Thermosalient (TS) Forms: Carryover of TS Behavior of Coformers

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Thermosalient (TS) Forms: Carryover of TS Behavior of Coformers from Single Component to Multicomponent Forms? Hemant Rawat, Ranita Samanta, Biswajit Bhattacharya, Shubham Deolka, Archisman Dutta, Somnath Dey, Bal Raju K, and C. Malla Reddy Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.8b00006 • Publication Date (Web): 28 Mar 2018 Downloaded from http://pubs.acs.org on March 28, 2018

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Crystal Growth & Design

Thermosalient (TS) Forms: Carryover of TS Behavior of Coformers from Single Component to Multicomponent Forms? Hemant Rawat§, Ranita Samanta§, Biswajit Bhattacharya§, Shubham Deolka, Archisman Dutta, Somnath Dey, K Bal Raju and C. Malla Reddy* Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur, Nadia-741246, West Bengal, India. E-mail:[email protected] ______________________________________________________________________________ ABSTRACT: The solids, salinazide (Slz) and 3-chloro-2-nitrobenzoic acid (CNB) are thermosalient in nature in their single component forms; upon co-crystallization with pentafluorobenzoic acid (PNB) and 4,4′-bipyridine (BPY), respectively, they produced a salt (Slz-PFB) and a cocrystal, CNB-BPY, which are also TS in nature. A detailed structural analysis of all the forms in question is carried out to verify if a solid that shows TS behavior in its single component form can be used as a TS template to generate new TS multicomponent solid forms. The study is significant as the multicomponent approach may allow the generation of a library of new TS forms, for instance to alter the response time, temperature, etc. This may also allow imparting an additional functionality (eg. mechanochromic luminescence, conductivity, chemical reactivity etc.) to the new solids upon appropriate selection of co-former(s).

______________________________________________________________________________ INTRODUCTION Thermomechanical effects of single crystals like bending, hopping, jumping, splitting and exploding have potential applications in mechanical sensors, probes for smart medical devices, artificial muscles, bioelectronics including components of microfluidic devices.1-4 Modern advancement of research unveiled several single crystalline systems that are potent as stimuli responsive materials; single crystals may offer certain advantages over polymers and liquid crystals as their dense and ordered packing can incite the rapid mechanical response and, fast and efficient energy transfer relevant to the conversion of heat or light or other sources of energy to mechanical motion.1-4 In this context self-actuating single crystals can be remarkably useful due

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to their inherent high sensitivity to external stimulus, coupled with actuating behavior.1-10 Recently, Naumov and others have reported several interesting single component TS materials and correlated the structural changes to the actuation behavior.5-10 Most of the TS effects studied are either due to phase transitions or chemical reactions associated with anisotropic changes in molecular conformation and crystal packing. As designing of phase transitions currently remains elusive, the design of thermosalient behavior has also remained a formidable challenge.11-16 Here we hypothesized that it may be possible to form TS crystals by utilizing molecular or supramolecular subunits that respond to heat change and trigger phase transformations, for instance, when incorporated in multicomponent solids (eg. co-crystals or salts). The multicomponent strategy has been extensively used in recent years to tune physicochemical properties of active pharmaceutical ingredients (APIs),17 luminescence in solid-state fluorophores18 and sensitivity of explosives.19 However, binary TS co-crystals have remained completely unexplored. This approach to TS solids can potentially allow generating a library of new forms, which can bring some unique advantages. For instance, co-crystallization approach may allow combining the TS behavior of a compound with an additional functionality from a co-former, such as photosalient property, mechanochromic luminescence, response temperature of a TS compound,

altering it to operate at an ambient temperature,

response time, mechanical

durability and so on.20

Scheme 1. Preparation of TS co-crystal/salt using potential TS templates (i.e. the compounds that show TS behaviour in their single component solid form) as precursors. In search of TS behavior in multicomponent solids we have screened several single component Schiff bases and substituted benzoic acids for TS property, as they have been shown

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to possess such behavior. We identified Slz and CNB, with TS behaviour as potential candidates for co-crystallization. Further, as we hypothesized, the thermoresponsive Slz and CNB (TS templates), upon co-crystallization with thermally innocent PFB and BPY, form TS salt (SlzPFB) and TS co-crystal (CNB-BPY), respectively (Scheme 1).

RESULTS AND DISCUSSION Single component Slz and CNB crystals were crystallized from MeOH by slow evaporation. The multi-component crystals, Slz-PFB and CNB-BPY, were prepared from methanol through solvent (MeOH) assisted grinding of 1:1 mixture of Slz with PFB, and 2:1 mixture CNB with BPY, respectively. All the single crystals suitable for X-ray crystallography were obtained in 4-6 days and characterized by 1H NMR, FT-IR (Figure S1-S6) and differential scanning calorimetry (DSC).

Figure 1. Macroscopic jumping of crystals of Slz-PFB and CNB-BPY upon heating on hot plate [(a) to (b) at 100 °C for Slz-PFB and (c) to (d) at 100-110 °C for CNB-BPY]. The pictures were produced from the movies S2 (a and b) and S4 (c and d), Supporting Information. The blue and red arrows indicate the positions of crystals before and after the jump, respectively.

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When heated on a hot plate the single component crystals of Slz and CNB rapidly jump at around 130-140 °C and 210-220 °C, respectively, whereas the multi-component crystals of SlzPFB and CNB-BPY show jumping at around 100 °C and 100-110 °C, respectively (Figure 1 and S7; Video S1-S4). In other words the single component Slz and CNB which themselves show TS phenomenon, produce multicomponent TS crystals, Slz-PFB and CNB-BPY from thermally innocent conformers, PFB and BPY, respectively. It should be noted that these are the first examples of binary molecular crystals with TS phenomenon, whereas a thermally induced selfhealing behavior and thermo-mechanical response has been found in the coronene–TCNB cocrystal.16

Figure 2. DSC profiles displaying phase transformations in (a) Slz, (b) salt Slz-PFB, (c) CNB and (d) co-crystal CNB-BPY. DSC profiles of heat-cool cycle below melting temperature are in supporting information (Figures S8-S11).

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To interpret the ancestry of TS phenomenon, we carried out differential scanning calorimetry experiments at 2 °C/min heating flow rates, which confirmed the phase transformation behaviour of the crystals. Principally we have performed heating and cooling experiments on each sample to assure whether on cooling, the crystal re-jumps or not. On heating the crystal of compound Slz, spiky sawtooth profile is observed around at 130 °C (∆H ≈ -36.359 J/g). Sawtooth profile is generally associated to the martensitic phase transition which permits the cooperative movement of atoms/molecules in the single crystal resulting in TS phenomenon. A sharp endotherm has been registered at θ↑ = 252 °C which is the melting endotherm (Figure 2a). On cooling, before reaching melting temperature, no characteristic sawtooth profile is observed; thereby confirms irreversible phase transformation in Slz (Figure S8). On heating the salt Slz-PFB, an endotherm is observed at θ↑ = 97 °C which is the signature of phase transition accountable for jumping phenomenon (∆H ≈ -5.973 J/g) (Figure 2b). A sharp endotherm is observed at θ↑= 195 °C which is the characteristic melting endotherm. On cooling the crystal, before reaching melting temperature, the thermal profile of Slz-PFB indicates the irreversibility of the phase transition (Figure S9). In case of CNB, one sharp endotherm at 212 ºC indicates the phase transition responsible for TS phenomenon (∆H ≈ -69.491 J/g). The endotherm at 240 °C is characterized as the melting temperature (Figure 2c). On heating-cooling and re-heating the same sample, the same pattern of endotherms was observed, which indicated to the reversibility of phenomenon with hysteresis (∆T ≈ 23 °C) (Figure S10). In case of CNB-BPY, two endotherms were observed at 105 °C (∆H ≈ -78.083 J/g) and 133 °C (∆H ≈ -18.9402 J/g), which indicating two phase transitions (Figure 2d). The endotherms at 105 ºC and 195°C are characterized as the TS and the melting temperatures, respectively. Heating-cooling and reheating cycle (before melting temperature) confirmed that the TS phenomenon of CNB-BPY is also reversible with hysteresis (∆T ≈ 23 °C) (Figure S11). The TS phenomenon was very much noticeable for all the crystals in the hot plate as well; the crystals literally fly off the hot plate (Video S1-S4 ESI), around at the same temperature ranges seen in the DSC. In addition, we have collected DSC data of grinded samples of single crystals of all compounds to check the effect of grinding on phase transition. But surprisingly, we could not find any phase transition peak in DSC on these powder samples. This could be because of smaller particles with varied sizes and defect densities in the powder sample after the mechanical grinding. Hence, the phase transition in different particles is

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triggered at different times (spread over a large time period), hence is probably not captured in DSC, unlike in large as grown single crystals. In order to examine the phase transformations observed from DSC measurements associated with TS phenomenon, temperature-dependent lattice parameters were measured from single crystal X-ray diffraction (SCXRD) experiments on these crystals. The lattice parameters as a function of increasing temperature show that their thermal variations are generally anisotropic in nature (Figure S13 and Table S1-S4). In case of Slz and salt Slz-PFB crystals, the large estimated standard deviations (e.s.ds) of the lattice parameters make it difficult to confirm the exact phase transformation temperature region from their plots (Figure S13 a, b). However, for the CNB crystal the length of the c-axis increases steadily in the temperature range 25–155 ºC, decreases suddenly in the temperature range 155–175 ºC and again takes a sharp increase in the temperature range 175–195 ºC K (Figure S13c), thereby exhibiting discontinuity close to the phase transition temperature of 212 ºC as observed from DSC measurements. Similar discontinuous behavior is also observed in case of its co-crystal (CNB-BPY) where the length of the c-axis increases monotonously in the temperature range 25–100 ºC and decreases steeply in the temperature range 100–110 ºC (Figure S13d) which is again close to its phase transition temperature of 105 ºC as observed during DSC measurements.

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Figure 3. (a) Crystal packing to show the hydrogen bonded zigzag 1D tape of Slz; (b) corrugated wave like 2D packing in Slz mediated by several interactions (N−H···N in magenta, C‒H···O in green and π···π in cyan dotted lines); (c, d) Angle between the planes of phenyl and pyridyl rings of Slz at room and high temperature phases, respectively. To understand the underlying forces on atomic scale responsible for such TS phenomenon in these crystals, SCXRD experiments were performed on the crystals of Slz, salt (Slz-PFB), CNB and co-crystal (CNB-BPY) at 25 ºC and at their phase transition temperatures (Figure 2). Crystal of CNB was found to degrade at the phase transition temperature as observed from diffuse peaks and powder rings from the diffraction pattern which precluded structural analysis. This is possibly due to the close temperature range of phase transition and melting point. Single crystal

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analysis at room temperature revealed that Slz crystallizes in the monoclinic P21/n space group with one molecule in the asymmetric unit in which the angle between the planes of phenyl and pyridyl rings is about 21.2°. The individual molecules are connected by strong N−H···N (2.19 Å, 170°; Table S10) hydrogen bond forming a zigzag tape along (101) direction (Figure 3a). The adjacent tapes are connected via C−H···O (2.57 Å, 142°) interactions resulting in corrugated 2D sheets perpendicular to the c-axis (Figure 3b). The 2D sheets are stacked (3.85 Å) nearly along aaxis (Figure 3b) and as a consequence, the centroids of adjacent Slz molecules of neighboring tapes are at a distance of 3.93 Å (Figure S21). The 406 K structure of Slz did not show any significant visual changes compared to the RT structure, except a marginal change in the molecular conformation (Figure 3c & 3d). The 1:1 Slz-PFB salt crystallizes in the monoclinic P21/c space group with one protonated Slz molecule and one anion of PFB in the asymmetric unit. The electron density map showed that proton from the acid group of salt former (PFB) is transferred to the pyridine nitrogen of Slz molecule resulting in an N+−H···O‾ (1.90 Å, 162°; Table S10) ionic synthon. Each dimeric unit is hydrogen bonded to two adjacent dimeric units via strong N−H···O (1.73 Å, 165°) interaction between Slz and PFB, forming a zigzag tape along the b-axis (Figure 4a). The neighboring tapes of Slz-PFB form multiple weak interactions as well as π-stacking between pentafluoro and salicylamine rings (Figure 4b). The 2D sheets are assembled through slip stacked aromatic (3.62-3.67 Å) interactions along with C‒H···O (2.51 Å, 164°; 2.54 Å, 144°; 2.26 Å, 151°; 2.40 Å, 152°) interactions between Slz and PFB molecules. Other interactions like C−F···π (3.40-3.80 Å) and type-I F···F interactions (2.90 Å, θ1 = 124.1°, θ2 = 126.4°) between PFB molecules are also observed in the structure. Upon heating of Slz crystal to 133 ºC, it underwent a phase transition, accompanied by small changes in the crystallographic unit cell parameters [expansion of a (1.3%), b (0.3%), c (0.7%) and V (1.9%) respectively; Table S9]. Whereas, the salt Slz-PFB endured phase transformation at around 100 ºC with slight expansion along the a and b axes (a = 1.0% and b = 0.7%), and negligible shrinkage along the c-axis with total expansion of the volume by about 1.6 % (Table S9). Structurally, both the high temperature phases of Slz and Slz-PFB have almost similar packing patterns with respect to their room temperature phases, but differ only (slightly) in their respective molecular conformation and metrics of the interactions. The interplanar angle between phenyl−pyridyl rings experienced

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nominal change for Slz (from 21.2° to 21.5°; Figure 3c-3d) and for Slz-PFB from 8.2° to 7.9° (Figure 4c-4d). We believe that these changes are very small but possibly good enough to cause TS effect due to quick release of structural stress. As expected, the intra-tape N−H···N interactions (2.17 Å, 172°) and inter-tape C−H···O (2.61 Å, 142°) along with π···π (3.89 Å) interactions become slightly weaker in the high temperature phase of Slz (Table S10). In case of Slz-PFB crystal, the π···π (3.65-3.70 Å), C‒H···O (2.56 Å, 164°; 2.60 Å, 143°; 2.26 Å, 151°; 2.44 Å, 153°) interactions between Slz and PFB and C−F···π (3.48-3.85 Å) interactions between PFB are slightly weaker at high temperature than room temperature phase (Table S10). On the otherhand, F···F interactions between PFB anions in high temperature phase of Slz-PFB diminish due to the change of torsion angle in PFB anion [150.9° to 153.5° of O(4)-C(14)-C(15)C(16)].

Figure 4. (a) View of hydrogen bonded zigzag 1D tape of salt Slz-PFB along the ab-plane; (b) Notable interactions in Slz-PFB (N+−H···O‾ and O‒H···N in magenta, C‒H···O in green, π···π, C‒F··· π in cyan & type I F···F in red dotted lines); (c, d) Dihedral angle between phenyl and pyridyl rings of Slz molecules in Slz-PFB at room and high temperature phases, respectively.

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The other class of TS compound studied by us, CNB, crystallizes in triclinic P-1 space group with one molecule of CNB in the asymmetric unit. The −COOH group of CNB forms dimer via strong O‒H···O interactions (1.72 Å, 175°; Figure S23a). The adjacent dimers are further connected by C‒H···O (2.53 Å, 149°) interactions to form ladders along the b-axis (Figure S23b) which are supported by Cl···O (3. 20 Å, 170°), π···π (4.02 Å) and C‒O···π (3.64 Å) interactions21 (Figure S22c). The 2:1 co-crystal CNB-BPY crystallizes in monoclinic C2/c space group with one molecule of CNB and half molecule of BPY in asymmetric unit. Two pyridine rings connected by pivotal bond in BPY are twisted by a dihedral angle of 34.8°. Here, each BPY molecule is connected with two CNB molecules by strong O‒H···N interaction (1.63 Å, 172°) forming a trimeric unit (Figure 5a). The neighboring trimeric units further interact laterally by C‒H···O (2.43 Å, 169°; 2.46 Å, 168°) to form corrugated 2-dimensional (2D) sheets along the ab-plane (Figure 5b). Other interactions like Cl···O (3.15 Å, 166°), π···π (3.85 Å) and C−Cl···π (3.60 Å) interactions also support the structure (Figure 5c). Despite several attempts to obtain the structure of the high temperature forms of CNB by SCXRD, unfortunately we failed due to generation of severe defects and macroscopic cracks in the crystals. But the measured variable temperature unit cell parameters from SCXRD show that c-axis is expanded by 2.56%, whereas the changes in the other two axes are negligible (Table S3 and Figure S13c). In case of co-crystal CNB-BPY, around 110 ºC, there is an anisotropic cell expansion along the b-axis by about 1.8% with total volume expansion by ~2.0%, whereas the change is negligible along the a and c-axes (Table S9). The packing pattern of high temperature phase of CNB-BPY is also almost similar to the room temperature phase as was observed in the previous two crystals (Slz and Slz-PFB). But the dihedral angle between two pyridine rings of BPY of CNB-BPY slightly decreases from 34.8° to 34.0° (Figure 5d-5e). Strong O‒H···N (1.76 Å, 164°) interactions become weaker because of change of dihedral angle of BPY. Additionally, C‒H···O (2.42 Å, 170°; 2.50 Å, 167°), Cl···O (3.18 Å, 165°), π···π (3.91 Å) and C−Cl···π (3.66 Å) interactions experienced slight shortening due to the change of torsion angles between benzene ring and nitro group of CNB in co-crystal CNB-BPY (Table S10). Although the DSC experiments clearly indicated to the phase transformation, the extensive single crystal and powder diffraction experiments suggest to very small unit cell changes corresponding to the phase transformation in the TS crystals. From the variable temperature diffraction experiments, the observed unit cell and packing changes corresponding to a regular

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Figure 5. (a) Trimer unit of co-crystal CNB-BPY assembled by hydrogen bonds; (b) The 2D packing in CNB-BPY (O-H···N in magenta & C‒H···O in cyan dotted lines); (c) π···π and C‒Cl··· π interactions in CNB-BPY; (d, e) Dihedral angle between two pyridyl rings of BPY molecules in CNB-BPY at room and high temperature phases, respectively. thermal expansion/compression of the same phase or due to a phase transformation. Hence, we have performed the Hirshfeld surface analysis to elucidate the differences of intermolecular interactions in both the room temperature and high temperature crystals of all the forms. The Fingerprint images clearly distinguish and emphasize the changes (although small) in weak interactions between the two phases (before and after jumping temperatures) (Figure S25-S28). Additionally, comparison of simulated PXRD patterns of room temperature and high temperature

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forms (except for CNB) revealed the emergence and/or splitting of some new peaks in the high temperature phases, which also confirms the minor structural differences between the two phases (Figure S28-S30). Thus the thermosalient effects of all the crystals which belong to class-III thermosalient crystals,8 can be attributed to the combination of slight conformational changes of the molecules as well as changes in comparatively weak intermolecular interactions. The changes observed in crystal packing during phase transformation in the present case are very subtle. Such small changes have also been observed earlier in 1,2,4,5-tetrabromobenzene5 and high temperature phases of polyglutamic acid.22-23 Thus, it can be conjectured that TS behaviour of these crystals is in response to the structural strain induced by the packing forces which trigger sudden jump while the crystal packing above the phase transition temperature assumes a conformation not drastically different from their low temperature forms. CONCLUSION In conclusion, we demonstrated the TS phenomenon in multicomponent solid forms for the first time. The multicomponent forms were prepared by utilizing single component TS co-formers as possible templates for co-crystallizing with other thermally innocent co-formers. We believe that small changes in conformation and intermolecular interactions give rise to possible structural strain and lead to TS effect in these multi-component crystals. The phase transition temperatures corresponding to TS phenomenon of the co-crystals are found to be significantly lower as compared to the single component TS ones. Although the exact molecular/structural reason for the carryover of TS phenomenon from single component forms to the corresponding multicomponent solid forms was not obvious from our studies, we feel that further studies on the mechanism of TS phenomenon may help in designing multicomponent TS forms in future. Identification of thermophores (molecules, synthons or certain structural motifs that respond to heat) may help in engineering multicomponent crystals using crystal engineering principles. We are currently exploring other molecular systems that are conformationally flexible with potential to undergo conformational changes upon heating, to test the reliability of this TS template approach for rational design and synthesis of new TS materials.

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EXPERIMENTAL SECTION Materials and Methods. Salicyldehyde, isoniazid, 3-chloro-2-nitrobenzoic acid (CNB), 4,4'bipyridine (BPY) and pentafluorobenzoic acid (PFB) were purchased from Sigma-Aldrich. Commercially available solvent methanol was used for crystallization without further purification of the solvents. Experimental details of single crystals preparation and characterization techniques, which we used in this study, are available in the Supporting Information. ASSOCIATED CONTENT Supporting Information The figures related to 1H NMR, IR, DSC and PXRD patterns of compounds along with different structural figures and tables related to the crystal structures reported in this paper and jumping videos are available as SI. CCDC 1813956-1813962 contains the supplementary crystallographic data for this paper in CIF format. AUTHOR INFORMATION Corresponding Author E–mail: [email protected] and [email protected]. Tel: +91-3325873119. Fax: +91-(0)33-25873020. Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS CMR gratefully acknowledges the financial assistance given by DST (DST/SJF/CSA-02/201415). Authors gratefully acknowledge the infrastructure facilities given by IISER Kolkata. B.B. (PDF/2016/000262) and K.B.R. (PDF/2015/000953) are thankful to DST-SERB, India for the award of National Postdoctoral Fellowship.

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2. Al-Kaysi, R. O.; Müller, A. M.; Bardeen, C. J. Photochemically Driven Shape Changes of Crystalline Organic Nanorods. J. Am. Chem. Soc. 2006, 128, 15938-15939. 3. Kobatake, S.; Takami, S.; Muto, H.; Ishikawa, T.; Irie, M. Rapid and reversible shape changes of molecular crystals on photoirradiation. Nature 2007, 446, 778-781. 4. Naumov, P.; Sahoo, S. C.; Zakharov, B. A.; Boldyreva, E. V. Dynamic Single Crystals: Kinematic Analysis of Photoinduced Crystal Jumping (The Photosalient Effect). Angew. Chem. Int. Ed. 2013, 52, 9990 –9995. 5. Sahoo, S. C. ; Sinha, S.B.; Kiran, M. S. R. N.; Ramamurty, U.; Dericioglu, A. F.; Reddy, C. M.; Naumov, P. Kinematic and Mechanical Profile of the Self-Actuation of Thermosalient Crystal Twins of 1,2,4,5-Tetrabromobenzene: A Molecular Crystalline Analogue of a Bimetallic Strip. J. Am. Chem. Soc. 2013, 135, 13843-13850. 6. Panda, M. K.; Runcevski, T.; Sahoo, S. C.; Belik, A. A.; Nath, N. K.; Dinnebier, R. E.; Naumov, P. Colossal positive and negative thermal expansion and thermosalient effect in a pentamorphic organometallic martensite. Nat. Commun. 2014, 5, 4811-4819. 7. Sahoo, S. C.; Panda, M. K.; Nath, N. K.; Naumov, P. Biomimetic Crystalline Actuators: Structure–Kinematic Aspects of the Self-Actuation and Motility of Thermosalient Crystals. J. Am. Chem. Soc. 2013, 135, 12241-12251. 8. Nath, N. K.; Panda, M. K.; Sahoo, S. C.; Naumov, P. Thermally induced and photoinduced mechanical effects in molecular single crystals—a revival. CrystEngComm 2014, 16, 18501858. 9. Ghosh, S.; Mishra, M. K.; Ganguly, S.; Desiraju, G. R. Dual Stress and Thermally Driven Mechanical Properties of the Same Organic Crystal: 2,6-Dichlorobenzylidene-4-fluoro-3nitroaniline. J. Am. Chem. Soc. 2015, 137, 9912-9921. 10. Skoko, Z.; Zamir, S.; Naumov, P.; Bernstein, J. The Thermosalient Phenomenon. “Jumping Crystals” and Crystal Chemistry of the Anticholinergic Agent Oxitropium Bromide. J. Am. Chem. Soc. 2010, 132, 14191-14202. 11. Panda, M. K.; Runcevski, T.; Husain, A.; Dinnebier, R. E.; Naumov, P. Perpetually SelfPropelling Chiral Single Crystals. J. Am. Chem. Soc. 2015, 137, 1895-1902. 12. Lusi, M.; Bernstein, J. On the propulsion mechanism of “jumping” crystals. Chem. Commun., 2013, 49, 9293-9295.

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13. Naumov, P.; Chizhik, S.; Panda, M. K.; Nath, N. K.; Boldyreva, E. Mechanically Responsive Molecular Crystals. Chem. Rev. 2015, 115, 12440-12490. 14. Krishnan, R. S.; Srinivasan, R.; Devnarayanan, S. Thermal Expansion of Crystals; Pergamon: Oxford, 1979. 15. Medishetty, R.; Sahoo, S. C.; Mulijanto, C. E.; Naumov, P.; Vittal, J. J. Photosalient Behavior of Photoreactive Crystals. Chem. Mater. 2015, 27, 1821−1829. 16. Liu, G.; Liu, J.; Ye, X.; Nie, L.; Gu, P.; Tao, X.; Zhang, Q. Self-Healing Behavior in a Thermo-Mechanically Responsive Cocrystal during a Reversible Phase Transition. Angew. Chem., Int. Ed. 2017, 56, 198 –202. 17. Gopi, S. P.; Ganguly, S.; Desiraju, G. R. A Drug–Drug Salt Hydrate of Norfloxacin and Sulfathiazole: Enhancement of in Vitro Biological Properties via Improved Physicochemical Properties. Mol. Pharm. 2016, 13, 3590−3594. 18. Zhu, W.; Zheng, R.; Zhen, Y.; Yu, Z.; Dong, H.; Fu, H.; Shi, Q.; Hu, W. Rational Design of Charge-Transfer Interactions in Halogen-Bonded Co-crystals toward Versatile Solid-State Optoelectronics. J. Am. Chem. Soc. 2015, 137, 11038−11046. 19. Aakerçy, C. B.; Wijethunga, T. K.; Desper, J. Chem. Eur. J. 2015, 21, 11029 – 11037. 20. Nauha, E.; Naumov, P.; Lusi, M. Fine-tuning of a thermosalient phase transition by solid solutions, CrystEngComm 2016, 18, 4699–4703. 21. Yang, X.; Wu, D.; Ranford, J. D.; Vittal, J. J. Influence of the C=O···π Interaction on the Thermal Dehydration Behavior of [Cu2(sgly)2(H2O)]·1H2O Cryst. Growth Des. 2005, 5, 41– 43. 22. Wu, H.; Reeves-McLaren, N.; Pokorny, J.; Yarwood, J.; West, A. R. Polymorphism, Phase Transitions, and Thermal Stability of l-Pyroglutamic Acid. Cryst. Growth Des. 2010, 10, 3141–3148. 23. Wu, H.; West, A. R. Thermally-Induced Homogeneous Racemization, Polymorphism, and Crystallization of Pyroglutamic Acid. Cryst. Growth Des. 2011, 11, 3366–3374.

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For Table of Contents Use Only Thermosalient (TS) Forms: Carryover of TS Behavior of Coformers from Single Component to Multicomponent Forms? Hemant Rawat§, Ranita Samanta§, Biswajit Bhattacharya§, Shubham Deolka, Archisman Dutta, Somnath Dey, K Bal Raju and C. Malla Reddy*

Coformers that show TS phenomenon in their single component forms have been used to prepare multicomponent forms and the TS phenomenon is found to carryover to the latter.

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