Flexibility in a Molecular Crystal Accomplished by Structural

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Flexibility in a Molecular Crystal Accomplished by Structural Modulation of Carbohydrate Epimers Manas K. Panda, Kumar Bhaskar Pal, Gijo Raj, Rajesh Jana, Taro Moriwaki, Goutam Dev Mukherjee, Balaram Mukhopadhyay, and Pance Naumov Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.6b01749 • Publication Date (Web): 08 Feb 2017 Downloaded from http://pubs.acs.org on February 8, 2017

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Crystal Growth & Design

Flexibility in a Molecular Crystal Accomplished by Structural Modulation of Carbohydrate Epimers Manas K. Panda,1,┴, ‡, * Kumar Bhaskar Pal,2,┴ Gijo Raj,1,┴ Rajesh Jana,3 Taro Moriwaki,4 Goutam Dev Mukherjee,3 Balaram Mukhopadhyay,2,* Panče Naumov1 1New

York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates

2Department

of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur 741 246, India 3Department

of Physical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur Campus, Mohanpur 741 246, India 4Japan

Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo, Sayo, Hyogo 679-5198, Japan

‡

Current affiliation: Photo Science & Photonics Section, Chemical Science and Technology Division, CSIR-National Institute for Interdisciplinary Science & Technology, Trivandrum 695019, India ┴ These authors contributed equally in this study ABSTRACT Plastic bending of organic crystals is well known, yet mechanistically poorly understood phenomenon. On three structurally related epimers, derivatives of galactose, glucose and mannose, it is demonstrated here that small changes in the molecular structure can have profound effect on the mechanical properties. While the galactose derivative affords crystals, which can be easily bent, the crystals of the derivatives of glucose and mannose are brittle and do not bend. Structural, microscopic and mechanical evidence is provided that hydrogen bonding of water molecules is the key element for sliding over the slip planes in the crystal and accounts for the plastic bending.

1. Introduction Ability to deform, elastically or plastically, is common for biogenic architectures such as tissues, cells, stems, and cartilage. Many of these complex natural architectures are endowed with extraordinary mechanical strength and flexibility required to respond to external mechanical impacts without major damage.1‒4 Developing synthetic mechanically complaint structures that mimic these mechanical properties is of primary interest to applications that require flexible materials, such as those used in bendable electronics.5‒10 Crystalline molecular solids emerge as a new platform to dynamic materials, and can be very efficient in transducing external energy to macroscopic motion by cooperative amplification of nanoscopic motion and expression on a macroscopic scale.11‒16 The macroscopic consequence is usually manifested as timely continuous (bending, curling, swimming) or discontinuous effects (hopping, blasting, explosion).17‒ 51 Even that these properties are now being reported for increasing number of crystalline molecular materials, systematic studies into the contribution from the different intra- and intermolecular factors to the mechanical effects are not available yet; the observations remain serendipitous rather than systematic, and achieving control over the mechanical properties remains a major challenge. It has been postulated52‒53

Scheme 1. Synthesis and molecular structures of the galactose (1), glucose (2) and mannose (3) derivatives used in this study. that the plasticity of crystal deformation depends on the mobility of dislocations, which is governed by slip planes and weak/strong intermolecular interactions. A prerequisite for anisotropic plastic deformation is spatial orthogonality between weak and strong intermolecular interactions, whereas elastic bending requires isotropic interactions.54‒57 Placing these conclusions on a firmer basis necessitates comparison of the mechanical properties and molecular/crystal structures in a series of structurally re-

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lated compounds that exhibit very different mechanical response. Here we report that crystals of three structurally related epimers, namely substituted galactose, glucose and mannose (1‒3 in Scheme 1), exhibit drastically different response when subject to mechanical force. While single crystals of the galactose derivative readily undergo plastic bending when local pressure is applied on their (100) face, the crystals of the analogous glucose and mannose derivatives are brittle and fracture immediately. Mechanostructural correlations between the three epimers described here confirm that the presence of slip planes and intermolecular interactions between these planes governs the ability of plastic deformation. The slip planes affect the compressibility, while the molecular packing and the nature of intermolecular interactions determine the compactibility. In fact, the tabletability of active pharmaceutical ingredients can be controlled by modulating these two parameters. The present study involves the investigation on the modulation of the mechanical properties by geometric isomerization of pharmaceutically important aldohexose derivatives,58,59 which could be relevant to their tabletability when they are used as drug excipients. 2. Results and Discussion The sugar derivatives 1‒3 were synthesized from the respective para-thiotolyl derivatives60 by selective benzoylation of the primary hydroxyl group using benzoyl cyanide in presence of triethylamine (Scheme 1). The products were characterized by 1H, 13C, 1H‒1H COSY and HSQC NMR spectroscopy (for details, see the Supporting Information Figures S1‒S12). The themal behavior of the compounds were studied by TGA-SDT and their melting points were also determined (Supporting Information Figures S21‒S23 and Table S4). Crystals of 1‒3 were obtained by slow evaporation from a solutions (~5 mg/mL) of methanol/water (1 : 1). Recrystallization of 1 from pure, dry methanol afforded different crystals (1A). Acicular crystals of the three derivatives 1‒3 were subject to bending forces manually in a three-point geometry, using forceps and needle under optical microscope. Surprisingly, only crystals of the galactose derivative 1 obtained from methanol/water mixture are flexible and bend under mechanical stress. Quite unexpectedly, the crystals of the same derivative obtained from pure dry methanol (1A) are brittle. Thus, mechanically behavior of galactose derivative crystal can be tuned by simply changing the solvent composition. As shown in Figure 1b,c, the crystals of 1 bend plastically up to 360⁰ upon application of local pressure on the (100) face. The bending is highly plastic, and can be induced at multiple locations along the long axis of the crystal. On the contrary, crystals of the glucose and mannose derivatives 2 and 3 do not undergo any plastic deformation; instead, they break readily when impacted on either of the two accessible crystal faces. Figure 2 depicts the surface features of a bent crystal of 1. Investigation of the lateral face (001) in the bent portion of the crystal using Scanning Electron Microscopy (SEM) revealed a striped surface with rims along the length of the

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crystal (Figure 2c, d and Supporting Information Figure S13) that corresponds to the macroscopic layers stacked along the longitudinal axis (b-axis). These layers are not clearly noticeable in the straight section of the crystal (Figure 2a, b) indicating that the layers have evolved as a result of shear stress during the bending. Topographic features recorded using Atomic Force Microscopy (scanned on the (001) face of the bent crystal) confirmed that the ridges that have evolved in the kink are thick 0.2 ‒ 0.5 µm (Figure 2g, h).

Figure 1. Structures and bending of the crystals of epimers 1‒ 3. (a) Crystal structures determined by using X-ray diffraction. (b) Appearance of typical crystals of 1, 2 and 3. (c) Snapshots of the bending of a single crystal of the galactose derivative 1.

In order to further support our observation, the bent crystal of 1 was poked and ruptured with a sharp needle near the kink and then observed under electron microscope. The SEM images of the poked crystal clearly showed the slices of separated macroscopic layers (, Supporting Information Figure S13). This separation of


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Crystal Growth & Design crystal, the layers are more closely stacked on the cc side. The step-edges of the layers are better resolved in the adhesion map when compared to the topography image. The interlayer distance varies between 130 nm and 300 nm. Compared to the straight part, this decrease in interlayer spacing can be attributed to the compressive forces acting on the cc side. On the cx side of the bent region, which is subject to maximal tensile forces, the layers are even more compact, with inter-layer distances of 120‒180 nm. Although the topographies of the cc and cx regions appear similar, the adhesion force maps show clear differences in the layered structure. While numerous layers and step-edges are visible on the cc side (Figure 3e), the layers in the cx region are more uniform (Figure 3h).

Figure 2. Surface morphology of a bent crystal of 1 observed with SEM and AFM. (a‒d) SEM micrographs of the straight section (a,b) and in the bent section (c,d). (e‒h) 2D and 3D AFM topography images of the straight section (e,f) and bent section (g,h) of the crystal.

macroscopic layers in a plastically bendable crystal is in accordance with our previous model for bending of crystals of hexachlorobenzene.61 Compared to the galactose crystal 1, the surface topographic feature of other epimer crystals (2, 3) are drastically different (Supporting information Figure S14). As observed by SEM and AFM, the crystals of 2 and 3 lack typical topographic features of plastically deformable crystal. In order to get a deeper insight into the nanoscopic changes in the surface features, we have carried out Atomic Force Microscopy (AFM) adhesion mapping on a bent crystal of 1. The adhesion map was obtained by approaching the tip to the sample surface followed by retraction to measure the “pull-off” force (adhesion force), the minimum tension needed to detach the tip from the sample. The adhesion force provides information on the surface inhomogeneity, weak surface-to-tip interactions and intermolecular interactions, among else. The adhesion of the surface of the bent crystal of 1 was mapped at three different locations: the straight portion, and at the convex (cx) and concave (cc) sides of the kink (Figure 3). The topography of the straight part of the crystal shows stacked/layered features with interlayer distances ranging from 350 nm to 1 µm (Figure 3a). In the bent section of the

Figure 3. AFM images of the straight and bent regions of a crystal of 1. AFM topography, adhesion force map and histogram of the straight section (a‒c), the concave part (cc, d‒f) and the convex part (cx, g‒i) of a bent crystal. (j,k) Optical images showing the positions of the tip on the straight part (j), and on the concave (1) and convex (2) regions (k) of the crystal analyzed by AFM.

The histograms of the adhesion forces show peak values of 18.50, 19.32 and 29.09 nN measured on the straight, cc and cx regions of the bent crystal, respectively. The adhesion force measured on the cc side of the crystal is not significantly different from that of the straight part. However, it is noteworthy that the distribution of the adhesion forces is narrow on the straight part (FWHM 6.41 nN) and broad on the concave part (FWHM 10.06 nN). The broad distribution of adhesion forces in the bent (cc and cx) section is associated with increased surface roughness and slightly disordered orientation of the molecules in the bent area of the crystal relative to the straight part. The RMS roughness of the crystal in the straight part is 1.92 nm while that in the cc and cx regions are 2.48 nm and 2.53 nm, respectively. This difference in roughness is attributed



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to increased mosaicity and reorientation of the molecule upon plastic bending. Despite similar surface roughness, the adhesion forces measured on the cx side of the crystal is significantly higher than the cc side. This difference in adhesion forces is attributed to changes in the molecular orientation in the layers, which further affects the mechanical response as compressive and tensile forces are exerted at the cc and cx regions, respectively. The stronger adhesive force on the cx side is presumably because of the increasing polarity of the molecules under stretching force.62 X-ray diffraction analysis of the crystal 1 was performed to correlate the mechanical property with the molecular packing (for details, see the Experimental section). Compound 1 crystallizes in the monoclinic space group C2 with four molecules of 1 and one water molecule in the asymmetric unit. As evident from the crystal structure (Figures 1a and 4), the two phenyl rings (from STol and OBz, Scheme 1) in the molecule are positioned at an angle of 42(1)⁰ relative to each other. One phenyl ring of the OBz groups interacts with an adjacent OBz phenyl ring via C— H•••π interactions (Figure 4) with C-to-centroid distances of 3.702 Å and 3.620 Å the crystallographic b axis. Similarly, the phenyl rings of the STol groups form slipstacks along the b-axis by intermolecular C—H•••π interactions having distances of 3.729 Å, 3.883 Å and 3.663 Å (C-to-centroid distance). These two sets of C—H•••π interactions act as a stitching thread in preserving the stacking of the phenyl rings during the gliding of slip-stack layers along b-axis and help to maintain macroscopic integrity. The water molecules present in the lattice are located between two slip layers and form intermolecular hydrogen bonds (O—H•••O or O—H•••S) with the galactose OH groups and the STol groups. The hydrogen bonding distances (D•••A distance) between the water and the hydroxyl groups of the galactose are 2.746(7), 2.851 (7), 2.741 (7), 2.774 (7) Å. Interestingly, unlike in 2 and 3, the orientation of the sulfur atom of the STol group in the crystal structure of 1 favors the formation of apparently weaker hydrogen bonding interaction with water molecules (O—H•••S). The D—A distances are 3.484 (6) Å, 3.407 (6) Å, 3.424 (6) Å and 3.381 (6) Å. The diffraction data indicates that these are much weaker interaction than the O—H•••O interaction of the hydroxyl group of the galactose 1, and are orthogonal to C—H•••π interactions. The suitable orientation of weak and strong intermolecular interactions faciliates the gliding of the slip planes along the crystallographic b axis. Thus, the water molecules in the crystal lattice act as “lubricant” that provides fluidity by dynamic exchange of interlayer hydrogen bonds and facilitate the slipping of the molecular layers for crystal bending. To validate the above argument, that is, the role of water molecule during bending, we have carried out several control studies. Firstly, few newly synthesized crystals of 1 were dehydrated by evacuation at 50 oC for 4 days. The dried crystals were brittle and did not show any plastic deformation under force on different faces; instead they were brittle and broke readily. Secondly, crystallization of

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1 from pure methanol affords very thin, needle-shaped crystals (1A). These crystals are monoclinic, space group P21, and are anhydrous (see Figure S16 and Supporting Information Table S1). The crystals are very brittle and do not exhibit any plastic deformation when they are pressed on any of the available faces. This suggests that the interlayer weak hydrogen-bonding interactions (O—H•••O or O—H•••S) involving the water molecules indeed facilitate the slipping. This behavior is similar to that reported by Martino and co-workers, where naproxen crystals exhibits different mechanical property in their hydrated and dehydrated form.63 In another study, Desiraju and co-workers reported that the mechanical properties of a crystal of one of the hydrates of sodium saccharinate are drastically changed upon dehydration.64 Thus, the lattice water molecules play crucial role in manipulating anisotropic stiffness and hardness of the crystal.

Figure 4. X-Ray diffraction packing analysis of a single crystal of 1. (a) Face indices of a crystal of 1. (b) A cartoon showing the bending faces of the crystal. (c) Packing in the crystal viewed down to b-axis showing different modes of H-bonding interactions involving lattice H2O molecules. (d) Slip planes (highlighted by pink shades) and water molecules in the slip channel (dotted circles) are highlighted. C—H•••π interaction which involves STol (blue dotted line) and OBz phenyl rings (green dotted line) are shown.

The glucose derivative 2 and mannose derivative 3 crystallize in the monoclinic P21 and orthorhombic P212121 space groups, respectively (Supporting Information Table S1). These molecules also contain water molecules in their crystal lattices that form strong interlayer hydrogen bonds (Supporting Information Figures S17 and S18). Contrary to 1, the crystals of 2 and 3 do not include O—H•••S hydrogen bonds between the slip layers. Consequently, they are brittle and do not exhibit plastic deformation. Moreover, compared to 1, the molecule of 2 forms much longer intermolecular C—H•••π interactions (2.989 Å).


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Both intramolecular (2.979 Å) and intermolecular (2.763 Å) C—H•••π interactions are present in the crystal of 3.

Figure 5. Water-molecule-assisted gliding of slip layers: (a) Molecular packing diagram of the slip planes in 1. (b) Cartoon showing intermolecular interactions and the location of water molecules in the slip channels of 1.

The dynamic role of lattice water during the bending of the galactose crystal (1) and the concomitant change in intermolecular hydrogen bonding interaction were analyzed by spatially resolved non-polarized and linearly polarized micro-IR spectroscopy using synchrotron radiation.65‒66 IR beam of size 4 × 8 µm2 was focused on the kink of 12 µm-thick, bent crystal of 1. The IR spectra of the bent crystal revealed the rearrangement of water molecules on the cc and cx side of the crystal upon plastic deformation. The blue shift (see cc 90o and cx 90o in Figure 6a, b) of the broad band from the OH (H2O) stretching mode at ~3365 cm‒1 corresponds to the strengthening of the O—H bond and weakening of hydrogen bonding interaction (O—H•••X, where X = O, S) during plastic deformation. This frequency shift suggests that the symmetry and orientation of the O—H bonds are changed during the bending. On the other hand, the band that corresponds to the O—H group that does not participate in hydrogen bonding, at ~3516 cm‒1, remains unchanged, indicating that the respective OH groups retains their symmetry and orientation upon bending. The aromatic and aliphatic C—H stretchings (~2933 and 2904 cm‒1) do not provide much information about structural change..

Figure 6. Micro-focus IR spectra and micro-Raman spectra of a crystal of 1. (a, b) Polarized and non-polarized (denoted WO) IR spectra in the OH and CH stretching regions recorded from the bent section of 1. (c,d) Non-polarized Raman spectra recorded from acutely bent (ab), slightly bent (sb) and unbent (straight, s) portions, and from the concave (cc), convex (cx) and unbent (straight, s) regions of an acutely bent crystal.

On a molecular level, the effect of bending on different intermolecular interactions can be observed from spatially resolved linearly polarized micro-Raman spectroscopy of a bent crystal of 1. Our attempts to observe the change in the OH Raman stretching mode from the lattice water upon bending was incoclusive because of the poorly resolved bands in the 3300—3600 cm‒1 region. The intensity of the aromatic C—C stretching vibration (1010 and 1608 cm‒1) progressively increses with the bending from s to ab (Figure 6c). This result could be a consequence of the molecular bending, where the aromatic rings come closer and contribute to higher intensity. The variation of the ester carbonyl streching frequency (1719 cm‒1) is less prononunced from the straight to acutely bent crystal region. This observation can be attributed to the gliding of the plane, where the hydrogen bond between the carbonyl group and the water molecule or the OH groups becomes weaker, resulting in weaker band. The sharp, intense bands in accutely bent crystal at 622 and 1101 cm‒1 can be assigned to C(aliphatic)—S and C (aromatic)—S stretching vibrations, respectively. The 622 cm‒1 band in the the ab portion is strong relative the straight and strongly bent sections. This result could be related to the advancement of the p-thiotolyl ring along with the C—S bond closer to each other because of the drifting of the planes while bending. In turn, conjugation between σ non-bonding and σ* antibonding orbital of the C—S bond increases which enhances the intensity of the band. Similarly, the symmetric CH3 deformation at 1384 cm‒1, gains intensity upon gliding. The bands at 2883, 2928 and 3003 cm‒1 are due to the symmetric C—H stretching. From the straight to acutely bent section these bands gradually become weaker, possibly due to twisting of the sugar molecules. The changes in the bands at 622, 1010, 1101 and 1608 cm‒


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are much pronounced between the s, cc and cx faces (Figure 6d); the bands are stronger in the cx than on the cc side, and they are weakest in the s layer. The increasing strain on the cx side leads to splaying of the molecules; in turn, the sugar molecules which are fixed by hydrogen bonding are twisted more, in line with the trend with the C—H bands.

The mechanical properties of the crystals at the nanoscale were studied with nanoindentation. Nanomechanical tests were performed using sharp Berkovich tip on smooth surface of crystals attached on the indenter stud. 4‒5 sets of experiment in continuous stiffness measurement (CSM) mode were perfomed at different locations of the crystal to verify the data and to obtain the average elastic modulus and hardness. During the experiment, the indenter axis was kept normal to the target surface on the crystal face. Despite the technical challenges, due to the small crytal thickness of the crystals of 1, reproducible values were obtained. A representative stress-strain curve is shown in Supporting Information Figure S19. The plastically bent crystal of 1 showed very irregular response owing to the packing heterogeneity, dislocation movement and change in intermolecular interactions upon plastic deformation. The respective average modulus and hardness values at the kink [(101) surface] of a bent crystal (1.5 mm × 0.05 mm × 0.03 mm) are 4.30 GPa and 0.39 GPa, while the same observed in the straight location are 4.57 and 0.29 GPa. These values are comparable to the previously reported plastically deformable organic crystals.61 The different values of Young‘s modulus in the bent section compared to the straight section can be attributed to the change in orientation of the molecules as well as to inhomogeneous packing rearrangement during the bending. Moreover, stress-induced structural perturbations of the unit cell during plastic deformation also account for the difference in elastic stiffness in the straight and bent locations. Unlike the galactose crystal 1, the indentation on the different locations on (001) face of the glucose crystal 2, which does not exhibit plastic deformation, was much regular with average elastic modulus 5.8 GPa (see Supporting Information Figure S20). Our attempt to perform nanoindentation of the mannose crystal 3 was not sucsessful because of the poor quality of of the thin platelike crystals which readily develop crack on their accessible surface upon indentation.

3. Conclusions In summary, we have successfully demonstrated that the plastic deformation can be achieved by structural modification of sugar epimers, where only the galactose derivative (1) undergoes plastic deformation while the glucose (2) and mannose (3) derivatives do not. To the best of our knowledge, this is the first example of mechanically flexible carbohydrate crystal. Moreover, we have also demonstrated that the mechanical flexibility of the galactose derivative can be tuned by changing the solvent composition

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during crystallization. By simply switching from methanol to water–methanol mixture, we generated an alternative structure of the galactose epimer 1 which displays different mechanical response. Inclusion of water molecules in the crystal lattice provides weaker hydrogen bonding interactions that facilitate the dynamic exchange of interactions during the gliding of the slip planes and favors plastic deformation. This strategy remains unexplored in this research field and could be employed to accomplish plastic deformation. The results described here could also provide a platform for tuning the mechanical behavior of pharmaceutically and industrially important crystals.

Experimental Section Materials. Benzoyl cyanide, triethylamine, acetonitrile and methanol were purchased from Sigma-Aldrich and were used directly for the experiments. Single crystals of 1, 2 and 3 were grown from 1:1 methanol-water mixture with a concentration of ~5 mg/mL. Crystals of 1A were grown from pure methanol. Scanning electron microscopy. Scanning electron microscopy (SEM) was carried out with a QUANTA FEG 450 electron microscope with primary electron energy of 2–5 kV at room temperature. The crystals were attached to silicon wafers with epoxy adhesive and coated with gold prioir to the SEM study. Atomic force microscopy. Atomic force microscopy (AFM) measurements were performed on an Agilent 5500 AFM in AC (“tapping”) mode. Nanosensors PPP-NCH tips with a nominal tip radius less than 7 nm were used as cantilevers at a resonant frequency of ~290 kHz. Scan arrays were 512 × 512 points and the scan speed was ~0.5 lines/second. Feedback control parameters were optimized for each scan. Thermal Studies. Thermal analysis were performed on a TA instrument SDT Q600 V20.9 Build 20, with a maximum temperature of 200 °C and heating rate of 10 °C per minute using nitrogen (50 mL/min) as purging gas. The melting point of the crystals were measured using a digital melting point apparatus SECOR INDIA. Nanoindentation. Agilent G200 nanoindenter having an XP head and a Berkovitch diamond indenter was used for nanoindentation experiments. Prior to actual indentation experiemnt on organic crystal, the tip stiffness and geometry was determined using Corning 7980 silica reference sample (Nanomechanics S1495-25). Several crystals of straight and bent galactose were tested and theresults were averaged out. Continuous stiffness method (CSM) with indentation depth of 1000‒2000 nm with strain rate of 0.5 nm was adopted for indentation experiment. The modulus was calculated using the Oliver-Pharr method, where a fit of the unloading curve is used to determine the stiffness, the contact depth, the reduced modulus of the system, and finally the modulus of the sample.67‒68 The value of the Poisson’s ratio was assumed to be 0.3 (typical of anisotropic crystalline solids). The hardness was calculated from the peak load divided by the contact area of the indenter.


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Micro-IR spectroscopy. Micro-focus Infrared measurements were performed at BL43IR beamline, SPring-8, Japan with Vertex70 FTIR spectrometer and Hyperion 2000 infrared microscope from Bruker. All spectra were taken with 2 cm–1 resolution and 2560-fold accumulation. The IR beam was constrained at 4 × 8 µm2 with a knife edge aperture in the microscope and focused normal to the bending plane of approximately 10 µm-thick, mechanically bent Galactose crystal. Micro-Raman spectroscopy. Micro-Raman spectroscopy was carried out with LABRAM HR from Horiba Jobin Yvon using excitation wavelength 632 nm (He-Ne laser) with spectral resolution 2 cm-1 using 1800 gr/mm grating and 20X infinitely corrected long working distance objective.

Corresponding Author: [email protected] (M. P), Tel: +91 471-253-5608, [email protected] (B. M.); Tel: +91-9748-261742, +91-33-2587 3020. Funding Sources: This work is financially supported by funding from New York University Abu Dhabi and Science and Engineering Research Board (SERB), India through the Grant SB/S1/OC-48/2013 to BM. This research was partially carried out using Core Technology Platform resources at New York University Abu Dhabi.

REFERENCES 1.

Single crystal X-ray diffraction analysis. Single crystal X-ray difraction data for 1 and 1A were collected on a Bruker SMART APEX II diffractometer with monochromated MoKα radiation (λ = 0.71069 Å) equipped with CCD area detector. The SAINT software was used for data reduction, which were analyzed for agreement using XPREP.69 Absorption correction was carried out with the SADABS program.70 The structure was determined by the method included in SHELXT program of the APEX software suite and refined using SHELXL-2014.71‒ 74 The non-hydrogen atoms were refined anisotropically. The hydrogen atoms bonded to oxygen atoms were located from the electron density map and refined by using an appropriate AFIX command. The single-crystal X-ray diffraction data of the crystals 2 and 3 were collected on a SuperNova, Dual Eos diffractometer at 292 K using graphite-monochromated MoKα radiation (λ = 0.71073 Å). The atomic coordinates, isotropic and anisotropic displacement parameters of all the nonhydrogen atoms of three compounds (2, 3) were refined using Olex2,75 and the structure was solved with the Superflip structure solution program using the charge flipping method,76 and refined with the SHELXL refinement package 71 using leastsquares minimization. Details of crystallographic parameters of the coumpounds are given in Supporting Information Table 1. The crystallographic data have been deposited with the Cambridge Crystallographic Data Centre (CCDC) under references 1530013 (1), 1495996 (1A), 1411668 (2), 1411667 (3). ASSOCIATED CONTENT

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Synthesis and characterization data (1H NMR, 13C NMR, COSY NMR, HSQC NMR, melting points, TGA-SDT), nanoindentation figures, packing figures, and the Tables for crystallographic parameters are provided in supporting information. These materials are available free of cost via the Internet at http://pubs.acs.org.

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Micro-IR spectroscopic measurements were carried out at BL43IR, Infrared beamline facility SPring-8, with the prior approval of the Japan Synchrotron Radiation Research Institute (JASRI) (Proposals No. (Proposals No. 2015A1598 and 2014B1461). We thank Dr. Liang Li and Dr. James Weston, Core Technology Platform, New York University Abu Dhabi for their help in AFM, Nanoindentation and thermal studies.

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For Table of Contents use only Figure for TOC graphics

Flexibility in a Molecular Crystal Accomplished by Structural Modulation of Carbohydrate Epimer Manas K. Panda, Kumar Bhaskar Pal, Gijo Raj, Rajesh Jana, Taro Moriwaki, Gautam Dev Mukherjee, Balaram Mukhopadhyay, Panče Naumov Plastic deformation behavior of three structurally related carbohydrate epimers, derivatives of galactose, glucose and mannose have been investigated. it is demonstrated here that small modification in the molecular structure can have profound effect in mechanical properties. While the galactose derivative affords crystals, which can be easily bent, the crystals of the derivatives of glucose and mannose are brittle and do not bend.


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Flexibility in a Molecular Crystal Accomplished by Structural

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