Molecular tectonics: tetracarboxythiacalix[4]arene derivatives as tectons for the formation of hydrogen-bonded networks

A series of thiacalix[4]arene derivatives blocked in the 1,3-alternate conformation and bearing four carboxylic acids have been designed and synthesized. These compounds, owing to the H-bond donor (OH moiety) and acceptor (CO group) nature of the carboxylic acid moieties, behave as self-complementary tectons and lead to the formation of tubular 1D H-bonded networks in the crystalline phase. Upon deprotonation of the self-complementary neutral compounds, i.e. transformation of carboxylic acid moieties into carboxylates, anionic tectons are generated. Due to their propensity to form H-bonded networks in the presence of a dicationic H-bond donor tecton of the cyclic bis-amidinium type, designed to behave as a molecular staple interconnecting two carboxylates moieties, 1- and 2-D H-bonded networks are formed under self-assembly conditions.


Introduction
Tubular architectures 1-3 are of interest as they form channels that may lead to the transport of neutral or charged species. Such entities may be either discrete or infinite networks displaying translational symmetry. For the latter category, they may be formed by self-assembly processes upon interconnection of cyclic entities using either hydrogen or coordination bonds. [4][5][6][7] Tubular architectures may also be helical assemblies. 8 Organisation of cyclic units into tubular architectures using liquid crystalline phases 9 or polymeric backbones 10 has been also reported.
Following the concepts developed in molecular tectonics 11 for the design and formation by self-assembly processes of infinite molecular networks in the crystalline phase, we are interested in tubular architectures based on H-bonds between macrocyclic entities behaving as tectons. 12 Owing to their cyclic nature, calix [4]arene 13 and thiacalix [4]arene 1-3 14,15 (Fig. 1) in their 1,3-alternate conformation are interesting backbones for the design of such tectons. Indeed the 1,3-alternate conformation of these two platforms allows up to 4 interaction sites to be positioned in a divergent fashion, i.e. two above and two bellow the main plane of the calixarene. We have previously exploited this feature and designed metallatubulanes based on calix [4]arene derivatives 16 or on [1]-metacyclophane in the 1,3-alternate fixed conformation, an analogous backbone to calix [4]arene. 17 Here we report on the design, synthesis and characterization of thiacalixarene based derivatives 4-8, in their 1,3-alternate conformation, bearing four carboxylic acid groups and thus behaving as self-complementary tectons. We describe their selfassembly in the crystalline phase into 1D tubular H-bonded networks as well as combinations of their deprotonated derivatives as anionic tectons with a dicationic tecton A 2+ , behaving as a molecular staple, capable of bridging consecutive anionic units, leading to extended H-bonded networks.
Compounds 4-7, and 8 are based on p-tert-butylthiacalixĳ4]arene and on the H-thiacalix [4]arene backbone in its 1,3-alternate conformation, respectively (Fig. 1). They are analogous derivatives bearing four carboxylic acid moieties and differ by the nature of the spacer connecting the carboxyl groups to the backbone. They have been designed in order to investigate the role played by the spacer in their ability to form tubular H-bonded networks (Fig. 2a) based on the formation of H-bonded dimeric nodes (Fig. 2b) between carboxylic acids belonging to consecutive selfcomplementary tectons. Owing to the acidic nature of compounds 4-8, upon their deprotonation leading to anionic species, they offer another possibility for the design of tubular H-bonded networks. Indeed these anionic tectons bearing carboxylate moieties may be combined with the dicationic organic tecton A 2+ (Fig. 1) designed to bridge two carboxylates, one on each of its faces, and thus behave as a molecular sta-ple ( Fig. 2c) connecting consecutive carboxylate-bearing components. 18, 19 Depending on the degree of deprotonation of neutral compounds 4-8 and the nature of the spacer connecting the calix backbone to the carboxylate units, one may expect the formation of 1D tubular H-bonded networks (Fig. 2a). The driving force for the formation of such extended architectures is the establishment of charge-assisted H-bonds. 20 Although few tetra-acid derivatives based on calix [4]arene 21 (CA) and thiacalix [4]arene 22 (TCA) backbones have been reported, to the best of our knowledge, no example of tetramercaptothiacalixarene (TMTCA) 3 ( Fig. 1) based derivatives has been documented to date.
Few examples of H-bonded nanotubular assemblies based on p-tert-butylthiacalixĳ4]arene 3 bearing carboxylic acid and/ or urea have been reported. 23 An interesting investigation dealing with the photoisomerization of a H-bonded network based on a p-tert-butylthiacalixĳ4]arene derivative bearing carboxylic acid moieties combined with bipyridylethene has been also reported. 24

Experimental
Characterization techniques 1 H-NMR and 13 C-NMR spectra were recorded at room temperature on a Bruker 300 MHz and 500 MHz.
FT-IR spectra were recorded on a Perkin Elmer ATR spectrometer.
Melting points were measured in capillary tubes on a Stuart Scientific Melting Point SMP-1 apparatus.
Elemental analyses were performed by the Service de Microanalyses de la Fédération de Recherche Chimie of the Université de Strasbourg.

Single-crystal studies
Data were collected at 173(2) K on a Bruker APEX8 CCD diffractometer equipped with an Oxford Cryosystem liquid N 2 device, using graphite-monochromated Mo-Kα (λ = 0.71073 Å) radiation. For all structures, diffraction data were corrected for absorption. Structures were solved using SHELXS-97 and refined by full matrix least-squares on F 2 using SHELXL-97. The hydrogen atoms were introduced at calculated positions and not refined (riding model). 25 CCDC: 1504484-1504490  and 1505426 (see Tables S4 and S5, ESI †).

Powder X-ray diffraction
Powder diffraction (PXRD) diagrams were collected on a Bruker D8 diffractometer using monochromatic Cu-Kα radiation in a scanning range between 3.8 and 40°using a scan step size of 2°mn −1 .
As already demonstrated and currently admitted, for all the compounds, discrepancies in intensity between the  Recognition patterns through H bonds between tectons: a) schematic view of tetra-substituted macrocyclic species leading to 1D tubular systems, b) a dimeric node involving two carboxylic acid moieties and c) dihapto mode between carboxylate and amidinium moieties, behaving as molecular staples.
observed and simulated patterns are due to the preferential orientations of the microcrystalline powders.

Synthesis
General: all reagents were purchased from commercial sources and used without further purification. The synthesis of 1, 14a 2, 26 3 27 and 8 28 has been previously reported. The synthesis of 4-7 was adapted from previously reported procedures. 22,29 The bisamidinium compound A 2+ , used as its ditosylate salt (A 2+ , 2TsO − ), has been prepared using an already reported procedure. 18b Synthesis of the tetraester derivative 4′ in 1,3-A conformation. Under argon, a mixture of TMTCA 3 (0.3 g, 0.38 mmol) and Cs 2 CO 3 (2.47 g, 7.6 mmol) in dry and degassed acetone (60 ml) was refluxed for 2 hours before BrCH 2 COOEt (0.85 ml, 7.6 mmol) was added. The reaction mixture was refluxed for 50 hours under argon. After cooling, the solid was filtered and the filtrate was evaporated. The residue was treated with MeOH (50 ml) affording the desired compound 4′ (0.2 g, 46% yield) in the 1,3-A conformation as a white powder.
Mp Synthesis of the tetraester derivative 5′ in 1,3-A conformation. Under argon, a mixture of 3 (0.5 g, 0.63 mmol) and Cs 2 CO 3 (4.12 g, 12.6 mmol) in dry and degassed acetone (60 ml) was refluxed for 2 hours before Br(CH 2 ) 3 COOEt (1.8 ml, 12.6 mmol) was added. The reaction mixture was refluxed for 50 hours under argon. After cooling, the mixture was filtered and the solvent was evaporated. The residue was treated with 2 M HCl (40 ml) and extracted with CHCl 3 (2 × 50 ml). The organic layers were combined, washed with water (100 ml) and dried over MgSO 4 . After filtration, the organic solvent was evaporated and addition of MeOH (100 ml) to the oily residue afforded compound 5′ (0.43 g, 60% yield) as a white precipitate.
In solution, all four compounds 4-8 were characterized by both 1 H-and 13 C-NMR spectroscopy which showed sharp signals indicating the presence of conformationally blocked 1,3-alternate isomers (see the Experimental section). Furthermore, among the five new compounds 4-8, four (compounds 4-7) have been also characterized in the solid state by X-ray diffraction methods on single crystals obtained upon slow diffusion or slow evaporation techniques (see the Experimental part and Table S4, ESI †). As expected, all compounds adopt the 1,3-A conformation (Fig. 4) Table S2, ESI †). In the case of 5, one of the four tertiobutyl groups is found to be disordered (Fig. 3).

Formation of extended 1D tubular architectures by selfcomplementary tectons 4-8
Owing to the propensity of carboxylic acids to form a H-bonded dimeric complex (Fig. 2b) and due to the 1,3-A conformation adopted by the tetracarboxyl compounds 4-8, the latter might behave as self-complementary tectons and self-assemble into 1D H-bonded tubular networks (Fig. 2a).
In the case of 4, the presence of disordered DMF molecules interacting with the carboxyl groups (O-O distances of 2.552Ĳ4)-2.806Ĳ7) Å) prevents the formation of dimeric H-bonded motives (Fig. 2b) and consequently, the generation of the extended 1D architecture. In this case, the isolated species is observed in the crystals.
For all three cases, the 1D tubular architectures are packed in a parallel fashion.
For tecton 6, no specific interactions between CHCl 3 solvent molecules and the network are found. For 7, however, whereas no interactions between CH 2 Cl 2 solvent molecules and the network could be spotted, the water molecules do form H-bonds with the carboxylic acid moieties of the tecton (O-O distance of 3.197(6) Å).  Owing to the instability of the crystals of 4, 5 and 7 outside the crystallization mother liquor, no PXRD powder patterns could be recorded on the corresponding microcrystalline powder. In marked contrast, the microcrystalline powder of 6 was found to be stable and thus it could be investigated by PXRD. The study revealed a good match between the simulated and observed patterns (Fig. 5).

Formation of extended networks by combinations of deprotonated compounds 4-8 and the dicationic H-bond donor tecton A 2+
As stated in the introduction, the dicationic organic tecton A 2+ (Fig. 1) is well suited to recognize two carboxylate moieties, through a dihapto mode of interaction (Fig. 2c). In other terms, tecton A 2+ may be regarded as a molecular staple interconnecting two consecutive carboxylate groups by charge assisted H-bonds. This particular mode of interaction may be considered as a structural node of extended H-bonded networks (Fig. 2a) resulting from mutual bridging between deprotonated anionic tectons 4-8 bearing divergently oriented carboxylate moieties as H-bond acceptors and the H-bond donor cationic tecton A 2+ .
The role played by the spacer connecting the four carboxylic acid moieties to the calixarene backbone in compounds 4-8 was systematically investigated. Furthermore, combinations of their deprotonated analogues, generated using 4 eq. of NEt 3 , as base, with tecton A 2+ (2 eq.) were also studied (see the Experimental section). Among several attempts, the fol-  Table S5, ESI †).
For the combination of 4 with A 2+ in the presence of 4 eq. of NEt 3 , probably because of the short nature of the spacer (-CH 2 -) and the presence of tertiobutyl groups, the expected tubular architecture (Fig. 2a) was not observed in the obtained crystals under the crystallization conditions used (see the Experimental section). Indeed, instead of the projected 1/2 stoichiometry [(4 4− )-(A 2+ ) 2 ], the calixarene derivative was partially deprotonated and found to be in its trianionic form. This was substantiated by C-O distances ranging from 1.187(9) to 1.291(8) Å (see Table S3 in the ESI †). In the crystal, a 2/3 stoichiometry between the trianionic compound 4 3− and the dicationic tecton A 2+ , leading to [(4 3− ) 2 -(A 2+ ) 3 ], is observed. The metrics observed for 4 3− is close to the one observed for 4 and the structural parameters observed for A 2+ are close to those already reported. 29 [(4 3− ) 2 -(A 2+ ) 3 ] crystallises in the presence of DMF and water solvent molecules. Interestingly, the interaction between all three carboxylate moieties of 4 3 and the dicationic tecton A 2+ , as expected from the design of A 2+ , takes place through a dihapto mode of H-bonding with N⋯O distances in the range of 2.669(10) to 2.818(10) Å (see ESI, † Table S3). Owing to the 3/2 anion/cation ratio, the overall architecture is a deformed honeycomb 2D H-bonded network in the xOy plane (Fig. 6) Owing to the decomposition of crystals of [(4 3− ) 2 -(A 2+ ) 3 ] in air, no PXRD measurements could be performed.
For the combination of 5 with A 2+ in the presence of 4 eq. of NEt 3 , again the formation of the tubular architecture ( Fig. 2a) was not observed under the crystallization conditions used (see the Experimental section). The calixarenebased tecton was in its dianionic state (5 2− ) resulting from the partial deprotonation of two out of the four carboxylic acid moieties. This was reflected by C-O distances ranging from 1.204(9) to 1.316(8) Å (see ESI, † Table S3).
Again, the metrics observed for 5 2− is close to the one observed for 5 and structural parameters for A 2+ are similar to those reported. 29 In the crystal, a 1/1 stoichiometry between   Table S3. the dianionic compound 5 2− and the dicationic tecton A 2+ leading to [5 2− -A 2+ ] is observed. The latter crystallises in the presence of 1 MeOH and 1 H 2 O solvent molecule. The two deprotonated carboxyl groups are in trans disposition, thus divergently oriented, and located above and under the main plane of the calix backbone.
The overall structure is a 1D H-bonded network (Fig. 7). The connectivity pattern between the components (tectons 5 2− , A 2+ and H 2 O and MeOH solvent molecules) is rather complex.
In marked contrast with the abovementioned combination of 4 3 The 1D arrangements are packed in a parallel fashion along the a and b axes. Water molecules are located between 1D networks without specific interactions with them.
Again, due to the decomposition of crystals of [5 2− -A 2+ ] in air, no PXRD measurements could be performed.
The combination of A 2+ in the presence of 4 eq. of NEt 3 , with either 7 or 8, afforded crystals which were investigated by X-ray diffraction on single crystals. The structural study revealed that both 7 and 8 are fully deprotonated and behave as tetra anionic tectons (7 4− and 8 4− ) (see ESI, † Table S3). The anion/cation stoichiometry is ½, leading to [X 4− -(A 2+ ) 2 ] (X = 7 or 8). The metrics observed for 7 4− and for 8 4− is similar to those for 7 and reported for 8. 27 Structural parameters for the dicationic tecton A 2+ within the networks are close to the one reported. 29 For [7 4− -(A 2+ ) 2 ], the crystal, in addition to the cationic and anionic tectons, contains two water molecules. For the anionic partner 7 4− , two out of the four phenyl groups bearing the carboxylate moieties are found to be disordered.
In both cases, as a result of the design of the complementary anionic and cationic tectons behaving as H-bond acceptor and donor sites, respectively, a dihapto mode of H-bonding with the N⋯O distance in the range of 2.625Ĳ15)-2.816Ĳ13) Å is observed (Fig. 8) (see ESI, † Table S3). Consequently, the mutual interconnection of the anionic tectons 7 4− and 8 4− and the cationic tecton A 2+ leads to the formation of 1D tubular H-bonded networks (Fig. 2a). For [7 4− -(A 2+ ) 2 ], the 1D network runs along the b axis ( Fig. 8a and c). For [8 4− -(A 2+ ) 2 ], the 1D network running along the a axis is not linear but corrugated (Fig. 8b and d).