Phase Transformation between Anhydrate and Monohydrate of

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Phase Transformation Between Anhydrate and Monohydrate of Sodium Dehydroacetate Xia Zhang, Qiuxiang Yin, Wei Du, Junbo Gong, Ying Bao, Meijing Zhang, Baohong Hou, and Hongxun Hao Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/ie504873p • Publication Date (Web): 22 Mar 2015 Downloaded from http://pubs.acs.org on March 30, 2015

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Industrial & Engineering Chemistry Research

Phase Transformation between Anhydrate and Monohydrate of Sodium Dehydroacetate Xia Zhang†, Qiuxiang Yin†, ‡, Wei Du †, Junbo Gong†, ‡, Ying Bao†, ‡, Meijing Zhang†, ‡, Baohong Hou†, ‡, Hongxun Hao†, ‡, * †School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, and ‡ Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin 300072, People's Republic of China *E-mail: [email protected]; Phone: 86-22-27405754; Fax: 86-22-27314971 ABSTRACT: The crystal structures of monohydrate and anhydrous substance were determined from the single crystals for the first time. The phase transformation between anhydrate and monohydrate of sodium dehydroacetate was in situ investigated by using Raman spectroscopy. The mechanism of the phase transformation was proposed. The results showed that the monohydrate crystalline phase of sodium dehydroacetate can transform to anhydrous phase through solid-solid transformation upon heating or solution-mediated phase transformation. From powder X-ray diffraction（PXRD）patterns and thermal gravimetric analysis (TGA) data, it was found that the anhydrous crystals obtained by these two methods are the same in structure. However, the scanning electron microscopy (SEM) results revealed that the surface

of

the

high-temperature

anhydrous dehydration

sodium was

dehydroacetate

much

rougher

crystals than

that

obtained

by

obtained

by

solution-mediated phase transformation. Furthermore, the dynamic vapor sorption (DVS) results showed that the anhydrous crystals with rough surface had faster hydration rate than the anhydrous crystals with smooth surface when increasing humidity. The reasons behind these phenomena were discussed. Keywords: sodium dehydroacetate, monohydrate, anhydrate, phase transformation,

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transformation mechanism

1. INTRODUCTION The formation of polymorphs, solvates, and hydrates is a prevalent phenomenon in organic molecules.1 Solvates are generally known as crystalline solid adducts containing solute molecules and solvent molecules within the crystal structure, and hydrates are the special type of solvates when the solvent is water.2,3,4 These compounds may undergo certain physical and chemical changes such as hydration-dehydration

during

environmental

conditions

changes,

including

temperature, pressure and relative humidity.5 In addition, different polymorphs, disordered and amorphous phases may form during industrial processes of drying, mixing and blending, wet granulating etc.6 These changes may result in great differences on hygroscopicity, stability, solubility, and bioavailability of the compounds.

1,7,8

In order to stabilize the product quality, it is essential to investigate

the possible transformation pathways and mechanisms in a polymorphic system under different conditions.9 Two categories of phase transformation of solvates have been proposed in literature.10 The first one is induced in a single phase purely by thermal means, with this type being exemplified by dehydration or desolvation phase transformation or solid-to-solid phase changes. The second one is caused by the intervention of a second phase, such as solution-mediated phase transformation or the vapor sorption in a solid. Recently, much attention has been paid to the phase transformation phenomenon of hydrates. Fujii Kotaro et al.1 observed that the dihydrate crystalline phase of erythromycin A transformed to the anhydrous phase I upon heating, and further heating gave a melt which then crystallized to form another anhydrous phase II. Then the phase I and phase II underwent hydration to form different stoichiometric hydrate when

increasing

the

humidity.

They

concluded

that

the

different

hydration/dehydration behaviors were due to the differences in the crystal structures. Yamauchi et al.11 studied the transformation of anhydrate and dehydrated hydrate of naproxen sodium and niclosamide to hydrate form during the water sorption. They


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confirmed that the surface energy and surface area were responsible for the different water uptake phenomena. However, the possible solid-state dehydration type and hydration reaction process model were not mentioned in their work. In this study, sodium dehydroacetate (DHA-S) was selected as the model compound, whose molecular structure is shown in Figure 1. DHA-S is a new type of food preservative which is safe and has a strong antimicrobial activity against food borne pathogens and spoilage organism.12,13 The objectives of this work can be described as follows: (1) probing the possible different phase transformation pathways between anhydrous phase and monohydrate, and (2) investigating the mechanism of the phase transformations. Raman spectroscopy was applied to in situ monitor the solution-mediated phase transformation process between the anhydrous form and monohydrate form of DHA-S. A combination of analytical techniques such as powder X-ray diffraction（PXRD）, thermal gravimetric analysis (TGA)，dynamic vapor sorption (DVS) and scanning electron microscopy (SEM) were also applied to determine the phase transformation behavior.

2. EXPERIMENTAL SECTION 2.1. Materials. Solid state sodium dehydroacetate monohydrate was purchased from Aladdin Chemistry Co. Ltd and was used without further purification (mass fraction purity is higher than 99 %). Methanol purchased from Tianjin Kewei Chemical Co. of China was analytical reagent grade (molar purity is higher than 99.5 %). Deionized water was prepared in our lab. The anhydrous phase of DHA-S was produced from solid-solid or solution-mediated polymorphic transformation of monohydrate. Both the two forms of DHA-S were identified and determined by PXRD (D/MAX 2500, Rigaku, Tokyo, Japan) 、 TGA (Mettler Toledo TGA/DSC 1/SF, Greifensee, Switzerland) and Raman Spectroscopy (RXN2, Kaiser Optical systems, Inc., Ann Arbor, MI ). In the Raman Spectroscopy, the spectral resolution and the excitation wavelength of the laser were 5 cm−1 and 785 nm respectively. 2.2. Single Crystal Growth and Crystal Structure Determination of DHA-S The single crystals of anhydrous phase and monohydrate of DHA-S were cultivated



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by using the solvent slow evaporation method. Certain amounts of saturated methanol solution and saturated aqueous solution of DHA-S with temperature of 298.15 K were separately placed into two 20 mL beakers and sealed with plastic film. Then the beakers with solution were placed into an oven and kept at 303.15 K. The crystals of anhydrate and monohydrate with suitable size for single crystal X-ray diffraction were collected after a few days. The single crystal X-ray diffraction data of these two forms were collected on a Rigaku-Rapid II diffractometer with a Mo Kα radiation source (λ = 0.71073 Å). 2.3. Solid-solid Polymorphic Transformation of DHA-S The solid-solid transformation behavior of monohydrate was observed under hot stage microscope ( HSM, Olympus UMAD3 ) at a heating rate of 5 °C /min from room temperature (18 °C) to 150 °C. Images were collected in the region where the transformation was occurring. 2.4. Solution-mediated Polymorphic Transformation of DHA-S The solution-mediated transformation from monohydrate to anhydrous form of DHA-S was also studied from suspensions of monohydrate in methanol solutions, which are initially saturated with respect to the anhydrous phase at 25 °C for 6 h. The transformation process was in situ monitored using Raman spectroscopy. The obtained crystals were collected by filtration, followed by drying at 40 °C for 4 h. The anhydrous phase was stored in a low relative humidity environment until analyzed. 2.5. Dynamic Vapor Sorption of DHA-S The water sorption and desorption processes of anhydrous phase were carried out using a dynamic vapor sorption analyzer (VTI-SA, VTI Corporation, USA). Accurately weighed samples were mounted on a balance, and the relative humidity (RH) was increased from 5 % to 95 % by steps of 5 %, then decreased to 5 % by steps of 5 %. During each step, the RH was maintained until the mass change was less than 0.01 wt%/min or a maximum step time of 180 min. The measurements were carried out at 25 °C. SEM（Hitachi TM3000, Japan）was used to observe the morphology of the anhydrous phase and hydrate samples. 3. RESULTS AND DISCUSSION


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3.1．Identification of DHA-S Anhydrous Phase and Monohydrate Powder X-ray diffraction patterns of DHA-S monohydrate and anhydrous forms are shown in Figure 2. It can be seen that the characteristic peaks presented in the X-ray patterns for these two forms are clearly different, confirming that the two compounds are distinct forms. As shown in Figure 3, the DSC and TGA data of DHA-S monohydrate show the first sharp endothermic peak at around 120 °C. The endothermic peak coincided with weight loss of 8.67 %, which is consistent with the calculated water content (8.66 %) in monohydrate of DHA-S. However, no endothermic peak and mass loss at about 120 °C can be observed from the DSC and TG data of anhydrous phase. In the Raman spectrum obtained from solid state products (Figure 4a), these two forms have many different characteristic Raman peaks, such as the characteristic peak at 1416 cm-1 for monohydrate and 1550 cm-1 for anhydrous phase. When the monohydrate and anhydrous phase were added into the methanol, the Raman spectra in Figure 4b were obtained. By comparison of Figure 4a and Figure 4b, the peak at 1416 cm-1 for monohydrate and 1550 cm-1 for anhydrous phase were selected as characteristic peaks to monitor the transformation process. By comparing the crystal structures of the monohydrate and anhydrate, the different Raman characteristic peaks reflect the crystal structure differences of the two forms due to water molecules included in the crystal lattice. 3.2. Crystal Structure Analysis of DHA-S anhydrous phase and monohydrate To better illustrate the solid-state transformation mechanism between monohydrate and anhydrous phase, the crystal structures of monohydrate and anhydrous phase are determined for the first time and compared with each other. The simulated PXRD patterns of monohydrate and anhydrate were obtained by using the crystal structure data. It can be seen the simulated results are consistent with the experimental results (Figure 2), which confirm the accuracy of the single crystals results. The crystallographic data of monohydrate and anhydrate are summarized in Table 1.



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The single crystal structure of DHA-S monohydrate shows that the monohydrate of DHA-S is a triclinic system with P 1 space group. The water molecule is arranged along the c-axis and form a water channel in the crystal lattice of monohydrate (Figure 5a and 5b). The forces stabilizing the packing of the DHA-S monohydrate are Na-O type interaction in the structure cell，and the sodium cation is surrounded by six oxygen atoms. Hydrogen bonds are also formed between oxygen of the ketone group and the hydrogen in water as well as among different water molecules. The structure of DHA-S monohydrate contains water molecules that are directly connected with sodium ion, which is a special type of hydrates called Metal Ion-Associated Hydrates.4,14,15 The consequent interactions between metal cation and the water molecules are so strong that the dehydration of these bounded water molecules typically can only take place at high temperatures. For the single crystal structure of the DHA-S anhydrate, it is a monoclinic system with P21/c space group. By comparison, the crystal structure of DHA-S anhydrate (Figure 5c and 5d) has different molecule packing from that of monohydrate. The hydrogen bond does not exist in the packing structure of anhydrate. So the Na-O type interactions become the dominant force to stabilize the packing of the DHA-S anhydrate. In addition, each sodium cation can form five different Na-O type interactions. It can be concluded that the water molecules have a great influence on packing structure of crystal lattice. 3.3. Phase Transformation from Monohydrate to Anhydate of DHA-S 3.3.1. Solid-solid Polymorphic Transformation The solid-solid polymorphic transformation from monohydrate to anhydrate was visualized using HSM (Figure 6). When heating was started, no change on the crystal was observed until temperature reached 110 °C. Upon further heating, the whole crystal changed from optically transparent to opaque. Meanwhile, some cracks appeared on the crystal surface. From the PXRD data and TGA data of the starting materials and the obtained materials after heating, it can be confirmed that monohydrate of DHA-S transformed into anhydrate when temperature is higher than


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110 °C. The crystal shape did not change during the polymorphic transformation process. In addition, the SEM of the sample obtained by transformation is shown in Figure 7a. It is worth noting that the particles are flat and rectangular and show some cracks on the crystal surfaces. They are called anhydrous crystals with rough surface in this work. By comparing the crystal structure of monohydrate and anhydrous phase, the water loss of DHA-S monohydrate leads to the changes in packing and conformation, which are essential to the transformation into the anhydrate. The cracks on the crystal surface of obtained anhydrate can also be explained by the removal of water molecules. A mechanism of water elimination and structure reorganization can be proposed to explain the observed transformation from DHA-S monohydrate to anhydrate. Since the water molecules are directly connected with metal ions, it is likely that the first step in the dehydration process should be the escape of water. The second step is conformation change and molecular rearrangement to form the anhydrous phase. Andrew K. Galwey10,15,16 had given a detail classification scheme for solid-state dehydrations ‘water evolution type’（WET）based on observations of the behavior of crystals during dehydration. In WET 3 type, the removal of water from the solid involves some contraction from the original reactant volume, which might cause cracking at the interface. At the same time, the removal of water molecules from its structure can lead to the reposition of the remaining units in the lattice.17,18 The experimental results are consistent with the theoretical model (WET 3). Therefore, the WET 3 model can be used to explain the dehydration of DHA-S. 3.3.2. Solution-Mediated Phase Transformation Solution-mediated phase transformation from monohydrate to anhydrate was also investigated in methanol solutions at 25 °C with the assistance of on line Raman spectroscopy. The changing trend of the Raman intensity of the characteristic peaks of the two forms is shown in Figure 8. After adding the monohydrate crystals into the solution, the intensity of monohydrate characterization peak (1416 cm-1) increased to the highest level and maintained for about 5 minutes, then it decreased gradually in



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the next 120 minutes and kept stable afterwards. At the same time, the intensity of anhydrate characterization peak (1550 cm-1) increased gradually. The decreasing of the characterization Raman peak intensity of monohydrate indicates the decrease of monohydrate crystals while the increasing of the characteristic Raman peak intensity of anhydrous phase indicates the crystallization of anhydrate crystals. The Raman data confirms that the monohydrate phase is less stable than anhydrous form in methanol solutions and it will transform into anhydrous form. These results also reveal that the solution-mediated transformation from monohydrate to anhydrate of DHA-S is co-governed by the dissolution of the monohydrate phase and the crystallization the anhydrous phase. 19 Powder X-ray diffraction patterns of the anhydrous phase obtained by the solution-mediated phase transformation are also shown in Figure 2, which is the same with that of anhydrous phase obtained from solid-solid dehydration. This indicates that the anhydrous phases obtained from solid-solid and solution-mediated dehydration processes are the same polymorphic form. In other words, they are the same anhydrous form. Furthermore, it can be observed that the crystal surface (Figure 7c) of the sample obtained by solution-mediated phase transformation is smooth. They can be called the anhydrate with smooth surface. This phenomenon might be explained by the transformation mechanism. During the solution-mediated transformation process of DHA-S monohydrate, structural rearrangement and the loss of water molecules occurred at the same time. Then anhydrate with smooth surface was obtained. According to the experimental results, solution mediated polymorphic transformation is an efficient method for converting hydrate to anhydrous phase. The solution-mediated transformations can be described by the mechanism: (1) dissolution of the DHA-S monohydrate, (2) nucleation and growth of the anhydrous phase. 3.4. Anhydrous Phase Transformation Caused by Vapor Sorption The isothermal hydration and dehydration behavior of anhydrous samples with both rough surface and smooth surface were investigated by DVS methods at 25 °C.11,20 The results are shown in Figure 9.


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Interestingly, the water sorption rate of anhydrous phase sample with rough surface (Figure 7a) is clearly different from that of anhydrous phase sample with smooth surface (Figure 7b). The anhydrate with rough surface started to absorb water from the beginning of experiment and their weight gradually increased with the RH increasing until it completely transformed into monohydrate at RH=80 %. However, the anhydrate with smooth surface remained unchanged until a critical relative humidity of 70 % was reached and it completed hydration until RH=90 %. Both samples exhibited mass gain of about 8.9 % which is consistent with the stoichiometric value of one water molecule (8.67 %). The crystals obtained from hydration in DVS are further confirmed to be monohydrate by PXRD data (Figure 10). The difference in the crystal surface of the anhydrous samples might be responsible for the observed water uptake variation. At the same time, the cracks on the crystal surface will result in larger surface-to-bulk ratio and increased degree of bulk diffusivity.11 This will also lead to water uptake variation. After hydration, the morphology (Figure 7b and 7d) of the samples is also obviously different. The morphology of the product obtained from anhydrous phase with rough surface is honeycomb. However, the morphology of the product obtained from the anhydrous phase with smooth surface is flat and rectangular with some cracks and small particles on the surface. According to the above experimental phenomena and the comparison of the crystal lattice, it can be concluded that the hydration process is controlled by the new phase surface nucleation and growth. 16,21The reaction model is shown in Figure 11. For the anhydrate with rough surface, the more cracks, the bigger crystal surface areas and bulk diffusivity. What’s more, these cracks were produced by the removal of water molecules. The crystal structures seem to have memory and the cracks can easily absorbed water (Figure 11a). Once the relative humidity reached a certain value, the crystal surfaces started to be covered by water molecules and form the liquid film (Figure 11b). Then the DHA-S monohydrate began to nucleation and growth at the surface (Figure 11c). According to this reaction model, the morphology of the product



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obtained by anhydrate with rough surface became honeycomb after hydration. However, for the anhydrate with smooth surface, the crystal surface is smooth and the crystal surface area is less than that of the anhydrous phase with rough surface. So the required critical relative humidity is higher. The formation of small particles was also due to the surface nucleation. As to the cracks on the hydration product surface, this can also explained by the hydration mechanism. During the hydration process, the Na-O type interaction in the structure cell might be fractured firstly and then water is absorbed and recombined into the crystal lattice. The fracture of bonds might result in contraction of lattice and then consequently cracks appear. According to this model， the surface area is important and responsible for the distinct water sorption. 4. CONCLUSIONS In this work, the crystal structures of anhydrate and monohydrate were determined for the first time. The possible transformation pathways between DHA-S monohydrate and anhydrate were investigated by PXRD, TGA, Raman, HSM，SEM and DVS. Crystals of DHA-S monohydrate underwent solid-solid transformation upon heating or solution-mediated transformation to give the anhydrous phase, which also can transformed to monohydrate through water vapor sorption. This indicated that the transformation between anhydrate and monohydrate form of DHA-S is reversible when the conditions are appropriate. According to the experiments results, mechanisms of the solid-state transformation between DHA-S monohydrate and anhydrate are proposed. By comparing the crystal structures and crystal surface, the mechanism of DHA-S monohydrate solid-solid transformation was consistent with the theoretical model (WET 3). The solution-mediated transformation was also investigated by using Raman spectroscopy. It was found that the solution-mediated transformation was co-governed by dissolution of monohydrate phase and crystallization of anhydrous phase. With the aid of SEM photographs, the hydration process model for anhydrous phase was also proposed. It was revealed that the hydration process was controlled by the surface nucleation and growth.


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■ ACKNOWLEDGEMENTS This research is financially supported by National Natural Science Foundation of China (No. 21376165) and Key Project of Tianjin Science and Technology Supporting Program (No. 13ZCZDNC02000)

■ SUPPORTING INFORMATION X-ray crystallographic information files （CIF） are available for structure of monohydrate and anhydrous phase of DHA-S. This information is available free of charge via the Internet at http: //pubs.acs.org.



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(13) Sakaguchi, Y.; Suga, S.; Oshida, K.; Miyamoto-Kuramitsu, K.; Ueda, K.; Miyamoto Y. Anticoagulant Effect of Sodium Dehydroacetate (DHA-S) in rats. J. Appl. Toxicol. 2008, 28, 524. (14) Kim, Y. S.; Rousseau, R. W. Characterization and Solid-State Transformations of the Pseudopolymorphic Forms of Sodium Naproxen. Cryst. Growth Des. 2004, 4, 1211. (15) Griesser, U. J. Polymorphism in the Pharmaceutical Industry; Hilfiker, R., Ed.; Wiley-VCH: Germany, 2006; PP 211-233. (16) Galwey, A. K. Structure and Order in Thermal Dehydrations of Crystalline Solids. Thermochim. Acta. 2000, 355, 181. (17) Lee, A. Y.; Erdemir, D.; Myerson, A. S. Crystal Polymorphism in Chemical Process Development. Annu .Rev. Chem. Biomol .Eng. 2011, 2, 259. (18) Bērziņš, A.; Actiņš, A. Dehydration of Mildronate Dihydrate a Study of Structural Transformations and Kinetics. CrystEngComm. 2014, 16, 3926. (19) Yang, L.; Hao, H.; Zhou, L. Chen, W.; Hou, B.; Xie, C.; Yin, Q. Crystal Structures and Solvent-Mediated Transformation of the Enantiotropic Polymorphs of 2,3,5-Trimethyl-1,4-diacetoxybenzene. Ind. Eng. Chem. Res. 2013, 52, 17667. (20) Raijada, D.; Bond, A. D.; Larsen, F. H. Cornett, C.; Qu H. Exploring the Solid-Form Landscape of Pharmaceutical Hydrates: Transformation Pathways of the Sodium Naproxen Anhydrate-Hydrate System. Pharm. Res. 2013, 30, 280. (21) Renou, L.; Coste, S.; Cartigny, Y.; Petit, M. N.; Vincent, C.; Schneider, J. M.; Coquerel, G. Mechanism of Hydration and Dehydration of Ciclopirox Ethanolamine (1:1). Cryst. Growth Des. 2009, 9, 3918.



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Figure captions: Figure 1. Chemical structure of sodium dehydroacetate. Figure 2. Powder X-ray diffraction patterns of DHA-S. Figure 3. DSC and TGA curves of DHA-S: (a) TGA curve of anhydrous phase, (b) TGA curve of monohydrate, (c) DSC curve of anhydrous phase, (d) DSC curve of monohydrate. Figure 4. Raman spectra of monohydrate and anhydrous phase of DHA-S: (a) Raman spectra obtained from powers, (b) Raman spectra obtained from methanol solution. Figure 5. Crystal structures of (a, b) DHA-S monohydrate and (c, d) anhydrous phase. For clarity, hydrogen atoms are omitted. The red spheres in (a) and (b) represent the oxygen atoms in water. Figure 6. Optical micrographs taken at different temperatures during the solid-solid transformation process: (a) 20 °C, (b) 115 °C , (c) 120 °C, (d) 125 °C. Figure 7. SEM photographs of DHA-S: (a) the anhydrous phase with rough surface, (b) product obtained by hydration of anhydrous phase with rough surface, (c) the anhydrous phase with smooth surface, (d) product obtained by hydration of anhydrous phase with smooth surface. Figure 8. Raman data changing trend of during the solution-mediated transformation from monohydrate to anhydrous phase. Figure 9. DVS plot of DHA-S anhydrous phases: (a) the anhydrous phase with rough surface and (b) the anhydrous phase with smooth surface Figure 10. Powder X-ray diffraction patterns of DHA-S: monohydrate (black),


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product obtained by hydration of anhydrous phase with smooth surface (red), product obtained by hydration of anhydrous phase with rough surface (blue). Figure 11. Hydration reaction process model: (a) crystal surface absorb water, (b) the liquid film formed on crystal surface, (c) nucleation and growth at the crystal surface.



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Figure 1. Chemical structure of sodium dehydroacetate.

Figure 2．Powder X-ray diffraction patterns of DHA-S.


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Figure 3. DSC and TGA curves of DHA-S: (a) TGA curve of anhydrous phase, (b) TGA curve of monohydrate, (c) DSC curve of anhydrous phase, (d) DSC curve of monohydrate.

Figure 4. Raman spectra of monohydrate and anhydrous phase of DHA-S: (a) Raman



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spectra obtained from powers, (b) Raman spectra obtained from methanol solution.

Figure 5. Crystal structures of (a,b) DHA-S monohydrate and (c,d) anhydrous phase. For clarity, hydrogen atoms are omitted. The red spheres in (a) and (b) represent the oxygen atoms in water.

Figure 6.Optical micrographs taken at different temperatures during the solid-solid transformation process: (a) 20 °C, (b) 115 °C, (c) 120 °C, (d) 125 °C.


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Figure 7. SEM photographs of DHA-S: (a) the anhydrous phase with rough surface, (b) product obtained by hydration of anhydrous phase with rough surface, (c) the anhydrous phase with smooth surface, (d) product obtained by hydration of anhydrous phase with smooth surface.

Figure 8. Raman data changing trend of during the solution-mediated transformation from monohydrate to anhydrous phase.



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Figure 9. DVS plot of DHA-S anhydrous phases : (a) the anhydrous phase with rough surface and (b) the anhydrous phase with smooth surface.

Figure 10. Powder X-ray diffraction patterns of DHA-S: monohydrate (black), product obtained by hydration of anhydrous phase with smooth surface (red), product


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obtained by hydration of anhydrous phase with rough surface (blue).

Figure 11. Hydration reaction process model: (a) crystal surface absorb water, (b) the liquid film formed on crystal surface, (c) nucleation and growth at the crystal surface.



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Table 1. Crystallographic Data of Monohydrate and Anhydrous Phase of DHA-S Phase

Monohydrate

Anhydrous

Empirical formula

C16 H18 Na2 O10

C16 H14 Na2 O8

Formula weight

416.28

380.25

Crystal system

triclinic

monoclinic

space group

P1

P21/c

a (Å)

8.7495

14.344

b (Å)

9.901

10.452

c (Å)

11.930

12.188

Volume(Å3)

957.6

1662.8

Density (g/cm3)

1.444

1.519

Z

2

4

Rint (%)

6.3

10.19

goodness-of-fit

1.016

1.005


Phase

Phase Transformation between Anhydrate and Monohydrate of

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