Key Parameters for Size- and Shape-Controlled Synthesis of Vaterite

Subscriber access provided by READING UNIV

Article

Key Parameters for Size- and Shape-Controlled Synthesis of Vaterite Particles Yulia I. Svenskaya, Hassan Fattah, Olga A. Inozemtseva, Anna G. Ivanova, Sergei N. Shtykov, Dmitry A. Gorin, and Bogdan V. Parakhonskiy Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b01328 • Publication Date (Web): 27 Nov 2017 Downloaded from http://pubs.acs.org on November 29, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Crystal Growth & Design is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 28 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

Crystal Growth & Design

Key Parameters for Size- and Shape-Controlled Synthesis of Vaterite Particles Yulia I. Svenskaya1*, Hassan Fattah1,2, Olga A. Inozemtseva1, Anna G. Ivanova3, Sergei N. Shtykov1, Dmitry A.Gorin1,4, Bogdan V. Parakhonskiy1,3,5* 1) Saratov State University, 410012 Saratov, Russia 2) Department of Mining, Metallurgy and Petroleum Engineering, Al-Azhar University, 11371 Cairo, Egypt 3) FSRC Crystallography and Photonics RAS, 119333 Moscow, Russia 4) Skoltech center of Photonics & Quantum Materials, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia 5) Department of Molecular Biotechnology, Ghent University, 9000 Ghent, Belgium

KEYWORDS. Calcium Carbonate, Vaterite, Crystallization, Biomaterials, Anisotropic Particles

ABSTRACT

Calcium carbonate (CaCO3) attracts scientific attention due to its essential role in both inorganic and bioorganic nature. Vaterite is the least thermodynamically stable CaCO3 polymorph, elicited

ACS Paragon Plus Environment

1

Crystal Growth & Design 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

Page 2 of 28

great interest as an advanced biomaterial for tissue engineering, drug delivery and a broad range of personal care products. Numerous methods of vaterite particle synthesis with different sizes and morphologies have highlighted the submicron porous particles of spherical or ellipsoidal shape as the most useful ones. In this regard, the proposing study is aimed at development of a reliable method for synthesis of such structures. Herein, submicron vaterite particles are synthesized by a dropwise precipitation from saturated sodium carbonate and calcium chloride solutions in the presence of ethylene glycol manipulating the concentration ratios of reagents. We demonstrate that our novel technique named as “dropwise precipitation” leads to changing calcium concentration in the reaction solution at each moment affecting the crystallization process. The proposed technique allows routine obtainment of vaterite particles of a required shape, either spherical or ellipsoidal, and a controlled size out of the range from 0.4 to 2.7 µm and (0.4x0.7) to (0.7x1.1) µm, respectively. The key parameters influencing the size, shape and percent of vaterite fraction for synthesized CaCO3 particles are discussed.

INTRODUCTION Over the past century, calcium carbonate (CaCO3) was one of the most studied water insoluble salt because of its importance in many biomineralization, geochemistry and industry processes 1– 3

. CaCO3 has at least three anhydrous polymorphs: smooth cubic-like calcite crystals, whiskers-

like aragonite and porous vaterite crystals of varied shapes4. High porosity of vaterite polycrystalline determines the possibility of bioactive substances incorporation 5, that makes such form of CaCO3 stand out among the other crystallographic modifications concerning its application as a smart container for various personal care and biomedical applications.


2

Page 3 of 28 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


Recently, it was found that vaterite spheres can be used as a drug delivery system due to their biocompatibility and high drug loading capacity 3,6–8. Incorporation of various proteins 9–12, drugs 4,7,13–15

and DNA4 into these matrices was demonstrated pointed out the possibility of therapeutic

effectiveness improvement for the loaded substance. These studies have raised the scientific interest towards the development of reproducible vaterite fabrication techniques decreasing the size of formed particles offering the opportunities of their application in drug encapsulation and delivery. Furthermore, the modern nanothechnological experimental methods together with possibility of the computer simulation allow the investigation of crystal growth process elucidating the formation mechanism of vaterite, calcite and aragonite polymorphs 16–21. In terms of drug delivery, geometry and size of particulate carrier play an important role, as these properties directly influence the cellular uptake and intracellular trafficking of the particles applied in vitro6,22–26, and affect their circulation, retention and bio-distribution when applied in vivo

26–29

. We have previously shown, that the anisotropy affects the rate and the pathway of

vaterite carrier uptake by cells26, meanwhile the size influences the time of carrier degradation 13. Thus, varying the size and the aspect ratio of forming vaterite particles one can control the properties which play a substantial role in their interaction with cells in living systems. By this means, synthesis of vaterite particles of required shapes, either spherical or elongated, and controlled sizes allows custom-design of the drug delivery system. Tuning of synthesis conditions for vaterite polycrystals formation is an important and challenging task by the virtue of relatively rapid re-crystallization of vaterite crystals to more thermodynamically stable non-porous calcite ones. For this goal, it is necessary to take into consideration many thermodynamic and kinetic factors governing the crystallization process, such as nucleation and following growth of nanocrystals, their aggregation into amorphous


3


Page 4 of 28

CaCO3 and to vaterite crystals, and the rate of dissolution of nonstable structure. Besides, the nature of the solvent used in the synthesis is an important factor affecting the dielectric constant of the medium, solvation of ions, supersaturation level, kinetics of nucleation, crystal growth and solubility of the product. By this means, a special attention of proposing study has been given to a precipitation of CaCO3 in presence of organic additives, like ethylene glycol (EG), that influences the rate of spontaneous precipitation of vaterite and favors its stabilization preventing the vaterite-calcite transformation

26,30–33

. It was proposed that the addition of EG into reaction

solution can change the surface energy of vaterite particle and make them more thermodynamically stable 34. However, at the moment the influence of a very few factors on CaCO3 particle formation in EG/water mixture was studied. It was shown that the initial concentration of reagents, temperature, EG/water ratio, stirring speed, and reaction time affect the size of calcium carbonate structures and their phase (vaterite, calcite and aragonite 2,31,32,34,35 as well as the morphology of the vaterite 26,30,31,36. Apart from that, none of these parameters plays a unique role and predetermines the properties of the synthesized particles. We hypothesize that only the combination of multiple factors can utmostly destine the vaterite particles size and shape. Moreover, the possibility of controlling [Ca2+] ions additive rate to the reaction mixture should also make a significant contribution. The proposing study introduces the influence of EG, reacting salts concentrations and dropping rate on the size and percent of forming spherical and ellipsoidal vaterite particles.

EXPREMENTAL SECTION Materials


4

Page 5 of 28 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


Sodium carbonate (Na2CO3), calcium chloride (CaCl2), ethylene glycol (EG), sodium hydroxide (NaOH) and sodium chloride (NaCl) were purchased from Sigma–Aldrich-Fluka and used without any additional purification. Milli-Q water was used in all experiments (Aquarius, Russia; Millipore Milli-Q, USA and Canada).

Preparation of calcium carbonate particles As a basis for the investigation, a previously described method was used 30. This method was modified by preliminary addition of sodium hydroxide (NaOH) and sodium chloride (NaCl) salts to the reaction mixture in order to control its pH and ionic strength. For this purpose, sodium carbonate (Na2CO3) was dissolved in deionised water and then EG, NaOH and NaCl were added. The pH value of the solution was adjusted to 9.0 to avoid pH fluctuations in the reaction solution at the moment of the second reagent addition. Calcium chloride (CaCl2) was separately dissolved in water with EG supplementation and added dropwise to Na2CO3 solution under continuous magnetic stirring at 800 rpm. The resulting precipitate was centrifuged and washed with deionised water and ethanol, whereupon it was dried at 60°C for 60 min. In order to optimize the synthesis parameters and study their influence on crystallographic modification, size and morphology of the obtaining particles, the concentration of reagents and the dropping rate were varied at a constant volume of the reaction mixture. Towards this, four different rates were tested: R1= 10 ml/min (meaning the instillation of the total 5-ml volume in 30 seconds), R2= 0.167 ml/min (5 ml of the reagent in 30 minutes), R3= 0.084 ml/min (5 ml in 1 hours) and R4= 0.042 ml/min (5 ml in 2 hours). The concentration of reagents was ranged as 0.05 M, 0.1 M and 0.33 M, the EG/H2O ratios were set at 1:1, 4:1 and 6:1.


5


Page 6 of 28

Particle Characterization The surface morphology of prepared calcium carbonate particles was characterized by scanning electron microscopy using MIRA II LMU instrument (Tescan) at an operating voltage of 20 kV at a magnification ranging from 100 to 40.000 times. Size distribution of CaCO3 particles was investigated by a set of SEM images in order to obtain a minimum of 100 measurements per sample. Image analysis and statistics were performed using Image J. Statistical analysis was performed by one-way ANOVA on n = 100 independent measurements followed by Tukey post-hoc test, significance was assigned at p-values < 0.05. Equality of variances was checked using the F-test with a significant level of 0.05. Powder x-ray diffraction analysis of the polycrystalline samples was performed with a Rigaku Miniflex-600 diffractometer (Rigaku Corporation, Tokyo, Japan). The XRD data were recorded using Cu-Kα radiation (40 kV, 15 mA, Ni-Kβ filter) in the 2θ range 20–60° at a scan speed 1°/min. The crystalline phases were identified with the use of integrated X-ray powder diffraction software. PDXL: Rigaku Diffraction Software) and ICDD PDF-2 datasets (Release 2014 RDB). The molecular structure of the CaCO3 particles was examined using Fourier Transform Infrared (FTIR) Spectroscopy (Vertex 70, Bruker). The particles were dried before the measurement. The spectrum was collected in the 250 cm-1 and 4205 cm-1 spectral range with a resolution of 4 cm-1 and an average of 25 scans.

RESULTS AND DISCUSSION Effect of dropping rate at different EG/H2O ratios and reagent concentrations on the size of forming calcium carbonate particles


6

Page 7 of 28 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


The effect of dropping rate of CaCl2 to Na2CO3 solution at different reagent concentrations and varied viscosity of the reaction mixture conditioned by EG addition at different ratios to H2O on CaCO3 particle size was investigated. The temperature of the synthesis was maintained at 25 °C accordingly.

34

After the washing of synthesized particles with water and ethanol, Fourier

Transform infrared spectroscopy was performed in order to check whether EG molecules are adsorbing on the surface or incorporating into the matrix. The spectrum presented in Figure S1 (see Supporting Information) has revealed the vaterite presence with no evidence of EG addition. The size of forming CaCO3 particles was investigated using Scanning electron microscopy. As herein we focused mostly on vaterite formation, the size of only spherical and ellipsoidal particles presented on SEM images were taken into account. The data are presented in Figure 1.

Figure 1. The effect of dropping rate and EG/H2O ratio on the vaterite particle size at salts concentration of 0.05 M, 0.1 M and 0.33 M. Dropping rates were set at R1 = 10 ml/min, R2 = 0.167 ml/min, R3 = 0.084 ml/min and R4 = 0.042 ml/min, the EG/H2O ratio at 1:1 (a), 4:1 (b), 6:1 (c).

Basing on the data obtained and followed by ANOVA test, one can see, that the particle size has been significantly decreased with decreasing the reagent concentration and dropping rate


7


Page 8 of 28

down to R3=0.084 ml/min. The smallest size of the forming vaterite particles corresponded to 0.4 µm was obtained at the rate R3 = 0.084 ml/min (instillation of 5 ml CaCl2 in 30 minutes), EG/H2O =4:1 and salts concentration of 0.05 M (Figure 1b). With an increase of ethylene glycol addition to the reaction mixture, the dielectric constant of the solvent lowers decreasing the salt solubility. According to the theory of homogeneous nucleation, a decrease in surface tension due to the addition of EG causes the decreasing of the critical nucleation radius34 and of the nucleation barrier, resulting in the nucleation rate enhancement. Furthermore, rising the EG content, the viscosity of the reaction mixture is increased, that slows down both processes: growth of the particles and dissolution of the already formed particles due to an ion diffusion decelerating. Thus, the combined action of the factors listed above results in decreasing of the size and its dispersion for the fabricated vaterite particles34. However, the slight increase in the particle size was established at the highest EG concentration at low dropping rate (Figure 1 c). Such an effect can be explained by the aggregation of CaCO3 crystals linked by the EG molecules. Furthermore, the higher viscosity of the reaction mixture in this case provides the ion diffusivity decrease that in combination with solubility reduction promotes an enhancement of local ion concentration and supersaturation. Reduction of initial CaCl2 and Na2CO3 concentrations and dropping rate in EG presence had a similar impact as an EG concentration increasing. The lower reagent concentrations and dropping rates were used, the smaller size of vaterite particles was obtained. Such an effect runs contrary to the classical theory of nucleation and growth, where a higher concentration of reagents increases the supersaturation resulting in a higher nucleation rate, providing a smaller particle size at the same total mass of precipitate. The possible explanation brings together


8

Page 9 of 28 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


various effects, which take place while synthesizing the calcium carbonate particles in EG presence, such as enhancement of the reaction mixture viscosity, reduction of the reagent solubility, decrease in the dielectric constant of solution and in the surface tension at the interface, surface modification of the nucleus formed in solution. 34,37–40 By this means, the presence of EG in the reaction mixture increases the local supersaturation, caused by association of calcium ions with alcohol groups of polyol. The enhanced viscosity of the reaction mixture slows down the diffusion of reactants to a nucleus inhibiting their growth. Furthermore, the resolvation of ions together with an essential reduction of the interfacial tension increase the nucleation rate in the presence of polyols (EG, glycerol)

34,37

. Thus, the lower

reagent concentrations provide the smaller size of forming particles. Obviously, operating with the smallest salt concentration (0.05 M) and dropping rates (R3 = 0.084 ml/min and R4 = 0.042 ml/min), which provide a smaller concentration of [Ca2+] in the reaction mixture, have made improvements.

Effect of dropping rate at different EG/H2O ratios and reagent concentrations on the phase of forming calcium carbonate particles As it was mentioned above, the crystallization process of vaterite particles starts with growth and aggregation of nanocrystals into amorphous CaCO3 following by the formation of vaterite crystals, which are nonstable and eventually transfer into stable calcite phase. Thus, it is important to consider the factors governing this process allowing the prevention of vateritecalcite transformation during the particle synthesis. In order to investigate the phase of forming calcium carbonate crystals, SEM and X-ray diffraction investigations were performed. The smallest crystals, which had been obtained at 4:1


9


Page 10 of 28

EG/H2O ratio and 0.05 M reagent concentration at different dropping rate (according to Figure 1b), were characterized and the data are presented in Figure 2.

Figure 2. SEM images (a-d) and XRD pattern (e) of the CaCO3 particles obtained at EG/H2O ratio of 4:1 and reagent concentration of 0.05 M with different dropping rate: (a) R1= 10 ml/min, (b) R2 = 0.167 ml/min, (c) R3 = 0.084 ml/min and (d) R4 = 0.042 ml/min; the amount of calcite and vaterite phase obtained by XRD spectra analysis via Rietveld method (f).

One can clearly see, that the dropping rate changing leads to variation of particle morphology and polymorphism: the presence of spherical and cubic-like particles refers to occurrence of vaterite and calcite phases in the sample, respectively (Figure 2 a-e). Thus, the most frequent particle form in the sample obtained at the fastest dropping rate R1 was a cube-shaped modification (Figure 2 a) representing the calcite phase of CaCO3 according to XRD data (Figure


10

Page 11 of 28 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


2 e, f). Such a synthesis conditions cause a local oversaturation resulting in direct nucleation of calcite particles bypassing the vaterite phase. Whereas, the slowing down of the dropping rate to R2 allows the formation of vaterite/calcite mixture with a prevalence of vaterite phase (Figure 2 b, e, f). Further reduction of the dropping rate to R3 leads to formation of pure vaterite particles (Figure 2 c, e, f). Moreover, such a synthesis conditions allows the decreasing of particle size to 0.4±0.1 µm, as it is shown in Figure 1 b and Figure 2 c, and their polydispersity (PDI 0.01), exhibiting by this means the best parameters for vaterite particle synthesis. A subsequent deceleration of the synthesis, setting the dropping rate at R4= 0.042 ml/min, allows the formation of pure vaterite particles as well, but leads nevertheless to the aggregation of the particles and gaining the size of forming crystals up to 0.7±0.2 µm (Figure 2 d). Moreover, increasing of the reaction time (dropping rate R4) in a presence of EG in a high EG/H2O ratio (4:1 or 6:1) gives a rise to the transformation of spherical vaterite crystals into ellipsoidal ones, that is illustrated in Figure 2 d (see the inset). Such an observation was previously obtained26,31,41 demonstrating the formation of ellipsoidal vaterite particles while increasing the reaction time, especially in the presence of EG. It was supposed that aggregation of nanoseeds into ellipsoidal particles is caused by increment of their number and total surface energy. However, the full mechanism of this process is still unclear. The X-ray diffraction patterns of the crystals obtained at 0.05 M reagent concentration and EG/H2O ratio 4:1 and varied dropping rate are presented in Figure 2e. The characteristic peaks of calcite at 2Ɵ of 29.40, 35.90 and 39.50 correspond to the (104), (110) and (113) crystallographic planes of calcite, respectively42. Vaterite presence has been established from more intense reflections corresponding to (004), (111), (112), (113) and (041) crystallographic planes at 24.800, 27.05 0, 32.70, 49.870 and 52.440, respectively43.


11


Page 12 of 28

More detailed estimation of the vaterite and calcite phases was done by semiquantative Rietveld analysis. Figure 2 f demonstrates, that a relatively low dropping rate (R3 and R4) provides the formation of pure vaterite particles with a small amount of calcite (less than 2%), meanwhile increasing of the dropping rate results in formation of calcite particles (up to 78% of forming particles at R1). Thus, these changes of vaterite percent indicate that the dropping rate affects the nucleation and crystal growth of vaterite. The estimation of crystallite size based on Scherer’s equation showed that the size of calcite and vaterite crystallites was ranged from 46 to 52 nm and 10.4 to 15.8 nm, respectively. The data obtained by a Rietveld analysis are in a good agreement with the SEM images (Table S1). For this reason, following investigation of the size and shape of polymorphs at different reagent concentrations, EG/H2O ratio and varied dropping rate was performed by SEM and summarized in Figures S2-S4 and Table S1 (see Supporting Information). The effect of these parameters on CaCO3 polymorphism is represented in Figure 3. For the illustrative purpose, the diagram was supplemented by SEM-images of the crystals corresponded to certain conditions in the critical points.


12

Page 13 of 28 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


Figure 3. The effect of reagent concentration, EG/H2O ratio and dropping rate on CaCO3 polymorphism.

In order to summarize and clarify the process of crystal formation in such a complex system, the data were split into three groups (g1 – g3) depending on EG concentration in the reaction solution. The first group (g1) is dedicated to the pure water without the addition of EG into the reaction mixture (0% of EG). At the highest dropping rate R1 = 10 ml/min, when the CaCl2 solution was pour out drop by drop during 30 seconds, the content of vaterite phase amounted to 82, 76 and 71% for reagent concentration of 0.05 M, 0.1 M and 0.33 M, respectively. Decreasing the dropping rate to R2-R4 for this group initiated the full transformation of CaCO3 crystals into


13


Page 14 of 28

pure calcite form (see the SEM image at the left bottom of the diagram in Figure 3). Such an effect is caused by the well-known tendency of rapid recrystallization of thermodynamically metastable vaterite phase into more stable calcite one. 44–46 The data joined into the second group (g2) were obtained in the reaction mixture containing 50% of EG (meaning 1:1 EG/H2O ratio) and illustrate the trend towards increase in vaterite content, while decreasing the dropping rate from R1 to R4. In particular, at the reagent concentration of 0.05 M the percent of vaterite phase was raised from 3% (see blue square at the top of figure) to 71% (brown triangle) by increasing the dropping rate from R1 to R2 and reached even 100% at the rates R3 and R4. For the third group (g3), including synthesis at EG concentrations of 80% and 85%, meaning 4:1 and 6:1 EG/H2O ratio respectively, further increasing of vaterite content took place. At the highest dropping rate R1 this parameter was grown up to 25% at 4:1 ratio and reached 85% at 6:1 ratio, as compared with 0% of vaterite content obtained at 1:1 EG/H2O ratio (50% of EG). At the lower dropping rates R2-R4 the percentage of vaterite phase was increased to 90-100% using such a high EG concentrations (80-85%). By this means, one can clearly see, that the fraction of vaterite is increasing in the presence of EG at high reagent concentrations and low dropping rates of calcium salt. The addition of calcium chloride drop-by-drop in this case predominantly leads to formation of new nucleation centers instead of providing the crystal growth. The reduced growth rate determines decreasing of vaterite recrystallization rate. Moreover, the presence of EG decreases the solubility of calcium carbonate slowing down the process of vaterite-calcite recrystallization as well. These factors cause a formation of vaterite particles with a negligible percent of calcite appearance.


14

Page 15 of 28 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


As far as variation of [Ca2+] ion concentration in the reaction mixture at each moment affects the crystallization process (Figure S5, Supporting Information), the rate of their input contributes significantly to particle size and morphology control. The input rate of [Ca2+] was calculated based on equation (1): Calcium rate ([Ca2+]/min) =R*t*c*Na,

(1)

where R - dropping rate, t - time, c - salt concentration, Na – Avogadro number.

The dependence of forming CaCO3 phase on the input rate of [Ca2+] ions is shown in Figure 4. Such an illustration allows selection of the most affecting parameters of the synthesis.

Figure 4. Vaterite content depending on the input rate of [Ca2+] ions at different concentration of reagents and varied dropping rate (R1-R4).

The dependence of vaterite content on [Ca2+] ions input rate can be described by two main trends: 1st - the synthesis performed in a pure water without the EG addition into the reaction


15


Page 16 of 28

mixture (yellow dots) results in increasing of vaterite content while accelerating the ion input; 2nd – the samples synthesized in EG presence (gray, orange and blue dots) contain the higher vaterite amount at the lower input rate of [Ca2+] ions. As far as the process of vaterite recrystallization in water is quick, the synthesis duration is one of the most critical parameters. Therefore, the shortest reaction time accompanied with high input rates provides an utmost vaterite content in the final sample in this case. On the contrary, the presence of EG during the synthesis slows down the recrystallization significantly defining the speed of ion distribution as a key parameter. Thus, formation of vaterite particles requires the lower dropping rate. Fast input of calcium ions to the reaction mixture with a greater content of water provides a higher local [Ca2+] concentration hereby resulting in a calcite formation. By this means, the current study determines key parameters for the shape- and size-controlled synthesis of calcium carbonate particles. The effect of ethylene glycol, reacting salts concentration and dropping rate on the size and percent of forming spherical and ellipsoidal vaterite particles is hereby discussed. As it was mentioned above, variation of the vaterite particle size and the aspect ratio allows control over the properties which play a substantial role in their interaction with cells in living systems and therefore are able to provide a custom-design of the drug delivery system. Determined key parameters of the calcium carbonate synthesis open up wide possibilities for complex mineral structure fabrication in terms of their application in tissue engineering, drug delivery and a broad range of personal care.

CONCLUSIONS An approach towards submicron vaterite particle formation named as “dropwise precipitation” was proposed in the present study. The approach involves a dropwise precipitation from


16

Page 17 of 28 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


saturated sodium carbonate and calcium chloride solutions in the presence of ethylene glycol manipulating the concentration ratios of reagents. It allows variation of [Ca2+] ion concentration in the reaction solution at each moment affecting the crystallization process. Reagent concentration, EG/H2O ratio and dropping rate were shown as key parameters allowing control of the particle size and morphology as well as the crystallite polymorphism. The combined effect of these parameters on calcium carbonate formation was investigated and the results revealed, that the input rate of [Ca2+] ions to the reaction mixture and the time of the synthesis make the most significant contribution. Pure vaterite particles were produced in both, pure water-based and EG/H2O reaction mixtures, requiring the shortest reaction time accompanied with the high [Ca2+] input rates for the synthesis in water and the low dropping rates of salts at low concentrations together with high EG content for the synthesis in EG/H2O mixture. Spherical and ellipsoidal vaterite particles with the size ranging from 0.4 to 2.7 µm and (0.4 x 0.7) to (0.7 x 1.1) µm, respectively, were obtained using these parameters. The smallest vaterite crystals with the size of 0.4±0.1 µm were synthesized in EG presence at (4:1) EG/H2O ratio at 0.084 ml/min of a dropping rate at lowest salt concentration equaled to 0.05 M. Current investigation may provide a guidance for the shape- and size-controlled synthesis of calcium carbonate particles. Determined key parameters accompanied with the demonstrated process of synthesis based on kitchenware technology allow one to fabricate complex mineral structures that simulates the design principles of functional biological materials.

Supporting Information Additional supporting information includes FTIR spectrum of calcium carbonate particles obtained in the EG presence, atlases of SEM images and the joint table summarizing the results


17


Page 18 of 28

of characterization of all the samples synthesized at different parameters, which contributes to understanding of the relationship between CaCO3 crystal growth conditions and resulting properties of the crystal. SI contains also the figure represented the amount of calcium ions depending on synthesis time of the samples with different reagent concentrations. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Authors *e-mail addresses: [email protected] (Yulia I. Svenskaya), [email protected] (Bogdan V. Parakhonskiy). Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Funding Sources Russian Foundation for Basic Research, project № 15-29-01172 OFI_m; Russian Science Foundation, project № 17-73-20172; Fonds Wetenschappelijk Onderzoek, postdoctoral scholarship; Russian Ministry of Education and Science, projects № 16.8144.2017/П220 and 11.8139.2017/П220.

ACKNOWLEDGMENT This work was supported by Russian Foundation for Basic Research (research project 15-2901172 OFI_m). We also acknowledge Russian Science Foundation (project № 17-73-20172) for


18

Page 19 of 28 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


supporting the experimental part of work related to preparation of calcium carbonate particles. B.V. Parakhonskiy acknowledges the FWO for postdoctoral scholarship, Yu.I. Svenskaya and O.A. Inozemtseva acknowledges Russian Ministry of Education and Science (projects 16.8144.2017/П220 and 11.8139.2017/П220, respectively). We would like to acknowledge Dr. A.M. Zakharevich for SEM measurements. X-ray data were collected using the equipment of the Shared Research Center FSRC “Crystallography and Photonics” RAS.

REFERENCES (1)

Cölfen, H. Curr. Opin. Colloid Interface Sci. 2003, 8, 23–31.

(2)

Trushina, D. B.; Bukreeva, T. V.; Kovalchuk, M. V.; Antipina, M. N. Mater. Sci. Eng. C 2014, 45, 644–658.

(3)

Bouville, F.; Studart, A. R. Nat. Commun. 2017, 8, 14655.

(4)

Cartwright, J. H. E.; Checa, A. G.; Gale, J. D.; Gebauer, D.; Sainz-Díaz, C. I. Angewandte Chemie - International Edition. 2012, 51, 11960–11970.

(5)

Volodkin, D. V.; Petrov, A. I.; Prevot, M.; Sukhorukov, G. B. Langmuir 2004, 20, 3398– 3406.

(6)

Parakhonskiy, B. V.; Foss, C.; Carletti, E.; Fedel, M.; Haase, A.; Motta, A.; Migliaresi, C.; Antolini, R. Biomater. Sci. 2013, 1, 1273.

(7)

Svenskaya, Y. I.; Pavlov, A. M.; Gorin, D. A.; Gould, D. J.; Parakhonskiy, B. V.; Sukhorukov, G. B. Colloids Surfaces B Biointerfaces 2016, 146, 171–179.

(8)

Dong, Q.; Li, J.; Cui, L.; Jian, H.; Wang, A.; Bai, S. Colloids Surfaces A Physicochem.


19


Page 20 of 28

Eng. Asp. 2017, 516, 190–198. (9)

Kilic, E.; Novoselova, M. V.; Lim, S. H.; Pyataev, N. A.; Pinyaev, S. I.; Kulikov, O. A.; Sindeeva, O. A.; Mayorova, O. A.; Murney, R.; Antipina, M. N.; Haigh, B.; Sukhorukov, G. B.; Kiryukhin, M. V. Sci. Rep. 2017, 7, 44159.

(10)

Donatan, S.; Yashchenok, A.; Khan, N.; Parakhonskiy, B.; Cocquyt, M.; Pinchasik, B.-E.; Khalenkow, D.; Möhwald, H.; Konrad, M.; Skirtach, A. ACS Appl. Mater. Interfaces 2016, 8, 14284–14292.

(11)

Volodkin, D. V.; von Klitzing, R.; Möhwald, H. Angew. Chem. Int. Ed. Engl. 2010, 49, 9258–9261.

(12)

Volodkin, D. V.; Schmidt, S.; Fernandes, P.; Larionova, N. I.; Sukhorukov, G. B.; Duschl, C.; Möhwald, H.; von Klitzing, R. Adv. Funct. Mater. 2012, 22, 1914–1922.

(13)

Svenskaya, Y.; Parakhonskiy, B. V.; Haase, A.; Atkin, V.; Lukyanets, E.; Gorin, D. A.; Antolini, R. Biophys. Chem. 2013, 182, 11–15.

(14)

Wang, C.; He, C.; Tong, Z.; Liu, X.; Ren, B.; Zeng, F. Int. J. Pharm. 2006, 308, 160–167.

(15)

Svenskaya, Y.; Gorin, D.; Parakhonskiy, B.; Sukhorukov, G. Proceedings on 2015 IEEE 15th International Conference on Nanotechnology (IEEE-NANO) 2015; 1513–1516.

(16)

Gebauer, D.; Völkel, A.; Cölfen, H. Science 2008, 322, 1819–1822.

(17)

Meldrum, F. C.; Cölfen, H. Nanoscale 2010, 2, 2326–2327.

(18)

Brecević, L.; Nielsen, A. E. J. Cryst. Growth 1989, 98, 504–510.


20

Page 21 of 28 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


(19)

Nielsen, M. H.; Aloni, S.; De Yoreo, J. J. Science 2014, 345, 1158–1162.

(20)

Wallace, A. F.; Hedges, L. O.; Fernandez-martinez, A.; Raiteri, P.; Gale, J. D.; Waychunas, G. A.; Whitelam, S.; Banfield, J. F.; Yoreo, J. J. De. Science 2013, 341, 885– 889.

(21)

Myerson, A. S.; Trout, B. L. Science 2013, 341, 855–856.

(22)

Daum, N.; Tscheka, C.; Neumeyer, A.; Schneider, M. Wiley Interdiscip. Rev. Nanomedicine Nanobiotechnology 2012, 4, 52–65.

(23)

Bhaskar, S.; Pollock, K. M.; Yoshida, M.; Lahann, J. Small 2010, 6, 404–411.

(24)

Lerch, S.; Dass, M.; Musyanovych, A.; Landfester, K.; Mailänder, V. Eur. J. Pharm. Biopharm. 2013, 84, 265–274.

(25)

Chithrani, B. D.; Ghazani, A. A.; Chan, W. C. W. Nano Lett. 2006, 6, 662–668.

(26)

Parakhonskiy, B. V.; Zyuzin, M. V; Yashchenok, A.; Carregal-Romero, S.; Rejman, J.; Möhwald, H.; Parak, W. J.; Skirtach, A. G. J. Nanobiotechnology 2015, 13, 53.

(27)

Simone, E. A.; Dziubla, T. D.; Muzykantov, V. R. Expert Opin. Drug Deliv. 2008, 5, 1283–1300.

(28)

De Jong, W. H.; Hagens, W. I.; Krystek, P.; Burger, M. C.; Sips, A. J. A. M.; Geertsma, R. E. Biomaterials 2008, 29, 1912–1919.

(29)

Sonavane, G.; Tomoda, K.; Makino, K. Colloids Surfaces B Biointerfaces 2008, 66, 274– 280.


21


(30)

Page 22 of 28

Parakhonskiy, B. V.; Haase, A.; Antolini, R. Angew. Chemie Int. Ed. 2012, 51, 1195– 1197.

(31)

Parakhonskiy, B. V.; Yashchenok, A. M.; Donatan, S.; Volodkin, D. V.; Tessarolo, F.; Antolini, R.; Möhwald, H.; Skirtach, A. G. ChemPhysChem 2014, 15, 2817–2822.

(32)

Flaten, E. M.; Seiersten, M.; Andreassen, J.-P. J. Cryst. Growth 2009, 311, 3533–3538.

(33)

Schmidt, S.; Volodkin, D. V. J. Mater. Chem. B 2013, 1, 1210.

(34)

Flaten, E. M.; Seiersten, M.; Andreassen, J.-P. Chem. Eng. Res. Des. 2010, 88, 1659– 1668.

(35)

Li, Q.; Ding, Y.; Li, F.; Xie, B.; Qian, Y. J. Cryst. Growth 2002, 236, 357–362.

(36)

Svenskaya, Y. I.; Fattah, H.; Zakharevich, A. M.; Gorin, D. A.; Sukhorukov, G. B.; Parakhonskiy, B. V. Adv. Powder Technol. 2016, 27, 618–624.

(37)

Trushina, D. B.; Bukreeva, T. V.; Antipina, M. N. Cryst. Growth Des. 2016, 16, 1311– 1319.

(38)

Wang, P.; Kosinski, J. J.; Anderko, A.; Springer, R. D.; Lencka, M. M.; Liu, J. Ind. Eng. Chem. Res. 2013, 52, 15968–15987.

(39)

Sun, T.; Teja, A. S. J. Chem. Eng. Data 2003, 48, 198–202.

(40)

Bohne, D.; Fischer, S.; Obermeier, E. Berichte der Bunsengesellschaft für Phys. Chemie 1984, 88, 739–742.

(41)

Chen, Y.; Ji, X.; Wang, X. J. Cryst. Growth 2010, 312, 3191–3197.


22

Page 23 of 28 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


(42)

Sitepu, H. Powder Diffr. 2009, 24, 315–326.

(43)

Le Bail, A.; Ouhenia, S.; Chateigner, D. Powder Diffr. 2012, 26, 16–21.

(44)

Beck, R.; Andreassen, J.-P. Cryst. Growth Des. 2010, 10, 2934–2947.

(45)

Flaten, E. M.; Seiersten, M.; Andreassen, J.-P. J. Cryst. Growth 2010, 312, 953–960.

(46)

Kitamura, M. J. Cryst. Growth 2002, 236, 323–332.


23


Page 24 of 28

For Table of Contents Use Only

Key Parameters for Size- and Shape-Controlled Synthesis of Vaterite Particles Yulia I. Svenskaya, Hassan Fattah, Olga A. Inozemtseva, Anna G. Ivanova, Sergei N. Shtykov, Dmitry A. Gorin, Bogdan V. Parakhonskiy

SYNOPSIS An approach towards calcium carbonate particle formation named as “dropwise precipitation” is proposed. The method provides variation of [Ca2+] ion concentration in the reaction solution at each moment affecting the crystallization process. Current investigation represents a guidance for the shape- (spherical or ellipsoidal) and size-controlled (0.4 to 2.7µm) synthesis of vaterite particles defining key parameters for functional biological material formation.


24

Page 25 of 28 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


Figure 1. The effect of dropping rate and EG/H2O ratio on the vaterite particle size at salts concentration of 0.05 M, 0.1 M and 0.33 M. Dropping rates were set at R1 = 10 ml/min, R2 = 0.167 ml/min, R3 = 0.084 ml/min and R4 = 0.042 ml/min, the EG/H2O ratio at 1:1 (a), 4:1 (b), 6:1 (c). 260x74mm (300 x 300 DPI)



Figure 2. SEM images (a-d) and XRD pattern (e) of the CaCO3 particles obtained at EG/H2O ratio of 4:1 and reagent concentration of 0.05M with different dropping rate: (a) R1= 10 ml/min, (b) R2 = 0.167 ml/min, (c) R3 = 0.084 ml/min and (d) R4 = 0.042 ml/min; the amount of calcite and vaterite phase obtained by XRD spectra analysis via Rietveld method (f). 226x130mm (300 x 300 DPI)


Page 26 of 28

Page 27 of 28 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


Figure 3. The effect of reagent concentration, EG/H2O ratio and dropping rate on CaCO3 polymorphism. 167x126mm (300 x 300 DPI)



Figure 4. Vaterite content depending on the input rate of [Ca2+] ions at different concentration of reagents and varied dropping rate (R1-R4). 132x71mm (300 x 300 DPI)


Page 28 of 28

Key Parameters for Size- and Shape-Controlled Synthesis of Vaterite

Recommend Documents