X-ray Structure Determination of Ion-Channel Crystalline Architectures

Article pubs.acs.org/crystal

X‑ray Structure Determination of Ion-Channel Crystalline Architectures Close to Bilayer Membrane-Confined Conditions Mihail Barboiu,* Dan Dumitrescu, and Arie van der Lee Adaptive Supramolecular Nanosystems Group, Institut Européen des Membranes, ENSCM-UMII- UMR-CNRS5635, Place Eugène Bataillon CC047, 34095 Montpellier Cedex 5, France ABSTRACT: Experimental evidence presented in this paper shows that long-range crystalline order as observed in the macrocyclic heteroditopic receptors’ single-crystal structures is preserved when embedded in the bilayer membranes. Investigations presented here showed that MCM41-type mesoporous hydrophobic hybrids can be used as biomimetic platforms for ion-channel biomimetic structure elucidation, while showing similar hydrophobic interactions with confined ligands/receptors as in bilayer membranes. This gives access to information concerning the structural pictures of the bilayer’s confined ion-channel structures, as well as of their relatives in the presence of ion effectors.

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We use a simple hybrid system, reminiscent with the membrane bilayer structure, in which oriented hydrophobic mesopores may be used as a host scaffolding matrix for the confinement of the guest ion-channel architectures. The confinement of the ion-channel crystalline superstructures within hydrophobic mesoporous MCM41,14 used as a biomimetic bilayer model system, is based on the following encoded features: (a) The insulator bilayer of the membrane (30−35 Å)9b is dimensionally compatible to the diameter of the MCM41 mesopores (40 Å).14 (b) The hydrophobic mesopores are structurally similar to the internal bilayer membrane constitution. The grafted octadecyl C18 alkyl chains with about a 20 Å length in their elongated geometry are dimensionally compatible with the radius of the cylindrical MCM41 mesopores. By presuming a homogeneous covering of the internal surface of the pore, two oppositely aligned chains will cover the whole diameter and meet together in the middle of the pore, like in bilayer systems (Figure 1a). (c) They present a “compartmentalized” host matrix for sequestering important amounts of the guest system presenting low mobility, essential for a good quality of X-ray powder diffraction (XRPD) data, which is difficult to obtain with a bilayer confining matrix (Figure 1a). (d) In terms of the orientation of a membrane spanning ion channel, our model certainly does not represent the best method to generally determine the “oriented” active structures, but it can clarify many structural issues of ordered assemblies of artificial channels embedded in a hydrophobic membrane system.

upramolecular artificial ion channels operate the collective information stored in sets of molecular constituents to achieve in a biomimetic manner,1,2 selective ionic diffusion across bilayer membranes. Crown ethers,3 cyclic peptides,4 Gquadruplexes,5 oligo-phenyl barrels,6 bola-amphiphiles,7 lipophilic metallic complexes,8 organic or inorganic capsules,9 and polymeric10 or dendrimeric11 systems have been designed to mimic functions of natural transmembrane proteins. The question as to how the electrolytes diffuse along the artificial self-assembled ion channels has been previously answered: most of the time, the internal constitutional topography of the ionic channels provides hydrophilic pathways for their translocation.1−11 The geometrical and structural behaviors of the artificial ion channels provided by single-crystal X-ray crystallography might offer possibilities to explain the channel behaviors within bilayer pore-confined conditions. Within this context, many systems for which the crystal structures have been reported show conductance states when embedded in lipid bilayers. However, two obvious arising questions are attracting our attention: 1 How robust are the resolved crystalline structures when embedded in a bilayer membrane system? 2 Are these structures still persistent in the presence of ions, or are they responsive to ion effectors? A short briefing of the literature on this subject does not always give a clear answer. However, NMR in bicelles12 or nanodiscs,13 for example, has progressed very much for functional reconstitution of integral membrane proteins. In order to enlarge the possibilities, toward artificial self-assembled systems, in this study, we describe a simple method that can be applied for the ion-channel X-ray structure determination and their possible structural transformation in the presence of ion effectors under similar bilayer membrane-confined conditions. © 2014 American Chemical Society

Received: March 5, 2014 Revised: April 9, 2014 Published: April 18, 2014 3062

dx.doi.org/10.1021/cg500323r | Cryst. Growth Des. 2014, 14, 3062−3068

Crystal Growth & Design

Article

Figure 1. (a) Confinement of self-assembled ion channels within bilayer membranes (left) in a hydrophobic mesoporous MCM41-ODS matrix (right) of the (b) heteroditopic macrocyclic receptors 1 and 2 binding both cations and anions. Note that hexylureidobenzo-18crown-6, 1, and hexylureidobenzo-15-crown-5, 2, bind selectively K+ and Na+, respectively.

Toward these objectives, we consider here simple systems developed by our team, the hexylureidobenzo-18-crown-6, 1, and hexylureidobenzo-15-crown-5, 2, macrocyclic heteroditopic receptors15 (Figure 1b), that allow the formation of supramolecular ion channels, so as to enable efficient iontranslocation pathways through lipid bilayers,3c liquid,16 solid,17 and mesoporous18a,b hybrid membranes. Methodology for the Synthesis of Mesoporous Systems. The hydrophobic host matrix, MCM41-ODS, is obtained from the mesoporous MCM41 silica (Aldrich), which was reacted for 12 h at 60 °C with octadecyltrichlorosilane (ODS) 5 × 10−2 M in toluene and then carefully washed with toluene and ether. Then, the hydrophobic MCM41-ODS powder was suspended in 5 × 10−2 M chloroformic solutions of 1 or 2. The pores were gently degassed under moderate vacuum, favoring the immersion of the solution within the pores and then stirred at room temperature for 48 h. Then, the powder was filtrated and washed with chloroform and ether. The noncovalent confinement of 1 and 2 in a lipophilic mesoporous MCM41ODS matrix results in the formation of M1 and M2 materials, respectively. Finally, the resultant M1 and M2 powders were suspended in aqueous solutions (10−1 M) of KNO3 and stirred for 48 h, resulting in the formation of macrocyclic heterotopic salts confined within the mesopores. After the experiment, these compounds are not present in residual aqueous solution as confirmed by ESI-MS studies. The decrease of scattering intensity upon the successive filling of the mesoporous matrix MCM41 is consistent with the progressive incorporation of ODS and then with the confinement of the macrocycles 1 and 2 into the hydrophobic pores. Three well-resolved peaks in the range of 1.5−4.5° (2θ = 2.1, 3.6, and 4.2, respectively, Figure 2a) were indexed as 10, 11, and 20 reflections, based on the two-dimensional hexagonal arrangement of MCM41, already reported,19a with a = 4.8 nm, indicating that this hydrophobic mesoporous silica still has a highly ordered structure, which remains unaltered by covalently linking the ODS moiety or by confining the heteroditopic receptor. It is known that the reflection intensities are proportional to the scattering contrast between the pore walls and the inner part of the pores.19b These results are supported by the decreasing of specific surface area, SBET, and total pore volume, V pores, values estimated from N2 adsorption− desorption isotherms (Figure 2b), strongly supporting that 1 and 2 are confined inside the pores of MCM41, as opposed to

Figure 2. (a) Low-angle XRPD patterns and (b) the specific surface area, SBET, and the total pore volume, Vpores, values of MCM41, MCM41-ODS, and M1 mesoporous materials (similar results are obtained for M2).

crystallized on its surface. They show a partial filling of 70% after the covalent incorporation of ODS and then an almost complete filling of 98% after noncovalent confinement of the macrocyclic receptors 1 or 2 inside the silica mesopores (Figure 2b). The amount of macrocyclic compounds confined within mesopores can be determined from single-crystal X-ray and adsorption−desorption data. We know that four molecules of 1 are present in the elementary cell of 2825 Å3 Thus, a molecule of 1 has about 700 Å3. From adsorption−desorption data, we determined that a volume of 150 mm3/g of MCM41-ODS can be filled with macrocyclic compound 1. This corresponds to x = [(150 × 1021)/(700 × 6.023 × 1023)] = 3.55 × 10−4 mol of 1/g of MCM410DS. Single-Crystal, Powder, and Confined Powder Structures of Compound 1. The crystal structure of 1 previously published by us3c shows that the crown ethers self-assemble in columnar arrays of channel-type stacks such that the crown ether molecules are disposed in an antiparallel packing (A) (Figure 3a) (i.e., no X-ray structure available for compound 2). It is interesting to note that the benzoureidobenzo-15-crown-5 analogue shows a parallel packing (P) of crown ethers.15a The parallel dipolar orientation of the crown ether molecules is compensated via multiple H-bonding/stacking interactions. The weak van der Waals interactions between the hexyl chains of 1 are not totally compensating this parallel orientation energy, resulting in an antiparallel self-assembly of hexylureidobenzo-crown ethers presenting alternative dipolar moments of opposite orientation. Comparing the X-ray structure solution of 1 with the XRPD results over the suite of compounds (C3H7−, C6H13− (1), C18H37−), we discovered that the preferential antiparallel (A) packing coexists in the bulk powders with a second residual parallel (P) packing polymorph.3a Comparing the diffractogram generated from the single-crystal structure solution of 1 (Figure 3b, red) with the experimental diffraction results of the bulk 3063



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fingerprint of the single-crystal structures, bulk powders of 1· KNO3 and 2·KNO3, and bulk-confined powders within M1 and M2 materials equilibrated with aqueous solutions of KNO3. Additional peaks were found in all cases, and we supposed that polymorphic forms are present in the confined mesospace. However, in all cases, a successful identification of the novel confined salt-macrocyclic superstructures in the presence of ionic salts was achieved. Single-Crystal, Powder, and Confined Powder Structures of 1·KNO3. The molecular and the crystal packing superstructures of 1·KNO3 are presented in Figure 4a. The unit cell of the crystal structure of 1·KNO3 was found to contain eight molecules of hexylureidobenzo-18-crown-6, 1, together with eight K+ cations and eight NO3− anions, as previously observed for the phenylureidobenzo-15-crown-5·NaNO3 macrocyclic complex.15a The fittest K+ ion is equatorially complexed within the 18-crown-6 macrocycle (average K+−O distance of 2.70 Å) and is also coordinated by an apical NO3− anion (K+−O distance of 2.72 Å). The NO3− anions are synergistically H-bonded to the urea N-H moieties (average O−H distance of 1.90 Å). They form two connecting bridges between two 1·K+ supermolecules, resulting in the formation of the heteroditopic antiparallel dimers (1·KNO3)2 strongly packed in close contacts (Figure 4a, left). The second apical position of the K+ cation is occupied by a carbonyl moiety of a vicinal dimer (average K+− O distance of 2.66 Å) so that each dimer is in very close contact with its neighbor (Figure 4a, center). This structure alternates alignments of the host−cation−anion layers. It results in a continuous development of solid-state ion channels penetrating the crystal lattice as viewed down the central axes of the macrocycles (Figure 4a, right). The difference between the calculated powder pattern of 1· KNO3 (Figure 4b, red) with the experimental diffraction results of the bulk powder of 1·KNO3 (Figure 4b, blue) and of the KNO3 equilibrated mesoporous material M1·KNO3, (Figure 4b, cyan) can be explained by the presence of a second polymorphic phase, but most probably by a symmetry lowering of the crystalline phase in the bulk powder and in the hybrid material, assuming the formation of the nonconnected single layers aligned along the mesopore. The space group symmetry of the single-crystal structure of 1·KNO3 is C2/c, which excludes reflection intensity for (hkl) reflections with indices h + k = 2n + 1 and also for (00l) reflections with indices l = 2n + 1 and (h0l) reflections with h + l = 2n + 1 (n an odd integer). The presence in the experimental diffractogram of diffraction peaks at 2θ = 4.81°and 2θ = 5.30° on both sides of the first main (200) peak can be explained by a symmetry lowering to a possibly triclinic phase with slightly offset cell parameters; the two peaks can then be indexed as (001) and (201̅) (Figure 4c). Similarly, the fairly intense peak at 2θ = 7.81° is indexed as (201), forbidden in the C-centered monoclinic phase and thus absent in the calculated powder diagram. With all these in mind, the confinement of two ribbons of dimers of variable length (section dimensions: 19.5 Å × 11.5 Å) can be confined within 40 Å diameter mesoporous material M1 (Figure 4d). Single-Crystal, Powder, and Confined Powder Structures of 2·KNO3. The molecular and the crystal packing superstructures of 2·KNO3 are presented in Figure 5a. The unit cell of the crystal structure of 2·KNO3 was found to contain four hexylureidobenzo-15-crown-5 2 molecules, together with two K+ cations and two NO3− anions. The crystal structure of 2·KNO3 reveals the formation of (2·KNO3)n supramolecular

Figure 3. Dynamic self-organization of macrocyclic receptor within the mesopores: (a) Top and side single-crystal packing of compound 1in stick representation. (b) Single-crystal (red) and X-ray powder diffraction patterns of 1 (blue) and M1 (cyan) material. (c) Equilibrium between parallelly packed oligomers (P) of 1, along the hydrophobic inner wall of the pore and antiparallel polymorphs (A) filling the central part of the pore as determined from XRPD analysis. The orientation of crown ether stacks is arbitrary.

powder of 1 (Figure 3b, blue), the preferential antiparallel packing (A) corresponding to the first (100) intense peak at 2θ = 5° coexists in the powder with a second residual parallel packing (P) corresponding to the second small peak at 2θ = 7.5°, respectively (see ref 3c for a detailed discussion). This residual peak is amplified when 1 is confined in a hydrophobic MCM41-ODS material (Figure 3b, cyan). We assume that the confinement of the macrocycles results in the formation of parallelly packed oligomers, not existing in the single crystal, via stronger hydrophobic contacts with the grafted octadecyl chains along the inner wall of the pore, whereas the antiparallel polymorphs are filling the central part of the pore (Figure 3c). It is noted as well that the crystallinity is not extremely high in view of the broadness of the diffraction peaks at low angles; however, different polymorphs may be detected due to crystallization conditions under pore confinement.18a,b However, the well-resolved peaks in the range of 2θ =18−22°, attributed to low-distance interactions (urea H-bonding, stacking interactions), are strongly preserved. Dynamic Supramolecular Reorganization of Confined Macrocyclic Stacks in Response of External Ionic Effectors. We know now that the macrocyclic ion-channeltype architectures 1 and 2 can be physically confined, without any covalent binding to the inner pore walls. The noncovalent hydrophobic interaction between alkyl chains of the macrocyclic receptors may render the confined architectures dynamic. If the structure is not robust enough, it might induce dynamic structural changes in the constitution of the supramolecular confined H-bonded networks in response to external stimuli (i.e., ionic salts, etc.) or environmental factors (solvent, temperature, etc.). In order to verify these hypotheses, we have investigated by XRPD the compatibility of the bulk X-ray 3064



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Figure 4. (a) (left) Crystal structure in stick representation of the dimer (1·KNO3)2 and (center) its lateral cation−carbonyl interactions. (right) Side view of the crystal packing of 1·KNO3 in the H-bond individual cationic and anionic channel-type superstructures. K+ cations as violet spheres, NO3− anions in CPK representation. (b) Single-crystal (red) and X-ray powder diffraction patterns (blue) of 1·KNO3 and M1 (cyan) materials. (c) Crystal cell packing of 1·KNO3. The forbidden peaks present in the XRPD of powder, 1·KNO3, and confined powder, M1, are reminiscent with the presence of (d) two dimeric ribbons [(1·KNO3)2]n in possibly triclinic phases under confined conditions. The orientation of crown ether stacks is arbitrary.

macrocycles (K−O distance of 2.86 Å). The NO3− anion is double H-bonded to four N-H groups (average O−H distance of 2.06 and 2.17 Å) of two urea moieties of two ureidocrown

polymers. Because of the dimensional incompatibility between the diameter of the K+ cation and the diameter of the 15crown-5 macrocycle, the cation is sandwiched between two 3065



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Figure 5. (a) Side (left) and top (center) view of the crystal structure in stick representation of the oligomer (2·KNO3)n. (right) Top view of the crystal packing of (2·KNO3)n oligomers as alternative rows of opposite dipolar orientation. K+ cations as violet spheres, NO3− anions in CPK representation. (b) Single-crystal (red) and X-ray powder diffraction patterns (blue) of 2·KNO3 and M2·KNO3 (cyan) materials. (c) Crystal cell packing of 2·KNO3. The peaks that are present at 2θ = 8.12° and 2θ = 10.14° in the XRPD of the crystal structure and the powder of 2·KNO3 are not more present in the XRPD of confined powder, M1·KNO3, reminiscent with the presence of (d) one ribbon [(2·KNO3)2]n within mesopores under confined conditions.

ether molecules, nonsandwiching the cation. It results in the formation of the knotting cationic and anionic centers connected via heteroditopic binding of ureido-crown ethers: the K+ cation and the NO3− anion may be considered as alternative connecting bridges between dimers of 12·NO3− and 12·K+, respectively. A continuous development of individual

solid-state ion channels for cations and anions, penetrating the crystal lattice, is observed as viewed down the central axes of the macrocycles (Figure 5a). When comparing the diffractograms generated from the 2·KNO3 single-crystal structure solution (Figure 5b, red) with the XRPD results of the bulk 2· KNO3 (Figure 5b, blue) and M2·KNO3 (Figure 5b, cyan) 3066



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the two acetonitrile molecules were refined with isotropic atomic displacement parameters. X-ray Single-Crystal Diffraction Data for Compounds 1· KNO3 and 2·KNO3. Crystals suitable for X-ray structure determination of 1·KNO3 and 2·KNO3 were obtained after a few days in acetonitrile/ipropylether mixtures. The diffraction intensities were collected at the joint X-ray Scattering Service of the Institut Charles Gerhardt and the Institut Européen des Membranes of the University of Montpellier II, France, at 175 K using an Oxford Diffraction Xcalibur-I and a Gemini-S diffractometer. The crystal-to-detector distance was 50 mm for all five measurements. The structures were solved by direct methods using SIR200220a or by ab initio (chargeflipping) methods using SUPERFLIP20b and refined by least-squares methods on F using CRYSTALS,20c against |F| on data having I > 2σ(I); R factors are based on these data. Hydrogen atoms were partly located from difference Fourier synthesis, partly placed based on geometrical arguments, and, in general, not refined. Non-hydrogen atoms were, in general, refined anisotropically, except where the datato-parameter ratio did not allow doing this. Full details can be found in the CIF files. CCDC 986002−986004 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html. X-ray powder diffraction XRPD measurements were performed with Cu Kα radiation at 20 °C using a Philips X’Pert Diffractometer equipped with an X’celerator detector. Nitrogen adsorption− desoption isotherms were measured on a Micrometrics ASAP2010 volumetric absorption analyzer with the sample outgased at 50 °C before measurement. 1·KNO3. C23H38KN3O10; Z = 8; crystal dimensions: 0.08 × 0.12 × 0.20 mm; cell dimensions: a = 35.590(3) Å, b = 8.2110(7) Å, c = 19.1126(15) Å, α = 90°, β = 98.928(8)°, γ = 90°, V = 5517.6(8) Å3; monoclinic, space group C2/c; ρcalcd = 1.338 g cm−3; μ = 0.250 mm−1; 9404 measured reflections, 3094 unique, 1652 with I > 2σ(I). Final R factors R1 = 0.1638 and wR2 = 0.1757; 170 parameters, 106 restraints; maximal residual electron density is −0.81/0.91 e·Å−3. The atomic displacement parameters of non-H atoms were refined isotropically and a number of them treated with thermal similarity and vibration restraints. The H atoms were positioned geometrically and refined with riding constraints. The crystal scattered only weakly, partially because of heavy disorder in the C6 tail, which was difficult to model and which makes the agreement factor rather high. Two tails could be identified. Each tail was refined with soft constraints on bond lengths and angles, and the occupancy factors of the two disordered parts were refined to 0.583(14)/0.417(14). The C28 atom is common to the two tails. The two tails are as follows: C28(H285,H286) - C29(H291,H292) - C32(H321,H322) - C33(H331,H332) - C36(H361,H362) - C38(H381,H382,H382) or C28(H283,H284) C30(H301,H302) - C31(H313,H314) - C34(H341,H342) - C35(H353,H354) - C37(H371,H372,H373). 2·KNO3. C40H64KN5O15; Z = 2; crystal dimensions: 0.20 × 0.23 × 0.28 mm; cell dimensions: a = 9.5165(8) Å, b = 13.8803(7) Å, c = 17.6742(12) Å, α = 90°, β = 99.517(7)°, γ = 90°, V = 2302.5(3) Å3; monoclinic, space group P2/c; ρcalcd = 1.290 g cm−3; μ = 0.185 mm−1; 18 294 measured reflections, 2287 unique, 641 with I > 2σ(I). Final R factors R1 = 0.1155 and wR2 = 0.1170; 126 parameters, 259 restraints including shift-limiting restraints on all parameters; maximal residual electron density is −0.38/0.52 e·Å−3. The crystal, although not particularly small, was a very weak scatterer, needing a 124 h data collection with frame counting times in between 100 and 500 s. Even after this long exposure, only 641 independent reflections with I > 2σ(I) could be extracted. The structure solution with Superflip was done using nondefault settings. Only the K atom was refined anisotropically. Restraints on 6 distances were needed in order to stabilize the refinement. The H atoms were positioned geometrically and refined with riding constraints. Disorder was observed in the C6 tail but was not modeled, because of the very poor data-to-parameter ratio, which led finally to a relatively high agreement factor.

powders, it can be observed that the 2·KNO3 single-crystal structure is representative for the crystal structures of the two bulk materials. The two clear peaks present at 2θ = 8.12° and 2θ = 10.14°, which can be indexed as the (011) and (002) diffraction lines, are nearly absent or at the most strongly broadened in the XRPD of the powder of M2·KNO3. This can be explained by a diminishing crystallite size and/or by a progressive symmetry change of the crystalline phase in the bulk powder (Figure 5c). These results lead us to believe that one column of ribbons of knotted oligomers (2·KNO3)n of variable length (section dimensions: 14.2 Å × 17.2 Å) can indeed be confined within the 40 Å pore diameter material M2 in a way as depicted in Figure 5d.

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CONCLUSION In conclusion, experimental evidence presented in this paper shows that long-range crystalline order observed in the macrocyclic heteroditopic receptors’ single-crystal structures is preserved when embedded in the hydrophobic mesopores structurally close to the bilayer membranes. Their crystallographic structures are, however, slightly changed inside the mesoporous hydrophobic M1 and M2 materials. Investigations presented here showed that MCM41-type mesoporous hydrophobic hybrids can be used as biomimetic platforms for ionchannel biomimetic structure elucidation, while showing similar constitutional interactions with confined ligands/receptors as in bilayer membranes. Interestingly, they present a modular mesoporous matrix, compartmentalized at the nanometric level, whose confined ion-channel superstructures can be easily characterized by XRPD and compared with the available singlecrystal superstructures in order to check their robustness when embedded in hydrophobic media. This gives access to information concerning the structural pictures of the bilayer’s confined ion-channel structures, as well as of their relatives in the presence of ion effectors.

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EXPERIMENTAL SECTION

Synthetic Procedures. The synthesis and the structural characterization of compounds 1 and 2 have been reported elsewhere.18 The mesoporous MCM41-type material (MESOSYL from SiliCycle Inc., 40 Å pore diameter) is successively reacted with octadecyltrichlorosilane (ODS) in order to obtain the hydrophobic mesopores, followed by the physical incorporation in solution of carriers 1 or 2 within the mesopores.3a,b X-ray Single-Crystal Diffraction Data for Compound 1.3a Xray diffraction data measurements for 1 were carried out at beamline ID11 at the European Synchrotron Facility (ESRF) at Grenoble. A wavelength of 0.51091 Å was selected using a double crystal Si(111) monochromator. Single crystals of 1, C27H44N4O7 (or C23H38N2O7· 2(C2H3N) in moiety notation), were grown from acetonitrile. Crystals were placed in oil, and a single crystal of dimensions 0.05 × 0.10 × 0.12 mm was selected, mounted on a glass fiber, and placed in a lowtemperature N2 stream. Data were collected using a Bruker “Smart” CDD camera system at fixed 2θ and reduced using the Bruker SAINT software. The unit cell was monoclinic with space group of P21/c. Cell dimensions were a = 20.094(8) Å, b = 8.227(3) Å, c = 17.955(7) Å, α = γ = 90°, β = 107.859(8) °, V = 2825.2(19) Å3, and Z = 4. Out of the 30 830 reflections collected, 8745 were unique with 2015 having I > 2σ(I). The final number of parameters and restraints were 232 + 28. Thermal similarity and vibration restraints were used for a number of carbon and nitrogen atoms. Hydrogen atoms were included at calculated positions by using a riding model. Final R factors were R1 = 0.0953 and wR2 = 0.0613, (I > 2σ(I)), and minimum and maximal residual electron densities were −0.65 and 0.68 e·Å−3. The atoms of 3067



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(19) (a) Hoffmann, F.; Cornelius, M.; Morell, J.; Froba, M. Angew. Chem., Int. Ed. 2006, 45, 3216−3251. (b) Sauer, J.; Marlow, F.; Scuth, F. Phys. Chem. Chem. Phys. 2001, 3, 5579−5584. (20) (a) Burla, M. C.; Camalli, M. B.; Carrozzini, G. L.; Cascarano, R.; Giacovazzo, C.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 2003, 36, 1103. (b) Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, K.; Watkin, D. J. J. Appl. Crystallogr. 2003, 36, 1487. (c) Palatinus, L.; Chapuis, G. J. Appl. Crystallogr. 2007, 40, 786−790.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS D.D. thanks the Labex Chemisyst, Pole Chimie Balard of Montpellier, for a postdoctoral fellowship. We thank Dr. Gavin Vaughan (ID11, ESRF, Grenoble France) and Dr. Adinela Cazacu for the preliminary X-ray measurements of compound 1 and the confinement work, respectively. This work was conducted within the framework of DYNANO, PITN-GA2011-289033.

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