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Preparation and characterization of several azoxystrobin channel solvates
Journal of Molecular Structure 1189 (2019) 40e50
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Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc
Preparation and characterization of several azoxystrobin channel solvates Dan Du a, Zhi-Ping Shi a, Guo-Bin Ren b, Ming-Hui Qi b, *, Zhong Li a, Xiao-Yong Xu a, ** a
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, No. 130 Meilong Rd., Shanghai, 200237, PR China b Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, No. 130 Meilong Rd., Shanghai, 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 24 January 2019 Received in revised form 13 March 2019 Accepted 1 April 2019 Available online 4 April 2019
Azoxystrobin is an important strobilurins fungicide. Nine channel solvates of azoxystrobin were obtained for the first time and six of them could be crystallized in single crystals. The crystallographic data, unit cell porosity, Hirshfeld surface, and fingerprint plot were analyzed. These solvates are isostructural, azoxystrobin forming a host framework through intermolecular interaction and the guest solvent molecules located in channels. These solvates were stabilized by p,,,p interaction, CeH,,,p interaction, and weak hydrogen-bonding interactions such as CeH,,,O interaction and CeH,,,C interaction. All solvates were characterized by PXRD, DSC, TG, FTIR, and FESEM, the stability of them were also examined. Moreover, because of the similarity of the channel solvates, solvent-replacement method could be used to prepare other solvates. © 2019 Elsevier B.V. All rights reserved.
Keywords: Azoxystrobin Channel solvates Isostructurality Hirshfeld surface Pseudopolymorph Solvent-replacement method Porosity
1. Introduction The search for new solid forms of chemical compound for many academic researchers has become more and more important in nowadays [1]. New solid forms include polymorphs, solvates [2], salts [3], cocrystals [4], or their combinations. Different solid forms may bring various properties, such as higher melting point [5], higher solubility [6], better chemical or physical stability [7], and even better bioavailability or clinical efficacy [8,9]. Another benefit of solid forms research is that solid form with desired properties could be prepared during scale-up production process, process time could be significantly shorten, and even product purity was improved [10]. The study of polymorphs may be the first step for later research, and can solve many problems such as poor stability and nonreproducibility in formulation producing. Due to the quite small energy differences between polymorphs, they often occur solid
* Corresponding author. ** Corresponding author. E-mail addresses: [email protected] (M.-H. Qi), [email protected] (X.-Y. Xu). https://doi.org/10.1016/j.molstruc.2019.04.011 0022-2860/© 2019 Elsevier B.V. All rights reserved.
state transformations [11] or concomitantly crystallizing, finally form polymorph mixtures [12]. Solvates have better properties than polymorphs in many aspects [13] mainly manifested in improve the solubility or stability of compounds. In addition, the digestion performance of solvates are often enhanced, because solvates generally have higher dissolution rate [14], which leads to higher supersaturation compared to polymorphs [15]. Furthermore, solvates can also be used for the preparation of various polymorphs through desolvation or for the preparation of some drugs that is difficult to obtain the target polymorphs by traditional crystallization method [16]. Thus, in current crystal engineering field, the research of solvates is very important. In some cases, the solvent molecules act as space fillers in some solvates and this type of solvates are classified as inclusion phases, as well as channel solvates [17]. This means that the solvent molecules are entrapped in the crystal lattice and had no significantly interaction with the host molecules. Azoxystrobin (AZX), methyl (E)-2-[2-[6-(2-cyanophenoxy)pirimidin-4-yloxy] phenyl]-3-methoxyacrylate (Fig. 1) is a broad spectrum, systemic, and soil-applied fungicide belonging to the bmethoxyacrylates group [18]. AZX is the first registered strobilurin analogues, which possess new mode of action and leading market
D. Du et al. / Journal of Molecular Structure 1189 (2019) 40e50
Fig. 1. Molecular structure of AZX.
share in the world [19e21]. It controls both foliar and soil-borne diseases such as powdery mildew rust [22], bacterial blight, net blotch [23], black shank, downy mildew, and rice blast [24,25]. Only two polymorphs (form 1 and form 2) and one amorphous form of AZX [26] were reported and no solvates of AZX had been reported in the Cambridge Structural Database. Form 1 mentioned in the patent is the most stable form and used as commercial product. In this paper, we prepared a series of AZX solvates. They were characterized by X-ray diffraction (PXRD and SXRD) [27], thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform-infrared spectrum (FTIR), and field emission scanning electron microscopy (FESEM). The results showed that the solvates obtained were all isostructural with AZX form 1 and the solvent-replacement method could be applied to preparing AZX solvates. X-ray crystallography, porosity, Hirshfeld surface, and fingerprint plot analysis were used to characterize the channel solvates. Solid-state stability experiments indicated that the stability of solvates are not good. They could transform to form 1 under certain conditions. 2. Experimental section 2.1. Materials and methods Azoxystrobin form 1 (purity > 98%) was purchased from BioChemPartner Company, Ltd. (Zhangjiang Road, Pudong New Area, Shanghai, China). Organic solvents with analytical or chromatographic grade (purity > 99%) were purchased from Sinopharm Chemical Reagent Co., Ltd. (China) and used without further purification. Water used in the experiments was purified from a deionizer with mixed bed purification system (Merck Millipore D 24 UV, Germany). 2.2. Preparation of azoxystrobin solvates Azoxystrobin form 2 (acetone solvate), form 3 (tetrahydrofuran solvate), and form 4 (butyl acetate solvate). Form 2, form 3, and form 4 was prepared by the evaporation of saturated solution of AZX in acetone, tetrahydrofuran, and butyl acetate separately at room temperature. After two weeks the solid powders were filtered and dried over 24 h under vacuum at room temperature. The single crystal of form 2 and form 3 can be obtained by slowing down the evaporation rate of the corresponding solution, the single crystal of form 4 was not obtained. Azoxystrobin form 5 (n-heptane solvate). 50 mg AZX was dissolved in 2-butanone, and then proper amount of n-heptane was added to the above solution, large amount of white solid precipitated, the solid powders were filtered and dried over 24 h under vacuum at room temperature. The bulk single crystal of form 5 was
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prepared by add small amount of n-heptane to the saturated 2butanone solution of AZX and seal it to stand for one month. Azoxystrobin form 7 (3-pentanone solvate). Form 7 was prepared from dissolving 50 mg AZX in 1 mL 3-pentanone followed by adding 5 ml n-hexane, large amount of white solid precipitated, the solid powders were filtered and dried over 24 h under vacuum at room temperature. The single crystal of form 7 was not obtained. Azoxystrobin form 10 (1,2-dichloroethan solvate). Form 10 was prepared from dissolving 50 mg AZX in 0.2 ml 1,2-dichloroethan, then adding this solution to 1 ml cyclohexane, large amount of white solid precipitated immediately, then the solid powders were filtered and dried over 24 h under vacuum at room temperature. The single crystal of form 10 was not obtained during the preparation. 2.3. X-ray crystallography X-ray diffraction data were collected on Bruker SMART-APEX DUO diffractometer (USA) equipped with a graphite monochromator and Mo-Ka fine-focus sealed tube (l ¼ 0.71073 Å). Data processing was performed using Bruker SAINT Software. Intensities were corrected for absorption using SADABS [28], and the structure was refined using SHELXL-97 [29]. All non-hydrogen atoms were refined anisotropically [30]. Hydrogen atoms on heteroatoms were located from different electron density maps and all CeH hydrogens were fixed geometrically. Hydrogen bond geometries were determined in Platon. X-Seed was used to prepare packing diagrams. Related crystallographic data have been deposited in the Cambridge Crystallographic Data Centre (CCDC Nos. 18476711847676). 2.4. Powder X-ray diffraction (PXRD) PXRD patterns were obtained using a Rigaku Ultima IV X-ray diffractometer (Cu-Ka radiation) [31]. The voltage and current of the generator were set to 40 kV and 40 mA, respectively. Data between the 2q angular ranges 5 e45 were collected at a scan rate of 20 /min at ambient temperature. The data were integrated with RINT Rapid and the peaks were analyzed with Jade 6.0 from Rigaku. 2.5. Differential scanning calorimetry (DSC) Differential Scanning Calorimetry (DSC) experiments were performed on a TA DSC Q2000 instrument [32] under a nitrogen gas flow of 50 mL/min. The samples weighing 3e5 mg were placed in crimped and sealed aluminium sample pans heating from 30 to 150 C at a heating rate of 10 C/min. The instrument was calibrated against with the melting properties of indium according to standard procedure. Each sample was analyzed in triplicate with RSD <2%. 2.6. Thermogravimetric (TG) analysis Thermogravimetric properties of the solvates of AZX were obtained using a TA TGA Q500 with platinum pans at a heating rate of 10 C/min under a nitrogen gas flow [33]. The instrument was calibrated with mass and temperature according to standard procedure. Each sample was analyzed in triplicate with RSD <2%. 2.7. Vibrational spectroscopy Fourier transform-infrared (FTIR) spectra were collected with a Nicolet-Magna FT-IR 750 spectrometer in the range from 4000 to 500 cm1 with a resolution of 4 cm1 under ambient conditions [34].
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2.8. Field emission scanning electron microscopy (FESEM)
2.11. Hirshfeld surface analysis
The shapes and morphologies of the crystals were examined on a Carl Zeiss model Merlin Compact 6027 FESEM (Germany) with a beam voltage of 3.0 kV [35]. The sample was spread on a carboncoated copper grid prior to FESEM imaging. In order to enhance the conductivity of the sample, an ultrathin layer of gold was coated on the sample.
The Hirshfeld surface analysis used Crystal Explorer software to identify a type and region of intermolecular interactions [40]. For a given crystal structure, all of the Hirshfeld surfaces and fingerprint plots were unique [41,42]. The fingerprint plots quantitatively summarize the nature and type of intermolecular contacts in the crystal. Molecular Hirshfeld surface in a crystal structure was constructed based on the electron distribution. For each point on that isosurface, two distances were defined: de, the distance from the Hirshfeld surface to the nearest nucleus outside the surface, and di, the corresponding distance to the nearest nucleus inside the surface [43]. The normalized contact distance (dnorm) based on de, di, and rvdw (the van der Waals [vdw] radius of the appropriate atom internal or external to the surface) [15].
2.9. Solvent-replacement method According to the single-crystal structure analysis of solvates form 2, form 3, and form 5, AZX was considered to possess the ability to form a frame-work with solvent molecules residing in channels, which suggests that a variety of solvent molecules could be accommodated. Thus, solvent-replacement method [36] was established to obtain new solvates of AZX. The operating steps of this method are as follows: excess amounts of AZX were suspended in diethyl oxalate, pyridine, and 1,4-dioxane separately at room temperature with a constant stirring rate for one day. The suspension was filtered and dried over 24 h under vacuum at room temperature to obtain the corresponding solvates. The new solvates prepared by solvent-replacement method are named as form 6 (diethyl oxalate), form 8 (pyridine), and form 9 (1,4-dioxane), respectively. The single crystal of form 6, form 8, and form 9 were obtained by preparing AZX saturated solution of diethyl oxalate, pyridine, and 1,4-dioxane separately followed by adding appropriate amount of cyclohexane, after standing for one week at room temperature, single crystals were obtained.
2.10. Unit cell porosity Unit cell porosity is used to characterize the void space in a crystal structure, and is a fraction of the volume of voids over the total cell volume, as a percentage between 0% and 100% [37]. The formula of unit cell porosity is as follows:
Unit cell porosity ¼
Solvent accessible void volume Per unit cell volume
The volume of solvent-accessible voids in solvates and the porosity were calculated using PLATON software [38,39].
3. Results and discussion 3.1. Crystal structures of AZX solvates Eight isostructural solvates of AZX has been published by Yang's work [44], three of them are the same as this paper, but we obtained the single crystals of 1,4-dioxane channel solvate. At the same time, the other six new channel solvates obtained in this paper were found for the first time, the crystallographic data of AZX obtained solvates are summarized in Table 1. It is obvious that AZX solvates all belong to monoclinic system and P 21/n space group, possess the same formula units per cell (Z ¼ 4) and similar unit cell parameters. All of these properties indicated that they are isostructural and had similar crystal arrangement pattern. The AZX molecular crystal structure was shown in Fig. 2g. These solvates were stabilized by p,,,p interaction, CeH,,,p interaction, and weak hydrogen-bonding interactions such as CeH,,,O interaction and CeH,,,C interaction. At the same time, the weak hydrogen-bonding interactions exist between AZX molecules and solvent molecules. In all of the solvates, the AZX molecules formed a host framework through intermolecular interaction and the guest solvent molecules occupied the channels along [010] direction. The inclusion of various solvents does not affect the packing arrangement, just to fill the channels between the host frameworks. The strong hydrogen-bonding interactions in all solvates do not exist, these solvates were stabilized by p,,,p interaction, and other weak hydrogen-bonding interactions, which also provided a strong
Table 1 Crystallographic data of AZX solvates.
Formula Temperature (K) Crystal system Space group a (Å) b (Å) c (Å) a ( ) b ( ) g ( ) Cell volume(Å3) Z CCDC No. Measured reflections Independent reflections Rint R1 (I > 2s(I)) uR2
Form 2
Form 3
Form 5
Form 6
Form 8
Form 9
C22H17N3O5,C3H6O 173 Monoclinic P 21/n 12.5045 (2) 7.7104 (1) 24.4479 (4) 90 98.883 (1) 90 2328.86 (6) 4 1847671 32877 5335 0.035 0.041 0.1168
C22H17N3O5,C4H8O 206 Monoclinic P 21/n 12.5061 (13) 7.6948 (7) 24.627 (2) 90 99.092 (7) 90 2340.1 (4) 4 1847672 29972 5382 0.097 0.070 0.1971
C22H17N3O5,1/2C7H16 206 Monoclinic P 21/n 12.448 (7) 7.803 (4) 24.574 (14) 90 98.394 (12) 90 2361 (2) 4 1847673 16811 4392 0.05 0.059 0.1889
C22H17N3O5,1/2C6H10O4 173 Monoclinic P 21/n 12.376 (3) 7.865 (2) 24.257 (8) 90 98.726 (9) 90 2333.7 (12) 4 1847674 17172 5334 0.06 0.062 0.1813
C22H17N3O5,C5H5N 205 Monoclinic P 21/n 12.511 (2) 7.7321 (14) 25.106 (5) 90 101.045 (4) 90 2383.7 (7) 4 1847675 20596 5420 0.084 0.062 0.198
C22H17N3O5,C4H8O2 205 Monoclinic P 21/n 12.3947 (19) 8.1230 (14) 24.583 (4) 90 99.224 (4) 90 2443.1 (7) 4 1847676 17059 4529 0.068 0.077 0.255
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Fig. 2. Packing profiles of solvates of AZX (a. form 2; b. form 3; c. form 5; d. form 6; e. form 8; f. form 9). The solvents were denoted with spheres for clarity.
evidence for channel solvates. Related crystallographic stacking arrangement and the solvent molecules located in the channels of AZX with continuous channels are shown in Fig. 2. The solvents are loosely stacked in these solvates, which may due to the fact that the solvent does not fit tightly enough in the channel. The loose packing of AZX framework results in its low
density and make solvents easy to enter. The inclusion of solvent molecules in the crystal lattice leads to almost no volume distinctions. The calculated volume of solvent-accessible voids in solvates form 2, form 3, form 5, form 6, form 8, and form 9 are 504.3, 517.2, 529.8, 505.5, 547.2, and 577.9 Å3, respectively. Accounting for approximately 21.7%, 22.1%, 22.4%, 21.7%, 23.0%, and 23.7% of the
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Table 2 Related volume parameters and porosity of AZX solvates.
Form Form Form Form Form Form
2 3 5 6 8 9
Solvent-accessible void volume (Å3)
Per unit-cell volume (Å3)
Porosity
Vsolvent (Å3)
Vsolvent (Å3) in per unit cell
504.3 517.2 529.8 505.5 547.2 577.9
2328.9 2340.1 2361 2333.7 2383.7 2443.1
21.7% 22.1% 22.4% 21.7% 23.0% 23.7%
80.58 91.05 174.82 159.65 103.94 104.82
322.32 364.2 349.64 319.3 415.76 419.28
per unit-cell volume, respectively. Related volume of solventaccessible void, per unit-cell volume, and porosity were listed in Table 2. Molecular structures of all solvates were optimized by performing DFT calculations at the B3LYP/6-31G (d, p) using Gaussian 09. The molecular volume of all solvates were calculated using Gaussian 09, and the values are listed in Table 2. Considering that form 2, form 3, form 5, form 6, form 8, and form 9 are containing a certain number of solvent molecules in per unit cell, the corresponding single solvent volume multiplied by the number of corresponding solvent molecules in one unit cell were also listed in Table 2. Since the results of solvent volume in per unit cell is close to the corresponding solvent-accessible void volume, it is assumed that all solvents with a volume less than 174.82 Å3 can form similar channel solvates with AZX. To verify this assumption, a large number of solvents were selected, and the corresponding experiments are in progress.
3.2. Powder X-ray diffraction PXRD is a practical tool for the analysis and characterization of different solid forms. Each crystalline form has a unique characteristic PXRD pattern. Therefore, the PXRD pattern can be used for solid-state identification. Form 1 and other solvates were clearly distinguished by their unique PXRD patterns (Fig. 3), however,
different channel solvates have slight differences in PXRD patterns and this is because the unit cell parameters between different solvates are similar, so PXRD cannot effectively identify different channel solvates. Detailed data of the peaks in PXRD patterns were listed in Table S1-S10. All displayed peaks in measured patterns of the bulk powders match well with those simulated patterns generated from the corresponding single-crystal X-ray diffractometric data, which confirmed the formation of highly pure phases (Fig. S1).
3.3. Thermal analysis Thermal analysis is a branch of materials science where the properties of compounds are studied as they change with temperature. DSC and TG curves of AZX form 1 and other solvates were shown in Fig. 4. The DSC curve of form 1 showed one sharp endothermic peak at 118.13 C (Tonset ¼ 115.64 C; DH ¼ 63.80 J/g). Through the TG curve of form 1, the conclusion can be proposed that form 1 had no solvent in the molecule structure. For solvates form 2, form 5, form 7, and form 9, the DSC curves exhibited two distinct peaks and the first endothermic peak position is close to the boiling point of the corresponding solvent (75.44 C for form 2 (acetone, b.p. ¼ 56.53 C); 85.91 C for form 5 (n-heptane, b.p. ¼ 98.50 C); 102.23 C for form 7 (3-pentanone, b.p. ¼ 115.20 C); 73.28 C for form 9 (1,4-dioxane,
Fig. 3. PXRD patterns of AZX polymorph and solvates.
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Fig. 4. DSC and TG curves of AZX polymorph and solvates (a) form 1, (b) form 2, (c) form 3, (d) form 4, (e) form 5, (f) form 6, (g) form 7, (h) form 8, (i) form 9, and (j) form 10.
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b.p. ¼ 101.00 C)). The second endothermic peak is nearby the melting point of form 1 (110.92 C for form 2; 112.21 C for form 5; 120.24 C for form 7; 118.07 C for form 9). This phenomenon is due to the fact that during the heating process, the solvent molecule escaped and the crystal transform to form 1. PXRD patterns of the corresponding verification experiments were shown in Fig. S2. For solvates form 3, form 4, form 6, form 8, and form 10, the DSC curves only showed one obvious endothermic peak (93.37 C for form 3; 95.19 C for form 4; 94.36 C for form 6; 74.10 C for form 8; 122.23 C for form 10) and these are their corresponding melting point. Related melting data of AZX form 1 and other solvates were listed in Table 3. The stoichiometry of solvates were also determined by calculating the mass loss from TG analysis. The values of mass loss (w/w) of solvates form 2, form 5, form 8, and form 9 were 11.80%, 10.71%, 15.80%, and 5.95%, respectively. Consequently, the molar ratios of AZX and solvents were calculated to be 1:0.93 for form 2, 1:0.48 for form 5, 1:0.96 for form 8, and 1:0.97 for form 9, perfectly match with the crystallographic data. The values of mass loss (w/w) of solvate form 3 and form 6 were 7.04% and 11.51%, respectively. The molar ratios of AZX and solvent was calculated to be 1:0.42 for form 3 and 1:0.36 for form 6, this is quite different from the theoretical molar ratio of 1:1 and 1:0.5, respectively. This may be caused by the easy diffusion of the solvent molecules during the test. Host/guest ratio for form 7 is speculated to be 1:0.5, since the values of mass loss (w/w) of solvate form 7 was 10.41% and the molar ratios of AZX and solvent were calculated to be 1:0.54. In addition, the values of mass loss (w/w) of solvates form 4 and form 10 were 17.92% and 15.02%, respectively, the molar ratios of AZX and solvents were calculated to be 1:0.76 for form 4, 1:0.72 for form 10. The ratio of AZX/solvent may be 1:1 in these two forms.
3.4. Spectroscopic characterization IR spectra is one of the means of identifying and distinguishing the different polymorphs, such as molecular conformations, and hydrogen bonding interactions through probing the vibrational frequencies of atoms. The sensitivity of these techniques makes it possible to detect subtle changes in crystal structure and leads to their comprehensive application in solid-state studies, including confirming the results obtained from PXRD analysis. But the polymorph and solvates of AZX showed small differences in IR spectra so IR spectra cannot be used to identify different channel solvates (Fig. S3).
3.5. FESEM morphologies FESEM provides vital information about morphology and particle size for powdery pharmaceutical samples in micro scale. FESEM images of these forms were presented in Fig. 5. It can be recognized that form 1, form 7 and form 10 were all block-like, while form 2, form 6 and form 8 were all clusters of columnar. Meanwhile, form 3, form 4, form 5 and form 9 were short rod-like.
3.6. Hirshfeld surface investigation The contribution of different intermolecular interactions of AZX solvates form 2, form 3, form 5, form 6, form 8, and form 9 were compared by Hirshfeld surfaces. Every AZX form exhibited different Hirshfeld surfaces shape, which means there are different packing motif and intermolecular arrangement in their micro structure. The Hirshfeld surface and 2D fingerprint plots were presented in Fig. 6. In all of the intermolecular contact 2D fingerprint plots, the C,,,H close contacts were characterized as “wings” in upper left and lower right regions. There were four mainly interactions that had a contribution to the Hirshfeld surface: H,,,H intermolecular contacts, C,,,H intermolecular contacts, O,,,H intermolecular contacts, and N,,,H intermolecular contacts. In every solvate, H,,,H interactions accounted for the largest proportion, C,,,H or O,,,H interactions accounted for the second, and N,,,H interactions accounted for the smallest among the four intermolecular contacts (Fig. 7). The order of the difference of four mainly interaction contribution among different solvates were H,,,H interaction contribution differences > O,,,H interaction contribution differences > C,,,H interaction contribution differences > N,,,H interaction contribution differences. As shown in Fig. 7, the relative contribution of intermolecular interactions to the Hirshfeld surface was significantly different in six AZX solvates. It is worth noting that due to the presence of diethyl oxalate, the interaction ratio of O,,,H and O,,,N in form 6 was higher than that of other solvates and leading to the smallest proportion of N,,,H intermolecular contact. At the same time, other solvates containing O atom (form 2 (acetone), form 3 (tetrahydrofuran), and form 9 (1,4-dioxane) also have higher O,,,H interaction contact ratios. Another interesting phenomenon was that the interaction between C,,,N and N,,,N in form 8 (pyridine solvate) were much higher than other solvates and this is caused by the inclusion of pyridine molecule. Detailed various contact contributions to the Hirshfeld surface of different AZX solvates were listed in Table S11. 3.7. Physical stability The stability of AZX solvates were investigated by slurry experiment, high temperature (60 ± 2 C) experiment, high humidity (92.5% ± 5% RH, 25 C) experiment, and strong light (4500 ± 500 lx) experiment. The results showed that all solvates were easily removed and transformed to form 1. Specific experimental methods were detailed in supporting information and the corresponding PXRD patterns were shown in Fig. S4-S12. 4. Conclusions In conclusion, the crystallization of AZX from different solvents results in several solvates and part of them were characterized by SXRD with acetone, tetrahydrofuran, n-heptane, diethyl oxalate, pyridine, and 1,4-dioxane, respectively. These solvates are
Table 3 Melting data of AZX polymorph and solvates.
Tonset ( C) Tpeak ( C)
DHf (J/g)
Form 1
Form 2
Form 3
Form 4
Form 5
Form 6
Form 7
Form 8
Form 9
Form 10
115.64 / 118.13 / 63.80 /
69.19; 102.36 75.44; 110.92 70.13; 12.77
91.28 / 93.37 / 76.19 /
91.55 / 95.19 / 78.51 /
78.67; 105.84 85.91; 112.21 81.57; 10.57
90.03 / 94.36 / 71.76 /
99.43; 115.65 102.23; 120.24 2.84; 52.89
68.01 / 74.10 / 56.99; /
64.54; 111.16 73.28; 118.07 6.68; 54.94
115.72 / 122.23 / 62.53 /
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Fig. 5. SEM microphotographs of AZX (a) form 1, (b) form 2, (c) form 3, (d) form 4, (e) form 5, (f) form 6, (g) form 7, (h) form 8, (i) form 9, and (j) form 10.
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Fig. 6. Hirshfeld surface and 2D fingerprint plots for the different intermolecular interaction of AZX solvates (a) form 2, (b) form 3, (c) form 5, (d) form 6, (e) form 8, and (f) form 9. Each row from left to right were Hirshfeld surface, all intermolecular contacts, H,,,H intermolecular contacts, C,,,H intermolecular contacts, O,,,H intermolecular contacts, and N,,,H intermolecular contacts.
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Fig. 7. The contribution of different intermolecular interaction to the Hirshfeld surface of AZX solvates.
isostructural with the same P21/n space group, similar unit cell parameters, and crystal packing in the respective unit cell. AZX molecules form a host framework and the solvent molecules are residing in the channels along [010] direction. The calculated volumes of solvent-accessible voids and unit cell porosities in these solvates are nearly the same and the crystal packing does not depend on the nature of the solvent molecules. Only some of these characterization methods could clearly distinguish different channel solvates. Hirshfeld surface analysis and 2D fingerprint plots were used for analysis the mechanism of the formation of isostructural solvates. Solid-state stability of these solvates were also investigated, the results indicated that their stability is not good and could transformed to form 1 under experimental conditions. It is the first time to report the channel solvates of pesticides. The research results can provide a reference for further study the channel solvates of pesticides. Furthermore, the solvents used in solvated form 2 (acetone), form 5 (n-heptane), form 6 (diethyl oxalate), and form 8 (pyridine) are allowed to be used in the rule of the United States Environmental Protection Agency, Office of Pesticide Programs, EPA-HQ-OPP-2014-0558. Thus, these solvates will probably have great potential to become the alternative fungicides in agricultural applications. The fungicidal bioactivities and the application research work is in progress.
Notes The authors declare no competing financial interest.
Acknowledgement This work was supported by National Key Research and Development Program of China (No. 2017YFD0200505), National Natural Science Foundation of China (No. 21706064), and Fundamental Research Funds for the Central Universities (No. 222201718004, No. 222201814049).
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.molstruc.2019.04.011.
References o s, First crystal [1] V. Zvoní cek, E. Skorepov a, M. Dusek, M. Babor, P. Zv atora, M. So structures of pharmaceutical ibrutinib: systematic solvate screening and characterization, Cryst. Growth Des. 17 (6) (2017). [2] J. Lee, D. Kim, J. Park, E.K. Kim, M.S. Lah, A. Kim, Pseudopolymorphs of LB30870, a direct thrombin inhibitor: one dimensional solvent channel structures explain reversible hydration/dehydration, Cryst. Growth Des. 18 (1) (2018). [3] M. Muresan-Pop, D. Braga, M.M. Pop, G. Borodi, I. Kacso, L. Maini, Crystal structure and physicochemical characterization of ambazone monohydrate, anhydrous, and acetate salt solvate, J. Pharm. Sci. 103 (11) (2014) 3594e3601. [4] M.P. Lipert, N. Rodriguez-Hornedo, Cocrystal transition points: role of cocrystal solubility, drug solubility, and solubilizing agents, Mol. Pharm. 12 (10) (2015) 3535e3546. [5] Z. Wang, J. Wang, A. Leping Dang, M. Zhang, Crystal structures and the solvent-mediated transformation of erythromycin acetone solvate to dihydrate during batch crystallization, Ind. Eng. Chem. Res. 46 (6) (2007) 1851e1858. [6] H. Furuta, S. Mori, Y. Yoshihashi, E. Yonemochi, H. Uekusa, K. Sugano, K. Terada, Physicochemical and crystal structure analysis of pranlukast pseudo-polymorphs II: solvate and cocrystal, J. Pharm. Biomed. Anal. 111 (2015) 44e50. [7] T. Mandai, K. Yoshida, S. Tsuzuki, R. Nozawa, H. Masu, K. Ueno, K. Dokko, M. Watanabe, Effect of ionic size on solvate stability of glyme-based solvate ionic liquids, J. Phys. Chem. B 119 (4) (2015) 1523e1534. [8] W. Xu, N. Gong, S. Yang, N. Zhang, L. He, G. Du, Y. Lu, Isostructurality among solvates of cabazitaxel: X-ray structures and new solvates preparation, J. Pharm. Sci. 104 (4) (2015) 1256e1262. [9] X. Zhang, L. Zhou, C. Wang, Y. Li, Y. Wu, M. Zhang, Q. Yin, Insight into the role of hydrogen bonding playing in the molecular self-assembly process of sulfamethazine solvates, Cryst. Growth Des. 17 (12) (2017). [10] K.J. Chavez, M. Guevara, R.W. Rousseau, Characterization of solvates formed by sodium naproxen and an homologous series of alcohols, Cryst. Growth Des. 10 (8) (2010) 3372e3377. [11] X.H. Tang, Y. Li, J. Liu, Y. Zhang, X.Z. Wang, PAT aided identification of operational spaces leading to tailored crystal size distributions in azithromycin crystallization via coordinated cooling and solution mediated phase transition, Org. Process Res. Dev. 21 (12) (2017) 1963e1971. [12] L. Yang, H. Hao, L. Zhou, C. Wei, B. Hou, C. Xie, Q. Yin, Crystal structures and solvent-mediated transformation of the enantiotropic polymorphs of 2,3,5Trimethyl-1,4-diacetoxybenzene, Ind. Eng. Chem. Res. 52 (49) (2013) 17667e17675. [13] C.E. Marjo, M. Bhadbhade, J.M. Hook, A.M. Rich, Polymorphism and a metastable solvate of duloxetine hydrochloride, Mol. Pharm. 8 (6) (2011) 2454e2464. ski, A. Matwijczuk, A. Niewiadomy, M. Gagos, [14] A.A. Hoser, D.M. Kamin K. Wo zniak, On polymorphism of 2-(4-fluorophenylamino)-5-(2,4dihydroxybenzeno)-1,3,4-thiadiazole (FABT) DMSO solvates, CrystEngComm 15 (10) (2013) 1978. [15] N. Gong, G. Zhang, G. Jin, G. Du, Y. Lu, Polymorphs and versatile solvates of 7hydroxyisoflavone, J. Pharm. Sci. 105 (4) (2016) 1387e1397. [16] P. Chakravarty, R. Suryanarayanan, Characterization and structure analysis of thiamine hydrochloride methanol solvate, Cryst. Growth Des. 10 (10) (2010)
50
D. Du et al. / Journal of Molecular Structure 1189 (2019) 40e50
4414e4420. [17] K. Nakano, K. Sada, M. Miyata, Novel additive effect of inclusion crystals on polymorphsecholic acid crystals having different hydrogen-bonded networks with the same organic guest, Chem. Commun. 8 (8) (1996) 989e990. [18] C. Lentza-Rizos, E.J. Avramides, K. Kokkinaki, Residues of azoxystrobin from grapes to raisins, J. Agric. Food Chem. 54 (1) (2006) 138e141. [19] W.F. Becker, J.G. Von, T. Anke, W. Steglich, Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors of the bc1 segment of the respiratory chain with an E-beta-methoxyacrylate system as common structural element, FEBS Lett. 132 (2) (1981) 329e333. [20] F. Hou, P.P. Teng, F. Liu, W.Z. Wang, Tebuconazole and azoxystrobin residual behaviors and distribution of field and cooked peanut, J. Agric. Food Chem. 65 (22) (2017) 4484e4492. [21] F.P. Wong, W.F. Wilcox, Comparative physical modes of action of azoxystrobin, mancozeb, and metalaxyl against Plasmopara viticola (grapevine downy mildew), Plant Dis. 85 (6) (2001) 649e656. [22] C.E. Windels, J.R. Brantner, Early-season application of azoxystrobin to sugarbeet for control of Rhizoctonia solani AG 4 and AG 2-2, J. Sugar Beet Res. 42 (1) (2005) 1e18. [23] A. Peres, P. Signoret, B. Poinso, P. Davet, [Health Conditions of Soybean Seed Production [Phomopsis Phaseolorum Sojae, Ascochyta sp., Rhizoctonia solani, Pythium, Fusarium, Macrophomina Phaseoli]], 1990. French. [24] R.K. Ghosh, N. Singh, Effect of organic manure on sorption and degradation of azoxystrobin in soil, J. Agric. Food Chem. 57 (2) (2009) 632e636. [25] S. Sundravadana, D. Alice, Azoxystrobin Activity on Rhizoctonia solani and its Efficacy against Rice Sheath Blight, 2007. [26] Inna Faktorovitch, Z. Sharona, F. Inna, Sharona ZAMIR, in: POLYMORPHS OF 3(E)-2-{2-[6-(2-CYANOPHENOXY) PYRIMIDIN-4-YLOXY] PHENYL}-3METHOXYACRYLATE, WO, 2009. n, D.S. Yufit, [27] R.K. Harris, P. Hodgkinson, T. Larsson, A. Muruganantham, I. Yme V. Zorin, Characterization of polymorphs and solvates of terbutaline sulfate, Cryst. Growth Des. 8 (1) (2008) 80e90. [28] I.L. Fedushkin, V.I. Nevodchikov, M.N. Bochkarev, S. Dechert, H. Schumann, Reduction of 2,5-di-tert-butylcyclopentadienone and pyridine with thulium diiodide. Structures of the complexes TmI2(THF)2[h5-But2C5H2O]TmI2(THF) 3 and [TmI2(C5H5N)4]2(m2-N2C10H10), Russ. Chem. Bull. 52 (1) (2003) 154e159. [29] C. Beghidja, G. Rogez, J. Kortus, M. Wesolek, R. Welter, Very strong ferromagnetic interaction in a new binuclear mu-methoxo-bridged Mn(III) complex: synthesis, crystal structure, magnetic properties, and DFT calculations, J. Am. Chem. Soc. 128 (10) (2006) 3140e3141. [30] D.R. Powell, Review ofX-ray crystallographyx-ray crystallography, 4, in: Gregory S. Girolami (Ed.), Journal of Chemical Education 2016, vol.
[31]
[32] [33]
[34]
[35]
[36]
[37]
[38]
[39] [40] [41] [42]
[43]
[44]
93University Science Books, Mill Valley, California, 2015, pp. 591e592, 300 pp. ISBN 9781891389771 (hardcover). $88. R.T. Macaluso, B. Wells, C. Wangeline, K. Cochran, B.K. Greve, Powder X-ray diffraction and electron microscopy studies of polycrystalline Au2PrIn, Polyhedron 114 (2016) 313e316. M. Brown, Determination of purity by differential scanning calorimetry (DSC), J Chem. Educ. 56 (5) (1979) 310. Z. Yao, X. Ma, Z. Wang, L. Chen, Characteristics of co-combustion and kinetic study on hydrochar with oil shale: a thermogravimetric analysis, Appl. Therm. Eng. 110 (2017) 1420e1427. J. Ji, Y. Ge, W. Balsam, J.E. Damuth, J. Chen, Rapid identification of dolomite using a Fourier Transform Infrared Spectrophotometer (FTIR): a fast method for identifying Heinrich events in IODP Site U1308, Mar. Geol. 258 (1) (2009) 60e68. M. Dieterich, B. Kutchko, A. Goodman, Characterization of Marcellus Shale and Huntersville Chert before and after exposure to hydraulic fracturing fluid via feature relocation using field-emission scanning electron microscopy, Fuel 182 (2016) 227e235. X. Wei, G. Ningbo, Y. Shiying, Z. Na, H. Lan, D. Guanhua, L. Yang, Isostructurality among solvates of cabazitaxel: X-ray structures and new solvates preparation, J. Pharm. Sci. 104 (4) (2015) 1256e1262. K.K. Mohanty, Porous media: fluid transport and pore structure, in: F.A.L. Dullien (Ed.), Aiche Journal 1992, vol. 38, Academic Press, 1992, p. 574, 8):1303-1304. A.L. Spek, PLATON SQUEEZE: a tool for the calculation of the disordered solvent contribution to the calculated structure factors, Acta Crystallogr. C71 (1) (2015) 9e18. A.L. Spek, Single-crystal structure validation with the program PLATON, J. Appl. Crystallogr. 36 (1) (2010) 7e13. A.D. Martin, K.J. Hartlieb, A.N. Sobolev, C.L. Raston, Hirshfeld surface analysis of substituted phenols, Cryst. Growth Des. 10 (12) (2010) 5302e5306. M.A. Spackman, D. Jayatilaka, Hirshfeld surface analysis, CrystEngComm 11 (1) (2009) 19e32. D.J. Carter, P. Raiteri, K.R. Barnard, R. Gielink, M. Mocerino, B.W. Skelton, J.G. Vaughan, M.I. Ogden, A.L. Rohl, Difference Hirshfeld fingerprint plots: a tool for studying polymorphs, CrystEngComm 19 (16) (2017) 2207e2215. J.J. Mckinnon, F.P.A. Fabbiani, M.A. Spackman, Comparison of polymorphic molecular crystal structures through Hirshfeld surface analysis, Cryst. Growth Des. 7 (4) (2007) 755e769. H. Yang, Y. Yang, L. Jia, W. Tang, S. Xu, S. Du, M. Li, J. Gong, The phase transformation and formation mechanism of isostructural solvates: a case study of azoxystrobin, Cryst. Growth Des. 19 (3) (2019) 1550e1558.
Contents lists available at ScienceDirect
Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc
Preparation and characterization of several azoxystrobin channel solvates Dan Du a, Zhi-Ping Shi a, Guo-Bin Ren b, Ming-Hui Qi b, *, Zhong Li a, Xiao-Yong Xu a, ** a
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, No. 130 Meilong Rd., Shanghai, 200237, PR China b Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, No. 130 Meilong Rd., Shanghai, 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 24 January 2019 Received in revised form 13 March 2019 Accepted 1 April 2019 Available online 4 April 2019
Azoxystrobin is an important strobilurins fungicide. Nine channel solvates of azoxystrobin were obtained for the first time and six of them could be crystallized in single crystals. The crystallographic data, unit cell porosity, Hirshfeld surface, and fingerprint plot were analyzed. These solvates are isostructural, azoxystrobin forming a host framework through intermolecular interaction and the guest solvent molecules located in channels. These solvates were stabilized by p,,,p interaction, CeH,,,p interaction, and weak hydrogen-bonding interactions such as CeH,,,O interaction and CeH,,,C interaction. All solvates were characterized by PXRD, DSC, TG, FTIR, and FESEM, the stability of them were also examined. Moreover, because of the similarity of the channel solvates, solvent-replacement method could be used to prepare other solvates. © 2019 Elsevier B.V. All rights reserved.
Keywords: Azoxystrobin Channel solvates Isostructurality Hirshfeld surface Pseudopolymorph Solvent-replacement method Porosity
1. Introduction The search for new solid forms of chemical compound for many academic researchers has become more and more important in nowadays [1]. New solid forms include polymorphs, solvates [2], salts [3], cocrystals [4], or their combinations. Different solid forms may bring various properties, such as higher melting point [5], higher solubility [6], better chemical or physical stability [7], and even better bioavailability or clinical efficacy [8,9]. Another benefit of solid forms research is that solid form with desired properties could be prepared during scale-up production process, process time could be significantly shorten, and even product purity was improved [10]. The study of polymorphs may be the first step for later research, and can solve many problems such as poor stability and nonreproducibility in formulation producing. Due to the quite small energy differences between polymorphs, they often occur solid
* Corresponding author. ** Corresponding author. E-mail addresses: [email protected] (M.-H. Qi), [email protected] (X.-Y. Xu). https://doi.org/10.1016/j.molstruc.2019.04.011 0022-2860/© 2019 Elsevier B.V. All rights reserved.
state transformations [11] or concomitantly crystallizing, finally form polymorph mixtures [12]. Solvates have better properties than polymorphs in many aspects [13] mainly manifested in improve the solubility or stability of compounds. In addition, the digestion performance of solvates are often enhanced, because solvates generally have higher dissolution rate [14], which leads to higher supersaturation compared to polymorphs [15]. Furthermore, solvates can also be used for the preparation of various polymorphs through desolvation or for the preparation of some drugs that is difficult to obtain the target polymorphs by traditional crystallization method [16]. Thus, in current crystal engineering field, the research of solvates is very important. In some cases, the solvent molecules act as space fillers in some solvates and this type of solvates are classified as inclusion phases, as well as channel solvates [17]. This means that the solvent molecules are entrapped in the crystal lattice and had no significantly interaction with the host molecules. Azoxystrobin (AZX), methyl (E)-2-[2-[6-(2-cyanophenoxy)pirimidin-4-yloxy] phenyl]-3-methoxyacrylate (Fig. 1) is a broad spectrum, systemic, and soil-applied fungicide belonging to the bmethoxyacrylates group [18]. AZX is the first registered strobilurin analogues, which possess new mode of action and leading market
D. Du et al. / Journal of Molecular Structure 1189 (2019) 40e50
Fig. 1. Molecular structure of AZX.
share in the world [19e21]. It controls both foliar and soil-borne diseases such as powdery mildew rust [22], bacterial blight, net blotch [23], black shank, downy mildew, and rice blast [24,25]. Only two polymorphs (form 1 and form 2) and one amorphous form of AZX [26] were reported and no solvates of AZX had been reported in the Cambridge Structural Database. Form 1 mentioned in the patent is the most stable form and used as commercial product. In this paper, we prepared a series of AZX solvates. They were characterized by X-ray diffraction (PXRD and SXRD) [27], thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform-infrared spectrum (FTIR), and field emission scanning electron microscopy (FESEM). The results showed that the solvates obtained were all isostructural with AZX form 1 and the solvent-replacement method could be applied to preparing AZX solvates. X-ray crystallography, porosity, Hirshfeld surface, and fingerprint plot analysis were used to characterize the channel solvates. Solid-state stability experiments indicated that the stability of solvates are not good. They could transform to form 1 under certain conditions. 2. Experimental section 2.1. Materials and methods Azoxystrobin form 1 (purity > 98%) was purchased from BioChemPartner Company, Ltd. (Zhangjiang Road, Pudong New Area, Shanghai, China). Organic solvents with analytical or chromatographic grade (purity > 99%) were purchased from Sinopharm Chemical Reagent Co., Ltd. (China) and used without further purification. Water used in the experiments was purified from a deionizer with mixed bed purification system (Merck Millipore D 24 UV, Germany). 2.2. Preparation of azoxystrobin solvates Azoxystrobin form 2 (acetone solvate), form 3 (tetrahydrofuran solvate), and form 4 (butyl acetate solvate). Form 2, form 3, and form 4 was prepared by the evaporation of saturated solution of AZX in acetone, tetrahydrofuran, and butyl acetate separately at room temperature. After two weeks the solid powders were filtered and dried over 24 h under vacuum at room temperature. The single crystal of form 2 and form 3 can be obtained by slowing down the evaporation rate of the corresponding solution, the single crystal of form 4 was not obtained. Azoxystrobin form 5 (n-heptane solvate). 50 mg AZX was dissolved in 2-butanone, and then proper amount of n-heptane was added to the above solution, large amount of white solid precipitated, the solid powders were filtered and dried over 24 h under vacuum at room temperature. The bulk single crystal of form 5 was
41
prepared by add small amount of n-heptane to the saturated 2butanone solution of AZX and seal it to stand for one month. Azoxystrobin form 7 (3-pentanone solvate). Form 7 was prepared from dissolving 50 mg AZX in 1 mL 3-pentanone followed by adding 5 ml n-hexane, large amount of white solid precipitated, the solid powders were filtered and dried over 24 h under vacuum at room temperature. The single crystal of form 7 was not obtained. Azoxystrobin form 10 (1,2-dichloroethan solvate). Form 10 was prepared from dissolving 50 mg AZX in 0.2 ml 1,2-dichloroethan, then adding this solution to 1 ml cyclohexane, large amount of white solid precipitated immediately, then the solid powders were filtered and dried over 24 h under vacuum at room temperature. The single crystal of form 10 was not obtained during the preparation. 2.3. X-ray crystallography X-ray diffraction data were collected on Bruker SMART-APEX DUO diffractometer (USA) equipped with a graphite monochromator and Mo-Ka fine-focus sealed tube (l ¼ 0.71073 Å). Data processing was performed using Bruker SAINT Software. Intensities were corrected for absorption using SADABS [28], and the structure was refined using SHELXL-97 [29]. All non-hydrogen atoms were refined anisotropically [30]. Hydrogen atoms on heteroatoms were located from different electron density maps and all CeH hydrogens were fixed geometrically. Hydrogen bond geometries were determined in Platon. X-Seed was used to prepare packing diagrams. Related crystallographic data have been deposited in the Cambridge Crystallographic Data Centre (CCDC Nos. 18476711847676). 2.4. Powder X-ray diffraction (PXRD) PXRD patterns were obtained using a Rigaku Ultima IV X-ray diffractometer (Cu-Ka radiation) [31]. The voltage and current of the generator were set to 40 kV and 40 mA, respectively. Data between the 2q angular ranges 5 e45 were collected at a scan rate of 20 /min at ambient temperature. The data were integrated with RINT Rapid and the peaks were analyzed with Jade 6.0 from Rigaku. 2.5. Differential scanning calorimetry (DSC) Differential Scanning Calorimetry (DSC) experiments were performed on a TA DSC Q2000 instrument [32] under a nitrogen gas flow of 50 mL/min. The samples weighing 3e5 mg were placed in crimped and sealed aluminium sample pans heating from 30 to 150 C at a heating rate of 10 C/min. The instrument was calibrated against with the melting properties of indium according to standard procedure. Each sample was analyzed in triplicate with RSD <2%. 2.6. Thermogravimetric (TG) analysis Thermogravimetric properties of the solvates of AZX were obtained using a TA TGA Q500 with platinum pans at a heating rate of 10 C/min under a nitrogen gas flow [33]. The instrument was calibrated with mass and temperature according to standard procedure. Each sample was analyzed in triplicate with RSD <2%. 2.7. Vibrational spectroscopy Fourier transform-infrared (FTIR) spectra were collected with a Nicolet-Magna FT-IR 750 spectrometer in the range from 4000 to 500 cm1 with a resolution of 4 cm1 under ambient conditions [34].
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2.8. Field emission scanning electron microscopy (FESEM)
2.11. Hirshfeld surface analysis
The shapes and morphologies of the crystals were examined on a Carl Zeiss model Merlin Compact 6027 FESEM (Germany) with a beam voltage of 3.0 kV [35]. The sample was spread on a carboncoated copper grid prior to FESEM imaging. In order to enhance the conductivity of the sample, an ultrathin layer of gold was coated on the sample.
The Hirshfeld surface analysis used Crystal Explorer software to identify a type and region of intermolecular interactions [40]. For a given crystal structure, all of the Hirshfeld surfaces and fingerprint plots were unique [41,42]. The fingerprint plots quantitatively summarize the nature and type of intermolecular contacts in the crystal. Molecular Hirshfeld surface in a crystal structure was constructed based on the electron distribution. For each point on that isosurface, two distances were defined: de, the distance from the Hirshfeld surface to the nearest nucleus outside the surface, and di, the corresponding distance to the nearest nucleus inside the surface [43]. The normalized contact distance (dnorm) based on de, di, and rvdw (the van der Waals [vdw] radius of the appropriate atom internal or external to the surface) [15].
2.9. Solvent-replacement method According to the single-crystal structure analysis of solvates form 2, form 3, and form 5, AZX was considered to possess the ability to form a frame-work with solvent molecules residing in channels, which suggests that a variety of solvent molecules could be accommodated. Thus, solvent-replacement method [36] was established to obtain new solvates of AZX. The operating steps of this method are as follows: excess amounts of AZX were suspended in diethyl oxalate, pyridine, and 1,4-dioxane separately at room temperature with a constant stirring rate for one day. The suspension was filtered and dried over 24 h under vacuum at room temperature to obtain the corresponding solvates. The new solvates prepared by solvent-replacement method are named as form 6 (diethyl oxalate), form 8 (pyridine), and form 9 (1,4-dioxane), respectively. The single crystal of form 6, form 8, and form 9 were obtained by preparing AZX saturated solution of diethyl oxalate, pyridine, and 1,4-dioxane separately followed by adding appropriate amount of cyclohexane, after standing for one week at room temperature, single crystals were obtained.
2.10. Unit cell porosity Unit cell porosity is used to characterize the void space in a crystal structure, and is a fraction of the volume of voids over the total cell volume, as a percentage between 0% and 100% [37]. The formula of unit cell porosity is as follows:
Unit cell porosity ¼
Solvent accessible void volume Per unit cell volume
The volume of solvent-accessible voids in solvates and the porosity were calculated using PLATON software [38,39].
3. Results and discussion 3.1. Crystal structures of AZX solvates Eight isostructural solvates of AZX has been published by Yang's work [44], three of them are the same as this paper, but we obtained the single crystals of 1,4-dioxane channel solvate. At the same time, the other six new channel solvates obtained in this paper were found for the first time, the crystallographic data of AZX obtained solvates are summarized in Table 1. It is obvious that AZX solvates all belong to monoclinic system and P 21/n space group, possess the same formula units per cell (Z ¼ 4) and similar unit cell parameters. All of these properties indicated that they are isostructural and had similar crystal arrangement pattern. The AZX molecular crystal structure was shown in Fig. 2g. These solvates were stabilized by p,,,p interaction, CeH,,,p interaction, and weak hydrogen-bonding interactions such as CeH,,,O interaction and CeH,,,C interaction. At the same time, the weak hydrogen-bonding interactions exist between AZX molecules and solvent molecules. In all of the solvates, the AZX molecules formed a host framework through intermolecular interaction and the guest solvent molecules occupied the channels along [010] direction. The inclusion of various solvents does not affect the packing arrangement, just to fill the channels between the host frameworks. The strong hydrogen-bonding interactions in all solvates do not exist, these solvates were stabilized by p,,,p interaction, and other weak hydrogen-bonding interactions, which also provided a strong
Table 1 Crystallographic data of AZX solvates.
Formula Temperature (K) Crystal system Space group a (Å) b (Å) c (Å) a ( ) b ( ) g ( ) Cell volume(Å3) Z CCDC No. Measured reflections Independent reflections Rint R1 (I > 2s(I)) uR2
Form 2
Form 3
Form 5
Form 6
Form 8
Form 9
C22H17N3O5,C3H6O 173 Monoclinic P 21/n 12.5045 (2) 7.7104 (1) 24.4479 (4) 90 98.883 (1) 90 2328.86 (6) 4 1847671 32877 5335 0.035 0.041 0.1168
C22H17N3O5,C4H8O 206 Monoclinic P 21/n 12.5061 (13) 7.6948 (7) 24.627 (2) 90 99.092 (7) 90 2340.1 (4) 4 1847672 29972 5382 0.097 0.070 0.1971
C22H17N3O5,1/2C7H16 206 Monoclinic P 21/n 12.448 (7) 7.803 (4) 24.574 (14) 90 98.394 (12) 90 2361 (2) 4 1847673 16811 4392 0.05 0.059 0.1889
C22H17N3O5,1/2C6H10O4 173 Monoclinic P 21/n 12.376 (3) 7.865 (2) 24.257 (8) 90 98.726 (9) 90 2333.7 (12) 4 1847674 17172 5334 0.06 0.062 0.1813
C22H17N3O5,C5H5N 205 Monoclinic P 21/n 12.511 (2) 7.7321 (14) 25.106 (5) 90 101.045 (4) 90 2383.7 (7) 4 1847675 20596 5420 0.084 0.062 0.198
C22H17N3O5,C4H8O2 205 Monoclinic P 21/n 12.3947 (19) 8.1230 (14) 24.583 (4) 90 99.224 (4) 90 2443.1 (7) 4 1847676 17059 4529 0.068 0.077 0.255
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43
Fig. 2. Packing profiles of solvates of AZX (a. form 2; b. form 3; c. form 5; d. form 6; e. form 8; f. form 9). The solvents were denoted with spheres for clarity.
evidence for channel solvates. Related crystallographic stacking arrangement and the solvent molecules located in the channels of AZX with continuous channels are shown in Fig. 2. The solvents are loosely stacked in these solvates, which may due to the fact that the solvent does not fit tightly enough in the channel. The loose packing of AZX framework results in its low
density and make solvents easy to enter. The inclusion of solvent molecules in the crystal lattice leads to almost no volume distinctions. The calculated volume of solvent-accessible voids in solvates form 2, form 3, form 5, form 6, form 8, and form 9 are 504.3, 517.2, 529.8, 505.5, 547.2, and 577.9 Å3, respectively. Accounting for approximately 21.7%, 22.1%, 22.4%, 21.7%, 23.0%, and 23.7% of the
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Table 2 Related volume parameters and porosity of AZX solvates.
Form Form Form Form Form Form
2 3 5 6 8 9
Solvent-accessible void volume (Å3)
Per unit-cell volume (Å3)
Porosity
Vsolvent (Å3)
Vsolvent (Å3) in per unit cell
504.3 517.2 529.8 505.5 547.2 577.9
2328.9 2340.1 2361 2333.7 2383.7 2443.1
21.7% 22.1% 22.4% 21.7% 23.0% 23.7%
80.58 91.05 174.82 159.65 103.94 104.82
322.32 364.2 349.64 319.3 415.76 419.28
per unit-cell volume, respectively. Related volume of solventaccessible void, per unit-cell volume, and porosity were listed in Table 2. Molecular structures of all solvates were optimized by performing DFT calculations at the B3LYP/6-31G (d, p) using Gaussian 09. The molecular volume of all solvates were calculated using Gaussian 09, and the values are listed in Table 2. Considering that form 2, form 3, form 5, form 6, form 8, and form 9 are containing a certain number of solvent molecules in per unit cell, the corresponding single solvent volume multiplied by the number of corresponding solvent molecules in one unit cell were also listed in Table 2. Since the results of solvent volume in per unit cell is close to the corresponding solvent-accessible void volume, it is assumed that all solvents with a volume less than 174.82 Å3 can form similar channel solvates with AZX. To verify this assumption, a large number of solvents were selected, and the corresponding experiments are in progress.
3.2. Powder X-ray diffraction PXRD is a practical tool for the analysis and characterization of different solid forms. Each crystalline form has a unique characteristic PXRD pattern. Therefore, the PXRD pattern can be used for solid-state identification. Form 1 and other solvates were clearly distinguished by their unique PXRD patterns (Fig. 3), however,
different channel solvates have slight differences in PXRD patterns and this is because the unit cell parameters between different solvates are similar, so PXRD cannot effectively identify different channel solvates. Detailed data of the peaks in PXRD patterns were listed in Table S1-S10. All displayed peaks in measured patterns of the bulk powders match well with those simulated patterns generated from the corresponding single-crystal X-ray diffractometric data, which confirmed the formation of highly pure phases (Fig. S1).
3.3. Thermal analysis Thermal analysis is a branch of materials science where the properties of compounds are studied as they change with temperature. DSC and TG curves of AZX form 1 and other solvates were shown in Fig. 4. The DSC curve of form 1 showed one sharp endothermic peak at 118.13 C (Tonset ¼ 115.64 C; DH ¼ 63.80 J/g). Through the TG curve of form 1, the conclusion can be proposed that form 1 had no solvent in the molecule structure. For solvates form 2, form 5, form 7, and form 9, the DSC curves exhibited two distinct peaks and the first endothermic peak position is close to the boiling point of the corresponding solvent (75.44 C for form 2 (acetone, b.p. ¼ 56.53 C); 85.91 C for form 5 (n-heptane, b.p. ¼ 98.50 C); 102.23 C for form 7 (3-pentanone, b.p. ¼ 115.20 C); 73.28 C for form 9 (1,4-dioxane,
Fig. 3. PXRD patterns of AZX polymorph and solvates.
D. Du et al. / Journal of Molecular Structure 1189 (2019) 40e50
45
Fig. 4. DSC and TG curves of AZX polymorph and solvates (a) form 1, (b) form 2, (c) form 3, (d) form 4, (e) form 5, (f) form 6, (g) form 7, (h) form 8, (i) form 9, and (j) form 10.
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b.p. ¼ 101.00 C)). The second endothermic peak is nearby the melting point of form 1 (110.92 C for form 2; 112.21 C for form 5; 120.24 C for form 7; 118.07 C for form 9). This phenomenon is due to the fact that during the heating process, the solvent molecule escaped and the crystal transform to form 1. PXRD patterns of the corresponding verification experiments were shown in Fig. S2. For solvates form 3, form 4, form 6, form 8, and form 10, the DSC curves only showed one obvious endothermic peak (93.37 C for form 3; 95.19 C for form 4; 94.36 C for form 6; 74.10 C for form 8; 122.23 C for form 10) and these are their corresponding melting point. Related melting data of AZX form 1 and other solvates were listed in Table 3. The stoichiometry of solvates were also determined by calculating the mass loss from TG analysis. The values of mass loss (w/w) of solvates form 2, form 5, form 8, and form 9 were 11.80%, 10.71%, 15.80%, and 5.95%, respectively. Consequently, the molar ratios of AZX and solvents were calculated to be 1:0.93 for form 2, 1:0.48 for form 5, 1:0.96 for form 8, and 1:0.97 for form 9, perfectly match with the crystallographic data. The values of mass loss (w/w) of solvate form 3 and form 6 were 7.04% and 11.51%, respectively. The molar ratios of AZX and solvent was calculated to be 1:0.42 for form 3 and 1:0.36 for form 6, this is quite different from the theoretical molar ratio of 1:1 and 1:0.5, respectively. This may be caused by the easy diffusion of the solvent molecules during the test. Host/guest ratio for form 7 is speculated to be 1:0.5, since the values of mass loss (w/w) of solvate form 7 was 10.41% and the molar ratios of AZX and solvent were calculated to be 1:0.54. In addition, the values of mass loss (w/w) of solvates form 4 and form 10 were 17.92% and 15.02%, respectively, the molar ratios of AZX and solvents were calculated to be 1:0.76 for form 4, 1:0.72 for form 10. The ratio of AZX/solvent may be 1:1 in these two forms.
3.4. Spectroscopic characterization IR spectra is one of the means of identifying and distinguishing the different polymorphs, such as molecular conformations, and hydrogen bonding interactions through probing the vibrational frequencies of atoms. The sensitivity of these techniques makes it possible to detect subtle changes in crystal structure and leads to their comprehensive application in solid-state studies, including confirming the results obtained from PXRD analysis. But the polymorph and solvates of AZX showed small differences in IR spectra so IR spectra cannot be used to identify different channel solvates (Fig. S3).
3.5. FESEM morphologies FESEM provides vital information about morphology and particle size for powdery pharmaceutical samples in micro scale. FESEM images of these forms were presented in Fig. 5. It can be recognized that form 1, form 7 and form 10 were all block-like, while form 2, form 6 and form 8 were all clusters of columnar. Meanwhile, form 3, form 4, form 5 and form 9 were short rod-like.
3.6. Hirshfeld surface investigation The contribution of different intermolecular interactions of AZX solvates form 2, form 3, form 5, form 6, form 8, and form 9 were compared by Hirshfeld surfaces. Every AZX form exhibited different Hirshfeld surfaces shape, which means there are different packing motif and intermolecular arrangement in their micro structure. The Hirshfeld surface and 2D fingerprint plots were presented in Fig. 6. In all of the intermolecular contact 2D fingerprint plots, the C,,,H close contacts were characterized as “wings” in upper left and lower right regions. There were four mainly interactions that had a contribution to the Hirshfeld surface: H,,,H intermolecular contacts, C,,,H intermolecular contacts, O,,,H intermolecular contacts, and N,,,H intermolecular contacts. In every solvate, H,,,H interactions accounted for the largest proportion, C,,,H or O,,,H interactions accounted for the second, and N,,,H interactions accounted for the smallest among the four intermolecular contacts (Fig. 7). The order of the difference of four mainly interaction contribution among different solvates were H,,,H interaction contribution differences > O,,,H interaction contribution differences > C,,,H interaction contribution differences > N,,,H interaction contribution differences. As shown in Fig. 7, the relative contribution of intermolecular interactions to the Hirshfeld surface was significantly different in six AZX solvates. It is worth noting that due to the presence of diethyl oxalate, the interaction ratio of O,,,H and O,,,N in form 6 was higher than that of other solvates and leading to the smallest proportion of N,,,H intermolecular contact. At the same time, other solvates containing O atom (form 2 (acetone), form 3 (tetrahydrofuran), and form 9 (1,4-dioxane) also have higher O,,,H interaction contact ratios. Another interesting phenomenon was that the interaction between C,,,N and N,,,N in form 8 (pyridine solvate) were much higher than other solvates and this is caused by the inclusion of pyridine molecule. Detailed various contact contributions to the Hirshfeld surface of different AZX solvates were listed in Table S11. 3.7. Physical stability The stability of AZX solvates were investigated by slurry experiment, high temperature (60 ± 2 C) experiment, high humidity (92.5% ± 5% RH, 25 C) experiment, and strong light (4500 ± 500 lx) experiment. The results showed that all solvates were easily removed and transformed to form 1. Specific experimental methods were detailed in supporting information and the corresponding PXRD patterns were shown in Fig. S4-S12. 4. Conclusions In conclusion, the crystallization of AZX from different solvents results in several solvates and part of them were characterized by SXRD with acetone, tetrahydrofuran, n-heptane, diethyl oxalate, pyridine, and 1,4-dioxane, respectively. These solvates are
Table 3 Melting data of AZX polymorph and solvates.
Tonset ( C) Tpeak ( C)
DHf (J/g)
Form 1
Form 2
Form 3
Form 4
Form 5
Form 6
Form 7
Form 8
Form 9
Form 10
115.64 / 118.13 / 63.80 /
69.19; 102.36 75.44; 110.92 70.13; 12.77
91.28 / 93.37 / 76.19 /
91.55 / 95.19 / 78.51 /
78.67; 105.84 85.91; 112.21 81.57; 10.57
90.03 / 94.36 / 71.76 /
99.43; 115.65 102.23; 120.24 2.84; 52.89
68.01 / 74.10 / 56.99; /
64.54; 111.16 73.28; 118.07 6.68; 54.94
115.72 / 122.23 / 62.53 /
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Fig. 5. SEM microphotographs of AZX (a) form 1, (b) form 2, (c) form 3, (d) form 4, (e) form 5, (f) form 6, (g) form 7, (h) form 8, (i) form 9, and (j) form 10.
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Fig. 6. Hirshfeld surface and 2D fingerprint plots for the different intermolecular interaction of AZX solvates (a) form 2, (b) form 3, (c) form 5, (d) form 6, (e) form 8, and (f) form 9. Each row from left to right were Hirshfeld surface, all intermolecular contacts, H,,,H intermolecular contacts, C,,,H intermolecular contacts, O,,,H intermolecular contacts, and N,,,H intermolecular contacts.
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Fig. 7. The contribution of different intermolecular interaction to the Hirshfeld surface of AZX solvates.
isostructural with the same P21/n space group, similar unit cell parameters, and crystal packing in the respective unit cell. AZX molecules form a host framework and the solvent molecules are residing in the channels along [010] direction. The calculated volumes of solvent-accessible voids and unit cell porosities in these solvates are nearly the same and the crystal packing does not depend on the nature of the solvent molecules. Only some of these characterization methods could clearly distinguish different channel solvates. Hirshfeld surface analysis and 2D fingerprint plots were used for analysis the mechanism of the formation of isostructural solvates. Solid-state stability of these solvates were also investigated, the results indicated that their stability is not good and could transformed to form 1 under experimental conditions. It is the first time to report the channel solvates of pesticides. The research results can provide a reference for further study the channel solvates of pesticides. Furthermore, the solvents used in solvated form 2 (acetone), form 5 (n-heptane), form 6 (diethyl oxalate), and form 8 (pyridine) are allowed to be used in the rule of the United States Environmental Protection Agency, Office of Pesticide Programs, EPA-HQ-OPP-2014-0558. Thus, these solvates will probably have great potential to become the alternative fungicides in agricultural applications. The fungicidal bioactivities and the application research work is in progress.
Notes The authors declare no competing financial interest.
Acknowledgement This work was supported by National Key Research and Development Program of China (No. 2017YFD0200505), National Natural Science Foundation of China (No. 21706064), and Fundamental Research Funds for the Central Universities (No. 222201718004, No. 222201814049).
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.molstruc.2019.04.011.
References o s, First crystal [1] V. Zvoní cek, E. Skorepov a, M. Dusek, M. Babor, P. Zv atora, M. So structures of pharmaceutical ibrutinib: systematic solvate screening and characterization, Cryst. Growth Des. 17 (6) (2017). [2] J. Lee, D. Kim, J. Park, E.K. Kim, M.S. Lah, A. Kim, Pseudopolymorphs of LB30870, a direct thrombin inhibitor: one dimensional solvent channel structures explain reversible hydration/dehydration, Cryst. Growth Des. 18 (1) (2018). [3] M. Muresan-Pop, D. Braga, M.M. Pop, G. Borodi, I. Kacso, L. Maini, Crystal structure and physicochemical characterization of ambazone monohydrate, anhydrous, and acetate salt solvate, J. Pharm. Sci. 103 (11) (2014) 3594e3601. [4] M.P. Lipert, N. Rodriguez-Hornedo, Cocrystal transition points: role of cocrystal solubility, drug solubility, and solubilizing agents, Mol. Pharm. 12 (10) (2015) 3535e3546. [5] Z. Wang, J. Wang, A. Leping Dang, M. Zhang, Crystal structures and the solvent-mediated transformation of erythromycin acetone solvate to dihydrate during batch crystallization, Ind. Eng. Chem. Res. 46 (6) (2007) 1851e1858. [6] H. Furuta, S. Mori, Y. Yoshihashi, E. Yonemochi, H. Uekusa, K. Sugano, K. Terada, Physicochemical and crystal structure analysis of pranlukast pseudo-polymorphs II: solvate and cocrystal, J. Pharm. Biomed. Anal. 111 (2015) 44e50. [7] T. Mandai, K. Yoshida, S. Tsuzuki, R. Nozawa, H. Masu, K. Ueno, K. Dokko, M. Watanabe, Effect of ionic size on solvate stability of glyme-based solvate ionic liquids, J. Phys. Chem. B 119 (4) (2015) 1523e1534. [8] W. Xu, N. Gong, S. Yang, N. Zhang, L. He, G. Du, Y. Lu, Isostructurality among solvates of cabazitaxel: X-ray structures and new solvates preparation, J. Pharm. Sci. 104 (4) (2015) 1256e1262. [9] X. Zhang, L. Zhou, C. Wang, Y. Li, Y. Wu, M. Zhang, Q. Yin, Insight into the role of hydrogen bonding playing in the molecular self-assembly process of sulfamethazine solvates, Cryst. Growth Des. 17 (12) (2017). [10] K.J. Chavez, M. Guevara, R.W. Rousseau, Characterization of solvates formed by sodium naproxen and an homologous series of alcohols, Cryst. Growth Des. 10 (8) (2010) 3372e3377. [11] X.H. Tang, Y. Li, J. Liu, Y. Zhang, X.Z. Wang, PAT aided identification of operational spaces leading to tailored crystal size distributions in azithromycin crystallization via coordinated cooling and solution mediated phase transition, Org. Process Res. Dev. 21 (12) (2017) 1963e1971. [12] L. Yang, H. Hao, L. Zhou, C. Wei, B. Hou, C. Xie, Q. Yin, Crystal structures and solvent-mediated transformation of the enantiotropic polymorphs of 2,3,5Trimethyl-1,4-diacetoxybenzene, Ind. Eng. Chem. Res. 52 (49) (2013) 17667e17675. [13] C.E. Marjo, M. Bhadbhade, J.M. Hook, A.M. Rich, Polymorphism and a metastable solvate of duloxetine hydrochloride, Mol. Pharm. 8 (6) (2011) 2454e2464. ski, A. Matwijczuk, A. Niewiadomy, M. Gagos, [14] A.A. Hoser, D.M. Kamin K. Wo zniak, On polymorphism of 2-(4-fluorophenylamino)-5-(2,4dihydroxybenzeno)-1,3,4-thiadiazole (FABT) DMSO solvates, CrystEngComm 15 (10) (2013) 1978. [15] N. Gong, G. Zhang, G. Jin, G. Du, Y. Lu, Polymorphs and versatile solvates of 7hydroxyisoflavone, J. Pharm. Sci. 105 (4) (2016) 1387e1397. [16] P. Chakravarty, R. Suryanarayanan, Characterization and structure analysis of thiamine hydrochloride methanol solvate, Cryst. Growth Des. 10 (10) (2010)
50
D. Du et al. / Journal of Molecular Structure 1189 (2019) 40e50
4414e4420. [17] K. Nakano, K. Sada, M. Miyata, Novel additive effect of inclusion crystals on polymorphsecholic acid crystals having different hydrogen-bonded networks with the same organic guest, Chem. Commun. 8 (8) (1996) 989e990. [18] C. Lentza-Rizos, E.J. Avramides, K. Kokkinaki, Residues of azoxystrobin from grapes to raisins, J. Agric. Food Chem. 54 (1) (2006) 138e141. [19] W.F. Becker, J.G. Von, T. Anke, W. Steglich, Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors of the bc1 segment of the respiratory chain with an E-beta-methoxyacrylate system as common structural element, FEBS Lett. 132 (2) (1981) 329e333. [20] F. Hou, P.P. Teng, F. Liu, W.Z. Wang, Tebuconazole and azoxystrobin residual behaviors and distribution of field and cooked peanut, J. Agric. Food Chem. 65 (22) (2017) 4484e4492. [21] F.P. Wong, W.F. Wilcox, Comparative physical modes of action of azoxystrobin, mancozeb, and metalaxyl against Plasmopara viticola (grapevine downy mildew), Plant Dis. 85 (6) (2001) 649e656. [22] C.E. Windels, J.R. Brantner, Early-season application of azoxystrobin to sugarbeet for control of Rhizoctonia solani AG 4 and AG 2-2, J. Sugar Beet Res. 42 (1) (2005) 1e18. [23] A. Peres, P. Signoret, B. Poinso, P. Davet, [Health Conditions of Soybean Seed Production [Phomopsis Phaseolorum Sojae, Ascochyta sp., Rhizoctonia solani, Pythium, Fusarium, Macrophomina Phaseoli]], 1990. French. [24] R.K. Ghosh, N. Singh, Effect of organic manure on sorption and degradation of azoxystrobin in soil, J. Agric. Food Chem. 57 (2) (2009) 632e636. [25] S. Sundravadana, D. Alice, Azoxystrobin Activity on Rhizoctonia solani and its Efficacy against Rice Sheath Blight, 2007. [26] Inna Faktorovitch, Z. Sharona, F. Inna, Sharona ZAMIR, in: POLYMORPHS OF 3(E)-2-{2-[6-(2-CYANOPHENOXY) PYRIMIDIN-4-YLOXY] PHENYL}-3METHOXYACRYLATE, WO, 2009. n, D.S. Yufit, [27] R.K. Harris, P. Hodgkinson, T. Larsson, A. Muruganantham, I. Yme V. Zorin, Characterization of polymorphs and solvates of terbutaline sulfate, Cryst. Growth Des. 8 (1) (2008) 80e90. [28] I.L. Fedushkin, V.I. Nevodchikov, M.N. Bochkarev, S. Dechert, H. Schumann, Reduction of 2,5-di-tert-butylcyclopentadienone and pyridine with thulium diiodide. Structures of the complexes TmI2(THF)2[h5-But2C5H2O]TmI2(THF) 3 and [TmI2(C5H5N)4]2(m2-N2C10H10), Russ. Chem. Bull. 52 (1) (2003) 154e159. [29] C. Beghidja, G. Rogez, J. Kortus, M. Wesolek, R. Welter, Very strong ferromagnetic interaction in a new binuclear mu-methoxo-bridged Mn(III) complex: synthesis, crystal structure, magnetic properties, and DFT calculations, J. Am. Chem. Soc. 128 (10) (2006) 3140e3141. [30] D.R. Powell, Review ofX-ray crystallographyx-ray crystallography, 4, in: Gregory S. Girolami (Ed.), Journal of Chemical Education 2016, vol.
[31]
[32] [33]
[34]
[35]
[36]
[37]
[38]
[39] [40] [41] [42]
[43]
[44]
93University Science Books, Mill Valley, California, 2015, pp. 591e592, 300 pp. ISBN 9781891389771 (hardcover). $88. R.T. Macaluso, B. Wells, C. Wangeline, K. Cochran, B.K. Greve, Powder X-ray diffraction and electron microscopy studies of polycrystalline Au2PrIn, Polyhedron 114 (2016) 313e316. M. Brown, Determination of purity by differential scanning calorimetry (DSC), J Chem. Educ. 56 (5) (1979) 310. Z. Yao, X. Ma, Z. Wang, L. Chen, Characteristics of co-combustion and kinetic study on hydrochar with oil shale: a thermogravimetric analysis, Appl. Therm. Eng. 110 (2017) 1420e1427. J. Ji, Y. Ge, W. Balsam, J.E. Damuth, J. Chen, Rapid identification of dolomite using a Fourier Transform Infrared Spectrophotometer (FTIR): a fast method for identifying Heinrich events in IODP Site U1308, Mar. Geol. 258 (1) (2009) 60e68. M. Dieterich, B. Kutchko, A. Goodman, Characterization of Marcellus Shale and Huntersville Chert before and after exposure to hydraulic fracturing fluid via feature relocation using field-emission scanning electron microscopy, Fuel 182 (2016) 227e235. X. Wei, G. Ningbo, Y. Shiying, Z. Na, H. Lan, D. Guanhua, L. Yang, Isostructurality among solvates of cabazitaxel: X-ray structures and new solvates preparation, J. Pharm. Sci. 104 (4) (2015) 1256e1262. K.K. Mohanty, Porous media: fluid transport and pore structure, in: F.A.L. Dullien (Ed.), Aiche Journal 1992, vol. 38, Academic Press, 1992, p. 574, 8):1303-1304. A.L. Spek, PLATON SQUEEZE: a tool for the calculation of the disordered solvent contribution to the calculated structure factors, Acta Crystallogr. C71 (1) (2015) 9e18. A.L. Spek, Single-crystal structure validation with the program PLATON, J. Appl. Crystallogr. 36 (1) (2010) 7e13. A.D. Martin, K.J. Hartlieb, A.N. Sobolev, C.L. Raston, Hirshfeld surface analysis of substituted phenols, Cryst. Growth Des. 10 (12) (2010) 5302e5306. M.A. Spackman, D. Jayatilaka, Hirshfeld surface analysis, CrystEngComm 11 (1) (2009) 19e32. D.J. Carter, P. Raiteri, K.R. Barnard, R. Gielink, M. Mocerino, B.W. Skelton, J.G. Vaughan, M.I. Ogden, A.L. Rohl, Difference Hirshfeld fingerprint plots: a tool for studying polymorphs, CrystEngComm 19 (16) (2017) 2207e2215. J.J. Mckinnon, F.P.A. Fabbiani, M.A. Spackman, Comparison of polymorphic molecular crystal structures through Hirshfeld surface analysis, Cryst. Growth Des. 7 (4) (2007) 755e769. H. Yang, Y. Yang, L. Jia, W. Tang, S. Xu, S. Du, M. Li, J. Gong, The phase transformation and formation mechanism of isostructural solvates: a case study of azoxystrobin, Cryst. Growth Des. 19 (3) (2019) 1550e1558.