Fast synthesis of La-substituted apatite by the dry mechanochemical method and analysis of its structure

Author’s Accepted Manuscript Fast synthesis of La-substituted apatite by the dry mechanochemical method and analysis of its structure Natalia V. Bulina, Marina V. Chaikina, Igor Yu. Prosanov, Dina V. Dudina, Leonid A. Solovyov www.elsevier.com/locate/yjssc

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S0022-4596(17)30167-6 http://dx.doi.org/10.1016/j.jssc.2017.05.008 YJSSC19782

To appear in: Journal of Solid State Chemistry Received date: 3 March 2017 Revised date: 3 May 2017 Accepted date: 7 May 2017 Cite this article as: Natalia V. Bulina, Marina V. Chaikina, Igor Yu. Prosanov, Dina V. Dudina and Leonid A. Solovyov, Fast synthesis of La-substituted apatite by the dry mechanochemical method and analysis of its structure, Journal of Solid State Chemistry, http://dx.doi.org/10.1016/j.jssc.2017.05.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Fast synthesis of La-substituted apatite by the dry mechanochemical method and analysis of its structure Natalia V. Bulina a,*, Marina V. Chaikina a, Igor Yu. Prosanov a, Dina V. Dudina b,a, Leonid A. Solovyovc a

Institute of Solid State Chemistry and Mechanochemistry SB RAS, Kutateladze street 18, Novosibirsk 630128, Russia b Lavrentyev Institute of Hydrodynamics SB RAS, Lavrentyev avenue 15, Novosibirsk 630090, Russia c Institute of Chemistry and Chemical Technology SB RAS, Federal Research Center "Krasnoyarsk Science Center SB RAS", Akademgorodok 50/24, 660036 Krasnoyarsk, Russia

Abstract: Compared to pure apatite, La-substituted apatites have improved thermal, mechanical and biological characteristics. In this article, a fast synthesis of La-substituted apatites by a dry mechanochemical method is presented. Structural studies by X-ray diffraction and Fourier transform infrared spectroscopy indicated the formation of a single-phase nanosized product after 30 min of high-energy ball milling of the reaction mixtures. The dry mechanochemical method is technologically attractive for the preparation of La-substituted apatites, as it allows reducing the processing time down to half an hour and does not require prolonged high-temperature annealing normally used in the synthesis practice of the substituted apatite. As the mechanochemically synthesized samples are nanosized, it is difficult to determine details of their crystal structure by the Rietveld refinement method. Therefore, a series of the mechanochemically synthesized samples with different concentrations of lanthanum were annealed at 1000 оС for 5 h. It was found that the annealed powders are microcrystalline La-substituted apatites Ca10-xLax(PO4)6Ox(OH)2-x, where 0 ≤ x ≤ 2. In their structure, the Ca2+ ions are replaced by the La3+ ions localized near the Ca2 sites, and the ОН– groups are replaced by the О2– ions in the hexagonal channels. Keywords: substituted apatite, lanthanum, mechanochemical synthesis 1. Introduction The structure of hydroxyapatite (Ca10(PO4)6(OH)2) offers possibilities for substitution (doping) in the cation and anion sublattices, which alters the physical and chemical properties of the compound and expands the range of its applications. In recent years, a number of articles dealing with substitution of lanthanides for calcium in the structure of hydroxyapatite have been published. The synthesized compounds are promising as materials for medicine [1-4] and luminescent materials [5-7]. There are studies, in which substitution of one [8] or more [9] trivalent metals for calcium has been implemented. Simultaneous substitution of lanthanides for calcium and silicate for phosphate is also possible [10-12]. The La-substituted apatite (HA-La) has a higher thermal stability, a higher flexural strength and a lower dissolution rate than the stoichiometric hydroxyapatite. The cytotoxicity of the non-substituted apatite and La-substituted apatite is comparable. However, the La-substituted apatite has a positive effect on the function of osteoblasts [1]. The morphology of osteoblasts (spindle-like shape with long mini-filopodias spreading, higher cell density) formed on the HA-La substrate indicates that the incorporation of La into the apatite promotes the prolifiration and adhesion of osteoblasts that stimulate the growth of new bone tissue [1].

*

Corresponding author. Tel.: +7 383 233 24 10; fax: +7 383 332 28 47.

E-mail address: [email protected] (N.V. Bulina)

The substitution of trivalent lanthanum for divalent calcium in the lattice is accompanied not only by the lattice deformation, but also by the change in the type of the synthesized product, namely, by the transformation of hydroxyapatite to oxyapatite. This is a consequence of the charge compensation upon the heterovalent substitution: La3+ + O2– → Ca2+ + (OH)–. As a result, the length of the bond between the lanthanum ion and oxygen ion located in the hexagonal channel on the 63 axis (instead of the OH groups) decreases and the bond becomes stronger than the bond between the calcium and the oxygen from the OH group [13]. Kazin et al. [13] noted that the bond between the La3+ ion and the intrachannel O2– in HA-La is the shortest La–O bond among the known lanthanum compounds. This decrease in the bond length upon substitution of lanthanum for calcium appears to be the reason for achieving a higher heat-resistance, a higher flexural strength, a lower dissolution rate compared with the non-substituted apatite and properties that are not observed in the non-substituted apatite, e. g. luminescence properties [5, 7]. HA-La can be obtained by the solid-state [1, 3, 13] and sol-gel [9] methods as well as by the synthesis in aqueous solution [4, 7]. Annealing of the products is a necessary step in all these methods. So, the synthesis usually takes longer than 10 h; in some cases, it may take a week. For example, Guo et al. synthesized HA-La with the La/(Ca+La) molar ratios of 0.05, 0.1 and 0.2 by a solid-state reaction [1]. After milling and homogenization of the stoichiometric mixtures of the reactants with ethyl alcohol in a planetary ball mill, the samples were annealed at 950 °C for 2 h. Then the product was crushed, ball milled again for 24 h and sintered at 1100 °C for 48 h. After that, depending on the number of substituents, the samples were annealed at 1200 °C for 24–60 h or at 1450 °C for 120 h. In the synthesis of HA-La from aqueous solution [7], the preparation of the solution took 2 h. The prepared solution was aged at 70 °C for 16 h. For making HA-La coatings, Lou et al. [4] prepared a stable sol by the wet chemical method by applying an ultrasonic vibration procedure, which required 5 days. The coatings were obtained from the prepared sol by the dip coating technique. Five cycles of coating and oven drying for 30 min at 150 оС were carried out. After that, the as-prepared coatings were annealed at 600 оС for 2 h. As can be seen from the above examples, the solid-state and aqueous syntheses of HA-La are rather time-consuming. In the present work, we propose a fast and simple synthesis method of HA-La – the mechanochemical method. We have shown that a single-phase nanocrystalline apatite can be obtained after 30 min of ball milling of the reaction mixture in a planetary ball-mill. A detailed structural characterization of the synthesized products has been conducted. 2. Material and methods The powder of HA-La was prepared by ball milling of the reaction mixture at room temperature and a relative humidity of 15 %. Chemically pure hydrophosphate СаНРО4 (VECTON, Russia), calcium oxide CaO (REACHIM, Russia) and lanthanum hydroxide La(OH)3 (VECTON, Russia) were taken as the reactants. The powders were mixed in the ratios corresponding to the following equation: 6CaHPO4 + (4–х)CaO + xLa(OH)3  Ca10-xLax(PO4)6Ox(OH)2-x + nH2O (1) where x is equal to 0, 0.2, 0.5, 0.8, 1.0, 1.2, 1.6 and 2.0. Mechanical treatment of the mixture was carried out in a planetary ball mill AGO-2 (Russia) with water-cooled steel vials. The milling time was 30 min. The rotation speed of the vials was 1200 rpm. Further details of the milling procedure can be found in ref. [14]. In order to avoid contamination of the synthesized powder by the material of the balls and vials, their surface was lined with the same powder prior to the synthesis. For this, a milling cycle was conducted, in which the powder was allowed to adhere to the surface of the balls and the walls of the vials. Samples obtained during the subsequent milling cycles were analyzed by Energy-Dispersive Spectroscopy using a detector attached to a Hitachi TM-100 Tabletop Scanning Electron Microscope (Japan). The analysis detected no iron in the samples processed in the coated vials. For conducting a more detailed investigation of the crystal structure, the mechanochemically synthesized powders were annealed in a high-temperature electrical furnace PVK-1.4-8 at 1000 °C for 5 h. A heating rate of 10 оC/min was used. The annealing conditions were chosen based on the results of our previous investigations [15].

The “HA-xLa” and “HA-xLa-T” sample notations are used for the mechanochemically synthesized and annealed samples, respectively, where x is the amount of added lanthanum. FTIR spectra were obtained with an Infralum–801 spectrometer in the range of 500–4000 cm–1 using the KBr pellet method. XRD patterns were recorded on a D8 Advance powder diffractometer with – geometry equipped with a one-dimensional Lynx-Eye detector and a K filter using Сu Kα radiation. XRD patterns were collected in the interval 10 о  2  120 о with a step size of 2 = 0.0195 о and a counting time of 177 s per step. The XRD structural analysis of the mechanochemically synthesized samples was performed by the Rietveld method [16] using Topas 4.2 software (Bruker AXS, Germany). The instrumental contribution was calculated by the fundamental parameters approach [17]. The average crystallite size was estimated using Lorentzian convolution varying in 2 as a function of 1/cos (). The analysis was carried out assuming no micro-strain in the particles. The initial structural information was taken from ref. [18]. The crystal structure of the annealed samples was refined using the derivative difference minimization (DDM) refinement technique [19]. The XRD peak shape was approximated by the TCH pseudo-Voigt function [20] taking into account the instrumental, microstrain, and crystallite size contributions. For the HA structure, the lattice parameters, atomic coordinates, occupancies and anisotropic thermal factors were refined taking into account the preferred orientation, anisotropic peak broadening, sample surface roughness and misalignment effects. 3. Results 3.1. Mechanochemically synthesized HA-La The FTIR spectra of the synthesized HA-xLa samples (Fig. 1) show the main characteristic absorption bands of hydroxyapatite: bending vibrations of the О–Р–О bond at 570 and 602 cm–1, stretching vibrations of the О–Р bond at 962, 1048 and 1088 cm–1, libration and stretching vibrations of the ОН group at 630 and 3572 cm–1, respectively. As even the most intensive absorption bands of the СО32– group (1400–1500 cm–1) are rather weak in the spectra, it can be concluded that the carbonate ions are present in the apatite structure in small concentrations. Carbon dioxide adsorbed by the initial reactants takes part in the synthesis along with carbon dioxide contained in the air, causing the subsequent incorporation of the carbonate ion into the apatite structure during the mechanochemical synthesis. A wide low-intensity band at 1640 cm–1 and a wide high-intensity band at 3000–3700 cm–1 belong to the О–Н bond of adsorbed water, which was released during the synthesis according to equation (1). The wide high-intensity band at 3000–3700 cm–1 overlaps with the narrow band of the stretching vibrations of the ОН group in the hydroxyapatite structure. This makes it difficult to confirm that the charge compensation upon substitution occurs by the removal of the OH groups (equation 1). Absorption bands belonging to the phosphate ions broaden with increasing lanthanum concentration; low-intensity bands at 962 and 1088 cm–1 disappear completely. These changes are associated with disordering of the phosphate ion environment upon incorporation of lanthanum into the apatite lattice: the higher the lanthanum concentration, the greater the disordering.

Fig. 1. FTIR spectra of the mechanochemically synthesized samples. The XRD patterns of the mechanochemically synthesized HA-xLa samples are presented in Fig. 2. All detected reflections belong to the hydroxyapatite structure of space group P63/m. With increasing concentration of added lanthanum, the intensities of the (100), (111) and (301) reflections decrease significantly causing their disappearance at high La concentration. All reflections are considerably broadened due to nanosized microstructure. The average crystallite size does not depend on the lanthanum concentration and has fluctuation in the 17-24 nm range (Table S1). The lattice parameters of the HA-xLa increase as the lanthanum concentration in the reaction mixture increases (Fig. 3). The increase in the lattice parameters suggests La3+ incorporation, but, as the substitution mechanism is believed to be described by the La3+ + O2–  Ca2+ + (OH)– scheme, the presence of O2instead of OH- should also be considered. However, the increase in the lattice parameters due to lanthanum substitution for calcium is likely to dominate, since the size of the lanthanum ion greatly exceeds the size of the calcium ion.

Fig. 2. XRD patterns of the mechanochemically synthesized samples. Miller indices are given for the reflections that disappear at high La concentrations.

6.93

9.47

6.92

9.46

6.91

c (Å)

а (Å)

9.48

9.45

6.90

9.44

6.89

9.43

6.88 0

0.5

1

1.5

0

2

0.5

1

1.5

2

Amount of added La (mol)

Amount of added La (mol)

538 537

V (Å) 3

536 535 534 533 532 531 0

0.5

1

1.5

2

Amount of added La (mol)

Fig. 3. Evolution of the unit cell parameters (a and с) and the unit cell volume (V) as a function of the amount of added lanthanum in the mechanochemically synthesized samples. Due to a small crystallite size of the samples and the presence of adsorbed water, the XRD analysis and FTIR spectroscopy do not allow determining the exact structure of synthesized material. Nevertheless, these methods show that the substitution does occur and a single-phase nanosized HALa can be obtained after 30-min ball milling of the reaction mixture in a high-energy planetary ball mill. The mechanochemical synthesis has advantages over other methods, especially when the synthesized material needs to be in the nanocrystalline state. For example, nanosized apatite ensures the formation of a more uniform suspension when apatite coatings are obtained by microarc oxidation in an electrolyte containing apatite as a dispersed phase [21]. 3.2. Annealed HA-La For a more detailed investigation of the crystal structure, the mechanically synthesized powders were annealed. Fig. 4a shows the FTIR spectra of the annealed HA-xLa-T samples. Compared to the HA-xLa samples (Fig. 3), the absorption bands are narrower, and the absorption bands corresponding to the carbonate ion and adsorbed water are no longer present. At a higher magnification, in the 500– 700 cm–1 and 900–1200 cm–1 ranges (Fig. 4b and 4c, respectively), it can be seen that lines corresponding to the vibrations in the hydroxyapatite structure broaden with increasing dopant concentration, similarly to the HA-xLa samples. Also, with increasing dopant concentration, the ratio of the absorption bands at 570 and 602 cm–1 (vibrations of the O–P–O) gradually changes, a band at 1016 cm–1 appears and bands at 1046 and 1090 cm–1 shift toward higher frequencies. This may be due to the fact that the symmetry of the phosphate group becomes lower and the degeneracy is removed. The OH libration vibration band at 630 cm–1 gradually shifts toward higher wave numbers as its intensity decreases (Fig. 4b). At x = 0.8, it disappears completely. The band at 3572 cm–1 corresponding to the OH stretching vibration disappears at x = 1.2. In accordance with equation (1),

OH groups are partially replaced by O2– ions. Hence, one can assume that the OH libration vibrations disappear at x = 0.8 due to the formation of hydrogen bonds between OH– and O2– ions. It is known that the position of the La–O absorption band depends on the substituent concentration in the La-substituted apatite and can be observed in the range of 500–525 cm–1 [1, 3, 13]. In our case, the absorption bands at 528 cm–1 (Fig. 4b) can be assigned to the La–O stretching vibrations. The band at 510 cm–1 can be attributed to the La–O stretching vibrations restricted by a hydrogen bond between O2– and OH–.

а

b

c

Fig. 4. FTIR spectra of the annealed samples: а – full spectra; b – enlarged 500–700 cm–1 range; с – enlarged 900–1200 cm–1 range. The XRD patterns of the HA-xLa-T samples are shown in Fig. 5. The hydroxyapatite reflections become much narrower in comparison to the HA-xLa samples, which points to the substantial growth of crystallites during annealing. Trace amounts of impurities were detected in some

samples after annealing: calcium oxide or lanthanum phosphate with concentrations less than 0.5 wt % were found in the HA-T, HA-0.5La-T and HA-0.8La-T samples (Table S2). The sample with the maximal concentration of lanthanum added during the synthesis differs from the rest of the samples. It contains 2 wt % of LaPO4, which may point to a lower thermal stability of its mechanochemically synthesized parent HA-2.0La. Fig. 5 shows that all reflections of the apatite phase in the HA-La-T samples are shifted to smaller diffraction angles. The higher the lanthanum concentration, the greater the shift of the reflections. This shift indicates larger lattice parameters and a larger cell volume. Similar to the mechanochemically synthesized samples, the intensity of the (100), (111) and (301) reflections fall sharply with increasing La concentration. In contrast to the mechanochemically synthesized samples, these reflections do not disappear at high lanthanum concentrations (Fig. 5a).

а

b Fig. 5. XRD patterns of the annealed samples: а – 10–65 o2 range; b – 31–33 o2 range.

9.46

6.92

9.45

6.91

c (Å)

а (Å)

The results of refinement of the HA-La lattice parameters for the HA-xLa-T samples are shown in Table S2. A graphical representation of these data (Fig. 6) shows that a and c parameters increase linearly as the lanthanum concentration increases, which is consistent with the literature data [3,13]. The crystallite size decreases with increasing lanthanum concentration (Table S2). It should be noted that the difference between the unit cell volumes of the mechanochemically synthesized HA and HA-2.0La is comparable to the difference between the unit cell volumes of these compounds in the annealed samples. They have values of 6.3 Å3 and 6.6 Å3, respectively (Table S1 and S2). This suggests that almost all lanthanum was incorporated into the apatite structure during the mechanochemical synthesis and the mechanochemical synthesis can be considered as an analog of the solid-state method. The difference between these methods is in the temperature of the synthesis.

9.44

6.90

9.43

6.89

9.42

6.88

0

0.5

1

1.5

0

2

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1

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Amount of added La (mol)

Amount of added La (mol)

536

V (Å)

3

534 532 530 528 0

0.5

1

1.5

2

Amount of added La (mol)

Fig. 6. Evolution of the unit cell parameters (a and с) and unit cell volume (V) as a function of the amount of added lanthanum in the annealed samples. The initial refinement of the HA-La crystal structure was carried out for all atom occupancies and atomic coordinates. It was found that the occupancies changed only for ions in the Ca2 site, the rest remaining unchanged with increasing lanthanum concentration. Therefore, they have been fixed in further refinement operations (the Ca1, P, O1, O2, O3 occupancies were equal to 1; the O4 occupancy was equal to 0.5). The change in the Ca2 occupancy shows that lanthanum replaces calcium only in the Ca2 site and that lanthanum-substituted apatite synthesized by the mechanochemical method is similar to that obtained by the ceramic method [3, 13]. DDM plots of the HA-1.0La-T and HA-2.0La-T samples are shown in Fig. S1. The values of the atomic coordinates, equivalent thermal factors, occupancies, reliability factors and geometric parameters of the apatite phase in the HA-xLa-T samples after the DDM refinement are shown in Table S3. A graphical representation of the evolution of the structural parameters depending on the amount of added lanthanum is shown in Fig. S2. From these data, it can be concluded that the Ca1

position remains practically unchanged over the whole range of the lanthanum concentrations. There is a small change in the Ca2 position. Positions occupied by the La3+ ions are slightly shifted from the Ca2 sites to the hexagonal axis, thereby forming channels of lanthanum ions filled with OH– and O2– anions (Fig. 7). With increasing lanthanum concentration, the shifts of РО43– tetrahedron and О2– anion from their initial positions become more significant (Fig. S2).

a b Fig. 7. Crystal structure of HA-2.0La-T: a – view along the с axis; b – view along the b axis. The displacement of the La ion (blue) from the site Ca2 (light green) is shown.

Occ.

Fig. 8 shows the evolution of the occupancies of the Ca2 and La2 sites by Ca2+ and La3+ cations. A decrease in the occupancy of the Ca2 site and an increase in the occupancy of the La2 site are detected with increasing substitution degree. The concentration of the lanthanum ions calculated from the occupancies is shown in Table. 1. It can be seen that the calculated values are significantly lower than the nominal ones (corresponding to the concentrations of added lanthanum during the synthesis). Kazin et al. [13] observed the same discrepancy in HA-La obtained by a high-temperature solid-state reaction and explained it by the incomplete reaction and a limited solid solubility at the processing temperature (1150 oC). Full substitution was observed by Serret et al. [3], who annealed the samples for a long time (24 – 120 h) at 1200-1450 oC. In the present study, 5-h annealing of the samples at 1000 oC, although leading to the crystallite growth, was seemingly not sufficient for the reaction completion. It is possible that unreacted lanthanum remained on the surface of the particles of the synthesized material. A similar observation was reported in our previous work [22] for the siliconCa2/La2 synthesized by the mechanochemical method. substituted apatite samples 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0

Ca2 La2

0.0

0.5

1.0

1.5

2.0

Am ount of added La (m ol)

Fig. 8. Evolution of the occupancies of the Ca2 and La2 sites with the amount of added lanthanum.

Table 1. Concentration of La in the annealed samples and the calculated chemical formulae. Sample Nominal Calculated from XRD Calculated formulae HA-T 0.0 0.00 Ca10(PO4)(OH)2 HA-0.2La-T 0.2 0.17 Ca9.83La0.17(PO4)6O0.17(OH)1.83 HA-0.5La-T 0.5 0.31 Ca9.69La0.31(PO4)6O0.31(OH)1.69 HA-0.8La-T 0.8 0.59 Ca9.41La0.59(PO4)6O0.59(OH)1.41 HA-1.0La-T 1.0 0.75 Ca9.25La0.75(PO4)6O0.75(OH)1.25 HA-1.2La-T 1.2 0.97 Ca9.03La0.97(PO4)6O0.97(OH)1.03 HA-1.6La-T 1.6 1.33 Ca8.67La1.33(PO4)6O1.33(OH)0.67 HA-2.0La-T 2.0 1.45 Ca8.55La1.45(PO4)6O1.45(OH)0.55 According to equation (1), incorporation of the substituent into the lattice reduces the number of the OH groups and increases the number of intrachannel oxygen in the substituted apatite structure. Thus, the O4 site is the position of the center of gravity of the averaged distribution density of O2– and OH–, which depends on their ratio and the presence of the hydrogen bonds. Fig. 9 shows that the length of the Ca2–O4 bond decreases monotonically with increasing lanthanum concentration. Since the Ca–O bond is shorter than the Ca–OH bond, a gradual decrease of the Ca2–O4 distance indicates a gradual increase of the concentration of the O2– ions located in the O4 site. 2.4

y = -0.0249x + 2.3816

Bond lenght (A)

2.36 2.32 2.28

Ca2-O4

2.24

La2-O4

2.2 2.16

y = -0.014x + 2.1389

2.12 2.08 0

0.5

1

1.5

2

Amount of added La (mol)

Fig. 9. Evolution of the Са2–О4 and La2–O4 bond lengths as a function of the amount of added lanthanum. Fig. 9 shows that La3+ cations form shorter bonds with O2– anions located in the O4 site in comparison to Ca2+ cations. Consequently, La3+ is closer to the O4 site and closer to the center of the hexagonal channel (Fig. 7). The length of the La2–O4 bond tends to decrease with increasing substituent concentration, similarly to the length of the Ca2–O4 bond, although the trend for the former is less noticeable, as the values have a greater measurement error at low lanthanum concentrations (low occupancy). The average La–O bond length in the HA-La samples synthesized by Kazin et al. [13] was 2.09 Å, which is considerably smaller than the length of the La–O bond in the known lanthanum compounds. The length of the La–O bond determined in the present work is 2.12 Å, which is comparable to the values reported by Kazin et al. The analysis of the bond lengths and angles of the PO4 tetrahedron shows that, although the constituent atoms of the PO4 tetrahedron gradually shift from their positions in the unit cell with increasing dopant concentration (Fig. S3), the average length of the P–O bond oscillates near a certain level and the mean value of the О–Р–О angle remains constant (Fig. S3). From the results of refinement of the structural parameters, the chemical formulae of the obtained compounds were suggested (Table 1). The data presented in Table 1 shows that all the synthesized compounds have the OH group, although the OH band vibrations were not detected in the FTIR spectra of the samples having high dopant concentrations. We believe that a hydrogen bond

forms between O2– and OH–, which are located in the hexagonal channel. The hydrogen bond restricts the vibrations of the OH group. According to Table 1, in the case of stoichiometric apatite (x = 0), the hexagonal channel is filled with the OH groups. At low lanthanum concentrations, the O2– ion substitutes for the OH group in the channel as a result of the charge compensation, which corresponds to the formation of Lacontaining oxy-hydroxyapatite. The introduction of 1.2 mol of lanthanum leads to the formation of a compound having practically equal concentrations of oxygen ions and OH groups in the apatite structure. As a result, the OH groups and the O2– ions alternate in the hexagonal channel. It is worth noting that the O2– ions are not observed separately without the OH groups (La-containing oxyapatite does not form). It is quite possible that prolonged annealing of the sample with the maximal concentration of the dopant would lead to a further increase in the concentration of lanthanum in the apatite structure and a concomitant increase in the concentration of the intrachannel oxygen. However, as can be seen from Table S2, the HA-2.0La-T sample contains 2 wt.% of LaPO4 as an admixture phase, which points to the instability of the apatite structure. So, prolonged annealing of HA-2.0La will lead to further destruction of its crystal structure. 4. Conclusion The present study has shown that mechanochemical treatment (ball milling) of a mixture of calcium hydrophosphate СаНРО4, calcium oxide CaO and lanthanum hydroxide La(OH)3 results in the formation of a single-phase nanosized lanthanum-substituted oxy-hydroxyapatite with an average crystallite size of ~ 20 nm. This synthesis method is fast and does not require heat treatment. Annealing of the synthesized samples at 1000 °C for 5 h leads to the growth of the crystallites and elimination of defects from their structure. It was found that with increasing dopant concentration, the unit cell parameters and the unit cell volume increase, while the crystallite size decreases. Lanthanum atoms occupy positions in the apatite lattice near the Ca2 site and form a wall of the hexagonal channel together with Ca2+ atoms. In the hexagonal channel, the number of OH– ions decreases and the number of O2– ions increases with increasing dopant concentration. The bond length between the oxygen ion located in the channel and the closest calcium or lanthanum ion decreases with increasing dopant concentration. Supporting information Supplementary data associated with this article can be found in the online version at http://…. References [1] D.G. Guo, A.H. Wang, Y. Han, K.W. Xu, Characterization , physicochemical properties and biocompatibility of Laincorporated apatites, Acta Biomaterialia 5 (2009) 3512–3523. doi:10.1016/j.actbio.2009.05.026. [2] C.A. Barta, K. Sachs-barrable, J. Jia, K.H. Thompson, M. Wasan, C. Orvig, Lanthanide containing compounds for therapeutic care in bone resorption disorders, Dalton Transactions 43 (2007) 5019–5030. doi:10.1039/b705123a. [3] A. Serret, M. V Cabanas, M. Vallet-Regi, Stabilization of Calcium Oxyapatites with Lanthanum (III) -Created Anionic Vacancies, Chem. Mat. 12 (2000) 3836–3841. [4] W. Lou, Y. Dong, H. Zhang, Y. Jin, X. Hu, J. Ma, J. Liu, G. Wu, Preparation and Characterization of LanthanumIncorporated Hydroxyapatite Coatings on Titanium Substrates, Int. J. Mol. Sci. 16 (2015) 21070–21086. doi:10.3390/ijms160921070. [5] M. Šupova, Substituted hydroxyapatites for biomedical applications: A review, Ceramics International 41 (2015) 9203–9231. doi:10.1016/j.ceramint.2015.03.316. [6] H. Liu, L. Liao, M.S. Molokeev, Q. Guo, Y. Zhang, L. Mei, A novel single-phase white light emitting phosphor Ca9La(PO4)5(SiO4)F2:Dy3+: synthesis, crystal structure and luminescence properties, RSC Adv. 6 (2016) 24577– 24583. doi:10.1039/C5RA23348H. [7] A. Yasukawa, K. Gotoh, H. Tanaka, K. Kandori, Preparation and structure of calcium hydroxyapatite substituted with light rare earth ions, Colloids and Surfaces A: Physicochem. Eng. Aspects. 393 (2012) 53–59. doi:10.1016/j.colsurfa.2011.10.024. [8] K. Kandori, M. Wakamura, M. Fukusumi, Y. Morisada, Effects of Modification of Calcium Hydroxyapatites by Trivalent Metal Ions on the Protein Adsorption Behavior, J. Phys. Chem. B. 114 (2016) 2399–2404. doi:10.1021/jp911783r. [9] X.G. Cao, S.P. Jiang, Y.Y. Li, Synthesis and characterization of calcium and iron co-doped lanthanum silicate oxyapatites by sole gel process for solid oxide fuel cells, J. Power Sources. 293 (2015) 806–814. doi:10.1016/j.jpowsour.2015.06.008.

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Highlights  a new approach to the synthesis of La-substituted apatites is proposed  dry mechanochemical method allows reducing the synthesis time down to 30 min  the product of synthesis is single-phase with an average crystallite size of 20 nm  the parameters and volume of the unit cell increase with dopant concentration  La-substituted apatites are Ca10-xLax(PO4)6Ox(OH)2-x, where 0 ≤ x ≤ 2