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Silicone Oil Induced Spontaneous Single-crystal-to-Single-Crystal Phase Transitions in Ethynyl substituted fluorinated benzamides Subhrajyoti Bhandary, and Deepak Chopra Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b00912 • Publication Date (Web): 09 Aug 2017 Downloaded from http://pubs.acs.org on August 11, 2017

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Crystal Growth & Design

Silicone Oil Induced Spontaneous Single-crystal-to-Single-Crystal Phase Transitions in Ethynyl substituted ortho and meta-fluorinated benzamides Subhrajyoti Bhandary, 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. Email: [email protected]; Fax: +91-0755-6692392

ABSTRACT: We present an unusual observation of facile Single-Crystal-to-Single-Crystal phase transition induced in hydrophobic silicone oil at ambient conditions which is fast in ortho-fluoro substituted ethynyl phenyl benzamide and relatively slow for the meta-isomer. These phase transitions are also observed in crystals, on heating, at high temperature, in absence of silicone oil. The extensive thermal and structural analyses reveal that the phase transition between the two polymorphs of the ortho-isomer is monotropic in nature and involves large supramolecular rearrangements, wherein, for the meta-isomer the same is enantotropic and is driven by altered molecular conformations. The structural features demonstrate the absence of prevalent and strong N-H···O=C hydrogen bonds in the crystal structures of both the polymorphs of the ortho-fluoro substituted benzamide. A plausible molecular mechanism based on energetically favoured “structural motifs” has been proposed and depicts that rotational and translational motion between the molecules present in the crystal relates molecular motifs and provides a rationale for the origin of nucleation and growth process during the phase transition.

The phenomenon of polymorphism is one of the most discussed area of science due to its tremendous fundamental interest1-3 as well as the practical importance.4-6 In spite of wider applications, the understanding of occurrence of polymorphs is still enigmatic due to closely related stability of different phases with variable physicochemical properties.7-8 Recently, the design and development of molecular crystals with switchable physical properties governed by external stimuli (temperature, pressure, light, mechanical forces etc.) has gained significant importance for their immense applications in molecular devices.9-14 This dynamic feature in molecular crystals is accompanied mainly through rapid solid-to-solid polymorphic phase transitions. Dedicated systematic efforts by many researchers have proposed over 300 mechanisms for solid state phase transition. In particular, Mnyukh has established that all these transitions occur via a nucleation and growth mechanism.15-16 Such mechanism in molecular point of view was further well described when Single-Crystal-to-Single Crystal (SCSC) transition occurs between two structurally similar polymorphs17 and they are enantiotropically related.18-19 But, irreversible (monotropic) SCSC phase transition for molecular crystal is still one of the rarest phenomena.20-21 This is because in the monotropic case, the metastable polymorph undergoes transition to the more stable polymorph with very different crystal packing patterns and this major structural change during the phase transition leads to the destruction of crystal integrity.22-25 Hence, the control on the phenomena of irreversible SCSC transition is limited and challenging to reveal the SCSC transition pathway. In addition to that, the stimuli which controls the SCSC phase transition is most important to obtain

insights into the kinetics of the macro or microscopic changes in the crystal. Herein, we report one striking example of monotropic (involving major structural changes) and one enantiotropic (structurally similar) SCSC phase transition induced by “silicone oil” (SO) at room temperature (RT; 24-28 °C) for two organic polymorphic systems. The similar SCSC transitions were also observed by the influence of high temperature without SO. The solution mediated preferential crystallization of polymorphs using polymer heteronuclei (such as SO; composed of linear polydimethylsiloxane) is of great significance due to their huge impact in pharmaceutical crystallization,26-27 but the spontaneous solid-state phase transition of molecular crystal triggered by any hydrophobic inert polymer (SO) at RT is unusual and demands considerable research attention towards the versatile applicability of SO from the physical and materials point of view.28-32 A complete structural analysis with quantitative inputs for different intermolecular interactions via energy decomposition analysis using the PIXEL method33-35 has been utilized to correlate the events at the molecular level.

RESULTS AND DISCUSSION As a part of our continuing investigation into structural aspects related to weak intermolecular interactions in fluorine conaining molecules, two isomeric organic compounds (Scheme 1), namely N-(3-Ethynylphenyl)-2-fluorobenzamide (ortho) and N-(3-Ethynylphenyl)-3-fluorobenzamide (meta) were newly synthesized and solution phase crystallization screening (Table S1-S2 and Figure S2-S4,) resulted in formation of dimorphs (Form I and Form II). It is be noticed

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that SO has been extensively used for Single Crystal X-ray Diffraction (SCXRD) data collection as cryo oil, but to our extreme surprise we observed that during the process of crystal mounting of block-shaped ortho-Form II, when placed in SO at RT, it underwent quick conversion to needle-shaped crystals at RT (Figure 1, above and movie M1 in Supporting Information). The subsequent SCXRD data collection performed on a single crystal of the obtained new needle form resulted in formation of ortho-Form I phase (Figure S5-S7 and Table S3). The dynamics of this phase transition is so fast that the appearance of needle crystals was observed immediately after addition of small drop of hydrophobic SO on block ortho-Form II crystal which was monitored in SEM (Figure S8). Similar events were also observed in SO for meta-isomer but the rate of the phase transition (from meta-Form II to meta-Form I) is relatively slow (Figure 1, below) in comparison to ortho polymorphs. However, the attempts to obtain similar results in hydrophilic polymers like hexaethylene glycol and poly (diallylamine) remain unsuccessful. Scheme 1. General route for the synthesis of two isomeric compounds (ortho and meta) and polymorphic interconversions

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of the polymorphic forms. For this purpose, Differential Scanning Calorimetry (DSC) experiments were performed on Form I and Form II single crystals of the ortho and meta isomers (Figure 2). It has been observed that Form I phases of both the isomers directly melt upon heating with sharp endothermic peak at around 77.7 °C (∆Hm= -94.2 J/g) for orthoisomer and at 102.8 °C (∆Hm= -103.7 J/g) for meta-isomer (red traces in Figure 2). Wherein, the Form II crystals of both (blue traces in Figure 2) underwent exothermic (for orthoisomer; 57.7 °C, ∆Hs= 2.1 J/g) and endothermic (for metaisomer; 91.1 °C, ∆Hs= -19.2 J/g ) solid-to-solid phase transition to Form I phase of each during heating (red circle) followed by melting. The exothermic nature of ortho-Form II to ortho-Form I transition suggests that it is the case of monotropic polymorphism and ortho-Form I phase is thermodynamically more favored than ortho-Form II phase.36 So, the transition is irreversible (Figure S9). By contrast, two polymorphs of meta-isomer are enantiotropically related as meta-Form II to meta-Form I transition is endothermic in nature and hence conversion of one polymorph to other is possible by changing the temperature at ambient pressure36. Moreover, the noticeable enthalpy contribution (∆Hs= 2.1 J/g for ortho and ∆Hs= -19.2 J/g for meta) of solid-to-solid phase change confirms the first-order nature of the transitions. These thermal events were also visualized in Hot Stage Microscopy (HSM) experiments for single crystals of ortho (Figure S10) and meta (Figure 3) polymorphs which is almost consistent with DSC results. The experiment clearly depicts that solid-to-solid phase transitions initiated on single crystals of ortho-Form II at 57.3°C (Figure S10) and at 91.1°C for meta-Form II (Figure 3) with the subsequent melting of two crystals simultaneously as post-transition Form I phase of each isomer on further heating. In addition to that, it is of interest to see the nucleation of meta-Form I phase on the crystal of meta-Form II during solid-to-solid transition at 91.1°C with propagation and growth of the new interface throughout the meta-Form II crystal, making the crystal cloudy before melting as meta-Form I phase at 102.2°C (Figure 3).

To rationlize the occurrences of the above-mentioned polymorphic inter-conversion at ambient conditions, it was of importance to investigate the thermodynamic stability profiles

Figure 1. Snapshots of Form II (block-shaped) to Form I (needle-shaped) fast conversion for ortho (above; in Olympus IX83 inverted microscope) and slow conversion for meta (below; in Leica polarizing microscope) at RT in SO.


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Figure 2. DSC traces of Form I and Form II crystals of ortho (above) and meta-isomers (below). Red cycles indicate the solid solid phase transition from Form II to Form I.

Figure 3. Hot Stage microscope snapshots @ 2°C/min heating rate of Form I (block) and Form II (plate) crystals for meta isomer. Purple arrows indicate the initiation of solid-to-solid-phase transition from Form II to Form I and melting of two crystals simultaneously.

The variable temperature PXRD experiments have been also performed on Form II crystals of each isomer (Figure S11-S12) which also ascertains the existence of the temperature induced polymorphic phase transition to Form I as observed in DSC and HSM. The experiment shows that diffraction peaks of Form II phase in both the isomers completely changed to Form I phase of each, at ~338 K (65°C) for ortho-isomer and ~367 K (97°C) for meta-isomer (Figure S12). Unfortunately, on cooling of the Form I for meta-isomer from high temperature to RT, the diffraction pattern remains unchanged after several hours, which suggest the irreversible nature of these enantiotropically related polymorphs. After confirming the temperature dependent transition from Form II to Form I for both the isomers, it was of interest to capture this event on the single crystal diffractome-

ter by slow heating, utilizing the cryogenic facility. The experiments show that single crystal of ortho-Form II converts to ortho-Form I at 335 K and the same at 360 K for meta-isomer (Figure 4a). However, the quality of single crystal decreases after phase transition at high temperature from Form II to Form I. Experiment details, crystallographic data of hightemperature phase, ORTEPs, overlay of structures and PXRD patterns for Form I crystal (after phase transition from Form II at high temperature) and pure Form I crystal for both the isomers are given in the Supporting Information (Table S3, Figure S7 and S13-S15). After the data collection at high temperature, the crystal was cooled to 100 K again with slow ramp rates, but we did not observe any reversible phase transition for both the cases, a case of thermal hysteresis in the transformed crystals. Now, it is important to notice that two polymorphs of the meta-isomer are enantiotropically related, but the reversible transition upon cooling from meta-Form I to meta-Form II is not observed in neither variable temperature PXRD (Figure S12) nor in SCXRD (Figure 4a). To obtain detailed insights into the irreversible nature of the transition, the SCSC phase transition experiments was further carried out on DSC instrument with different scanning rates (1 °C/min and 2 °C/min) for crushed single crystals as well as a few good quality single crystals of the meta-Form II (Figure 4b). In case of crushed single crystals (green colour traces in Figure 4b), meta-Form II transforms to meta-Form I around 88.2 °C (a small endothermic phase change), but during cooling, no reversible phase change was observed. For the good quality single crystals of meta-Form II (red and blue colour traces in Figure 4b), endothermic phase transition to meta-Form I was observed (Onset- 90.9 °C for 2 °C/min) and (Onset- 90.5 °C for 1 °C/min) followed by the exothermic reversible phase transition with significant (for 2 °C/min) to small (for 1 °C/min) hysteresis of the transition temperatures. On the basis of these observations, it could be anticipated that posttransition, meta-Form I, could possibly revert back to metaForm II upon cooling. To ensure further about this reversible phase transition, after cooling, the crystals were cautiously taken out from the aluminum pan after the reversible phase transition in each complete cycle and the unit cells of a few randomly picked crystals were checked via SCXRD instrument. From the unit cell measurements and subsequent data collection, a new metastable phase (Form ID) was identified (Table S2). So, it can be concluded that on cooling, the reversible phase transition is kinetically hindered37 and meta-Form I underwent phase transition to meta-Form ID (see Scheme 1, below).

Structural Aspects of Polymorphism To obtain molecular insights of observed polymorphic transitions a comparative structural analysis is needed for all polymorphs of the ortho and meta-isomers. The two polymorphic forms of the ortho-isomer crystallize in monoclinic system with very different unit cell parameters (Table S2). The molecular conformations (Table S4) of two polymorphs are similar due to the presence of N-H···F, and C-H···O intramolecular contacts (Figure S3). But, the 3D packing arrangement of molecules in both the polymorphs is notably different (Figure 5). In case of ortho-Form II, two symmetry independent molecules (Z'=2, orange and purple in color) form alternate columnar packing of molecules through π···π stacking with same type of molecules along the a-direction (motif



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I-III in Figure 5a). Molecules in alternate columns (red circle in Figure 5a) are also connected via several intermolecular

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fluorine atom is positionally disordered over two meta positions of the phenyl ring (Figure S4 and Table S2). The solid state geometries of all the three polymorphs are different due to alterations in the orientations of the fluorophenyl and

Figure 5. Formation of (a) columnar packing via π···π stacking in Form II, and (b) sandwich herringbone crystal packing in Form I connected through C(sp)-H···O, C(sp2)-H···π (ring) and π···π stacking for ortho-isomer. Red circles indicate the formation of molecular sheet (ortho-Form II) and chain (ortho-Form I).

Figure 4. (a) Form II crystal to Form I crystal conversion on SCXRD instrument upon heating for ortho and meta-isomers. (b) DSC traces for meta-Form II crystals showing SCSC transitions during heating/cooling at variable scanning rates.

interactions [C(sp/sp2)-H···O, C(sp/sp2)-H···F and C(sp2)H···π (C≡C)] forming sheet-like structure down the bc plane (Figure S16). In contrast, the molecules in ortho-Form I am packed in sandwich herringbone fashion down the bc plane (Figure 5b) and stacked to each other with a distance ranging from 3.48-3.52Å (motif I and II). The diads of herringbone molecules (Figure 5b) are also connected via C(sp)-H···O [motif VI] and C(sp2)-H···π(phenyl ring), C(sp2)-H···π (C≡C) hydrogen bonds [motif VII and VIII] and stacking interactions (motif IV) forming the 3D structure. In each diad (red cycle in Figure 5b), molecules are also translated along adirection forming one-dimensional chain of C(sp2)-H···O hydrogen bond associated with C(sp2)-H···F and C(sp2)H···π (triple bond) hydrogen bonds (Figure S17). It is indeed very important to mention that in spite of having a strong hydrogen bond donor N-H and a strong acceptor O=C in the molecular structure of the ortho-isomer, neither the orthoForm II nor the ortho-Form I have the classical N-H···O=C hydrogen bond which is energetically most favorable and common in the crystal structures of N-phenyl benzamides.3, 3842 The CSD search for non-existence of generalized N-H···O interaction in such type of N-Phenyl benzamides resulted in only 42 hits (see Supporting Information). The three polymorphs of the meta-isomer (Form II, Form I and Form ID) also belong to the monoclinic crystal system (Table S2). In the crystal structure of meta-Form ID,

the ethynyl phenyl rings with respect to the bridging C=O and N-H groups (see torsions; T1, T2 and T3 in Figure 6). Torsion angle (Table S4) for the three flexible parts further confirms that the meta-Form ID adopts (considering the major conformer, Figure 6) very near conformations as meta-Form I in terms of the orientation of the ethynylphenyl rings, but the extension of the fluorophenyl ring is similar to meta-Form II. In spite of these conformational alterations, the formation of the layered supramolecular structures in all the three polymorphs is via strong N-H···O hydrogen bonding chains with π…π stacking interactions (motif I, Figure 7a-c). The main difference in the three polymorphs originates from the direction of operation for such N-H···O hydrogen bonding chains in the two adjacent molecular layers (yellow and green arrows in Figure 7a-c) with respect to the donor C=O or acceptor N-H groups. Particularly, the alternate direction of NH···O chain in adjacent zigzag molecular layers of meta-Form II (yellow and green arrows in Figure 7a) rearrange to form the parallel layers in meta-Form I with the same direction of N-H···O chains (yellow arrows Figure 7b). Now, these parallel layers remain similar in meta-Form ID, but the direction of operations for N-H···O chain changes to alternative fashion (yellow and green arrows in Figure 7c). In addition to that C(sp2)-H···O, C(sp2)-H···π (phenyl ring), C(sp2)-H···π (triple bond) and C(sp/sp2)-H···F hydrogen bonding interactions also are found in the crystal packing of meta-Form I and metaForm ID (Figure S18). It is noteworthy that very short and highly linear C(sp)-H···F hydrogen bond42 (2.15 Å, 176°) involving the most acidic hydrogen (H15) and F1 was found to stabilize the packing network of meta-Form II phase (Figure S19). List of all possible non-covalent interactions along with interactions energies for all polymorphs are specified in Table S5.


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Figure 6. Structure overlay diagram (using Mercury 3.843) of all three molecules present in the asymmetric units (considering major disorder part of Form ID) of the three polymorphic forms of the meta-isomer. All hydrogen atoms attached to carbon are omitted for clarity. Curved arrows showing three conformational flexible parts (T1, T2 and T3).

Molecular level Approach towards the Mechanism of Polymorphic Phase Transition. In order to propose a plausible mechanism for the observed SCSC phase transition, it is important to investigate quantitatively the energetics of the different intermolecular motifs which predominantly build the supramolecular structure. For this reason, molecule-molecule interaction energy of all important molecular pairs (Table S5) in crystal packing along with total lattice energy (Table 1) of individual polymorphic forms were calculated by the PIXEL method. In the dimorphic forms of the ortho, the motifs originated by C(sp2)-H···O, C(sp)-H···O and C(sp2)H···π(C≡C) hydrogen bonds along with π···π stacking interactions mainly stabilize the overall structure (Figure 5). The energetic comparison with one-to-one correspondence of such energetically favorable motifs with interaction energy (IE) in crystal structures of both the ortho polymorphs are shown in Figure 8. 1. The π···π stacking interactions have been observed as the main building blocks in the supramolecular assembly for both the polymorphs of the ortho-isomer. The most energetically

2.

3.

stable motif I (IE -37.7 kJ/mole) and motif II (IE -35.6 kJ/mole) of orange molecules in orthoForm II complement the stacking as motif I (IE -31.7 kJ/mole) and motif II (IE -29.0 kJ/mole) in ortho-Form I (Figure 8). However, the orientation of stacking in between purple molecules in ortho-Form II are totally unique in which stacked columns are slanted and strained (Figure 5a). This uniqueness of stacking interactions in ortho-Form II is primly responsible for significant structural asymmetry in comparison to ortho-Form I. Apart from the crucial role of π···π stacking, few hydrogen bonding motifs were also observed to play a determining role in overall crystal packing for both the polymorphs. In orthoForm II, motif IV represents the most energetically favorable hydrogen bonding motif, which originates from C(sp2)-H···O, C(sp2)H···F and C(sp2)-H···π(triple bond) interactions with IE of -21.5 kJ/mole and which corresponds to motif III (IE -22.5 kJ/mole) of ortho-Form I (Figure 8). It is important to mention here that the absence of advantageous strong N-H···O interaction in both the polymorphs can be accounted as the preferential formation of intramolecular N-H···F interaction and intermolecular C(sp2)-H···π (C≡C) hydrogen bonds. The second most important hydrogen bonding motif is constructed by C(sp)-H···O hydrogen bond as motif V (IE -19.3 kJ/mole) and VI (IE 18.9 kJ/mole) in ortho-Form II. In correspondence, the same was found in orthoForm I as motif VI with IE- 12.1 kJ/mole (Figure 8). The greater stability in ortho-Form II motif than ortho-Form I arises due to additional C(sp2)-H···π(triple bond) interaction in orthoForm II.

Figure 7. Supramolecular layer structure of molecules connected via strong N-H···O hydrogen bonds and stacking interactions for (a) Form II (b) Form I (c) Form ID of the meta-isomer. Yellow and green arrows showing the direction of N-H···O chains.


Crystal Growth & Design 4.

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The next persistent motif as observed in crystal packing is C(sp2)-H···π(triple bond). The motif XI (IE – 7.7 kJ/mole) and XII (IE -7.7 kJ/mole) of ortho-Form II represents such interaction. The motif VIII (IE -10.7 kJ/mole) reflects the same in ortho-Form I (Figure 8).

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Page 6 of 10 Some weak C(sp2)-H···F hydrogen bonds were also found energetically harmonious in both the polymorphic forms. The motif XIII in orthoForm II (IE -7.2 kJ/mole) is likely compatible with motif IX (IE -6.9 kJ/mole) in ortho-Form I (Figure 8).

Figure 8. Complementary molecular motifs (red circle) with interaction energies in ortho-Form II (orange and purple colour- first and second symmetry independent molecule) and ortho-Form I (Grey Colour).


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In case of the meta-isomer, the comparative view of structure directing N-H···O chains of three polymorphs and the arrangement of molecules during phase transition from one polymorph to another is shown in Figure 9. In case of metaForm II, motif I (IE -45.8 kJ/mol) complements the motif I of meta-Form I with IE -52.6 kJ/mole originated mainly by N-H···O hydrogen bond (Figure 9). The corresponding complementary N-H···O hydrogen bonding motif was also found (motif I) in case of meta-Form ID with less stabilization energy (IE -34.2 kJ/mole). The less stabilization of such motif for meta-Form ID in comparison to meta-Form I and metaForm II makes the same metastable (see lattice energy in Table 1). It is clear that changes in the intra-molecular geometries of polymorphs which originates from conformational variations (Table S4) can justify the pathway of the phase transition. But preserving the robustness of energetically favorable structural motifs (N-H···O chains) is a necessity in the overall transformation. In meta-Form II, the rotation of torsions involving bridging atoms connected to phenyl rings (Green arrows in Figure 9) from -33.8° and 35.4° to 149.0° and 145.8° respectively (T1 and T3 in Table S4) results in an intermediate conformation. In this, the rearrangement of the molecules (in purple color), accompanied by a full molecule rotation (yellow arrows in Figure 9), leads to the formation of enantiotropically related meta-Form I polymorphic phase. Again the rotation of the fluorophenyl ring only of meta-Form I results in the formation of meta-Form ID in which fluorine atom exhibits positional disorder.

external stimuli (such as heat or SO) are exposed to Form II crystals, energetically favorable motifs rearrange themselves to direct a new supramolecular assembly (Form I). This new arrangement of molecules may or may not be similar to the mother phase because phase transition occurs via nucleation and growth, but energetically favored molecular pairs are always present in all crystalline phases of the same isomer. It is to be noticed that the propagation of interface of the Form I phase on Form II crystal surface was clearly observed for meta polymorphs during heating in HSM (Figure 3) as well as high temperature SCSC experiments (Figure S13) which further provides substantial evidence for the interface mechanism of nucleation and growth.22 In case of SO triggered phase transitions, depending upon the nature and orientation of the surface molecules,27, 44-45 these can interact with SO. It has been observed from the Bravais–Friedel–Donnay–Harker (BFDH) morphology46 that hydrophobic molecular fragments, such as phenyl rings and ethynyl groups, are exposed on the crystal surface, in case of the ortho-Form II, while only fluorophenyl rings are exposed for the same in case of the meta-isomer (Figure 10).

Table 1. Lattice Energy (kJ/mol) of all Polymorphs Calculated by the PIXEL method Form I

Form II

Form ID

ortho

-114.2

-109.1

-

meta

-120.7

-125.2

-78.6 Figure 10. BFDH morphologies filled with molecules (predicted using Mercury CSD 3.8) for all polymorphs showing exposed surface molecules on the Form II crystal surfaces and no exposed molecular fragments on Form I crystal surfaces.

Figure 9. Possible ring rotation and molecule rotation during the phase transition from Form II to Form I and Form ID keeping N-H···O chain intact in the meta-isomer. The corresponding equivalent view down the ac-plane for N-H···O chains of metaForm I and meta-Form ID are given for comparison purposes.

The above comparative analysis regarding energetics of intermolecular interactions confirms that complementary energetically favorable supramolecular motifs are preserved in both the polymorphic forms of the each isomer. When any

When the crystal surface of Form II comes in contact with SO, it can activate the loosely bound surface molecules via interactions on the surface between the SO and the exposed πelectron moieties. In the solid-state, these interactions must be weak and transient in nature on account of the hydrophobic nature of SO. As a consequence, the phase transition in the solid-state can be initiated from those crystal faces via the relocation of such exposed molecules which immediately facilitates the nucleation of Form I phase. Then the transformation spreads along the crystal, followed by growth of crystals of Form I (see the formation of needle shaped crystals mostly from the surface in Figure 1 and movie M1). It has also been observed that a small perturbation on the crystal surface of Form II containing SO, initiates the phase transition to Form I. The elongation in size and change in volume of the crystal suggests that it is a case of rapid solid-state recrystallization of Form I from Form II crystal in SO. Furthermore, the lattice energy calculations (Table 1) suggests that both the Form I and Form II polymorphs of each isomer have very closely related lattice energies and hence this subtle difference



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in can be the primary driving force for the observed SCSC phase transition.

CONCLUSIONS In this research article, we report a unique observation of polymorphism. The behavior of molecular crystals in the presence of hydrophobic SO is responsible for the occurrence of the spontaneous SCSC phase transition. This feature has been demonstrated for both structurally very dissimilar and relatively similar polymorphs of two isomeric organic compounds respectively. In addition to that, the extremely rare occurrence of monotropic phase transition (Form II to Form I) which is irreversible in an SCSC manner has been detected for the polymorphs of the ortho-isomer. The structural analysis reveals the absence of classical N-H···O=C H-bonds in both the polymorphs of an organic amide (ortho-isomer) and the occasional occurrence of a very short and linear C-H···F-C hydrogen bond with the presence of strong N-H···O=C hydrogen bonds in the Form II crystal structure of the meta-isomer. This is of significance in the field of crystal engineering and supramolecular chemistry. The fast SCSC phase transition triggered by SO at RT for the polymorphs in the ortho-isomer can be regarded to some extent as being similar to the behavior of dynamic molecular crystals which are observed in response to heat and light in the solid state. To the best of our knowledge, the quantitative molecular level mechanistic approach proposed here for the solid-state phase transition is a unique and straight forward one. Thus this approach can be extended to polymorphic transitions for other molecular crystals as well.

ASSOCIATED CONTENT This material is available free of charge via the Internet at http://pubs.acs.org.” Synthesis and characterizations (1H NMR), information regarding Silicone oil and 1H NMR spectrum. Crystallization and crystal growth, ORTEPs, PXRD patterns, HSM snapshots, crystallographic and refinements, phase transition experiments, theoretical calculations and CSD database search. Cif files (CCDC. 1555052-1555056), movie M1

AUTHOR INFORMATION Corresponding Author

Email: [email protected]; Fax: +91-0755-6692392 Notes The authors declare no competing financial interest.

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. We especially thank Dr. Yuri Mnyukh for insightful suggestions on the events related to phase transition. S. B. is grateful to Mr. Kaushik Pal for helping us in microscopic imaging.

REFERENCES (1) Bernstein, J. Polymorphism in Molecular Crystals; Oxford University Press: New York, 2002. (2) Cruz-Cabeza, A. J.; Bernstein, J. Chem. Rev. 2014, 114, 2170−2191.

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Silicone Oil Induced Spontaneous Single-crystal-to-Single-Crystal Phase Transitions in Ethynyl substituted ortho and meta-fluorinated benzamides Subhrajyoti Bhandary, Deepak Chopra*

Synopsis: A rare occurrence of hydrophobic silicone oil and temperature induced Single-crystal-to-Single-Crystal phase transitions was reported in polymorphs of two isomeric organic amides. A “structural motif” based quantitative molecular level mechanism was proposed to correlate the events at the molecular level.


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Silicone Oil Induced Spontaneous Single-Crystal ... - ACS Publications

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