Temperature Dependence of Mechanical Properties in Molecular

Subscriber access provided by STEVENS INST OF TECH

Article

Temperature dependence of mechanical properties in molecular crystals Reda M. Mohamed, Manish Kumar Mishra, Laila M AL-Harbi, Mohammed S. AlGhamdi, Abdullah M. Asiri, Chilla Malla Reddy, and Upadrasta Ramamurty Cryst. Growth Des., Just Accepted Manuscript • Publication Date (Web): 27 Mar 2015 Downloaded from http://pubs.acs.org on March 29, 2015

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Crystal Growth & Design is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Crystal Growth & Design

Temperature Dependence of Mechanical Properties in Molecular Crystals Reda M. Mohamed,1 Manish Kumar Mishra,2 Laila M. AL-Harbi,1 Mohammed S. Al-Ghamdi,3 Abdullah M. Asiri,1,4 Chilla Malla Reddy,5 and Upadrasta Ramamurty* 4,6 1

Chemistry Department, Faculty of Science, King Abdulaziz University, PO Box 80203, Jeddah 21589, Saudi Arabia 2 Solid State & Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India 3 Physics Department, Faculty of Science, King Abdulaziz University, PO Box 80203, Jeddah 21589, Saudi Arabia 4 Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia 5 Department of Chemical Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur 741 252, India 6 Department of Materials Engineering, Indian Institute of Science, Bangalore 560 012, India Abstract Quantitative evaluation of the mechanical behavior of molecular materials by nanoindentation technique has gained prominence recently. However, all the reported data has been on room temperature properties despite many interesting phenomena observed in them with variations in temperature. In this paper, we report the results of nanoindentation experiments conducted as a function of temperature, T, between 283 and 343 K, on the major faces of three organic crystals: saccharin, sulfathiazole (form 2), and L-alanine, which are distinct in terms of the number of strength of intermolecular interactions in them. Results show that elastic modulus, E, and hardness, H, decrease markedly with increasing T. While E decreases linearly with T, the variations in H with T are not so, and were observed to drop by ~50% over the range of T investigated. The slope of the linear fits to E vs. T the organic crystals was found to be around 1, which is considerably higher than the values of 0.3 to 0.5 reported in literature for metallic, ionic and covalently bonded crystalline materials. Possible implications of the observed remarkable changes in H for pharmaceutical manufacturing are highlighted.

1. Introduction Studies concerning the mechanical behavior of molecular materials have gained considerable research attention in the recent past.1–10 This is due to several reasons. (a) Mechanical properties such as hardness and fracture toughness of active pharmaceutical ingredients (APIs) play a dominant role in the context of drug manufacturing.11–20 Hence, there is always interest in the

ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

crystal structuremechanical property correlations of APIs. (b) Understanding of the mechanical properties of metal organic framework (MOF) materials21–25 and other organic crystals26–35 can help in the design of advanced materials with overall mechanical robustness or specific property such as highly flexible crystals.36 In certain specialized contexts such as reversible mechanochromism, understanding of the origins of plastic deformation can help in design of better materials.37 (c) Most importantly, realization that the nanoindentation technique, which allows for quantitative mechanical characterization of materials that are available only in small quantities, can be particularly useful for this purpose is a major reason for the spurt in the research activities on this front.21–35 However, all the studies that have been reported in literature hitherto were performed at room temperature. Many thermally responsive solid-state phenomena such as phase transitions, thermosalient effects, reversible mechanochromic luminescence, etc necessitate the evaluation of temperature sensitivity of the mechanical properties of molecular materials for designing future smart materials. The importance of evaluating, and in turn understanding, the mechanical properties of organic crystals as a function of temperature, T, can be highlighted through the following two points. (a) The melting point, Tm, of the organic materials is relatively low vis-à-vis metallic and other inorganic solids.29, 38 This means that a small variation in T can be significant in terms of the homologous temperature, T/Tm. (b) The intermolecular interactions that define crystal packing in molecular materials are considerably weaker as compared to metallic, ionic and covalent bonds.39,

40

The mechanical properties of crystalline materials, particularly elastic

modulus, E, depend on the crystal structure as well as the nature of the chemical bonds. With an increase in T, lattice thermal vibrations get amplified, which in turn change the lattice potential energy and reduce the curvature of the potential energy curve. Extensive literature is available of how these parameters change with T in metallic and inorganic materials.41, 42 Given that the energy of intermolecular interactions in organic crystals is substantially smaller, one can expect a high degree of temperature sensitivity in the mechanical behavior of organic crystals. Indeed, an early and preliminary study using sound velocity measurements on crystalline benzene conducted by Heseltine et al.43 in 1964, i.e. more than 50 years back, indicates to a high degree of temperature sensitivity, which was attributed to the ‘disturbance of the equilibrium between lattice phonons and the internal molecular vibrations.’ On the other hand, microhardness measurements were employed by Duncan-Hewitt and Weatherly44 to evaluate the deformation


Page 2 of 17

Page 3 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


kinetics of sucrose crystals between 296 and 376 K and by Sizova et al.45 to examine the hardness anisotropy in ammonium–nickel sulfate hexahydrate between 293 and 353 K. It is important to note that both ultrasonic and microhardness techniques require large and well defined crystals, which may not be possible to obtain for most organic materials.

2. Materials and experiments We have selected saccharin (Tm = 502 K), polymorphic form 2 of sulfathiazole (Tm = 469 K), and L-alanine (Tm = 588 K) for this study; reasons behind these choices are given in the next section. Commercially available compounds (saccharin: Loba Chemie, India, sulfathiazole and L-alanine: Sigma-Aldrich) were utilized for crystallization in conical flasks by slow evaporation of saturated solutions of different solvents (ethanol for saccharin, a solution of methanol, ethanol, and acetonitrile for sulfathiazole and water for L-alanine) at room temperature over a period of 2-3 weeks. The as-grown crystals were dried first and then washed with paraffin oil to remove any small crystals that might have gotten attached to the surface. Defect-free single crystals were carefully chosen after viewing them through an Olympus microscope supported by rotatable polarizing stage and were subjected first to single crystal X-ray diffraction (XRD) at 150 K on a Rigaku Mercury 375R/M CCD46 (XtaLAB mini) diffractometer using graphite monochromated Mo-Kα radiation, equipped with a Rigaku low temperature gas spray cooler. The Rigaku crystal clear software was used to process the XRD data. The structure solution was performed by direct methods, and refinements were performed by using SHELX9747 and WinGX suite.48 Face indexing of good quality single crystals was performed with the Rigaku CrystalClear software46 and the major faces were assigned. Saccharine, sulfathiazole form 2 and L-alanine crystals have rhombic, block and plate morphologies respectively. Large single crystals (average size: 2  2  1 mm3) were selected and firmly mounted on a stud using a thin layer of cyanoacrylate glue before the nanoindentation experiments. Each experiment was performed on the major face of the crystals, which are {100} for saccharine and sulfathiazole form 2, and {001} for of L-alanine. A nanoindenter (Triboindenter of Hysitron, Minneapolis, USA) equipped with a heating/cooling stage was utilized. To ensure accuracy in the measured data, a thermocouple was placed on the sample surface to accurately determine the temperature of crystal. In order to identify flat and smooth regions for the experiment, the crystal surfaces were imaged prior to indentation using the same indenter tip. Nanoindentation tests



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 17

were performed from temperatures, T of 283 to 343 K with 10 K intervals, with load, P, and displacement, h, resolutions of 1 nN and 0.2 nm, respectively. A three-sided pyramidal Berkovich indenter with a sharp zirconia tip (end radius ~ 100 nm) was used. Loading and unloading rates were 0.5 mN/s and the hold time at the peak load (5 mN) is 30 s. A minimum of 20 indentations were performed on each crystal at each T to ensure reproducibility. The P-h curves obtained were analyzed using the standard Oliver-Pharr (O-P) method to determine E and hardness, H. 49, 50

3. Crystal structures

(a) Saccharine

(b) Sulfathiazole

(c) L-alanine

Scheme 1. Chemical structures of (a) saccharine, (b) sulfathiazole, and (c) L-alanine. The crystal structures of all the three compounds examined in this work are already published in literature. Therefore, only the relevant and necessary information is presented here. Saccharin (C7H5NO3S; Scheme 1a) crystallizes in the monoclinic space group P21/c with unit cell parameters of a = 9.472(1), b = 6.923(1), c = 11.732(1) Å,  = 103.2(1) with (100) as the major face.51 The molecules form strong centrosymmetric N−H···O hydrogen bonds that stack down along [100] and make an oblique angle to the major plane (figure 1). Within a stack, the molecules are stabilized by nondirectional van der Waals (π···π) interactions. From these adjacent stacks, the saccharine molecules are also held by several C−H···O hydrogen bonds.


Page 5 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(a)

(b)

Figure 1. (a) Hydrogen bonds and (b) molecular packing in saccharin. Red line in (b) represents the trace of the major plane {100} on which nanoindentation is made. Five polymorphs of sulfathiazole (C9H9N3O2S2; Scheme 1b), a sulfonamide antimicrobial agent, exist.52, 53 Amongst these, form 2 is the most stable at room temperature and hence was chosen for the nanoindentation experiments. It crystallizes into the monoclinic space group, P21/c, with the crystallographic parameters: a = 8.220(5), b = 8.554(6), c = 15.499(9) Å, β = 94.018(10)°.53 Its crystal structure is constructed by the dimer growth, as shown in figure 2, which are linked through hydrogen bonds between sulfato oxygen and aniline hydrogen, and aniline nitrogen to amino hydrogen. There are two N−H···O intermolecular interactions, one fairly strong N−H···N interaction and many other C−H···O interactions. Since only one form of this compound is investigated in this study, we simply refer to it as ‘sulfathiazole’ here afterwards.

(a)

(b)



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 17

Figure 2. (a) Hydrogen bonds and (b) molecular packing in polymorphic form 2 of sulfathiazole. Red line in Fig. b represents the trace of the major face {100} on which indentation is made (the major face, L-alanine (C3H7NO2) (Scheme 1c), an amino acid, crystallizes as zwitterions, possessing charged ammonium and carboxylate moieties, in orthorhombic chiral space group, P212121 with crystallographic parameters: a = 5.6083(5), b = 5.5139(14), c = 11.815(3) Å.54 Each molecule forms four strong hydrogen bonds, originating from the ammonium terminal and all accepted by carboxylate oxygen are N−H···O and several weak C−H···O hydrogen bonds (figure 3). The hydrogen bonds connect the molecules into puckered layers in a-c plane, which are then stacked along b axis which result a three-dimensional hydrogen bond network structure.

(a)

(b)

Figure 3. (a) Hydrogen bond pattern and (b) molecular packing in L-alanine. Red line in (b) is the trace of the major plane {001} on which indentation is made. In summary, L-alanine is characterized by multitude of strong hydrogen bonds that are present in all the three directions (isotropic). Saccharin, in contrast, has relatively fewer hydrogen bonds, that are also highly directional (anisotropic). The intermolecular interactions in sulfathiazole are somewhat in between those of L-alanine and saccharin. Table 1 provides a summary of the various intermolecular interactions in the three crystalline compounds.


Page 7 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Table 1. Hydrogen bonds (neutron-normalized distances) in the three organic crystals examined in this work. Donor−H∙∙∙Acceptor Saccharin (SCCHRN)

Sulfathiazole Form 2 (SUTHAZ09)

L-alanine (LALNIN31)

H∙∙∙A (Å) 1.81 2.48 2.46 2.39 2.01 2.03 1.87 2.52 2.45 1.76 1.81 2.34 1.77 2.30 2.34 2.46

N1−H5∙∙∙O3 C1−H1∙∙∙O3 C2−H2∙∙∙O1 C4−H4∙∙∙O2 N1−H7∙∙∙O2 N1−H8∙∙∙O2 N3−H9∙∙∙N1 C3−H2∙∙∙O1 C3−H2∙∙∙O1 N1−H5∙∙∙O1 N1−H6∙∙∙O2 N1−H7∙∙∙O2 N1−H7∙∙∙O2 C3−H2∙∙∙O1 C3−H2∙∙∙O1 C3−H2∙∙∙O1

D∙∙∙A (Å) 2.79 3.20 3.41 3.40 3.00 2.98 2.84) 2.93 3.18 2.72 2.73 3.14 2.74 3.28 3.38 3.34

D−H∙∙∙A (°) 163 123 145 153 167 156 162 101 124 159 150 135 161 150 160 138

4. Mechanical properties

(a)

(b)

Figure 4. Representative load, P, versus depth of penetration, h, curves obtained on the three different molecular crystals at (a) 283 K and (b) 343 K.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 5. Representative P-h curves for saccharin obtained at various temperatures. Figure 4 displays representative P-h curves obtained on the three different molecular materials at temperatures, T = 283 and 343 K. The latter corresponds to the highest T at which nanoindentations were performed in this study. The following observations are made from them. (i) For a given P, h is smallest in L-alanine and highest in saccharin, while sulfathiazole’s is intermediate of the two. This implies that amongst the three compounds examined, L-alanine is the most robust. (ii) The order in which the P-h curves are arranged at room temperature is preserved at 343 K, indicating that, within the range of T investigated, the mechanical responses of the three molecular crystals do not cross-over as T is increased. However, for a given P, h increases significantly with T. This is illustrated through Figure 5 wherein the P-h responses obtained on saccharin at various T are plotted. (iii) While the loading part of the P-h curve obtained on L-alanine is smooth, those measured on saccharin and sulfathiazole is serrated, with several discrete displacement bursts. The latter observation is consistent with those reported earlier for room temperature nanoindentation on (100) facets of saccharin and sulfathiazole’s form 2 by Kiran et al.18 and Mishra et al.14 respectively. In those works, the average values of discrete displacement bursts, hpop-in, were found to correlate well with the inter-planar spacing, dhkl, of the respective slip planes. (iv) The serrations remain even at higher T, all the way up to 343 K. Analysis of the hpop-in indicates that its value remains an integral multiple of dhkl, in both saccharin and sulfathiazole, indicating that the mechanism of plastic deformation, i.e., collective slip of molecular layers, remains unaltered over the T range investigated. Further, we did not find


Page 8 of 17

Page 9 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


any correlation between hpop-in and T, which suggests that the slip distance associated with each pop-in does not necessarily get enhanced as the temperature is increased.

(a) Saccharin

(b) Sulfathiazole

(c) L-alanine Figure 6. Variations of E and H with T for (a) saccharin, (b) form 2 of sulfathiazole, and (c) Lalanine. The P-h responses were utilized to extract values of E and H at various T. Variations in them with T for each compound are plotted in Figures 6 (a) through (c). First, a comment about the relative values of E and H of the three compounds examined in this work. At room temperature (293 K), saccharin, sulfathiazole, and L-alanine’s E values are 13.94 ± 0.07, 21.88 ± 0.22, and 25.1 ± 0.72 GPa respectively whereas the corresponding H values are 0.530 ± 0.01, 0.9



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 17

± 0.03, and 0.99 ± 0.05 GPa. These data indicate that L-alanine’s stiffness and hardness are nearly-double that of saccharin, with sulfathiazole’s properties being intermediate of the two. These results are consistent with the nature and number of intermolecular interactions in the respective crystal structures.

From Figure 6, it is seen that E varies linearly with T and is well captured by the equation 𝑇

𝐸 (𝑇) = 𝐸0 [1 − 𝜓 (𝑇 )], m

(1)

which is generally used to describe the temperature dependence of elastic constants at most temperatures except close to 0 K.55 In Eq. 1, E0 is intercept of the linear fit with the ordinate, and ψ embodies the temperature-sensitivity of E and can be related to the Grüneisen parameter that describes the effect temperature variation on the crystal lattice dynamics and hence captures the properties of the lattice vibrations.56 A high value of ψimplies that the E of solid under consideration decreases rapidly with T. The values of E0 and ψ for the three organic crystals of this study are listed in Table 2. For comparison purposes, literature data available for various metals, oxide ceramics and covalent solids is also listed in Table 2.57–63 It is seen that ψ values obtained for the three organic crystals examined in this work range between 0.85 and 1.12. In comparison, ψ values in materials with metallic bonds (metals) range between 0.26 and 0.36, with covalent bonds (oxides) range between 0.3 and 0.46, and with ionic bonds (LiCl and RbCl) 0.57 to 0.66. Clearly, ψ values of organic crystals are substantially higher and indicate to considerable lattice softening as T is increased. Amongst the molecular crystals examined, saccharin’s ψ value is the highest, consistent with the low values of E seen in it. Interestingly, ψ value of L-alanine is slightly higher than that of sulfathiazole’s. Reasons for this need further investigations. In metallic and inorganic solids, the decrease in E with T arises exclusively due to the softening of the acoustic modes of phonon frequency dispersion. In organic crystals, very high values of ψ indicate to the possibility of softening of the optical modes also contributing. This has interesting implications in terms of mechanochromic properties exhibited by certain organic crystals, and requires further studies.


Page 11 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Table 2. Constants for the linear correlation between E and T for the organic crystals of this study, along with those for some metals, ceramics, metallic salts and oxides. Substance

E0 (GPa)

ψ

Tm (K)

Reference

Saccharin Sulfathiazole Form 2 L-alanine Aluminum Copper Silver Molybdenum Iron LiCl RbCl Benzene Alumina (Al2O3) Thoria (ThO2)

40.0 46.7 47.2 117.4 178.7 132.6 454 244.9 59.8 45.7 12.0 417.3 208.1

1.12 0.85 0.94 0.28 0.26 0.27 0.28 0.36 0.57 0.66 0.54 0.30 0.47

502 469 588 933.5 1358 1235 2896 1811 878.15 991 278.65 2345.2 3663.2

This work This work This work 57 58 59 60 61 62 62 43 63 63

Finally, we turn our attention to the variations of H with T. While H’s decrease with T tracks that of E initially, a marked reduction is seen at the intermediate temperatures, indicating to considerable softening of the organic crystals with increase in T. Over a T range of 60 K, the reductions in H are seen to be ~46%, 35%, and 34% for saccharin, sulfathiazole, and L-alanine respectively. (Compare these with ~35%, 22%, and 17% reductions in respective E values over the same T range). In this study, only a relatively small range of T probed. However, it is indeed close to the processing conditions of most organic materials in various practical applications. Therefore, such marked reductions in H indicate to the possibility of exploiting temperature as an additional processing parameter for enhancing tabletability of some APIs, wherein H plays a dominant role.13, 17, 64 If the H is too high, the resistance to plastic flow would be high and hence tabletability would be poor. In such a case, increasing the temperature of tableting by a few tens of degrees may yield substantially better products.65 Likewise, some APIs, such as voriconazole, are extremely soft (low H values) and difficult to mill.66,

67

In such cases, decreasing the

temperature at which milling is performed may yield good results. In all such contexts, temperature dependent nanoindentation can give quantitative insights, replacing the highly empirical studies performed on crystalline aggregates.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 17

5. Summary and conclusions Nanoindentation technique was employed to investigate the temperature-sensitivity of the mechanical properties, namely elastic modulus, and hardness, of three distinctly different molecular crystals, within the temperature range of 283 and 343 K. Experimental results show that both E and H decrease with T, with a substantial reduction in the latter over a relatively small temperature range of 60 K. The decreases E with T is linear, which is consistent with that seen for metallic and inorganic crystalline materials; the slope however is substantially larger for the organic crystals examined, which is due to the fact that the intermolecular interactions in them are much weaker vis-à-vis the metallic, covalent and ionic bonds that prevail in nonorganic materials. The average values of hpop-in remain integral multiples of respective slip plane’s dhkl, in both saccharin and sulfathiazole, indicating the mechanism of plastic deformation due to collective slip of molecular layers. Results of this study show that temperature dependence of mechanical property evaluation of organic crystals performed through nanoindentation has the potential for fine tuning some of the pharmaceutical manufacturing steps such as tableting and milling. Such studies can also help understand the structure-property relationship in many dynamic phenomena such as single-crystal-to-single crystal phase transitions, thermosalient effects, thermal reversible mechanochromic luminescence, etc.

Author Information Corresponding Author E-mail: [email protected]

Acknowledgements This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, under grant No (16-130-35-HiCi). The authors, therefore, acknowledge technical and financial support of KAU.


Page 13 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


References (1)

Karunatilaka, C.; Bučar, D. -K.; Ditzler, L. R.; Friščić, T.; Swenson, D. C.; MacGillivray, L. R.; Tivanski, A.V. Angew. Chem. Int. Ed. 2011, 50, 8642.

(2)

Reddy, C. M.; Basavoju, S; Desiraju, G. R. Chem Commun. 2005, 2439.

(3)

Reddy, C. M.; Kirchner, M. T.; Gundakaram, R. C.; Desiraju, G. R. Chem. Eur. J. 2006, 12, 2222.

(4)

Reddy, C. M.; Krishna, G. R.; Ghosh, S. CrystEngComm. 2010, 12, 2296.

(5)

Ghosh, S.; Reddy, C. M. Angew. Chem. Int. Ed. 2012, 51, 10319.

(6)

Sun, J.; Li, W.; Chen, C.; Ren, C.; Pan, D.; Zhang, J. Angew. Chem. Int. Ed. 2013, 52, 6653.

(7)

Terao, F.; Morimoto, M.; Irie, M. Angew. Chem. Int. Ed. 2012, 51, 901.

(8)

Ghosh, S.; Reddy, C. M. Angew. Chem. Int. Ed. 2012, 124, 10465-10469.

(9)

Mukherjee, A.; Desiraju, G.R. IUCrJ 2013, 1, 49-60.

(10) Turner, M. J.; Thomas, S. P.; Shi, M. W.; Jayatilaka, D.; Spackman, M. A. Chem. Commun., 2015, 51, 3735-3738. (11) Varughese, S.; Kiran, M. S. R. N.; Solanko, K. A.; Bond, A. D.; Ramamurty, U.; Desiraju, G. R. Chem. Sci. 2011, 2, 2236. (12) Karki, S.; Friščić, T.; Fábián, L.; Laity, P. R.; Day, G. M.; Jones, W. Adv. Mater., 2009, 21, 3905. (13) Chattoraj, S.; Shi, L.; Sun, C. C. CrystEngComm, 2010, 12, 2466. (14) Mishra, M. K.; Sanphui, P.; Ramamurty, U.; Desiraju, G. R. Cryst. Growth Des. 2014, 14, 3054. (15) Sun, C. C.; Grant. D. J. W. Pharm. Res. 2001, 18, 274. (16) Bag, P. P.; Chen, M.; Sun, C. C.; Reddy, C. M. CrystEngComm. 2012, 14, 3865. (17) Fabbiani, F. P. A.; Allan, D. R.; David, W. I. F.; Davidson, A. J.; Lennie, A. R.; Parsons, S.; Pulham, C. R.; Warren, J. E. Cryst. Growth Des. 2007, 7, 1115. (18) Kiran, M. S. R. N.; Varughese, S.; Reddy, C. M.; Ramamurty, U.; Desiraju, G. R. Cryst. Growth Des. 2010, 10, 4650. (19) Sanphui, P; Mishra, M. K.; Ramamurty, U; Desiraju, G. R. Mol. Pharmaceutics, 2015, 12, 889.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 17

(20) Chattoraj, S.; Shi, L.; Chen, M.; Alhalaweh, A.; Velaga, S.; Sun, C. C. Cryst. Growth Des. 2014, 14, 3864. (21) Tan, J. C.; Cheetham, A.K. Chem. Soc. Rev., 2011, 40, 1059. (22) Bundschuh, S.; Kraft, O.; Arslan, H. K.; Gliemann, H.; Weidler, P. G.; Woll, C. Appl. Phys. Lett., 2012, 101, 101910. (23) Kumar, R.; Raut, D.; Ahmad, I.; Ramamurty, U.; Maji, T. K.; Rao, C. N. R. Mater. Horiz., 2014,1, 513. (24) Spencer, E. C.; Kiran, M. S. R. N.; Li, W.; Ramamurty, U.; Ross, N. L.; Cheetham, A. K. Angew. Chem. Int. Ed. 2014, 53, 5583. (25) Henke, S.; Li, W.; Cheetham, A. K. Chem. Sci., 2014, 5, 2392. (26) Kaupp, G.; Naimi-Jamal, M. R. CrystEngComm. 2005, 7, 402. (27) Kaupp, G.; Schmeyers, J.; Hangen, U. D. J. Phys. Org. Chem. 2002, 15, 307. (28) Ghosh, S.; Mondal, A.; Kiran, M. S. R. N.; Ramamurty, U.; Reddy, C. M. Cryst. Growth Des. 2013, 13, 4435. (29) Mishra, M. K.; Varughese, S.; Ramamurty, U.; Desiraju, G. R. J. Am. Chem. Soc., 2013, 135, 8121. (30) Mishra, M. K.; Desiraju, G. R.; Ramamurty, U.; Bond, A. D. Angew. Chem. Int. Ed. 2014, 53, 13102. (31) Panda, M. K.; Ghosh, S.; Yasuda, N.; Moriwaki, T.; Mukherjee, G. D.; Reddy, C. M.; Naumov, P. Nature Chem. 2015, 7, 65. (32) Krishna, G. R.; Kiran, M. S. R. N.; Fraser, C.; Ramamurty, U.; Reddy, C. M. Adv. Funct. Mater. 2013, 23, 1422. (33) Sahoo, S. C.; Sinha, S. B.; Kiran, M. S. R. N.; Ramamurty, U.; Dericioglu, A. F.; Reddy, C. M.; Naumov, P. J. Am. Chem. Soc. 2013, 135,13843. (34) Zhu, L.; Tong, F.; Salinas, C.; Al-Muhanna, M. K.; Tham, F. S.; Kisailus, D.; Al-Kaysi, R. O.; Bardeen, C. J. Chem. Mater. 2014, 26, 6007. (35) Mishra, M. K.; Ramamurty, U.; Desiraju, G. R. J. Am. Chem. Soc., 2015, 137, 1794. (36) Ghosh, S; Mishra, M. K.; Kadambi, S. B.; Ramamurty, U.; Desiraju, G. R. Angew. Chem. Int. Ed. 2015, 54, 2674. (37) Krishna, G. M.; Kiran, M. S. R. N.; Fraser, C. L.; Ramamurty, U.; Reddy, C. M. Adv. Funct. Mater. 2013, 23, 1422.


Page 15 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(38) Hosford, W. F. Mechanical Behavior of Materials; Cambridge University Press: New York, 2005. (39) Varughese, S.; Kiran, M. S. R. N.; Ramamurty, U.; Desiraju, G. R. Angew. Chem. Int. Ed. 2013, 52, 2701. (40) Ramamurty, U.; Jang, J. CrystEngComm. 2014, 16, 12. (41) Varshni, Y. P. Phys. Rev., 1970, B 2, 3952. (42) Rahemi, R.; Li, D. Scripta Materialia, 2015, 99, 41. (43) Heseltine, J. C. W.; Elliott, D. W.; Wilson Jr. O. B. J. Chem. Phys. 1964, 40, 2584. (44) Duncan-Hewitt, W. C.; Weatherly, G. C. Pharm. Res. 1989, 6, 1060. (45) Sizova, N. L.; Manomenova, V. L.; Rudneva, E. B.; Voloshin, A. É. CRYSTALLOGRAPHY REPORTS,2007, 52, 884. (46) RigakuMercury375R/M CCD, CrystalClear-SM Expert 2.0 rc14; Rigaku Corporation: Tokyo, Japan, 2009. (47) Sheldrick, G. M. A short history of SHELX. ActaCrystallogr. 2008, A64, 112−122. (48) Farrugia, L. J. WinGX suite for small-molecule single-crystal crystallography. J. Appl. Crystallogr. 1999, 32, 837−838. (49) Oliver, W. C.; Pharr, G. M. J. Mater. Res. 1992, 7, 1564-1583. (50) Oliver, W. C.; Pharr, G. M. J. Mater. Res. 2004, 19, 3-20. (51) Wardell, J. L.; Low, J. N.; Glidewell, C. Acta Crystallogr., Sect. E 2005, 61, 1944. (52) Kruger, G. J.; Gafner, G. Acta Crystallogr. 1971, B27, 326. (53) Hughes, D. S.; Hursthouse, M. B.; Threlfall, T.; Tavener, S. Acta Crystallogr. 1999, C55, 1831. (54) Simpson, Jr. H. J.; Marsh, R. E. Acta Cryst. 1966. 20, 550. (55) Roesler, J.; Harders, H.; Bäeker, M. Mechanical Behaviour of Engineering Materials: Metals, Ceramics, Polymers; Teubner Verlag Wiesbaden: Spring Berlin Heidelberg New York, 2007. (56) Born, M.; Kun, H. Dynamical Theory of Crystal Lattices; Clarendon Press: Oxford, 1954. (57) Kamm, C. N.; Alers, G. A. J. Appl. Phys. 1964, 35, 327. (58) Overton, Jr. W. C.; Gaffney, J. Phys. Rev. 1955, 98, 969. (59) Neighbours, J. R.; Alers, G. A. Phys. Rev. 1958, 111, 707. (60) Dickinson, J. M.; Armstrong, P. E. J. Appl. Phys. 1967, 38, 602.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(61) Rayne, J. A.; Chandrasekhar, B. S. Phys. Rev. 1961, 122, 1714. (62) Marshall, B. J.; Pederson, D. O.; Dorris, G. G. J. Phys. Chem. Solids, 1961, 28, 1061. (63) Wachtman, Jr. J. B.; Tempt, W. E.; Lam, Jr. D. G.; Apstkin, C. S. Phys. Rev. 1961, 122, 1754. (64) Duncan-Hewitt, W. C.; Weatherly, G. C. J. Mater. Sci. Lett. 1989, 8, 1350. (65) Cespia, M.; Bonacucinaa, G.; Casettarib, L.; Ronchic, S.; Palmieria, G. F. Int. J. Pharm., 2013, 448, 320. (66) Butters, M.; Ebbs, J.; Green, S. P.; MacRae, J.; Morland, M. C.; Murtiashaw, C. W.; Pettman, A. Org. Process Res. Dev. 2001, 5, 28. (67) Taylor, L. J.; Papadopoulos, D. G.; Dunn, P. J.; Bentham, A. C.; Dawson, N. J.; Mitchell, J. C.; Snowden, M. J. Org. Process Res. Dev. 2004, 8, 674.


Page 16 of 17

Page 17 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


For Table of Contents Use Only Temperature Dependence of Mechanical Properties in Molecular Crystals Reda M. Mohamed,1 Manish Kumar Mishra,2 Laila M. AL-Harbi,1 Mohammed S. Al-Ghamdi,3 Abdullah M. Asiri,1,4 Chilla Malla Reddy,5 and Upadrasta Ramamurty* 4,6

Synopsis: The temperature dependence of the mechanical properties of single crystals of three different molecular solids was evaluated by employing nanoindentation. The elastic modulus decreases linearly with temperature, but with a larger slope than that reported for inorganic materials with either metallic or ionic bonds. Marked reductions in hardness with temperature indicate to the possibility for exploitation of temperature as a processing parameter during pharmaceutical manufacturing.


Temperature Dependence of Mechanical Properties in Molecular

Recommend Documents