54%), while only one host–guest pair is present in 1 and 1a–c. Thus, only the crystals 1a–c are isostructural. Both cell similarity (π) and isostructurality (I s) indices [13, 14] calculated for 54 non-hydrogen atoms of the ethyl substituted host molecule in its inclusion crystals 1a–c (Table 2) are high. The cell itself and the host conformation and placement in the cell are somewhat closer in the THF (1a) and CH2Cl2 (1c) inclusion structures compared to the CHCl3 containing solvate (1b).

Fig. 2
figure 2

Molecular structures of 1, 1a and 1c. Heteroatoms are shaded

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Table 2 Cell similarity index (π) and isostructurality index (I s) calculated for 54 non-hydrogen atoms of the ethyl substituted tetra-tert-butyltetramethoxycalix[4]arene 1 in its solvates 1a–c
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In a more detailed examination, similar to the laterally unsubstituted calix[4]arene 2a [12], due to the absence of any intramolecular hydrogen bonding at the lower rim, the framework of the ethyl derivative 1 adopts a partial cone conformation, which has already been calculated to be the lowest energy conformer [10]. The calice exhibits a nearly coplanar arrangement of the aromatic units A and C, whereas the rings B and D enclose an angle of 49.7° (Table 3). The calixarene conformation of 1 can also be characterized by the angle of the arene rings with reference to the plane determined by the bridging methylene units (Table 3). In accordance with the lateral unsubstituted calixarene 2 [17], all methoxy groups point out of the cavity and therefore maintain no intramolecular interactions. In comparison with 2a, the solvent-free lateral ethyl pendant 1 shows a similar molecular conformation, represented by high molecular isometricity indices I m [13, 14] of 95.07% for 1/2a1 and 97.45% for 1/2a2 (Fig. 3a).

Table 3 Selected conformational parameters of the calixarene molecule in the compounds studied
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Fig. 3
figure 3

Overlay of the host calix[4]arene molecules. The upward arene group opposite to the downward oriented one of each host are fitted in the figures only to visually enhance the geometrical differences. Assignment: 1 (A), 1a (B), 1b (C), 1c (D), 2a1 (E), and 2a2 (F). a Hosts from the structures 1, 1a, 2a1, and 2a2. b Hosts from the structures 1a, 1b, and 1c

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In contrast, the molecular geometry of the calixarene host in the three solvates 1a–c is marginally affected by the enclosed solvent molecules, which are always located interstitially in the vicinity of the aromatic ring C neighbouring the lateral ethyl substituent. Obviously, as a result of the C–H···π interactions [18] with the aromatic ring C (Table 4), the clathrate-like included solvent molecules in the complexes of 1 lead to a slight flattening of the calice in comparison to the guest free structure 1. The opposing arene units A and C in all three solvates of 1 differ slightly from coplanarity (8.1–8.9°, Table 3), but the rings B and D enclose a perspicuously lower angle of 42.8–43.8° compared to the solvent-free calixarene 1. The calixarene host molecular conformation is assisted by two weak C–H···O intramolecular secondary interactions [19] (C7–H7···O1 and C14–H14···O3) in all 1, 1a–c and 2a structures, reducing the flexibility of the calixarene moiety where the arene units are placed upwards. The calculated molecular isometricity indices I m [13, 14] prove the high molecular conformational similarity of the calix[4]arene hosts (Fig. 3b): 1a/1b 98.99%, 1a/1c 99.44% and 1b/1c 99.47% calculated for all 54 non-hydrogen atoms. This value I m of 97.98% for 1/1a is getting lower comparing the calix[4]arene hosts’ 54 non-hydrogen atoms as a result of guest inclusion into the crystal. As a subsidiary effect of the lateral ethyl substituent, the molecular similarity decreases compared to the unsubstituted parent compound 2a (Fig. 3a). Considering the two crystallographically different host molecules in the asymmetric unit of 2a, the molecular isometricity indices (I m) calculated for the host framework excluding the lateral ethyl substituent and the tert-butyl groups are 94.99% for 1a/2a1 and 95.68% for 1a/2a2.

Table 4 Parameters of possible hydrogen-bond type interactions of the compounds studied
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Owing to the absence of strong hydrogen donor sites and the non-polar nature of the calixarene host, the packing arrangement of all 1, 1a–c and 2a structures is controlled by weak intermolecular C–H···π-interactions (Table 4) and van der Waals forces, meanwhile no π···π interactions [20] at all are observed. In detail, in the guest free structure 1, a weak C–H···π-interaction is observed involving a tert-butyl group and the aromatic ring C of a neighbouring calixarene molecule [C(49)–H(49A)···centroid(C) 3.7164(4)]. A typical interaction between one methoxy group and an aromatic unit of the neighbouring calixarene molecule [C(33)–H(33C)···centroid(B) 3.475(4) Å (1a); C(33)–H(33A)···centroid(B) 3.4855 Å (1b); C(43)–H(43C)···centroid(B) 3.4874(4) Å (1c)] occurs in each of the three solvate structures 1a–c.

As a further point of interest, we focused on the mode of molecular packing in each of the calixarene inclusions. For this reason, the potential solvent accessible area in the presence and absence of the solvent molecules, as well as the Kitaigorodskii Packing Index (KPI) [21] are calculated for all reported structures (Table 3). For comparison, the expected volume for a hydrogen bonded water molecule is around 40 Å3, and for a small molecule like toluene it may range between 100 and 300 Å3. The ethyl substituted calix[4]arene 1 can be well packed even without a solvent molecule having a packing coefficient average value of 64.1% and a small residual potential solvent accessible area of 2.7% as distinct voids in the crystal structure (Fig. 4a). A rather small inter-layer distance of about 7.77 Å between the nearest calixarene aromatic core centroids prevents any inclusion of solvent molecules. In a completely different manner, the guest solvent molecules in all 1a–c and 2a structures are located in channels. In the case of the calix[4]arene host 2a featuring no lateral substituent, the serpentine like channels are running along the crystallographic b direction in the space group P21/c (Fig. 4b). Absence of lateral substitution and inclusion of THF in the crystal structure as in 2a result in a moderate well packing, giving rise to a packing coefficient of 63.2% and a small solvent accessible void of 1.6% additional to the THF. As an effect of the lateral substitution of the host, the channels are straightened in the crystals of 1a–c and are running in the crystallographic c direction in the space group Pca21 (Fig. 5). The lateral substitution of the host decreases the packing ability of the inclusion crystals. The extra potential solvent accessible void in the presence of guest molecules increases (2.2–7.5%) in comparison to the laterally unsubstituted solvate 2a (1.6%), while the packing coefficient decreases (Table 3). However, the total room available for guest molecules in the host structure is approximately the same, around 18% in all inclusion compounds 1a–c, while it is smaller (13.9%) in the case of 2a. The intermolecular distances between the nearest calixarene aromatic core centroids of 13.51 Å (1b) and 13.40 Å (1c) meet the requirements for a close packing arrangement [21], which is also reflected by the KPI packing indexes of 61.7(1b) and 60.9 (1c), respectively.

Fig. 4
figure 4

a Packing arrangement of 1 viewed along the crystallographic a direction. There are small voids among the semi-rigid calix[4]arene molecules. b Solvent channels in the crystal structure of 2a. The serpentine like channels are in the crystallographic b direction, space group P21/c

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Fig. 5
figure 5

Straightened solvent channels in the crystal structure of 1a viewed along the crystallographic a, b and c direction (a), (b) and (c), respectively. Crystals of 1a–c are isostructural, space group Pca21

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Conclusion

In comparison with the parent lateral unsubstituted tetramethoxycalix[4]arene inclusion structure 2a, the introduction of a lateral ethyl substituent scarcely affects the molecular conformation of the calixarene framework, as indicated by similar conformational parameters in 1a–c. Due to the non-polar nature of the calixarene core, the intramoleular interactions within the different structures are highly limited to differently strong C–H···π contacts [18]. However, the inclusion of solvent molecules of different size and polarity causes a greater change of the packing behaviour. Primarily, the presence of solvent molecules induces the formation of the higher symmetrical orthorhombic crystal structures 1a–c, being isostructural irrespective of the included guest molecule. Besides, the lateral attachment of one ethyl group leads to a staggered arrangement of calixarene molecules along the crystallographic b-axis. As a consequence, the serpentine like channels observed in the laterally unsubstituted calixarene structure 2a are straightened to linear channels running along the crystallographic c direction. This fact seems to be an interesting crystal engineering aspect [22], as the channel geometry of a calixarene lattice can be straightened by the effect of a simple lateral monosubstitution to the host molecule. Moreover, it is shown that the introduction of a lateral substituent may expand the total room available for guest molecule inclusion by nearly 30%, being another promising fact for crystal inclusion chemistry (For examples in regard to reversible guest exchange of calix[4]arenes, see: ref. [23]).

Supplementary data

CCDC-804619 (1), CCDC-804620 (1a) and CCDC-804621 (1c) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/data_request/cif (or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0) 1223-336033; e-mail: deposit@ccdc.cam.ac.uk).