DOI: 10.1021/cg9007262
Solvent Effect on Pseudopolymorphism of Hemicyclohexylcucurbit[6]uril Yitao Li, Lin Li, Yanping Zhu, Xianggao Meng, and Anxin Wu*
2009, Vol. 9 4255–4257
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, P. R. China Received June 29, 2009; Revised Manuscript Received September 16, 2009
ABSTRACT: Novel covalent macrocycle, hmcyCuc6, has been synthesized and its four pseudopolymorphs were reported. HmcyCuc6 is highly selective to CH2Cl2, CHCl3, and CCl4 in the crystal growth, and the selectivity of the hmcyCuc6 toward these solvent molecules may be related to the symmetry of the solvent molecules. In addition, four pseudopolymorphs can be simply controlled by changing the crystallization solvent system. To our best knowledge, the pseudopolymorphism of the cucurbit[n]uril homologues is reported for the first time. The influence of the solvent on the organization of supramolecular systems is well-known. Thus, solvent-modulated molecular packing and stacking is a phenomenon that has important consequences, for example, the denaturation of proteins resulting in dramatic changes in their biological activities.1 Synthetic systems also show solvent-dependent properties. For example, the assembly of metal-organic frameworks (MOFs),2 inorganic and organic functional nanomaterials,3 and supramolecular structures are all showing solvent dependencies.4 Pseudopolymorphism is commonly defined as the existence of structurally different crystalline modifications of a host compound, embracing both unsolvated forms and various solvates (inclusion compounds) of the host.5 Indeed, in a broad context, solvent inclusion may be considered as polymorphic modifications of the host component, which are stabilized by the presence of a template guest. While some hosts persistently form the same architecture across a wide range of guests,6 others exhibit different inclusion architectures to accommodate different guests.7 In addition, there are examples where the same host forms several different crystalline clathrates with the same guest.8 This phenomenon also is referred to as solvatomorphism.9 Finally, some inclusion compounds have exactly the same composition but different crystal structures, thus as true polymorphs.10 However, controlling the formation of a specific polymorph or pseudopolymorph of desired properties has not been studied systematically even though it is perceived to be of general importance, especially in the pharmaceutical industry.11 In a supramolecular context, pseudopolymorphs of a compound are different chemical systems and should be treated as such. Herein, we present a facile method to prepare a novel macrocyclic host hemicyclohexylcucurbit[6]uril (hmcyCuc6). We find that four pseudopolymorphs of hmcyCuc6, including two solvatomorphs of CHCl3, can be obtained simply by changing the crystallization solvent system. As previously reported, hmCuc6 (hemicucurbit[6]uril) and hmCuc12 (hemicucurbit[12]uril) can be prepared by simply mixing equimolar amounts of ethyleneurea and 37% formalin in 4 N HCl (Scheme 1).12 Unlike cucurbit[n]uril, both hmCuc6 and hmCuc12 do not form complexes with common metal ions, possibly because of its “zigzag” conformation.13 However, hmCuc6 can encapsulate an anion other than Cl-, notably a thiocyanate and neutral molecules, such as water, formamide, and propargyl alcohol. Interestingly, hmCuc12 is sparingly soluble and highly crystalline in common organic solvents except for CHCl3 solvent, and the macrocycle appears surrounded by
Scheme 1. Chemical Structures of hmCuc6 and hmCuc12
Scheme 2. Chemical Structures of hmcyCuc6
*Corresponding author. Phone: þ86 27 67867129. Fax: þ86 27 67867954. E-mail:
[email protected].
CHCl3 molecules as a combination of the inclusion of the CHCl3 molecules and the packing forces in the solid state. Since the hmCucn can be easily formed by condensation of ethyleneurea with formaldehyde in aq. HCl, we tried the reaction using cis-octahydro-2H-benzimidazol-2-one to form hemicyclohexyl-cucurbit[n]uril (hmcyCucn) under the common conditions used for synthesizing hmCucn. However, when mixing cis-octahydro-2H-benzimidazol-2-one with 37% formalin in 4 N HCl, no hmcyCuc6 was obtained at room temperature and a trace amount of hmcyCuc6 was produced at 55 °C. We therefore reinvestigated the condensation reaction under a wide range of temperature and reaction time and found the optimum conditions for the preparation of hmcyCuc6. Heating an equimolar mixture of the urea derivative and paraformaldehyde in 4 N HCl at 70 °C for 4 h gave a yield as high as 78% of hmcyCuc6 (1) (Scheme 2). Unfortunately, hmcyCuc12 could not be isolated under any conditions. HmcyCuc6 (1) was characterized by 1H and 13C NMR, mass, and IR spectroscopy and untimately confirmed by single-crystal X-ray diffraction measurement (Figure 1). The refinement of the structure reveals that only the 1,2-alternate conformation is present in the X-ray structure of hmcyCuc6 (1). Initially, we were fortunate to obtain single crystals of hmcyCuc6 (1) as cuboids from a pure CHCl3 solution and as
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octahedrons from a mixed solution in CHCl3/MeOH by a slow diffusion of MeOH into a CHCl3 solution. Single-crystal data sets were recorded on a Smart Apex CCD area detector in a sealed glass tube at 298(2) K because the crystals are susceptible to solvent loss. The crystal structure from CHCl3 was solved in the triclinic P1 space group, whereas the structure of the crystals obtained from CHCl3/MeOH was solved in the cubic Fd-3c space group. These two crystals are solvatomorphs because the packings of hmcyCuc6 (1) within both crystals are quite different even though the compositions are the same for both crystals. In general, packing and overall structural motifs of the resulting pseupolymorphs depend greatly on different types of supramolecular interactions. To gain more insight in our current system, namely, the C-H 3 3 3 O and C-H 3 3 3 Cl interactions, we then first examined the cuboid crystals obtained from pure CHCl3. An X-ray structure model of the present complex 1 3 6CHCl3 in the crystal (Figure 2) reveals an amazing crown formation. Six CHCl3 molecules cooperate with hmcyCuc6 and are held in place by C-H 3 3 3 O interaction (C27-H27 3 3 3 O1, d = 2.04 A˚ and θ = 164.5°) with an octahydro-2H-benzimidazole-2one unit. The crystal contains three CHCl3 molecules from above and three CHCl3 molecules from below, hydrogen bonded to the macrocycle which adopts the alternate conformation. The 1,6bonded CHCl3 is shared by another two neighboring hmcyCuc6’s through the weak C-H 3 3 3 Cl interaction (C17-H17A 3 3 3 Cl7, d = 2.94 A˚ and θ = 152.2°; C13-H13A 3 3 3 Cl8, d = 2.94 A˚ and
Li et al. θ = 175.0°), thus making a rigid hydrogen-bonded network (Figure S1, Supporting Information). We also examined the octahedral crystals obtained from a mixed solution of CHCl3/MeOH because the shape of the crystals was quite different from the crystals grown in pure CHCl3. The X-ray crystal structure of a single clathrate-type compound is shown in Figure 3. Four macrocyclic molecules are linked together by hydrogen bonds (C8-H8B 3 3 3 O1, d = 2.79 A˚ and θ = 152.2°), to form a large nanocage (D/2 = 5.5 A˚) in which a disordered CHCl3 molecule is encapsulated. However, it does seem that the cage can accommodate larger molecules as evidenced by the large cell dimensions for the CHCl3 crystal. These complexes are stacked directly on each other from four directions, with each macrocycle shared by two clathrate-type compounds. In order to describe the structure in detail, the packing stack of the macrocycle clathrate was shown along the b axis (Figure S2a, Suppporting Information). The compound was found to crystallize in a cubic crystal system with the space group Fd-3c (Figure S2b, Supporting Information). Although common for inorganic compounds, the cubic space groups are relatively rare for pure organic compounds, especially organic macrocycles. On the basis of the analysis of the two crystal structures above, two interesting problems remain to be solved: (1) Is hmcyCuc6 highly selective to CHCl3 in the process of the crystal growth? (2)
Figure 3. View of the 2(1) 3 CHCl3 inclusion complex, with a disordered CHCl3 molecule in the cage.
Figure 1. ORTEP drawing and atom numbering (right) for hmcyCuc6. Thermal ellipsoids are drawn at the 30% probability level. Solvent molecules and H atoms have been omitted for clarity.
Figure 4. View of the 2(1) 3 CCl4 inclusion complex, with a CCl4 molecule in the cage.
Figure 2. The structure of the 1 3 6CHCl3 inclusion complex, with the principal cooperative interactions shown in broken lines (cross-eyed stereoviews).
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Figure 5. (a) Packing in the 1 3 2CH2Cl2 crystal illustrating C-H 3 3 3 O interactions (cross-eyed stereoviews).
Can the pseudopolymorphs of hmcyCuc6 be controlled simply by changing the crystallization solvent system? To address these problems, we chose various solvent systems in the crystal growth process, such as pure CH2Cl2, CHCl2/X (X = CCl4, CHCl3, MeOH, EtOH, n-PrOH, DMF, acetone, THF, n-hexane, cyclohexane, ethyl acetate), CHCl3/Y (Y = CCl4, EtOH, n-PrOH, DMF, acetone, THF, n-hexane, cyclohexane, ethyl acetate) (Table S1, Supporting Information). Because hmcyCuc6 is only soluble in CH2Cl2 and CHCl3, either of these two solvents is indispensible in the solvent system selection. Good quality crystals from all 23 solvent systems were obtained and characterized. Two new kinds of crystal packing patterns were discovered, namely, 1 3 2CH2Cl2 and 2(1) 3 CCl4. From the data, the hmcyCuc6 is highly selective to CH2Cl2, CHCl3, and CCl4, and the selectivity of hmcyCuc6 to these solvent molecules may be related to the symmetry of the solvent molecules. Because of the C3h axis in the molecules of CHCl3 and CCl4, hmcyCuc6 may form cubic crystal systems with these template guest molecules. To gain a better understanding of the new crystal packing patterns, we first examined complex 2(1) 3 CCl4. The structures of 2(1) 3 CCl4 and 2(1) 3 CHCl3 are very similar except for slight differences of some bond lengths and bond angles. Moreover, the cages were occupied by CHCl3 molecules in 2(1) 3 CHCl3, whereas in those of 2(1) 3 CCl4 were occupied by CCl4 molecules (Figure 4). Because of the larger volume of the CCl4 molecule compared to the CHCl3 molecule, the size of the cage in 2(1) 3 CCl4 (D/2 = 5.7 A˚) is larger than that in 2(1) 3 CHCl3. We also examined the crystals of complex 1 3 2CH2Cl2 (crystals obtained from pure CH2Cl2 or mixed solvents of CH2Cl2) and revealed another packing pattern of this compound in the solid state. The macrocycle is linked together with neighboring macrocycles and CH2Cl2 molecules by hydrogen bonding (C16-H16A 3 3 3 O3, d = 2.68 A˚ and θ = 133.3°; C8-H8A 3 3 3 O2, d = 2.34 A˚ and θ = 151.6°; C25-H25A 3 3 3 O1, d = 2.44 A˚ and θ = 166.5°; C25-H25B 3 3 3 O3, d = 2.44 A˚ and θ = 133.8°), to form a two-dimensional network (Figure 5). It is interesting to note that the bowl-shaped cavities of hmcyCuc6s are packed parallel to each other and form infinite channels. The free space outside these channels (again a channel of approximately the same diameter) is occupied by CH2Cl2 guest molecules (Figure S4, Supporting Information). In summary, we present a facile synthesis of hmcyCuc6, a novel macrocyclic host. In addition, four pseudopolymorphs of hmcyCuc6 were identified. We also find that the host is highly selective to CH2Cl2, CHCl3, and CCl4. The selectivity of the hmcyCuc6 toward these solvent molecules may be related to the symmetry of the solvent molecules. Meanwhile, each pseudopolymorph of hmcyCuc6 could be controlled simply by changing the solvent systems used in the crystal growth process. The accurate mechanism is under further investigation and will be reported in due course. Acknowledgment. We gratefully acknowledge the financial support by Central China Normal University and the National Natural Science Foundation of China (Grants 20672042 and 20872042).
Supporting Information Available: Procedures, characterization data, additional figures and table, and 1H and 13C NMR spectra for compound 1. Crystallographic information files for 1 (.cif). This material is available free of charge via the Internet at http://pubs.acs.org.
References (1) Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K.; Walter, P. Mol. Biol. Cell Garland Science, Taylor & Francis Group: New York, 4th ed., 2002; p 134. (2) (a) Tynan, E.; Jensen, P.; Kruger, P. E.; Lees, A. C. Chem. Commun. 2004, 776–777. (b) Du, M.; Zhao, X. J.; Guo, J. H.; Batten, S. R. Chem. Commun. 2005, 4836–4838. (c) Hill, D. J.; Moore, J. S. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 5053–5057. (d) Baxter, P. N. W.; Khoury, R. G.; Lehn, J.-M.; Baum, G.; Fenske, D. Chem.; Eur. J. 2000, 6, 4140–4148. (e) Khatua, S.; Harada, T.; Kuroda, R.; Bhattacharjee, M. Chem. Commun. 2007, 3927–3929. (f) Mamula, O.; Lama, M.; Stoeckli-Evans, H.; Shova, S. Angew. Chem., Int. Ed. 2006, 45, 4940–4944. (3) (a) Yamada, M.; Shen, Z. R.; Miyake, M. Chem. Commun. 2006, 2569–2571. (b) Seo, K. S.; Han, C.; Wee, J. H.; Park, J. K.; Ahn, J. W. J. Cryst. Growth 2005, 276, 680–687. (c) Chen, S. F.; Yu, S. H.; Yu, B.; Ren, L.; Yao, W. T.; Colfen, H. Chem.;Eur. J. 2004, 10, 3050–3058. (d) Chen, S. F.; Yu, S. H.; Jiang, J.; Li, F. Q.; Liu, Y. K. Chem. Mater. 2006, 18, 115–122. (4) (a) Huang, X. C.; Zhang, J. P.; Lin, Y. Y.; Chen, X. M. Chem. Commun. 2005, 2232–2234. (b) Gale, P. A.; Light, M. E.; Quesada, R. Chem. Commun. 2005, 5864–5866. (c) Schnatwinkel, B.; Stoll, I.; Mix, A.; Rekharsky, M. V.; Borovkov, V. V.; Inoue, Y.; Mattay, J. Chem. Commun. 2008, 3873–3875. (d) Das, D.; Barbour, L. J. Chem. Commun. 2008, 5110–5112. (5) (a) Threlfall, T. L. Analyst 1995, 120, 2435–2460. (b) Bechtloff, B.; Nordhoff, S.; Ulrich, J. Cryst. Res. Technol. 2001, 12, 1315–1328. (c) Prabakaran, P.; Umadevi, B.; Panneerselvam, P.; Muthiah, P. T.; Bovelli, G.; Righi, L. CrystEngComm 2003, 5, 487–489. (6) (a) Iwamoto, T. J. Inclusion Phenom. 1996, 24, 61–132. (b) Nakano, K.; Sada, K.; Kurozumi, Y.; Miyata, M. Chem.;Eur. J. 2001, 7, 209–220. (7) (a) Soldatov, D. V.; Enright, G. D.; Ripmeester, J. A. Supramol. Chem. 1999, 11, 35–47. (b) Rahman, A. N. M. M.; Bishop, R.; Craig, D. C.; Scudder, M. L. Eur. J. Org. Chem. 2003, 72–81. (8) (a) Kumar, V. S. S.; Kuduva, S. S.; Desiraju, G. R. J. Chem. Soc., Perkin Trans., 2 1999, 1069–1073. (b) Udachin, K. A.; Enright, G. D.; Brown, P. O.; Ripmeester, J. A. Chem. Commun. 2002, 2162–2163. (d) Aladko, L. S.; Dyadin, Yu. A.; Mikina, T. V. Russ. J. Gen. Chem. 2003, 73, 503–506. (9) Ibragimov, B. T. Solvatomorphism or an Existence of the Same Solvate in Different Crystal Modifications, In Ixth International Seminar on Inclusion Compounds, Prog. Abstr., Novosibirsk (Russia), 2003, p 32. (10) (a) Beketov, K. M.; Ibragimov, B. T.; Talipov, S. A.; Makhkamov, K.; Aripov, T. F. J. Inclusion Phenom. 1997, 27, 105–112. (b) Beketov, K. M.; Ibragimov, B. T.; Talipov, S. A. J. Inclusion Phenom. 1997, 28, 141–150. (11) Byrn, S. R. Solid-State Chemistry of Drugs; Academic Press, New York, 1982. (12) Miyahara, Y.; Goto, K.; Oka, M.; Inazu, T. Angew. Chem., Int. Ed. 2004, 43, 5019–5022. (13) (a) Miyahara, Y.; Abe, K.; Inazu, T. Angew. Chem. 2002, 114, 3246–3249. Angew. Chem., Int. Ed. 2002, 41, 3020-3023. (b) Buschmann, H. J.; Cleve, E.; Schollmeyer, E. Inorg. Chim. Acta 1992, 193, 93–97.
