Communication Cite This: Cryst. Growth Des. 2018, 18, 27−31
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Observation of Rapid Desolvation of Hexafluorobenzene Involving Single-Crystal-to-Single-Crystal Phase Transition in a Nonporous Organic Host Published as part of a Crystal Growth and Design virtual special issue on pi−pi Stacking in Crystal Engineering: Fundamentals and Applications Subhrajyoti Bhandary and Deepak Chopra* Crystallography and Crystal Chemistry Laboratory, Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal By-Pass Road, Bhopal, Madhya Pradesh, India 462066 S Supporting Information *
ABSTRACT: We report an unusual occurrence of an extremely fast singlecrystal-to-single-crystal phase transition induced by rapid desolvation of hexafluorobenzene at room temperature mediated by a subtle interplay of π···π stacking interactions in N-(3-ethynylphenyl)-4-fluorobenzamide. The nature of the host−guest stacking interaction has been explored in terms of interaction energy, electrostatic complementarity, and topological analysis with the inputs from reduced density gradient-noncovalent interactions fingerprint descriptor. Furthermore, the compound also exists in two other nonsolvated polymorphic forms.
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noncovalent interactions, and nature tends to maximize the attractive interactions to minimize the empty space to form a densely packed crystalline lattice.21 In such a scenario, the solvent molecules can incorporate into the lattice through potential host−guest interactions which provides additional stability to the framework structure.22 The loss of the guest molecule from such a molecular host in the absence of intrinsic porosity does not allow quick solid state rearrangement to maintain the three-dimensional (3D) periodicity and leads to disruption of single crystallinity,23which makes the event of desolvation involving single-crystal-to-single-crystal (SCSC) phase transition extremely rare.15,24−27 Moreover, the structural transformation with the removal of guest molecules from crystal lattice often needs potential stimuli such as elevated temperature, light, or mechanical forces which often destroy the crystalline nature of the material with reduced properties. In this regard, spontaneous solvent elimination at room temperature (RT, 20−25 °C) from a nonporous organic host lattice with quick reorganization to another polymorphic form in SCSC fashion demands significant attention in both fundamental and application based research. During our investigation of the effect of fluorinated solvents on the crystallization outcomes of a newly synthesized fluorine containing compound, namely, N-(3-ethynylphenyl)-4-fluorobenzamide (SYF33; Scheme 1),we observed that the crystals
he structural diversity which exists in crystalline solids is a key attraction in supramolecular chemistry.1,2 Particularly, the occurrence of multiple crystalline phases of a given compound (polymorphs), including crystallization with guest solvent molecules (pseudopolymorphs/solvatomorphs), has distinct physicochemical and material properties which provides great opportunities to tune the structure−function relationships at the molecular level.3−6 The inclusion of guest solvent molecules in the crystal lattice of the host is quite common during the solution-mediated crystallization process.7−10 The investigation of the phenomenon of desolvation from a crystal lattice is of topical interest in chemistry and material science.11−16 In the area of pharmaceutical research, solvent removal from the crystalline state of the drug plays an important role resulting in the formation of new polymorphic forms which are not accessible by conventional crystallization techniques.17 Importantly, the phenomenon of desolvation is one of the potential strategies not only to form porous extended frameworks but also small molecular solids with promising gas adsorption abilities9,13,18 and photoemission properties.19,20 The process of solvent elimination (desolvation) is system specific. In an extended framework lattice, solid state dynamics is entirely controlled by strong coordination bonds, and hence the evacuation of guest solvent molecules may occur from such a robust system without breaking the periodicity of the crystalline lattice, resulting in permanent porosity and making them suitable candidates for single crystal device materials.9,13 By contrast, organic molecular systems are stabilized by weak © 2017 American Chemical Society
Received: September 14, 2017 Revised: October 25, 2017 Published: November 20, 2017 27
DOI: 10.1021/acs.cgd.7b01309 Cryst. Growth Des. 2018, 18, 27−31
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Scheme 1. Chemical Structure of the Compound SYF33 with Multiple Solid Forms
Figure 2. Displacement ellipsoids (50% probability level) of solvated (left) and desolvated (right) phases. Dotted lines show intra- and intermolecular interactions.
obtained from hexafluorobenzene (HFB) solvent undergo very fast transition at RT outside the mother liquor. The event of phase transition proceeds rapidly as is reflected in the crystal turning opaque from transparent (Figure 1, and movie M1 in the Supporting Information).
pairs for all crystalline phases along with their total lattice energy were calculated using PIXEL. 28,29 List of all intermolecular interactions with their IE is summarized in Table S3. The solvated phase (Form FB) of the compound crystallizes in monoclinic P21/n space group with a 1:1 stoichiometric ratio for the host−HFB solvent (Figure 2). The supramolecular assembly is mainly guided by intermolecular strong N−H···O hydrogen bonding chains (motif I, IE −50.9 kJ/mol) operating in alternate directions (see purple arrows in Figure 3a), which also consists of stacking between fluoro- and ethynyl-phenyl rings (Figure S5). Such adjacent chains are held by weak
Figure 1. Images of very fast desolvation at RT (outside mother solvent) from Form FB followed by SCSC phase transition to Form III.
In order to capture this phenomenon, we cautiously collected the single crystal X-ray diffraction (SCXRD) data of the initial crystalline phase at very low temperature (100 K), which confirms the presence of guest HFB solvent molecule in the crystal lattice (Form FB). After that, the crystal settled down to RT to make the crystal fully opaque (within a minute) and again SCXRD data was collected. It is quite rare and interesting to observe that after the rapid phase transition at RT, the monocrystallinity of the crystal is maintained through the complete elimination of solvent molecule in an SCSC manner resulting in the appearance of a new solvent-f ree polymorphic phase (Form III). The absence of the guest solvent molecule after desolvation in Form III phase was also confirmed by thermogravimetric analysis (Figure S2) and via an overlay of the experimental and simulated powder X-ray diffraction patterns (Figure S3). In addition to that, the crystallization screening in other organic solvents (Table S1) generates in addition two new polymorphic forms (Form I and Form II) for the compound SYF33. It is noteworthy that the single crystal of Form III could not be obtained from any other solution mediated crystallization techniques, and the exposure of HFB solvent on Form III crystal (desolvated form) shows no reversible uptake of solvent molecule. Interestingly, dissolving the Form III crystals in HFB solvent by gentle heating results in “immediate recrystallization” of the solvated form (Form FB). All crystallographic and refinement details are tabulated in Table S2, and ORTEPs are given in Figure 2 and Figure S4. To rationalize the above unusual facile desolvation induced SCSC transition and the origin of occurrence of polymorphism in the case of the compound SYF33, a detailed investigation into the intermolecular interactions which are present in the crystal packing is of extreme importance. For this purpose, intermolecular interaction energies (IE) of important molecular
Figure 3. Supramolecular layer of molecules connected via strong N− H···O, weak C−H···F hydrogen bonds, and stacking interactions in (a) Form FB, (b) Form III, (c) Form I, and (d) Form II. Purple arrows indicate the direction of N−H···O interactions along their interaction energies. 28
DOI: 10.1021/acs.cgd.7b01309 Cryst. Growth Des. 2018, 18, 27−31
Crystal Growth & Design
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C(sp)−H···F hydrogen bonds (motif IX, IE −5.1 kJ/mol), formed between the highly acidic acetylenic hydrogen with the fluorine atom. The guest HFB solvent molecule is trapped in between such N−H···O chains (red circle in Figure 3a) in the crystal lattice through the presence of parallel-displaced stacking with fluorophenyl ring (motif III, IE −17.8 kJ/mol) and also with ethnylphenyl ring of the host (motif II, IE −19.0 kJ/mol) which bridges the two criss-cross N−H···O layers forming a 3D crystal lattice (Figure 4). The driving force is the
Once the key structural features of all four crystalline phases have been quantitatively characterized, it is of extreme interest to understand the affinity of the guest HFB solvent toward the host molecule via π···π stacking interactions in the Form FB (Figure 5a) as well as the sudden removal of the guest, resulting
Figure 4. Preservation of a similar supramolecular framework in Form III after quick desolvation at RT from Form FB.
Figure 5. (a) Host−guest stacking, and electrostatic potential (ESP) mapped over the Hirshfeld surfaces30 of (b) HFB solvent molecule and (c, d) host molecule of Form FB with top and down view. Color range −0.02 au (red) through 0.00 (white) to +0.02 au (blue).
presence of donor···acceptor interactions between the electron deficient HFB and relatively electron-rich fluoro- and ethynylphenyl ring to stabilize the solvated structure of Form FB. It is also evident from the fact that the presence of both electrostatic (27−30%) along with dispersive contributions is significant for these stacking interactions (motif II and III, Table S3). Likely in Form FB, the robustness of most stabilized N−H···O chains (motif I, IE −51.2 kJ/mol) with C(sp)−H···F (motif VI, IE −7.0 kJ/mol) along with the C(sp2)−H···F (motif IV, IE −10.2 kJ/mol) interactions direct the supramolecular packing of molecules in Form III (Figure 3b). It is important to note that the IE of the most advantageous N−H··· O hydrogen bonds in both the Form FB (−50.9 kJ/mol) and Form III (−51.2 kJ/mol) remains same which also operates in a similar fashion (purple arrows in Figure 3a−b). Moreover, the host−guest stacking interactions in Form FB is compensated by direct stacking of the f luorophenyl and ethynylphenyl rings forming a nonporous crystal structure in Form III (red circle in Figure 3a−b). This structural uniqueness leads to the preservation of the overall framework structure of Form III without losing monocrystallinity (SCSC transition) even after the abrupt removal of the solvent from the Form FB crystal lattice (Figure 4). In contrast, the Form I and Form II polymorphs are structurally very different (Figure 3c−d) from the above two forms (Form FB and Form III). The orientation of the two phenyl rings with respect to bridging N−H and CO groups are altered from that of Form FB and Form III as a consequence of conformational flexibility at τ1, τ2, and τ3 in the molecule (Scheme 1, and see torsion angles in Table S4). The two symmetrically unique molecules (green and purple) in both Form I and Form II polymorphs rearrange to exhibit layered packing of the molecules (Figure 3c−d). In Form I, alternate layers of each symmetry unique molecules (Figure 3c) are stabilized by strong N−H···O chains along with stacking interactions (motif I, IE −48.7 kJ/mol and motif II, IE −47.8 kJ/mol) and weak C(sp)−H···F hydrogen bonds (motif XIII and XV). Each molecular layer in Form II (Figure 3d) contains both the symmetrically unique molecules by similar strong N− H···O chains (motif I, IE −52.1 kJ/mol and motif II, IE −45.6 kJ/mol) and connected by weak C(sp2)−H···F and C(sp2)− H···π(triple bond) interactions (motif VII).
in the formation of Form III in terms of the quantitative complementarity in the molecular electrostatic potential (MESP). For this purpose the MESP was mapped for both the guest and the host molecules at the crystal geometry for the Form FB (Figure 5b−d). The center of the ring for HFB molecule exhibits strong electropositive character (0.035 au) due to the presence of six highly electronegative fluorine atoms, whereas both the faces correspond to the presence of the fluorophenyl and the ethynylphenyl rings for the host molecule, showing nearly neutral [0.001 au (top view) and 0.005 au (down view)] to strongly electronegative [−0.012 au (top view) and −0.007 au (down view)] regions as is shown in Figure 5b−d. The clear demarcation of the magnitude of the electrostatic potentials between the phenyl rings of the host− guest molecule facilitates the effective parallel-displaced type of stacking (Figure 5a).31 However, it is noteworthy to mention that in spite of the presence of highly electropositive character on the phenyl ring on the HFB molecule, it was found to stack preferably near the neutral-to-mild electropositive fluorophenyl ring (top view) in preference to the strongly electronegative ethynylphenyl ring in the crystal structure (asymmetric unit) of the Form FB (Figure 2, left). However, the final crystal structure does get further stabilized via interaction of the HFB molecule with the more electronegative MESP of the ethynylphenyl (down view) on the other side. This preferential stacking between the solvent-fluorophenyl ring (motif III) of the host can also be elucidated using the topological treatment of the electron density by QTAIM.32 The result shows the multiple presence of critical points (BCPs, RCP, and CCP) in between the stacking of two rings due to the characteristic presence of closed-shell C···C as well as C···F and C···O contacts (Figure 6). The value of all topological parameters at the BCPs for such contacts is given in Table S5. The nature and strength of the host−guest complementarity were further visualized in real space through reduced density gradient (RDG) isosurfaces surrounding the noncovalent interactions (NCI) regions (Figure 7).33,34 The fingerprint of RDG-NCI analysis is the sign of the second eigenvalue (λ2) of the Hessian matrix that decides the characteristic of the interaction (λ2< 0 for attractive and λ2 > 0 for repulsive). The color of the RDG isosurface for stacking of solventfluorophenyl ring clearly indicates a combination of light blue 29
DOI: 10.1021/acs.cgd.7b01309 Cryst. Growth Des. 2018, 18, 27−31
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Figure 6. Molecular graph for the solvent and fluorophenyl ring interaction in Form FB.
Figure 8. DSC traces recorded at 2 °C/min for crystals of all three polymorphs (Form I, Form II, and Form III).
to most stable Form I phase followed by the subsequent melting of Form I phase in the second endotherms (b) at 118.4 and 115.4 °C respectively. Hence, they are monotropic polymorphs.5 Visual insights into all these thermal events were also obtained from hot stage microscopy (Figure S6). Thus, thermal experiments also establish the highest stability of Form I followed by Form II to Form III phase, which is consistent with the trends as obtained from calculated lattice energies. In summary, a unique desolvation with SCSC phase transition has been observed at ambient conditions from Form FB to Form III phase in the crystal landscape of N-(3ethynylphenyl)-4-fluorobenzamide which also consists of two other nonsolvated polymorphic forms (Form I and II). The structural study reveals that the occurrence of desolvation involving SCSC transition undergoes by the preservation of the supramolecular structure with the subtle balance involving stacking interactions. This process involves the conservation of the crystal structure in a nonporous organic host. This study can provide potential insights into the design and development of new molecular crystals in future based on the features of electrostatic complementarity that exist between the host− guest molecules.
Figure 7. (a) RDG isosurface (the isovalue is 0.6 colored over the range of 0.02 < ρ*sign λ2 < 0.02 au.) and (b) Plot of RDG versus ρ*sign (λ2) for the solvent-fluorophenyl ring stacking in Form FB.
(weakly destabilizing) and light green (weakly stabilizing) regions (Figure 7a). The plot of RDG versus electron density multiplied by the sign of the second Hessian eigenvalue [ρ*sign (λ2)] (Figure 7b) clearly depicts low gradient spike in the negative region which corresponds to the weakly attractive dispersion interaction due to the presence of interatomic BCPs. The spikes in the positive regions is indicative of steric clashes between the highly electron deficient phenyl ring of the solvent and the nearly neutral fluorophenyl ring of the host molecule. Thus, the affinity of HFB solvent toward the host in the crystalline phase Form FB depends on the net balance of both stabilizing and destabilizing stacking interactions which contribute to the overall metastability and facilitate the rapid elimination of the solvent from the crystal lattice at RT leading to the formation of the solvent free Form III phase. Furthermore, the stability of all crystalline phases was obtained from lattice energy calculations which clearly suggests that Form FB has reduced lattice energy (−84.2 kJ/mol) in comparison to the other three polymorphs (Table S6). This might be the driving force for the spontaneous phase transition at RT by desolvation of the metastable Form FB to the relatively stable Form III (lattice energy −127.4 kJ/mol). It is important to observe that although Form I and Form II have greater lattice energies (−130.9 kJ/mol and −128.0 kJ/mol respectively) than Form III, but Form FB transforms to Form III preferably after desolvation in accordance with the Ostwald’s rule of crystallization of polymorphs. The three stable forms were characterized via differential scanning calorimetry (DSC) and hot stage microscopy experiments performed on crystals of each form (Figure 8 and S6). The DSC results reveal that the Form I crystals (red trace in Figure 8) melt directly with sharp endothermic peak at 119.4 °C. The crystals of both the polymorphs Form II and Form III show typical melting and immediate recrystallization endotherms (a) at 110.6 and 105.4 °C respectively (blue and green traces). It was expected that both the Form II and Form III after the melting in first endotherm (a) underwent quick recrystallization
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.cgd.7b01309. Details of synthesis, NMR, crystallizations, single crystal data collections, ORTEPs of polymorphs, hot stage microscopy images, PXRD patterns, FTIR, and theoretical calculations (PDF) Movie M1 (MPG) Accession Codes
CCDC 1558393−1558396 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033. 30
DOI: 10.1021/acs.cgd.7b01309 Cryst. Growth Des. 2018, 18, 27−31
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(27) Costa, J. S.; Rodríguez-Jimenez, S.; Craig, G. A.; Barth, B.; Beavers, C. M.; Teat, S. J.; Aromí, G. J. Am. Chem. Soc. 2014, 136, 3869−3874. (28) Gavezzotti, A. New J. Chem. 2011, 35, 1360−1368. (29) Maschio, L.; Civalleri, B.; Ugliengo, P.; Gavezzotti, A. J. Phys. Chem. A 2011, 115, 11179−11186. (30) Spackman, M. A.; Jayatilaka, D. CrystEngComm 2009, 11, 19− 32. (31) Gung, B. W.; Amicangelo, J. C. J. Org. Chem. 2006, 71, 9261− 9270. (32) Bader, R. F. W. Atoms in Molecules: A Quantum Theory; Oxford University Press: Oxford, U.K., 1990. (33) Johnson, E. R.; Keinan, S.; Mori-Sanchez, P.; Contreras-García, J.; Cohen, A. J.; Yang, W. J. Am. Chem. Soc. 2010, 132, 6498−6506. (34) Saleh, G.; Lo Presti, L.; Gatti, C.; Ceresoli, D. J. Appl. Crystallogr. 2013, 46, 1513−1517.
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]; fax: +91-0755-6692392. ORCID
Deepak Chopra: 0000-0002-0018-6007 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work is financially supported by funding from DST-SERB, India. We acknowledge IISER Bhopal for research facilities and infrastructure. S.B. thanks IISER Bhopal for the research fellowship. S.B. is grateful to Mr. Kaushik Pal for helping us in imaging using a microscope.
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DOI: 10.1021/acs.cgd.7b01309 Cryst. Growth Des. 2018, 18, 27−31
