Comparative Study of Calcium Carbonates and Calcium Phosphates

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Comparative study of calcium carbonates and calcium phosphates precipitation in model systems mimicking the inorganic environment for biomineralization Iva Buljan Mei#, Jasminka Kontrec, Darija Domazet Jurašin, Branka Njegi# Džakula, Lara Štajner, Daniel M. Lyons, Maja Dutour Sikiri#, and Damir Kralj Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.6b01501 • Publication Date (Web): 30 Jan 2017 Downloaded from http://pubs.acs.org on January 30, 2017

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Crystal Growth & Design

Comparative study of calcium carbonates and calcium phosphates precipitation in model systems mimicking the inorganic environment for biomineralization Iva Buljan Meić1, Jasminka Kontrec1, Darija Domazet Jurašin2, Branka Njegić Džakula1, Lara Štajner1, Daniel M. Lyons3, Maja Dutour Sikirić2, Damir Kralj1* 1 Ruđer Bošković Institute, Division of Materials Chemistry, Bijenička cesta 54, Zagreb, Croatia 2 Ruđer Bošković Institute, Division of Physical Chemistry, Bijenička cesta 54, Zagreb, Croatia 3 Ruđer Bošković Institute, Center for Marine Research, Giordano Paliage 5, Rovinj, Croatia Abstract The aim of this study is to contribute to understanding the mechanisms underlying the formation of biologically relevant minerals by comparing the properties of solid phases formed in calcium phosphate (CaP) or calcium carbonate (CaCO3) precipitation systems, at defined initial experimental conditions: supersaturation, constituent ions ratio, ionic strength and/or presence of relevant inorganic ions. Thus, three systems of different chemical complexity were investigated: (a) system containing constituent ions, (b) system containing additional co-ions and (c) system with higher ionic strength and addition of Mg2+. The respective precipitation diagrams were constructed and supersaturation domains of different CaP and CaCO3 solid phases formation were identified. The obtained results may have implication not only for biomineralization and geochemistry, but also for materials science in general.

* Corresponding authors: Damir Kralj Division of Materials Chemistry Ruđer Bošković Institute Bijenička cesta 54, 10 000 Zagreb, Croatia Phone: + 385 1 468 0207 Fax: + 385 1 468 0098 E-mail: [email protected]

Maja Dutour Sikirić Division of Physical Chemistry Ruđer Bošković Institute Bijenička cesta 54, 10 000 Zagreb, Croatia Phone: + 385 1 456 0941 Fax: + 385 1 468 0245 E-mail: [email protected]

1 ACS Paragon Plus Environment


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Comparative study of calcium carbonates and calcium phosphates precipitation in model systems mimicking the inorganic environment for biomineralization

Iva Buljan Meić1, Jasminka Kontrec1, Darija Domazet Jurašin2, Branka Njegić Džakula1, Lara Štajner1, Daniel M. Lyons3, Maja Dutour Sikirić2*, Damir Kralj1* 1

Ruđer Bošković Institute, Division of Materials Chemistry, Bijenička cesta 54, Zagreb, Croatia

2 3

Ruđer Bošković Institute, Division of Physical Chemistry, Bijenička cesta 54, Zagreb, Croatia

Ruđer Bošković Institute, Center for Marine Research, Giordano Paliage 5, Rovinj, Croatia

[email protected], [email protected]

Abstract

The aim of this study is to contribute to understanding the mechanisms underlying the formation of biologically relevant minerals by comparing the properties of solid phases formed in calcium phosphate (CaP) or calcium carbonate (CaCO3) precipitation systems, at defined initial experimental conditions: supersaturation, constituent ions ratio, ionic strength and/or presence of relevant inorganic ions. Thus, three systems of different chemical complexity were investigated: (a) system containing constituent ions, (b) system containing additional co-ions and (c) system with higher ionic strength and addition of Mg2+. The respective precipitation diagrams were constructed and supersaturation domains of different CaP and CaCO3 solid phases formation were identified. The obtained results may have implication not only for biomineralization and geochemistry, but also for materials science in general.


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Introduction Calcium carbonates (CaCO3) and calcium phosphates (CaPs), sparingly soluble salts of carbonic and phosphoric acid, continuously attract attention due to their role in biomineralization, technological processes and synthesis of advanced materials with tailored properties.1, 2 Calcium carbonates are the most abundant biominerals in invertebrates, including mollusks, sponges, corals and crustaceans. They appear in three polymorphic modifications (calcite, aragonite and vaterite) and three hydrated forms (calcium carbonate monohydrate, MHC), calcium carbonate hexahydrate and amorphous calcium carbonate, ACC) (Table SI1).3-6 Of these, only calcite and aragonite are regularly deposited as biominerals. Many types of seashell contain both minerals that are spatially separated: the outer, prismatic, layer of the shell consists of calcite, while the inner region (nacre) is built of plate-like aragonite crystals. This remarkable switching between polymorphs is controlled by a layer of closely packed cells, the outer epithelium, which is separated from the inner shell surface by the extrapallial space and fluid. In spite of the predominating abundance of aragonite and calcite in biominerals, experimental evidence also points toward the presence of less stable CaCO3 modifications: amorphous calcium carbonate (ACC), as a hydrated, poorly ordered and metastable precursor for the formation of crystalline CaCO3 polymorphs and vaterite as a solid-state transition phase from the amorphous phase.7-10 In addition, because of the ACC's instability and relatively high solubility, it is found in various organisms of different taxonomic groups as a temporary storage medium for calcium and carbonate ions.11 Unlike the calcium carbonates which form different polymorphs, CaPs appear in organisms as chemically different compounds (Table SI1). For biomineralization, certainly the most important phases are amorphous calcium phosphate (ACP), octacalcium phosphate [OCP,

Ca8(HPO4)2(PO4)4·5H2O],

calcium

hydrogenphosphate


dihydrate

[DCPD,


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CaHPO4·2H2O], calcium deficient apatite [CaDHA, Ca10−x(HPO4)x(PO4)6−x(OH)2−x, 0 < x < 1] and hydroxyapatite [HAP, Ca10(PO4)6(OH)2].1, 12 CaPs can be found in different organisms, ranging from bacteria to vertebrates,13 and it is believed that in primitive organisms, the formation of calcium phosphate is relevant for storage and regulation of essential elements. In these organisms, ACP appears as small intracellular nodules often located in mitochondria.14 However, in vertebrates, calcium phosphates are the main inorganic component of normal (bones, teeth, fish enameloid) and pathological hard tissues (dental and urinary calculi, atherosclerotic lesions). The dominant calcium phosphate phase in vertebrates is poorly crystalline, non-stoichiometric, calcium deficient, Na-, Mg- and carbonate hydroxyapatite, often called biological apatite.1 Calcium deficient hydroxyapatite (CaDHA) is of great biological interest because of its supposed important role during bone formation and remodeling.15 However, there is much evidence that during the formation of hard tissues in vertebrates, ACP formation is the first step.16, 17 Due to their properties, superior to any geologically or man-made material, elucidation of formation mechanisms of CaCO3 and CaPs hard biocomposites are of special interest in materials science.11, 18 Although CaCO3 and CaPs do occur in different organisms, a number of similarities in the mechanisms of their formation, as well as in their physiological roles, have been found.2 Because of that, a number of researchers have pointed to the suitability of comparing the formation mechanism of different salts. Nevertheless, such an approach for revealing the basic mechanism of biomineralization has still not been fully exploited.19 In addition, biomimetic precipitation of both salts, at conditions close to physiological, attracts attention as a model of green synthesis.20 At that, an apparently simple synthetic process, precipitation offers a possibility to tune the size, morphology, chemical and structural composition of products by strict control of thermodynamic parameters, including pH, temperature, reactants concentrations or addition of different soluble inorganic and organic


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molecules,21 as well as kinetic and/or hydrodynamic parameters of respective reactions. However, it should be noted that it is not possible to directly compare simple precipitation in two component systems and processes underlying the formation of solid phases in living organisms.22, 23 The key difference between these processes is the rather complex role which insoluble organic matrix, soluble organic (macro)molecules and confined volumes have in the formation of biominerals in vivo.2, 22, 23, 24 The aim of this study is to compare the properties of solid phases formed under comparable initial experimental conditions (supersaturation, constituent ions ratio, ionic strength and presence of relevant inorganic additives) in CaCO3 and CaPs systems of various complexity. Thus, the purpose of simple systems, containing only constituent ions, was to elucidate the role of principle precipitation parameters: supersaturation, constituent ions ratio and ionic strength. More complex systems, containing sodium and chloride co-ions as well, were chemically more similar to natural systems, while the systems of increased ionic strength and addition of magnesium ions were designed with the aim of simulating the inorganic chemical environment in living organisms. The proposed experimental methodology allowed the construction of the respective precipitation diagrams in the broader physiological concentration domain of constituent ions relevant for both systems (Fig. SI1), while relatively short aging time enabled an investigation of the role of metastable and amorphous phases in the process of CaCO3 and CaPs formation in simple inorganic systems. The comparison of CaCO3 and CaPs precipitation diagrams may contribute to a deeper understanding of the role of different precipitation parameters, such as the relatively simple role of supersaturation or, on the other hand, kinetically influenced transformation of precursors which is affected by the presence of common inorganic ions (Mg2+). Therefore, the obtained results may be of interest for materials science, as well as for biomineralization and geochemistry, as a valuable starting point for more complex investigations. Ultimately, this



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research may contribute to the goal of fully employing the apparent advantages of the biomimetic bottom-up approach in the synthesis of new materials.

Experimental Materials. Analytical grade chemicals, calcium hydroxide (Ca(OH)2), calcium chloride (CaCl2), phosphoric acid (H3PO4), sodium carbonate (Na2CO3), sodium hydrogen phosphate (Na2HPO4), sodium chloride (NaCl) and magnesium chloride (MgCl2) were obtained from Sigma Aldrich, Germany. Milli-Q water (Millipore) was used in all experiments. In order to prevent the contamination of calcium hydroxide solution with CO2, Milli-Q water was bubbled with N2. Stock solutions were prepared from the analytical grade chemicals or by diluting the concentrated solutions to appropriate concentration. The concentrations were determined by ion chromatography. Calcium hydroxide stock solution was prepared by the addition of excess of calcium hydroxide to water and subsequent filtering of the suspension through a 0.22 µm membrane filter. The saturated solution was kept under a nitrogen atmosphere while the exact concentration was determined by potentiometric titration using a standard HCl solution (c = 0.10 mol dm-3). Carbonic acid stock solution was prepared by bubbling high-grade carbon dioxide gas into water until apparent constancy of the pH was obtained. The exact concentrations of freshly prepared stock solutions of carbonic and phosphoric acid were determined by potentiometric titration using a standard NaOH solution (c = 0.10 mol dm-3).

Precipitation systems Six precipitation systems of different chemical complexity were investigated and corresponding precipitation diagrams were constructed: - simple precipitation systems (containing constituent ions only) 6 ACS Paragon Plus Environment

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(a) Ca(OH)2 - H2CO3 (b) Ca(OH)2 - H3PO4 - complex precipitation systems (containing constituent ions and their counter ions) (c) CaCl2 – Na2CO3 (d) CaCl2 – Na2HPO4 - physiological precipitation systems (containing constituent ions, NaCl and MgCl2) (e) CaCl2 – Na2CO3 – NaCl (c = 0.15 mol dm-3) – MgCl2 (c(CaCl2) : c(MgCl2) = 1:2) (f) CaCl2 – Na2HPO4 – NaCl (c = 0.15 mol dm-3) – MgCl2 (c(CaCl2) : c(MgCl2) = 1:2) The precipitation of CaCO3 and CaP was investigated within a wide range of initial reactant concentrations: 1.0·10-5 mol dm-3 < ci(Ca)tot < 1.0·10-2 mol dm-3; 1.0·10-5 mol dm-3 < (ci(CO3)tot or ci(P)tot) < 1.0·10-2 mol dm-3). The range of reactant concentrations was chosen with the aim of mimicking physiological concentrations of the constituent ions in which calcium carbonates and calcium phosphates precipitate in living organisms and seawater (Figure SI1). The highest value of the concentration range was limited by the solubility of Ca(OH)2 and CO2. However, in the CaCO3 (e) and CaP (f) physiological precipitation system (increased ionic strength and additional Mg2+ ion pairing) the highest concentrations applied were, c = 4.0·10-2 mol dm-3, so the relative supersaturations were comparable to the simple systems. The initial pH has not been adjusted in any system. In order to provide reproducible and comparable hydrodynamic conditions in all experiments, the initial mixing of reactant, as well as the agitation of the suspension were identical. Thus, the precipitation was initiated by pouring carbonate or phosphate solution into an equal volume of calcium or calcium-magnesium solution of the appropriate concentration. During the precipitation, the systems were continuously stirred at a constant rate by means of a Teflon-coated magnetic bar and the progress of the process was



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followed by monitoring the pH changes. All experiments were performed at 25 °C, in a tightly closed vessel, thus minimizing the exchange of CO2 between the reaction system and the air. The samples for analyses were taken after 1 hour of ageing. The entire volume of suspension was filtered through a 0.22 µm membrane filter. Obtained precipitates were thoroughly washed with small portions of Milli-Q water and dried at 105 °C (CaCO3), or in a stream of nitrogen (CaPs) and kept in a desiccator until further analysis. Composition and structure of the obtained precipitates were determined by FTIR spectroscopy (Tensor II, Bruker), X-ray diffraction (Rigaku Ultima IV Multipurpose diffractometer using CuKα radiation). The baselines of powder XRD patterns were corrected and when needed the data were smoothed using 5-point Savitzky-Golay algorithm in order to be able to assign all reflections. The average size of the CaDHA particles was estimated using Debye-Scherrer method from the full width at half maximum of the observed reflections. The morphology was observed by FE-SEM (JEOL JSM-7000F microscope), while the chemical composition of the selected samples was determined by ion chromatography.

Data analyses From the known total concentrations of reactants initially added to the precipitation system, the molar concentrations and the corresponding activities of all relevant ionic species that were assumed to initially exist at significant concentrations in the solution (CaCO3 systems: H+, OH-, CO32-, HCO3-, CaCO30, CaHCO3 +, Ca2+, CaOH+; CaP systems: Ca2+, CaOH+; CaH2PO4+, CaHPO40, CaPO4-, H+, H2PO4-, H3PO40, HPO42-, OH-, PO43-) have been calculated

by

using

our

own

algorithm

or

by

VMINTEQ

3.0

(available

at

http://vminteq.lwr.kth.se/download/). The activity coefficients (yz) were calculated using the Davies approximation of the Debye–Hückel equation:


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-log yz = Az2[I1/2/(1+I1/2)-0.3I], where A is the Debye – Hückel constant (A = 0.509 for aqueous solution at 25 °C), z is the charge of the ion and I is ionic strength. Based on calculated ionic activities and known solubility constants, the relative supersaturations for calcite and OCP were calculated. At that, the initial supersaturation was defined as relative supersaturation, S-1: S-1 = (Π / Ksp0)1/n - 1 where Π is the ion activity product and Ksp0 is the solubility product for the respective solid phase. More specifically, in the case of CaCO3, S-1 = ((c(Ca2+)·c(CO32-)·γ22)/Ksp0)1/2 - 1, where Kspo is the thermodynamic equilibrium constant of calcite dissolution (solubility product); Kspo = 3.313·10-9 at 25 °C. In the case of CaP, relative supersaturation with respect to OCP was defined as, S-1 = {[ c(Ca2+)4·c(PO43-)3·c(H+)·γ24γ33γ1]/ Kspo}1/8 - 1. The solubility product of OCP is Kspo = 1⋅10-47.95 at 25 °C. However, it should be emphasized that OCP is not thermodynamically the most stable phase but it was selected because of the ill-defined composition of CaDHA, while the solubility of DCPD is higher than the values corresponding to the majority of the concentration domain of reactants investigated in this work, (S-1) < 0.

Results and discussion The precipitation diagrams are plots depicting the concentration domains of the existence of solid phases of definite composition, morphology or crystal habit, formed under well defined experimental conditions and at predetermined aging time.25 Since precipitation diagrams comprise a range of basic information about precipitates, their construction is



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considered to be the first step for any additional and more complex investigation of a specific system. The distribution of solid phases formed in specific CaCO3 or CaP systems, and for the given range of reactant concentrations, is represented by the respective precipitation diagrams shown in Figure 1. Thick lines denote the precipitation boundaries, i.e. boundary between the regions in which precipitate was detected (perceived as changes of solution composition and measured as pH drop) and those in which no precipitate was observed after 1 hour of reaction. Thin lines denote isergones, i.e. isograms of constant relative supersaturation, S-1. The line corresponding to S-1 = 0 represents the solubility boundary, considering calcite (CaCO3 systems) or OCP (CaP systems) as solid phases in equilibrium. For the sake of clarity, the equivalence lines (c(Ca(OH)2 = c(H2CO3) or c(Ca(OH)2 = c(H3PO4)) are shown as well. The supersaturated regions in the diagrams delimited by the precipitation and solubility boundaries are metastable zones in which no precipitation has been observed at the predetermined time (60 minutes). The formation of precipitates of similar and specific composition with respect to their thermodynamic stability (stable, metastable, stable/metastable, amorphous and stable/amorphous) is indicated by differently shaded areas in each diagram. It should be noted that in all investigated systems two distinct precipitation regions, based on the composition of precipitate, have been observed; one at relatively high supersaturations (S-1)high and other at lower relative supersaturations (S-1)low. However, it should be emphasized that in the precipitation systems which are supersaturated with respect to several polymorphic or solid modifications, formation of specific modifications, their morphologies or size distribution may be influenced by hydrodynamics as well. Therefore, the initial mixing of reactants and the agitation of the suspensions have been strictly controlled and kept identical in all systems.


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CaP

Complex

Simple

CaCO3

Physiological

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Figure 1. Precipitation diagrams of CaCO3 (a,c,e) and CaP systems (b,d,f): simple (a,b), complex (c,d) and physiological (e,f) obtained after 1 hour reaction time. Precipitation boundaries are denoted with thick lines and isergones with thin lines (numbers denote the S-1 value). The precipitation regions are denoted according to precipitate composition. Full circles denote systems in which the precipitate was analysed, and empty circles the first systems in which precipitate was not observed.



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Simple precipitation systems: Precipitation diagrams obtained in the simple CaCO3

and CaP systems, prepared by neutralization of calcium hydroxide solution with respective acid (H2CO3 or H3PO4), are shown in Figure 1a,b. A significant uniqueness of these precipitation systems is the presence of only the constituent ions∗, so the obtained solid phases could not contain any cationic or anionic impurities incorporated in the crystal structure. Indeed, it was shown previously that the co-ions, particularly anions like Cl-, NO3-, or SO42-, originating from respective soluble calcium salts used as reactants, could co-precipitate with calcite and change its morphology26, 27. Thus, the obtained precipitates could be considered as chemically pure and used as reference material in comparison to the samples obtained in other model systems investigated in this work. According to Težak28, the noticeably asymmetric shape of precipitation and solubility boundaries observed in both systems could indicate the formation of specific ion pairs or complexes in solution or, in the specific cases in which the reactants were calcium hydroxide and the respective acids, increased solubility of solid phases at higher concentrations of acids. It should be emphasized that the initial pH was not preadjusted in any system and it was found to vary significantly (5.6 < pHi < 12.3 in CaCO3 and 2.2 < pHi < 12.3 in the case of the CaP system). Accordingly, in the precipitation domains at high H2CO3 concentration and (c(H2CO3)/c(Ca(OH)2) > 1), the systems were undersaturated with respect to any solid phase that could precipitate, not only calcite, and the width of the metastable zone was significantly narrower in comparison to the low H2CO3 and high Ca(OH)2 domain. Similar to the CaCO3 diagram, in the case of CaP, at high Ca(OH)2 concentration and (c(H3PO4)/c(Ca(OH)2) > 1) domain, the increased solubility of solid phases, as well as the narrow metastable zone, were observed. On the other hand, within the Indeed, only the Ca2+, CO32- or PO43-, their protonated ionic species , water molecules and the products of water autoprotolysis (H3O+, OH-) were present in the systems.

∗


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high Ca(OH)2 and low H3PO4 concentration domain, the width of the metastable zone is relatively narrow in comparison to CaCO3. The observed difference is certainly a consequence of the higher acidity of phosphoric than carbonic acid, as well as of the essential difference between calcium carbonate and calcium phosphate solid phases. In particular, calcium carbonates are 1:1 compounds made up from calcium and carbonate ions only, while in calcium phosphate structures, calcium, phosphate (PO43-) and hydrogen phosphate (HPO42-) ions, in different proportions, are regularly present (Table SI1). The same explanation could be given for the difference of the shape, and particularly for the width, of metastable zones observed at lower concentrations of carbonic and phosphoric acid (close to the equivalence line) in CaCO3 and CaP diagrams. Precipitation diagrams of similar shape have been described previously for the calcium carbonate system, but for shorter aging time (20 minutes), narrower concentration domain of Ca(OH)2 / H2CO3 and stirring by means of a flat-bladed pedal.26 On the other hand, systematic investigations of CaP precipitation systems, in which Ca(OH)2 and H3PO4 solutions were used have been described in only a few cases. Thus, similar chemical reactions was proposed for the synthesis of DCPD29 and for biomimetic whitlockite synthesis.30 In addition, solubility of different calcium phosphate solid phases in Ca(OH)2 - H3PO4 systems was determined,31 but to the best of our knowledge, no systematic precipitation studies in a wider concentration range have been conducted so far. Simple CaCO3 system. The analysis of results of structural and morphological characterization of the precipitate obtained after 1 hour of aging in the CaCO3 precipitation system showed essentially two precipitation domains. Thus, at lower and medium supersaturations (approximately (S-1) < 20; ci(Ca(OH)2) < 0.007 mol dm-3 and ci(H2CO3) < 0.007 mol dm-3) precipitation started after a well-defined induction time and the obtained solid phase was almost exclusively calcite. However, it is known that under conditions of low



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relative supersaturations, particularly in the calcium carbonate system, nucleation of the stable phase is thermodynamically favored.32, 33 PXRD pattern of the typical precipitates obtained in (S-1)low region (Fig. 2a, Table SI2) shows only diffraction peaks characteristic for calcite (FTIR spectra, Fig. SI2a, also confirmed the presence only of calcite). SEM micrographs of respective samples show that the morphology of crystals changes as a function of two parameters: supersaturation and calcium to carbonate ratio. Thus, at low supersaturation (S-1 ≈ 5) polydispersed and predominantly irregular rhombohedral calcite particles could be found (Fig. 2b), while in the medium supersaturation domain (S-1 ≈ 10) calcite precipitates in a number of distinct forms: at Catot/CO3tot ≈ 1/1 rhombohedral particles precipitated (Fig. 2c), at Catot/CO3tot ≈ 8/1 predominantly scalenohedrons (Fig. 2d), while at Catot/CO3tot ≈ 10/1 predominantly spherulitic agglomerates (Fig. 2e) of calcite have been found. The observed formation of polar scalenohedral and spherulitic calcite particles at higher alkalinity (pH ≈ 12) is consistent with literature data34-37 and can be explained by the predominant adsorption of hydroxyl ions. However, in similar systems, in which mechanical stirring was applied for a range of reactant concentrations and low supersaturations (0.005 mol dm-3 < ci < 0.01 mol dm-3), calcite was also found as a predominant solid phase, though predominantly in a rhombohedral form.26


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a (104) I / a.u.

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(018) (116)

(113)(202) (110)

20

30

40 ο 2θ /

50

60

Figure 2 PXRD patterns and SEM micrographs of the precipitates formed in simple Ca(OH)2 - H2CO3 precipitation systems after 1 hour aging. Equimolar systems at S-1 ≈ 5 (a, b), S-1 ≈ 10 and increasing Ca(OH)2/H2CO3 ratio 1/1 (c), 8/1 (d), and 10/1 (e) and S-1≈ 30 (f, g). The precipitation domain of the samples are indicated in Figure 1a.



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In the (S-1)high region (approximately (S-1) > 20; ci(Ca(OH)2) = ci(H2CO3) ≥ 0.007 mol dm-3) calcite precipitates as a mixture with vaterite (Fig. 2f). At that, vaterite was identified by typical PXRD (110) reflection at 2θ = 24.9 and characteristic IR absorption band of vaterite (746 cm-1, ν4) (Fig. 2f, Table SI2, Fig. SI2b). The appearance of vaterite is consistent with the literature findings, according to which formation of metastable phases during spontaneous precipitation from highly supersaturated solutions is quite common and is kinetically controlled. The SEM analysis of respective samples of dried precipitates showed typical (regular) rhombohedral calcite crystals and cauliflower-like vaterite particles (Fig. 2g). In these systems very high turbidity and a sharp drop of pH, observed immediately after mixing the Ca(OH)2 and H2CO3 solutions (pH-time curve in Fig. SI3b), indicate the formation of precursors, most probably the amorphous phase(s).26 Simple CaP system. Just as for CaCO3, the structural and morphological characterization of the solid phases obtained in CaP system indicated the existence of two precipitation domains: (S-1)high corresponds to, (c(Ca(OH)2 = c(H2CO3) ) > 0.007 mol dm-3, while (S-1)low corresponds to (c(Ca(OH)2 = c(H2CO3) ) < 0.007 mol dm-3, Figure 1b. At lower initial supersaturations only CaDHA precipitated, as confirmed by structural analyses. The PXRD diffraction pattern showed two broad peaks at 2θ = 25.96° and 31.97° superimposed on an amorphous halo, which are characteristic of poorly crystalline CaDHA (Fig. 3a).38 The average size of CaDHA particles, calculated from PXRD patterns using the Debye-Scherrer method, was about10 nm. FTIR spectra of the same samples (Fig. SI2c) showed specific bands of phosphate and water. Thus, the asymmetric stretching mode of PO 34 − has been found at 1108 cm-1 and 1030 cm-1, symmetric stretching at 958 cm-1, with bending modes of PO 34 − at 602 cm-1, 562 cm-1 and 472 cm-1. The band at 874 cm-1 corresponds to HPO 24 − vibration. A broad band at 3700-2600 cm-1, as well as a band at 1636 cm-1, correspond to vibration of water molecules. However, no carbonate bands were observed in FTIR spectra, indicating that 16 ACS Paragon Plus Environment

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phosphate and/or hydroxyl group in the CaDHA structure were not substituted with carbonate ions. In addition, Ca/P ratio of 1.5, obtained by chemical analysis of the precipitates, confirmed formation of CaDHA. SEM micrographs of CaDHA showed formation of typical dense sheet-like precipitate in the entire (S-1)low region (Fig. 3b). Unlike CaCO3, in the (S-1)high region of the CaP system, only one solid phase, DCPD, was found after one hour of aging. The pH-time curves (Fig. SI3d) showed an immediate drop of pH after mixing the reactants, thus indicating homogeneous nucleation, i.e. a fast and continuous process of DCPD formation. The PXRD pattern of typical samples obtained at high supersaturation (Fig. 3c) shows the diffraction peaks characteristic for DCPD at 2θ = 11.63o, 20.86o, 23.34o, 29.23o, 30.57o and 34.09o, corresponding to the reflections at (020), (021), (040), (041), ( 2 21) and ( 2 20) planes, respectively. The FTIR spectra (Fig. SI2d) confirmed formation of DCPD only. Relatively large and thin, plate-like DCPD crystals of the representative samples of precipitate were observed by SEM (Fig. 3d). It should be noted that the entire region of higher initial reactant concentrations is slightly acidic (pH ≈ 6.4, lower PO43-) that favors the formation of solid phases build up by partially protonated phosphate ions. The formation of DCPD under such conditions is in accordance with a number of studies that pointed to its direct formation (no precursors) at pH < 6.5.39 Further, it is thought that HAP is the most stable CaP phase at near neutral pH and DCPD is the most stable at low pH, although a recent study by Pan challenged such an opinion.40-42 Summary of the simple systems. In conclusion, in the simple calcium carbonate system, calcite is dominant polymorph which precipitate at low and medium initial supersaturation. At that, the morphology of crystals (rhombohedrons, scalenohedrons and spherulites) depends on initial supersaturation and calcium to carbonate ratio. At highest supersaturation domain, a mixture of stable and metastable polymorphs, calcite and vaterite, could be observed after one hour of aging. Similarly, in the CaP simple system at low and



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medium supersaturations, only one solid phase (CaDHA) was found. Since CaDHA is inherently unstable crystal modification with not well defined structure, the morphology was found to be poorly defined and no significant correlation between supersaturation and morphology has been observed. At highest supersaturations applied in CaP system, after 60 minutes of aging only DCPD, stable calcium phosphate phase at low pH, was found.


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Figure 3. PXRD patterns and SEM micrographs of the precipitates formed in the simple Ca(OH)2 - H3PO4 precipitation systems after 1 hour aging: S-1low (a, b) and S-1high (c, d). The precipitation domain of the samples are indicated in Figure 1b. Major DCPD reflections are denoted.



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Complex precipitation systems: Although chemical distinction of the complex

precipitation systems, with respect to the simple, is just the presence of sodium and chloride co-ions originating from reactants CaCl2, Na2CO3 or Na2HPO4, the shape of the appropriate precipitation and solubility boundaries and isergones in precipitation diagrams are significantly different (Fig. 1c,d). It may be seen that in both systems the precipitation boundaries and isergones were approximately symmetrically placed with respect to the equivalence line, even at the highest c(Na2CO3) or c(Na2HPO4). A bending of isergones and deviation from ideal straight line shape is a result of ion pair formation, which lower the concentration of constituent ions, i.e. free Ca2+ or CO32- and, consequently, the supersaturation28. Thus, it was calculated that for high initial concentration of carbonate: (log(c(Na2CO3)i/mol dm-3) = -2.0 and log(c(CaCl2)i/mol dm-3) = -2.5, -3.1 or -3.6), concentration of CaCO30 ion pair is: c(CaCO30)/c(CaCl2) = 0.73, 0.77 or 0.78, respectively. Similarly, when initial concentration of the calcium component is high (log(c(CaCl2)i/mol dm3

) = -2.0 and log(c(Na2CO3)i/mol dm-3) = -2.5, -3.0 or -3.5) then c(CaCO30)/c(Na2CO3)i =

0.68, 0.67 or 0.59, respectively. However, a critical role of CaCO30 ion pair in calcium carbonate crystallization (nucleation) has been postulated before, wherein this neutral species is considered as a growth unit.43 In addition, the initial pH measured after mixing the reactants in all investigated systems was higher than in the respective simple systems in which acids were used: 10.0 < pHi < 11.0 in the CaCO3 and 6.8 < pHi < 8.6 in the CaP system. It should also be noted that the domain of metastability of solutions is larger in the CaP than in the CaCO3 system. However, for more than a century spontaneous precipitation and seeded growth of calcium carbonate in CaCl2 - Na2CO3 (or NaHCO3) solutions has attracted significant interest but, to the best of our knowledge, just a few attempts of systematic investigation of the broader concentration domain are described in the literature.44,

45

Thus, Kawano et al. showed the


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precipitation diagrams at 20 °C, 50 ºC and 80 ºC, for concentration of reactants varying in the range (1·10-3 mol dm-3 < ci < 5·10-3 mol dm-3), constant Ca/CO3 ratio and the ionic strength, adjusted with the addition of NaCl, Ic=0.1 mol dm-3.45 On the other hand, investigations of the CaCl2 - Na2HPO4 system, particularly those containing NaCl, are described as simplified inorganic models for normal and pathological CaP biomineralization.46-48 It should be noted that the characteristics of the precipitation diagram shown in this work are rather similar to those described in the literature, though aged for 24 hours. Complex CaCO3 system. Structural analyses (PXRD, FTIR) of the precipitate formed in the complex CaCO3 system at low and medium initial supersaturation, which correspond approximately to the entire (S-1) < 10 and partly to (S-1) > 10, showed that vaterite is a principal solid phase obtained after 1 hour of aging (Fig. 1c, Fig. 4a, Fig. SI5a, Table SI5). Typical vaterite particles observed in the complex system precipitated in the form of aggregates of primary crystallites: at lower supersaturations, S-1 ≈ 5, crystallites associate into layered, irregular, lens-like structures (Fig. 4b), while at higher supersaturations, S-1 ≈ 10, more compact and spherical structures are observed (Fig. 4c). Indeed, higher carbonate content causes the formation of even smoother spheres (Fig. 4d). On the other hand, in a part of 10 < S-1 < 20 region and in whole S-1high region (S-1 > 20) a vaterite/calcite mixture appeared, as confirmed with PXRD and FTIR (Fig. 1c, Fig. 4e, Table SI5). Morphological characterization of typical precipitate isolated from the respective systems showed relatively smooth vaterite spheres, larger than vaterite precipitated at medium and low supersaturations, and twins of calcite rhombohedrons (Fig. 4f). Similarly to the simple precipitation system, high turbidity and a sudden pH drop have been detected after mixing the reactants in the system of high relative supersaturations, thus indicating a homogeneous nucleation and the formation of the precursor (amorphous) phases at early stages of the process (pH-time curve in Fig. SI4b). The available literature data indicated the appearance of only vaterite, or 21 ACS Paragon Plus Environment


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vaterite in a mixture with calcite under experimental conditions comparable to those applied in this work.45, 49 Complex CaP system. In the complex CaP precipitation system (Fig. 1d), at lower relative supersaturations, (S-1) < 8, CaDHA was the only phase detected, which is similar to the solid phase composition in the corresponding concentration domain of the simple system. PXRD pattern (Fig. 5a) shows, not only the most intensive reflections typical for CaDHA at 2θ = 25.99° and 32.04° superimposed on amorphous halo, but also some small intensity reflections at 2θ = 28.13°, 39.49°, 46.67°, 49.41° and 53.15°, which indicate the increased crystallinity of the samples.38, 50 The average size of the crystallites was about 9 nm, which is comparable to the CaDHA particles obtained in the simple system. Similarly, the FTIR spectra (Fig. SI5c) contained only phosphate and hydroxyl bands typical for CaDHA and no carbonate bands. The respective Ca/P ratio was 1.5, as found for the precipitates obtained at lower supersaturations in simple CaP system. However, two different morphologies of CaDHA have been observed in the lower supersaturation domain: small sheet like crystals and spherulitic aggregates of tiny crystals (Fig. 5b,c). On the contrary, at the highest supersaturations attained in this system, (S-1) > 8, a mixture of DCPD and CaDHA was obtained, as confirmed by PXRD analysis. Thus, (020), (021), (041), ( 2 21) and ( 2 20) DCPD reflections as well as reflections at 2θ = 25.91° and 31.88°, typical for poorly crystalline CaDHA, were observed Fig. 5d.35 SEM observations revealed a mixture of large, thin, platelike DCPD crystals and smaller sheet-like CaDHA particles (Fig. 5e,f). It should be noted that these particular sheet-like CaDHA crystals are less dense in comparison to a similar precipitate obtained in the simple CaP system.


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Figure 4 PXRD patterns and SEM micrographs of the precipitates formed in complex precipitation systems CaCl2 - Na2CO3 after 1 hour aging. Equimolar systems at S-1 ≈ 5 (a, b), S-1 ≈ 10 and high calcium (c) or high carbonate concentration (d) and S-1 ≈ 30 (e, f). The precipitation domain of the samples are indicated in Figure 1c.



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The literature data about the composition of the precipitate, obtained after 24 hours in the respective CaCl2-Na2HPO4 or CaCl2-Na2HPO4 - 0.15 M NaCl systems at pH = 7.4 and without stirring, indicated a similar distribution of CaP phases and just a slight influence of NaCl addition.46,

47

However, the most significant difference between the precipitate

composition observed in this work and those described in the literature, correspond to the phases detected in the highest supersaturation domain: in the literature, mixtures of DCPD and apatite have been observed and that is most probably a consequence of prolonged aging (24 hours) of initially formed calcium deficient apatite, detected in the present work after 1hour.47 A generally accepted opinion about the mechanism of CaP precipitation in aqueous systems that simulate physiological conditions postulates direct nucleation of DCPD, while OCP, CaDHA and HAP are supposed to be formed from precursor ACP phases.12,

40

However, the results of this study, as well as those obtained by Füredi-Milhofer et al.47, indicated that the mentioned mechanisms can occur simultaneously. The proposed mechanism of simultaneous nucleation of several phases40, 51 comply with the calculated composition of solutions, which showed that in the particular case described in this work the precipitation systems have been supersaturated with respect to more than one CaP phase. Summary of complex systems. In summary, in the complex calcium carbonate system (calcium, carbonate, sodium and chloride ions) vaterite is dominant polymorph that precipitate at low and medium initial supersaturation. At that, vaterite appears in a form of aggregate of primary crystallites. Size of primary crystallites decrease with increasing initial supersaturation. At highest supersaturations applied, mixture of calcite and vaterite precipitate. However, the primary crystallites of vaterite precipitated at highest supersaturation are even smaller. In the complex CaP system, metastable CaDHA formed in whole investigated concentration region, either as only formed solid phase at low and medium


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supersaturations, or in mixture with DCPD at highest supersaturations. At that, different CaDHA morphologies were observed, depending on supersaturation, i.e. dense sheet like crystals at higher supersaturation and their mixture with spherulitic aggregates of tiny crystals at low and medium supersaturations.



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Figure 5. PXRD patterns and SEM micrographs of the precipitates formed in the complex CaCl2 – Na2HPO4 precipitation systems after 1 hour aging. S-1low (a, b, c) and S-1high (d, e, f). The precipitation domain of the samples are indicated in Figure 1d.


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Physiological precipitation diagrams: In order to closely mimic the inorganic environment

of in vivo formation of calcium carbonates or calcium phosphates, systems containing Mg2+ and increased ionic strength were investigated: CaCl2 – Na2CO3 – 0.15 M NaCl – MgCl2, or CaCl2 – Na2HPO4 – 0.15 M NaCl – MgCl2 (Ca: Mg = 1:2) (Fig. 1e,f). However, a principle difference between these so-called physiological systems and the other systems described in this work is the presence of magnesium. Magnesium is an inorganic component regularly present in biological fluids at concentrations higher than the concentration of calcium ions. It is well known that Mg2+ ions have an important role in geochemical systems and in biomineralization, mostly as an inhibitor of both calcium carbonate and calcium phosphate precipitation.52-54 Thus, it was found that magnesium can either become incorporated in the calcite crystal lattice,26, 55 induce aragonite precipitation or even stabilize amorphous calcium carbonate.56 A recent study by Ding et al. has shown that adsorbed Mg2+ ions are more efficient in inhibiting the ACP transformation than incorporated ones.52 In addition, Salimi et al. have shown that Mg2+ has a strong inhibiting effect on HAP growth and to a lesser extent on OCP, while no effect on DCPD was observed.53 Also, incorporating Mg2+ in CaPs is considered an efficient way of increasing bioactivity of designed biocompatible materials.57, 58 However, except for Jang et al.30 who investigated ternary Ca(OH)2-Mg(OH)2-H3PO4 systems with the objective of a large-scale synthesis of pure whitlockite (Ca18Mg2(HPO4)2(PO4)12), no systematic study of the influence of Mg2+ ions in broader CaP constituent ions concentrations has been described in the literature. Calculations show that the addition of sodium chloride, as well as magnesium chloride, effectively resulted in a decrease of supersaturation in comparison to the corresponding simple and complex systems. Therefore, in order to attain the relative supersaturation comparable to simple and complex systems (approximately the maximum (S-



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1) = 35 in CaCO3 and (S-1) = 9 in CaP), the reactant concentration domains in both systems were increased. The addition of NaCl and MgCl2 to the CaCO3 system also caused a systematic broadening of the metastable zone, while the precipitation boundary was additionally shifted at the highest CaCl2 concentrations applied. Thus, the calculation of solution composition showed that under given conditions the pH is lower, while the concentration of magnesium ions pair is much higher than at high Na2CO3 concentration and similar supersaturations. In the CaP system the precipitation boundary was somewhat shifted towards lower phosphate concentrations, as compared to the complex precipitation system. However, the metastability zone was narrower, thus reflecting the change in solution composition. Physiological CaCO3 system. Structural analyses (PXRD, FTIR) of the precipitate formed in the CaCO3 system of low supersaturation, but also under highly supersaturated conditions, showed that the dominant solid phase present after one hour of aging was aragonite (Fig. 1e). The aragonite was identified by (221) reflection at 2θ = 45.9° (Fig. 6a) and characteristic IR absorption bands (700 cm-1 and 713 cm-1 that correspond to ν2 andν4 modes, respectively, Figure SI7a,b, Table SI8). However, many literature sources indicate that aragonite formation in geochemical and biological environments is strongly influenced by the presence of Mg2+ ions and at Mg/Ca molar ratios higher than 4, while at lower Mg/Ca ratios, mixtures of calcite, magnesium calcite and/or aragonite could be obtained. Therefore, we intentionally applied Mg/Ca = 2, in order to be able to study the role of supersaturation, aging time, Ca2+/CO32- ratio and specific hydrodynamic conditions on possible polymorph selection. It should be mentioned that the generally accepted opinion about the formation of aragonite at Mg/Ca > 4 is generated on the basis of very different systems, in which specific interactions of critical precipitation factors, like temperature, supersaturation, dissolved small organic, macromolecular or inorganic additives, substrate, hydrodynamics, confinement, as well as


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many others, have been affected.23, 24, 59, 60, 61 Actually, in the systems of artificial seawater (similar to this study) in which precipitation of calcium carbonates have been investigated as a function of temperature and Mg/Ca molar ratio, aragonite was also found to be the dominant polymorph at Mg/Ca = 2 and t > 25 °C.62, 63 Figure 6b-e shows SEM of aragonite particles, precipitated at different supersaturations and calcium to carbonate ratio. Typically, aragonite particles are agglomerates of smaller crystallites: at lower supersaturation (S-1 ≈ 5) lens-like structures (Fig. 6b,c) could be observed, while in the medium supersaturation domain (S-1 ≈ 10) wheat sheaves forms (Fig. 6d,e) are predominant. At that, calcium to carbonate ratio has no significant influence on morphologies at constant supersaturation. However, the morphology of aragonite precipitated at the highest supersaturations (Fig. 6f) applied in this work (S-1 ≈ 33) is similar to low-supersaturation aragonite. Such seemingly inconsistent findings actually point to different mechanisms of aragonite formation. Namely, at such high supersaturation the first solid phase that nucleated is ACC, which subsequently transformed by a solution mediated process into aragonite within 60 minutes. Thus, aragonite (Fig. 6f) nucleates and grows at effectively lower supersaturation, comparable to lens-like samples Figure 6b,c. However, in a part of the precipitation diagram, corresponding approximately to the concentration domain: (0.003 < ci(CaCl2) < 0.01 mol dm-3) and (0.007 < ci(Na2CO3) < 0.023 mol dm-3; grey area in Fig. 1e), almost exclusively amorphous calcium carbonate precipitated. The PXRD patterns of typical ACC samples (Fig. 7a) show no sharp diffraction peaks and only broad reflections (from 2θ = 25º to 38º and 2θ = 40º to 54º), identical to those reported by Faatz et al.64 In addition, the FTIR spectrum shows characteristic bands for amorphous CaCO3 (Fig. SI7e, Table SI8). The existence of a highly stable amorphous calcium carbonate phase in contact with the aqueous solution, even one hour after its formation, could be explained by presence of magnesium which strongly inhibits ACC dissolution and/or



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nucleation of more stable polymorph(s).56, 65 The SEM micrographs of typical ACC show that it appears in a form of smooth spherical agglomerates with diameters of about 0.7 µm (Fig. 7b). Although the appearance of aragonite and ACC in the presence of magnesium could be anticipated56,

66

the observed precipitation and stabilization of monohydrocalcite

(CaCO3·H2O) in the systems that correspond to the concentration domain at the border between the ACC / aragonite precipitation domain is somewhat surprising. Namely, the occurrence of MHC (lake sediments, speleothems or otoliths), as well as the data from standard protocols for its preparation67, 68 are related to low temperature conditions, yet our results indicated that the magnesium is also a relevant factor for its stabilization. Mg2+ probably inhibits the dissolution of MHC during the solution-mediated process of its transformation into stable modifications. The MHC was identified by means of PXRD and FTIR analyses (Fig. 7c, Fig. SI7c,d, Table SI9).67-70


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Figure 6. PXRD patterns (a) and SEM micrographs of the aragonite precipitated in the physiological CaCl2 – Na2CO3 - 0.15 M NaCl - MgCl2 precipitation systems after 1 hour aging: S-1 ≈ 5 and Ca2+/CO32- = 10/1 (b), S1 ≈ 5 and Ca2+/CO32- = 1/1 (c); S-1 ≈ 10 and Ca2+/CO32- = 1/1 (d) and S-1 ≈ 10 and Ca2+/CO32- = 10/1 (e) and at highest supersaturation, S-1 = 34 (f). The precipitation domain of the samples observed by SEM are indicated in Figure 1 e.



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The SEM micrographs of MHC samples (Fig. 7d,e) show that morphology depends on supersaturation. Thus, typical MHC precipitated at lower supersaturation, (ci(CaCl2)= 0.003 mol dm-3; ci(Na2CO3)= 0.01 mol dm-3) consists of 5-10 µm long, compact agglomerates of primary particles, while MHC obtained at ci(CaCl2)=0.015 mol dm-3 and ci(Na2CO3)= 0.023 mol dm-3, is smaller, more elongated and intimately enfolded (Fig. 7d). However, it should be noted that precipitation of MHC described in the literature, but performed at low temperatures, significantly higher Mg2+ content and ultra sonication, caused a formation of regular spherical particles.67 Physiological CaP system. Contrary to CaCO3, the stabilization of amorphous phases in the CaP physiological system caused by the presence of Mg2+ ions has been observed within the entire precipitation domain (Fig. 1f). Thus, at lower supersaturations (S-1 < 5.6) after 60 min only ACP was detected, as identified by PXRD (amorphous maximum in the region 2θ = 26°-34°, Table SI10, Fig. 8a).38 The obtained FTIR spectra (Fig. SI7f) also shows characteristic ACP vibrations: phosphate bands (asymmetric stretching mode of PO 34 − at 1048 cm-1, HPO 24 − band at 871 cm-1, bending mode of the PO 34 − at 555cm-1) and water bands (broad band at 3700 – 2600 cm-1 and band at 1654 cm-1).38, 71 SEM observations of typical samples show chain-like aggregates of spherical particles characteristic for ACP (Fig. 8b). At higher relative supersaturations, in addition to ACP, DCPD was found to precipitate, as confirmed by PXRD data (Fig. 8c, Table SI11). Typical PXRD diffractograms contained sharp peaks corresponding to DCPD, superimposed on ACP’s amorphous halo, while the FTIR spectra contained only bands characteristic for DCPD (Fig. SI7g). The SEM micrographs of respective samples revealed the formation of a mixture of large plate-like DCPD crystals (Fig. 8d) and aggregates of spherical ACP particles (Fig. 8e). It should be emphasized that the inhibitory role of Mg2+ in ACP stabilization is well recognized52, 53, 72 as well as the fact that it has almost no effect on DCPD precipitation.53 32 ACS Paragon Plus Environment

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Figure 7. PXRD patterns of ACC (a) and ACC (c) precipitated in the physiological CaCl2 – Na2CO3 - 0.15 M NaCl - MgCl2, Ca:Mg = 1:2 precipitation systems after 1 hour aging. SEM micrographs of ACC at S-1 ≈ 20 (b), MHC at S-1 ≈ 13 (d) and S-1 ≈ 24 (e). The precipitation domain of the samples observed by SEM are indicated in Figure 1e.



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Figure 8.PXRD patterns of ACP (a) and DCPD (c) precipitated in the physiologicalCaCl2 – Na2HPO4 - 0.15 M NaCl - MgCl2, Ca:Mg = 1:2 precipitation systems after 1 hour aging. SEM micrographs of ACP at S-1low (b) and ACP/DCPD mixture at S-1high (d,e). The precipitation domain of the samples observed by SEM are indicated in Figure 1f.


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Summary of physiological systems. In the physiological calcium carbonate system (Ca2+, CO32-, Na+, Cl- and Mg2+), aragonite is dominant polymorph, which precipitate at low, medium and highest initial supersaturation. At low supersaturation domain, aragonite appears in a form of lens-like aggregate of primary crystallites, while at medium supersaturation wheat sheaves-like structures could be found. The aragonite particles precipitated at highest supersaturations applied in this work are larger and their morphology is similar to lowsupersaturation aragonite, which pointed to different mechanism of formation and effectively low supersaturation at which it nucleates and grows. At high supersaturations and c(CaCl2)/c(Na2CO3) < 1 domain, formation and temporary stabilization of precursors phases, ACC and MHC, is observed. In the physiological CaP system dominant phase is ACP, which forms in whole investigated region in the form of aggregates of spherulitic particles. At highest supersaturations ACP precipitate in mixture with DCPD. No significant difference in DCPD morphology obtained in different precipitation systems was observed.

Conclusions

In this work, the results of a systematic and comparative study of calcium carbonate and calcium phosphate formation in well-defined precipitation systems of different complexity are shown. Thus, three precipitation systems were investigated: (a) a system containing constituent ions, (b) a system containing co-ions, Na+ and Cl-, and (c) a system with increased ionic strength and addition of Mg2+. At that, the initial supersaturation, ionic strength, presence of relevant inorganic additives, aging time and hydrodynamics were considered as relevant experimental conditions and parameters that control the mineralogical composition and morphology of solid phase(s) isolated from suspension.



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Despite the intrinsic difference between CaCO3 and CaP solid phases, in all investigated systems thermodynamically metastable and/or amorphous phases (vaterite, aragonite, MHC, ACC, CaDHA, ACP) are the dominant solids that precipitated in the lower supersaturation domain. The only difference is the simple CaCO3 system in which a stable polymorph, calcite, was detected after 60 minutes of aging. In general, the formation of metastable phases, having lower equilibrium solubility under given conditions,25 is kinetically favored and precede the formation of thermodynamically stable phases, as suggested by Ostwald's rules of stages.73, 74. According to this rule the formation of metastable phases is expected when precipitation is fast, i.e. at higher supersaturations, yet the observed appearance of metastable phases in lower supersaturation domains of the investigated systems could be explained by the influence of other experimental conditions, particularly hydrodynamic factors. A presence of sodium and chloride ions in complex systems additionally stabilizes the respective metastable phases in higher relative supersaturation domains, in which they appeared in a mixture with stable phases (calcite and vaterite in the CaCO3 systems, DCPD in CaP systems), while increased ionic strength and the presence of Mg2+ ions in physiological systems stabilizes amorphous phases. Coexistence of different solid phases in the aqueous system indicates that several basic precipitation processes; nucleation, growth, dissolution and/or aging of respective stable and metastable phases, take place simultaneously.40 In such a case, in addition to thermodynamics, kinetic factors play a role in determining the chances of certain phase formation and it is often found that a kinetically favoured phase forms in large proportion, in spite of lower thermodynamic driving force.40 It is also demonstrated that the stabilization of metastable and amorphous phases could be efficiently achieved by the presence of common inorganic constituents and/or supersaturation.


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The obtained results may contribute to development of simple protocols for preparation of novel (bio)materials, as well as a valuable starting point for more complex investigations relevant for biomineralization and geochemistry.

Acknowledgment

This work has been fully supported by Croatian Science Foundation under the project (IP2013-11-5055). The authors are indebted to Mrs. Nevenka Nekić and Mrs. Biserka Špoljar for technical assistence.

Supporting information available

Lists of main calcium carbonate and phosphate phases, FTIR spectra of formed precipitates, assigements of IR bands and peaks in PXRD patterns, pH curves.

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For Table of Contents Use Only

Comparative study of calcium carbonates and calcium phosphates precipitation in model systems mimicking the inorganic environment for biomineralization Authors: Iva Buljan Meić, Jasminka Kontrec, Darija Domazet Jurašin, Branka Njegić Džakula, Lara Štajner, Daniel M. Lyons, Maja Dutour Sikirić, Damir Kralj

The observed existence of metastable calcium carbonate and calcium phosphate phases at early stages of solid phase formation showed that their additional stabilization could be achieved by presence of common inorganic constituents or supersaturation.


Comparative Study of Calcium Carbonates and Calcium Phosphates

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