Sodium Induces Octacalcium Phosphate Formation and Enhances Its

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Sodium Induces Octacalcium Phosphate Formation and Enhances its Layer Structure by Affecting to Hydrous Layer Phosphate Yuki Sugiura, and Yoji Makita Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.8b01030 • Publication Date (Web): 27 Aug 2018 Downloaded from http://pubs.acs.org on September 4, 2018

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Crystal Growth & Design

Sodium Induces Octacalcium Phosphate Formation and Enhances its Layer Structure by Affecting to Hydrous Layer Phosphate

Yuki Sugiura*, and Yoji Makita Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan KEYWORDS: Octacalcium phosphate, Na, Layer structure, Crystallinity, Calcium phosphate

Abstract: Octacalcium phosphate (OCP), a layered calcium phosphate compound, has attracted attention in areas such as biomaterial and pharmacy, as well as the environmental industry, because of its excellent biocompatibility and low environmental load. However, little is known about the effect of alkaline metal ions on OCP formation, even though the Na ion is always present as a pH neutralizing or ionic strength-adjusting agent. Therefore, in this study, we investigated the role of the Na ion in OCP formation from dicalcium phosphate dihydrate (DCPD) through hydrolysis by using solutions with various Na concentrations. When the Na concentration in the treatment solutions increased, the formation of hydroxyapatite (HAp) as a residual material was inhibited and the purity of OCP was increased. Furthermore, at higher concentrations, OCP crystals evolved layer structures because Na affects to the P5 PO4 in the OCP lattice and enhances the HPO4-OH layer structure, which significantly contributes to OCP crystallinity and crystal structure. Thermal stability measurements

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indicate that the thermal stability of OCP decreases with increasing Na content. This study suggests that Na incorporation into OCP crystals can induce OCP formation but simultaneously decrease the OCP stability.

INTRODUCTION Octacalcium phosphate [OCP: Ca8(PO4)4(HPO4)2·5H2O]—a layered calcium phosphate compound, space group P-1, triclinic—is a component of (particularly aquatic) vertebrate hard tissues such as bone and teeth that binds considerable PO4 and affects the environmental water chemistry, aqueous materials, geochemistry processes, and life cycles.1-7 In addition, OCP has attracted attention in various industrial fields such as biomaterials and pharmacy as a key and novel next-generation biomaterial or drug carrier because of its excellent biocompatibility, unique crystal structure, and low environmental load.1,8,9 A unit cell of OCP consists of the following two parts: the apatitic layer, in which Ca2+ and PO43- occupy the same relative positions as in hydroxyapatite [HAp: Ca10(PO4)6(OH)2], and the hydrous layer, which consists of PO4(HPO4) and OH(H2O) structures. There are six PO4 ions in a unit cell, P1 to P4, located in the apatitic layer, and P5 and P6, located in the hydrous layer (Scheme 1).10 Each of these phosphates are also strongly affected by conjugation to Ca and OH(H2O).


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Scheme 1 Unit cell of OCP toward the c-axis, with phosphates labeled as P1 to P6. OCP is also known to be able to substitute various molecules and ions within its structure by replacement of its component ions. For example, carboxylic molecules, especially dicarboxylates such as succinate11,12 and citrate,4,13 can replace the PO4(HPO4) and OH(H2O) anions of hydrous layer.4,11-17 However, the effects of extra ionic incorporation into the apatite layer have been rarely studied. The crystal structures and thermodynamic stability of other calcium phosphates such as HAp and β-tricalcium phosphate [β-TCP: Ca3(PO4)2] are significantly affected by the addition of ions such as Mg2+.18-21 However, except for a few studies on F- and CO32- incorporation or inhibition into an OCP lattice and its effects,22,23 little study has been conducted on the cation effect on OCP formation compared to cationic incorporation and its effect on HAp or β-TCP. Indeed, Boanini et al.24 reported that divalent cations such as Sr2+ and Mg2+ can be incorporated into the OCP crystal lattice and thermally stabilize its collapsed structure. However, little is known about the effects of monovalent cations such as alkaline metals, even though such ions must be used as salts for starting materials and pH- or ionic strength-adjustment agents for solution-mediate reactions. The ionic radius of Na (1.02 Å) is close to that of Ca (1.00 Å); therefore, it seems



that the Na ion can likely replace Ca in OCP. Furthermore, Na salts are mostly used in life sciences and biomineralization studies for ionic strength adjustment in the form of NaCl (e.g., in saline) and for pH adjustment in the form of NaOH because the Na ion is abundant in an extracellular fluid. Herein, we report the results of a structural and chemical investigation carried out on the solid products obtained from the fabricated OCP in the presence of various Na concentrations, with a focus on the Na incorporation site and its crystallographic effect on the OCP layer structure. EXPERIMENTAL SECTION Materials and solutions All reagents were purchased from Wako Pure Inc., Japan, as reagent grade. Both (NH4)2HPO4 and Na2HPO4 were dissolved in distilled water as 1 mol/L solutions. The pH of Na2HPO4 was adjusted to ~8.0 with 1 mol/L HCl at 60 °C before solution concentration adjustment. (NH4)2HPO4 and Na2HPO4 solutions were mixed at different concentrations to produce solutions with varying Na concentration but fixed 1.0 mol/L PO4 concentration. A high PO4 concentration was used so that PO4 could induce OCP formation via hydrolysis of dicalcium phosphate dihydrate [DCPD: CaHPO4·2H2O].25 A 2.39 g sample of DCPD (14 mmol) was immersed in 20 mL of various phosphate solutions at 60 °C for 1 day. The final pHs of the solutions were recorded with a pH electrode (LAQUA ToupH 9615S-10D with pH meter D-72, Horiba Co., Kyoto, Japan). The treated samples were washed with distilled water several times to remove the residual solutions, and then placed in a drying oven at 60 °C for several hours. Characterization


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Crystallographic information on samples was obtained by X-ray diffraction (XRD: MiniFlex600, Rigaku Co., Japan) at an acceleration voltage and amplitude of 40 and 15 kV, respectively. The diffraction angle was continuously scanned for 2θ values ranging from 3° to 70° at a scanning rate of 5°/min for characterization and 2° to 12° at a scanning rate of 2°/min for crystallographic parameter analysis. The integral intensities of each peak (Ix: x = each peak) in the obtained XRD patterns of the samples were calculated by quantitative analysis with PDXL2 software (Rigaku Co., Japan). The relative rate of the yield in each sample was calculated from the d(100), d(200), and d(110) of OCP at ~4.7°, ~9.4°, and ~9.7°. Although the strongest peak of HAp is d(003) at ~32.7°, it is likely that it contains overlapping peaks of other calcium phosphates, and so the d(100) of HAp at ~10.5° was used instead. The proportion of each phase (Rx: x = phase or intensity of peaks) in the samples is given as

Rx = C * Ix1/Ix2

(1)

where C is the phase or diffraction coefficient, which in the case of HAp/OCP is given as 7.69. In other cases, C = 1.00 is used. The chemical bonding structure of the samples was determined by Fourier transform-infrared spectroscopy (FT-IR: Nicolet NEXUS670, Thermofisher Scientific Co., US) using a triglycine sulfate (TGS) detector (64 scans, resolution 2 cm-1) with an attenuated total reflection (ATR) prism made of GeSe. The background for the measurements was atmosphere. The fine structure of the samples was assessed by field emission-scanning electron microscopy (FE-SEM: JSM-6700F, JEOL Co., Japan) at acceleration voltage of



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5 kV after Os spattering. The Ca, P(PO4) and Na contents of the samples were measured by inductivity coupled plasma atomic emission spectroscopy (ICP-OES: 5110VDV, Agilent Technology Co., Japan) after dissolving the samples in 1% HNO3. The

thermal

stability

of

the

samples

was

determined

by

thermogravimetry-differential thermal analysis (TG-DTA; ThermoPlus, TG8110, Rigaku Co., Japan). The heating rate was 10 °C/min up to 200 °C using Al2O3 as a standard. The heated samples for XRD measurements were obtained by the same manner of TG-DTA method. RESULTS AND DISCUSSION The main focus of this study was to ascertain how soluble Na affects OCP formation and OCP crystallographic structure. Previous studies have shown that, among other factors, pH value significantly affects OCP formation.1,8,9,26 Therefore, the initial pH of 1 mol/L PO4-containing solution was adjusted to 8.0 and the final pH values of all solutions were 6.7 ± 0.1 regardless of Na concentration (Figure 1). Thus, all reactions occurred at around neutral pH.

Figure 1 Final pH values of treatment solutions. The fine structures of the materials produced in the reactions were observed by scanning electron microscopy (SEM). Figure 2 shows the micrographs of DCPD before


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reaction (a, b) and after treatment with a solution containing 0.01 mol/L of Na (c, d), 0.1 mol/L Na (e, f), 1.0 mol/L Na ion (g, h), and 2.0 mol/L Na ion (i, j). The morphology and surfaces of DCPD crystals before the reaction exhibited typical rhombohedral shapes and smooth surfaces. After the treatment, the macroscopic structure of the crystals was preserved, but the surfaces contained closely packed ribbon-like crystals ranging ~2 µm in length, ~0.5 µm in width, and ~100 nm in thickness; we refer to these as “pseudomorph” structures. The thickness of ribbon-like crystals increased with Na concentration in the treatment solutions.

Figure 2 SEM micrographs of DCPD crystals before (a, b) treatment and after treatment



with 0.00 mol/L (c, d), 0.01 mol/L (e, f), 0.1 mol/L (g, h), and 2.0 mol/L (i, j) Na solutions. The materials were next characterized by XRD, and Figure 3 presents the wide-range XRD patterns of the materials. In the case of 0 mol/L Na, OCP (100), (200), and (110) diffraction peaks at ~4.7°, ~9.4°, and ~9.7° and an HAp (100) peak at 10.5° were observed at a low angle. Unique, continuous calcium phosphate peaks at 30–35° exhibited a typical hk diffraction band structure, which indicates poor crystallinity, and particularly, poorly layered structure formation. As Na concentrations increased, the relative intensity of OCP (100) also increased significantly, while those of OCP (200) and OCP (400) did not. In addition, the HAp diffraction peak at ~10.5°, which was obvious at low Na concentrations, disappeared at high concentrations. The fine data from low-angle XRD ranging from 2° to 12° are shown in Figure 4 to facilitate a comparison.

Figure 3 Wide-range XRD patterns of DCPD before (a) and after treatment with 0.00 mol/L (b), 0.01 mol/L (c), 0.05 mol/L (d), 0.1 mol/L (e), 0.5 mol/L (f), 1.0 mol/L (g), and 2.0 mol/L (h) Na solutions. ◆: DCPD, ●: OCP, and ▼: HAp.


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Figure 4 High magnification of the small-angle region of XRD patterns of DCPD before (a) and after treatment with 0.00 mol/L (b), 0.01 mol/L (c), 0.05 mol/L (d), 0.1 mol/L (e), 0.5 mol/L (f), 1.0 mol/L (g), and 2.0 mol/L (h) Na solutions. ◆: DCPD, ●: OCP, and ▼: HAp. A crystallographic analysis of the materials was conducted using the XRD patterns. The relation between HAp ratio and Na concentration was first analyzed by examining the phase ratio of OCP and HAp (Figure 5). The HAp/OCP ratio decreased steeply in the presence of Na concentrations of 0.2–0.6 and fell to nearly 0 at >0.10 mol/L Na. The HAp phase was entirely absent above 0.5 mol/L Na and the resulting materials were all monophasic OCP.

Figure 5 Phase ratio of Hap to OCP calculated from HAp-d(100) and OCP-d(100) as a



function of Na concentration. The integral intensity rate of each OCP peak was investigated. Figure 6 shows the ratio of OCP (100) and (200) (a) and that of OCP (200) and (110) (b). The ratio of (100) and (200) increased significantly with Na concentration, indicating the development of a layered structure along the a-axis. The comparison of (200) and (110) OCP showed a slight increase in the relative intensity of (200) OCP. These phenomena suspended the development of layered structures along the a-axis.

Figure 6 Ratios of relative intensities of XRD peaks as a function of Na concentration. (a) OCP d(100)/ OCP d(200). (b) OCP d(200)/ OCP d(110). The crystallite size analysis enabled us to obtain crystallinity information on the materials. Indeed, the analysis for the integral intensity of each peak revealed that Na induces significant development of an OCP layered structure. Figure 7 shows the OCP crystallite sizes calculated from (100) (a) and (110) (b) as a function of Na concentration. The OCP crystallite sizes increased with Na concentrations and reached a maximum at around 0.5 mol/L Na. This indicates that crystallinity is consistent with the development of a layered structure at low Na concentrations. Beyond this Na concentration, crystallite sizes decreased.


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Figure 7 Crystallite size of OCP calculated using d(100) (a) and d(110) (b), as a function of Na concentration. The Na content of the materials was measured by ICP-AES, and was relatively low at Na concentrations below 0.5 mol/L) and varied considerably (Figure 8). This suggests that residual HAp affected Na content because Na is likely to be incorporated into the HAp unit lattice.8,9 This phenomenon also occurred with the Ca/PO4 ratio of the obtained materials (Figure 9). These ICP-AES data suggest that Na was incorporated into the OCP unit lattice by intercalation (replacement of the Ca ion).

Figure 8 Na content of samples after treatment as a function of Na concentration.



Figure 9 Ca/PO4 ratio of samples after treatment as a function of Na concentration. The spectroscopic properties of PO4 in the crystalline phases are strongly affected by conjugating ions. Therefore, it is possible to detect ion conjugation toward PO4 by spectroscopically analyzing the PO4 optical properties. Figure 10 shows the wide-range FT-IR spectra of the obtained materials. The materials exhibit typical OCP peaks across the entire wavelength range. We, therefore, conducted a finer analysis focused on P5 PO4 vibration (~866 cm-1), which corresponds to the root of the layer structure altered by Na. Figure 11 shows the expanded FT-IR spectra (800—900 cm-1) of the obtained materials. In the absence of Na, the assignments for P5 PO4 at ~866 cm-1 (red line) for OCP and for PO4 at ~878 cm-1 (green line) for HAp vibration were observed. As Na concentrations increased, the P5 PO4 assignment of the ~866 cm-1 band was red-shifted, while the intensity of the ~878 cm-1 band was attenuated, which was consistent with the XRD measurements. At 0.5–1.0 mol/L Na, the P5 PO4 assignment became a single band at 860 cm-1, which represents the highest level of OCP crystallinity. Above this, the P5 PO4 assignment was divided between ~866 cm-1 and ~854 cm-1 (blue line). This strongly suggests that Na ions replaced Ca ions that were conjugated to P5 PO4 (Scheme 1). In short, Na replacement induced a different P5 PO4 vibration.


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Figure 10 Wide-range FT-IR spectra of DCPD before (a) and after treatment with 0.00 mol/L (b), 0.01 mol/L (c), 0.05 mol/L (d), 0.1 mol/L (e), 0.5 mol/L (f), 1.0 mol/L (g), and 2.0 mol/L (h) Na solutions.

Figure 11 High magnification of the small-angle region of FT-IR spectra of DCPD before (a) and after treatment with 0.00 mol/L (b), 0.01 mol/L (c), 0.05 mol/L (d), 0.1 mol/L (e), 0.5 mol/L (f), 1.0 mol/L (g), and 2.0 mol/L (h) Na solutions. TG-DTA analysis enables determination of the thermal stability of samples. When OCP is heated, its crystal structure decomposes at approximately 150–200 °C because of the collapsing HPO4-OH layer structure of OCP.24,27-29 Figure 12 shows the DTA curves of the obtained materials. Every sample demonstrated the dehydration peak of



adsorbed water at approximately 50–70 °C. In the absence of Na, a DTA peak was observed at 150 °C. This peak shifted toward low temperature with increasing Na concentration. Furthermore, an additional DTA peak at 128 °C was also observed in the presence of Na. In the case of 2.0 mol/L Na, an additional DTA peak was observed at 110 °C. Boanini et al.24 reported that OCP upon thermal decomposition forms collapsed-OCP, which has typical XRD peaks at 5.2–5.5° and 10.2°. Figure 13 shows the XRD pattern of the obtained materials through heating treatment at 100 °C (a) and 200 °C (b). In the case of 100 °C, all the obtained materials could not be converted. However, in the case of 200 °C, collapsed-OCP is observed in all the obtained materials. In the case of 0.5 mol/L Na, the peak intensity of collapsed-OCP at 5.2–5.5° is much higher than that of OCP (100).

Figure 12 DTA curves of the obtained materials treated with 0.00 mol/L (a), 0.01 mol/L (b), 0.05 mol/L (c), 0.1 mol/L (d), 0.5 mol/L (e), 1.0 mol/L (f), and 2.0 mol/L (g) Na solutions.


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Figure 13 The small-angle region of XRD patterns of the obtained materials heated at 100 °C (a) and 200 °C (b). Red broken line: OCP. Blue dot line, green rough broken line: Collapsed-OCP. Until now, since the discovery of OCP almost 200 years ago,30 it has been regarded as consisting of three components: Ca, PO4, and H2O, and, in 1962, Brown et al.31 first reported its crystal structure. However, this study clearly indicates that Na ions are not only essential for OCP formation, particularly for the evolution of its layered structure, a unique structure of OCP, but also for decreasing its thermodynamic stability. 10,31

In addition, this study showed that NH4 has little effect on OCP formation in this

reaction system. A high possibility of this phenomenon is Na replacement of Ca conjugated to P5 PO4. The reason why the Na ion can replace the Ca ion in the OCP site might be that the ionic radius of the Na ion (1.02 Å) is close to that of the Ca ion (1.00 Å). In contrast, the ionic radius of NH4 (1.75 Å) is much larger than either, and so it may not be able to replace Ca. Besides, P5 PO4 contributes to hydrous layer structure formation.10,30,32 When the Na ion replaces the Ca ion, the atomic bonds of PO4(HPO4) gain an extra bond because the Na ion is monovalent, whereas the Ca ion is divalent. This extra bond



strongly contributes to bond formation with the opposite PO4(HPO4) or OH(H2O) in the hydrous layer structure because of difference of valent of cations. However, in this study, we were unable to directly observe the Na ion replacement of Ca conjugated to P5 PO4. Therefore, we should mention that this phenomenon is also caused by vacancy replacement of Ca conjugated to P5 PO4. Previous studies, especially those using solid-state nuclear magnetic resonance (NMR) or crystallography, have indicated that the HPO4-OH layer structure is likely to be affected and replaced by additives such as carboxylic acids.4,14,33,34 However, little is known about how the cation affects this structure. This study revealed that Na ions induce both a layered structure in OCP and crystallinity. Thus, addition of an appropriate amount of Na ions is needed during OCP fabrication because Na contributes to HPO4-OH layer structure formation. However, this study has demonstrated the role of Na ions in OCP formation under only limited conditions using a simple NH4-Na-PO4 system. Future studies should investigate the role of other ions in OCP formation as well as kinetics and precursor formation. For example, it is still unclear how the behavior of a combination of molecules with Na or other counter ions affects the OCP crystal lattice and incorporates their behaviors. Further, it is still unclear whether this phenomenon will allow for the incorporation of molecules such as drugs into the OCP unite lattice. Furthermore, OCP crystallinity and thermodynamic stability significantly affect its pharmacokinetic properties such as dissolution ratio and biocompatibility.35,36 The technique described here, however, will significantly contribute to the development of uses for OCP in various industrial fields such as biomaterials and pharmacy. CONCLUSION


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We demonstrated that during OCP formation from DCPD through hydrolysis, Na concentration in the treatment solutions affects OCP formation and its crystallographic structure. With an increase in soluble Na concentrations, OCP was more likely to form a hydrous layer structure which decomposes lower temperature. AUTHOR INFORMATION Corresponding Author *Yuki Sugiura.

E-mail: [email protected]

Notes The authors declare no competing financial interests. ACKNOWLEDGMENTS This study is financially supported by priority issues of Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) and, KAKENHI for Young Researcher (B), JP16K20505. We thank Drs. Y. Uryu and T. Nakanishi for helping with FT-IR measurement. This study is partially supported by the Research center for Industrial Science & Technology, Kagawa Industry Support Foundation (RIST Kagawa). REFERENCES (1) Dorozhkin, S.V.; Epple, M. Biological and medical significance of calcium phosphates. Angew. Chem., Int. Ed. 2002, 41, 3130−3146. (2) Mann, S. Biomineralization, Principles and Concepts in Bioinorganic Materials Chemistry. Oxford University Press, UK, 2001. (3) Newman, W.F.; Newman, M.W. The Chemical Dynamics of Bone Mineral. Chicago University Press, US, 1958. (4) Davies, E.; Muller, K.H.; Wong, W.C.; Pickard, C.J.; Reid, D.G.; Skepper, J.N.;



Duer, M.J. Citrate bridges between mineral platelets in bone. Proc. Nat. Acad. Sci. USA 2014, 111, E1354-E1363. (5) Habraken, W.; Habibovic, P.; Epple, M.; Bohner, M. Calcium phosphates in biomedical applications: materials for the future? Mater. Today 2016, 19, 69-87. (6) Amjad, Z. Calcium Phosphates in Biological and Industrial Systems. Springer Science+Business Media LLC., US, 1998. (7) Lee, D.E.; Brandt, E.L.M.; vanLoenen, R.E.; Rose, Jr. H.J. The chemistry of five accessory rock-forming apatites. J. Res. US Geol. Survey 1973, 1, 267-272. (8) Wang, L.; Nancollas, G.H. Calcium Orthophosphate: Crystallization and Dissolution. Chem. Rev. 2008, 108, 4628-4669. (9) Elliott, J.C. Structure and Chemistry of the Apatites and Other Calcium Orthophosphates. Elsevier Co., Nederland, 1994. (10) Berry, E.E.; Baddiel, C.B. Some assignments in the infra-red spectrum of octacalcium phosphate. Spectrochim. Acta 1967, 23A, 1781-1792. (11) Monma, H.; Goto, M. Succinate-complexed Octacalcium Phosphate. Bull. Chem. Soc. Jpn. 1983, 56, 3843-3844. (12) Monma, H.; Goto, M. Thermal alteration of succinate-complexed octacalcium phosphate. J. Mater. Sci. Lett. 1985, 4, 147-150. (13) Sharma, V.K.; Johnsson, M.; Sallis, J.D.; Nancollas, G.H. Influence of Citrate and Phosphocitrate on the Crystallization of Octacalcium Phosphate. Langmuir 1992, 8, 676-679. (14) Tsai, T.W.T.; Chou, F.C.; Tseng, Y.H.; Chan, J.C.C. Solid-state P-31 NMR study of octacalcium phosphate incorporated with succinate. Phys. Chem. Chem. Phys. 2010, 12, 6692-6697.


Page 18 of 22

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


(15) Yokoi, T.; Kamitakahara, M.; Ohtsuki, C. Continuous expansion of the interplanar spacing of octacalcium phosphate by incorporation of dicarboxylate ions with a side chain. Dalton Trans. 2015, 44, 7943-7950. (16) Markovic, M.; Fowler, B.O.; Brown, W.E. Octacalcium Phosphate Carboxylates. 1. Preparation and Identification. Chem. Mater. 1993, 5, 1401-1406. (17) Markovic, M.; Fowler, B.O.; Brown, W.E. Octacalcium Phosphate Carboxylates. 2. Characterization and Structural Considerations. Chem. Mater. 1993, 5, 1406-1416. (18) Chickerur, N.S.; Tung, M.S.; Brown, W.E. A Mechanism for Incorporation of Carbonate into Apatite. Calcif. Tissue Int. 1980, 32, 55-62. (19) Jang, H.L.; Jin, K.; Lee, J.; Kim, Y.; Nahm, S.H.; Hong, K.S.; Nam, K.T. Revisiting Whitlockite, the Second Most Abundant Biomineral in Bone: Nanocrystal Synthesis in Physiologically Relevant Conditions and Biocompatibility Evaluation. ACS Nano 2014, 8, 634-641. (20) Li, H.; Hermann, J. Apatite as an indicator of fluid salinity: An experimental study of chlorine and fluorine partitioning in subducted sediments. Geochim. Cosmochim. Acta 2015, 166, 267-297. (21) Li, X.; Ito, A.; Sogo, Y.; Wang, X.; LeGeros, R.Z. Solubility of Mg-containing b-tricalcium phosphate at 25 °C. Acta Biomater. 2009, 5, 508-517. (22) Iijima, M.; Kamemizu, H.; Wakamatsu, N.; Goto, T.; Doi, Y.; Moriwaki, Y. Effects of CO32- ion on the formation of octacalcium phosphate at pH 7.4 and 37 °C. J. Cryst. Growth 1994, 135, 229-234. (23) Iijima, M.; Nelson, D.G.A.; Pan, Y.; Kreinbrink, A.T.; Adachi, M.; Goto, T.; Moriwaki, Y. Fluoride Analysis of Apatite Crystals with a Central Planar OCP Inclusion: Concerning the Role of F− Ions on Apatite/OCP/Apatite Structure Formation.



Calcif. Tissue Int. 1996, 59, 377-384. (24) Boanini, E.; Gazzano, M.; Rubini, K.; Bigi, A. Collapsed Octacalcium Phosphate Stabilized by Ionic Substitutions. Cryst. Growth Des. 2010, 10, 3612-3617. (25) Sugiura, Y.; Ishikawa, K. Effect of Calcium and Phosphate on Compositional Conversion from Dicalcium Hydrogen Phosphate Dihydrate Blocks to Octacalcium Phosphate Blocks. Cryst. 2018, 8, 222-229. (26) Vereecke, G.; Lemaitre, J. Calculation of the solubility diagrams in the system Ca(OH)2-H3PO4-KOH-HNO3-CO2-H2O. J. Cryst. Growth 1990, 104, 820-832. (27) Nelson, D.G.A.; McLean, J.D. High-Resolution Electron Microscopy of Octacalcium Phosphate and its Hydrolysis Products. Calcif. Tissue Int. 1984, 36, 219-232. (28) Kamitakahara, M.; Ito, N.; Murakami, S.; Watanabe, N.; Ioku, K. Hydrothermal synthesis of hydroxyapatite from octacalcium phosphate: effect of hydrothermal temperature. J. Cera. Soc. Jpn. 2009, 117, 385-387. (29) Tseng, Y.-H.; Mou, C.-Y.; Chan, J.C.C. Solid-State NMR Study of the Transformation of Octacalcium Phosphate to Hydroxyapatite: A Mechanistic Model for Central Dark Line Formation. J. Am. Chem. Soc. 2006, 128, 6909-6918. (30) Berzelius, J.J. Lehrbuch der Chemie Vol 4, Arnoldischen Buchhandlung, Germany, 1836. (31) Brown, W.E.; Smith, J.P.; Lehr, J.R.; Frazier, A.W. Crystallographic and Chemical Relations between Octacalcium Phosphate and Hydroxyapatite. Nature 1962, 196, 1050-1055. (32) Davies, E.; Duer, M.J.; Ashbrook, S.E.; Griffin, J.M. Applications of NMR Crystallography to Problems in Biomineralization: Refinement of the Crystal Structure


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and 31P Solid-State NMR Spectral Assignment of Octacalcium Phosphate. J. Am. Chem. Soc. 2012, 134, 12508-12515. (33) Sugiura, Y.; Onuma, K.; Yamazaki, A. Enhancement of HPO4–OH layered structure in octacalcium phosphate and its morphological evolution by acetic acid. J. Cera. Soc. Jpn. 2016, 124, 1178-1184. (34) Sugiura, Y.; Onuma, K.; Nagao, M.; Yamazaki, A. The effects of immobilized carboxylic-functional groups on the dynamics of phase transformation from amorphous to octacalcium phosphate. Am. Min. 2015, 100, 1624-1632. (35) Sopyan, I.; Pusparini, E.; Ramesh, S.; Tan, C.Y.; Ching, Y.C.; Wong, Y.H.; Zainal-Abidin, N.I.; Chandran, H.; Ramesh, S.; Bang, L.T. Influence of sodium on the properties of sol-gel derived hydroxyapatite powder and porous scaffolds. Cera. Int. 2017, 43, 12263-12269. (36) Tripathi, G.; Sugiura, Y.; Kareiva, A.; Garskaite, E.; Tsuru, K.; Ishikawa, K. Feasibility evaluation of low-crystallinity β-tricalcium phosphate blocks as a bone substitute fabricated by a dissolution–precipitation reaction from α-tricalcium phosphate blocks. J. Biomater. Appl. 2018, 33, 259-270.



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Sodium Induces Octacalcium Phosphate Formation and Enhances its Layer Structure by Affecting to Hydrous Layer Phosphate

Yuki Sugiura and Yoji Makita

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Synopsis: We investigated how Na affects octacalcium phosphate (OCP) formation and its crystallographic structure during OCP formation via hydrolysis. Soluble Na not only induce OCP formation but also decrease OCP thermodynamical stability.


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Sodium Induces Octacalcium Phosphate Formation and Enhances Its

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