Synthesis of hollow BaSO₄ nanospheres templated by core–shell–corona type polymeric micelles

Abstract

Hollow barium sulfate (BaSO₄) nanospheres were synthesized by templating a polymeric micelle of a triblock copolymer poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG). This polymer is known to form a micelle with a PS core, a PAA shell and a PEG corona in aqueous solutions. Barium chloride and sodium sulfate were used as precursors of BaSO₄. In the synthesis, the PS core acts as a template for cavities of the hollow particles, the PAA shell is beneficial for arresting Ba²⁺ ions to produce BaSO₄, and the PEG corona stabilizes the BaSO₄/polymer nanocomposite to prevent secondary aggregate formation. Hollow BaSO₄ nanospheres were obtained by removing the polymeric template from the BaSO₄/polymer nanocomposite by calcination. The hollow BaSO₄ nanospheres thus fabricated were characterized by various techniques including transmission electron microscopy and X-ray diffraction analysis. The average diameter of the spheres is around 25 nm and the average cavity diameter is around 16 nm. The significance of the present method is that it can avoid formation of large crystals which is generally unavoidable in other methods.

---

Introduction

Barium sulfate (BaSO₄) has industrial and medical relevance due to its inertness and opacity to UV and X-ray radiation.¹ It is frequently used clinically as a radio-contrasting agent for X-ray imaging, a radio-opaque filler in commercial bone cement, and in other diagnostic procedures.^1d The synthesis of morphologically controlled BaSO₄ nanoparticles has been the object of numerous studies.² Several strategies have been suggested for the controlled growth of BaSO₄ nanocrystals. Surfactants,³ organic(polymeric) inhibitors,⁴ organic additives,⁵ inorganic stabilizers⁶ and different reaction media⁷ were used. BaSO₄ nanoparticles can also be synthesized by using double hydrophilic block copolymers with different functional groups such as carboxylic acids, aspartic acids, sulfonates, and phosphonates.⁸ Mann et al. synthesized a variety of well defined morphogenesis of BaSO₄ such as bundled fibres, brush-like and cone-shaped structures, using a block copolymer as a nucleation and stabilizing agent.⁹ They also used a mixture of two double hydrophilic block copolymers to control the crystallization and organization of BaSO₄ microstructures.¹⁰ These structures are of several hundred micrometres in length. Such large (microsized) BaSO₄ particles have a disadvantage that they limit the stain penetration during micro-computed tomography.^1d

Recently, there has been a great deal of interest in the synthesis of hollow nanoparticles because of their potential applications in controlled drug delivery, catalysis, sensors, light weight fillers, photonic crystals, biomedical diagnosis and therapy, and so on.¹¹ Their capacity for encapsulating sensitive materials such as therapeutics, fluorescent markers, and field-responsive agents has been exploited by many groups for drug delivery and biomedical imaging.^11d,12

Various methods, such as templating, sonochemical, and hydrothermal, have been reported as the procedures for the preparation of inorganic materials with hollow spherical structures. In recent years, the use of a polymeric micelles template to synthesize inorganic hollow nanoparticles has proven to be successful.¹³ Lee and Char demonstrated a morphological change of silica from tubules to large hollow spheres to small hollow spheres by adjusting the intermolecular interactions within micelles of a poly(styrene-b-vinylpyridine) block copolymer.¹⁴ This method can improve the quality of the product in terms of controlling the size and morphology of hollow particles.¹⁵

Herein, we present a facile synthesis of hollow BaSO₄ nanospheres with a size of several tens of nanometres. We employed a template for polymeric micelles of poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG), which has a PS core, a PAA shell and a PEG corona in aqueous solutions. We incorporated Ba²⁺ ions into PS-b-PAA-b-PEG micelles by interaction between Ba²⁺ ions and the anionic PAA block of the polymer. The interaction of Ba²⁺ ions with the PAA shell of the polymeric micelles was elucidated by dynamic light scattering (DLS), zeta-potential, and transmission electron microscopy (TEM). Ba²⁺/PS-b-PAA-b-PEG chelated particles were then used as a template for the fabrication of hollow BaSO₄ nanospheres. In this synthesis, the PS core acts as a template for hollow cavities, the PAA shell works as a nanoreactor and nanocontainer for the precursors of BaSO₄, and the PEG corona prevents the polymer–BaSO₄ composite nanospheres from forming secondary aggregates by steric repulsion between PEG chains in aqueous solutions. The hollow BaSO₄ nanospheres were obtained after removing the template polymer by calcination. The hollow nanospheres thus obtained were characterized by various techniques including TEM and X-ray diffraction (XRD). The fabrication of nanometre-sized hollow BaSO₄ spheres is generally difficult because, after initial mixing of Ba²⁺ and SO₄²⁻ ions the growth of BaSO₄ is uncontrollably rapid to give large (micrometre-sized) crystals. However, the use of a PS-b-PAA-b-PEG micelle template overcomes this problem of crystal overgrowth, allowing the formation of nanometre-sized hollow spheres with uniform void space.

Experimental

Materials

A polyethylene glycol-based chain transfer agent (PEG-CTA) was prepared as previously reported.¹⁶ We first prepared the diblock copolymer poly(ethylene glycol-b-acrylic acid) (PEG-b-PAA) by reversible addition–fragmentation chain transfer polymerization using PEG-CTA. Styrene, 2,2′-azobis(isobutyronitrile), and PEG-b-PAA were dissolved in DMF. The solution was deoxygenated by purging with Ar gas for 30 min. The polymerization was carried out at 60 °C for 24 h. The polymerization mixture was dialyzed against acetone for 3 days and pure water for one day. The obtained PS-b-PAA-b-PEG was recovered by a freeze-drying technique. The details of synthesis were reported elsewhere.¹⁷ The number-average degrees of polymerization of the PS, PAA, and PEG blocks are 80, 90, and, 47, respectively, as estimated by ¹H NMR (Fig. S1, ESI†). The synthetic procedure is shown in Scheme 1. BaCl₂ (Katayama, 99%), Na₂SO₄ (Katayama, 99%), and phosphotungstic acid hydrate (Alfa Aesar) were used without purification.

Scheme 1 Synthesis of PS-b-PAA-b-PEGvia RAFT-controlled radical polymerization.

Preparation of polymeric micelles

A known amount of PS-b-PAA-b-PEG was dissolved in water and gently agitated with a magnetic stirrer at room temperature till a clear solution was obtained. The solution was then transferred to a volumetric flask to obtain a stock solution. The final concentration of polymeric micelles is 1 g L⁻¹.

Incorporation of Ba²⁺ ions into micelles

A known amount of PS-b-PAA-b-PEG micelle solution was titrated with Ba²⁺ ions. The amount of added Ba²⁺ ions is expressed in terms of the apparent degree of charge neutralization (DN), which is defined asAll the experiments were carried out under pH 7–8, where almost all carboxylic groups of the PAA block have an anionic form.

Synthesis of hollow BaSO₄ nanospheres

The hollow BaSO₄ nanospheres were synthesized using the micelle of PS-b-PAA-b-PEG as a template (Scheme 2). To induce BaSO₄ mineralization in polymeric micelles, an aqueous BaCl₂ solution (50 μL, 0.94 M) was first added to a stirred solution of polymeric micelles at pH 7–8 and equilibrated for 2 h under stirring. An aqueous solution of Na₂SO₄ (50 μL, 0.94 M) was slowly added drop-wise to the reaction mixture, and the solution was stirred magnetically at room temperature. The BaSO₄/PS-b-PAA-b-PEG composite particles were recovered by centrifugation. The composite particles were thoroughly washed with de-ionized water and dried in an oven at 50 °C. The polymeric template was removed by calcination at 500 °C for 4 hours.

Scheme 2 Synthesis of hollow BaSO₄ nanospheres from a PS-b-PAA-b-PEG micelle template.

DLS measurements

The DLS measurements were carried out using an Otsuka ELS Z zeta-potential and particle analyzer. All the measurements were carried out at 25 °C. All the solutions were passed through a 0.2 μm cellulose filter before the measurements. The scattered light of a vertically polarized He–Ne laser (632.8 nm) was measured at an angle of 90° and was collected by an autocorrelator. The correlation functions were analyzed by the contin method and used to determine the diffusion coefficient (D) of the particles. The hydrodynamic diameter (D_h) was calculated from D using the Stokes–Einstein equation:

D_h= k_BT/(3πηD) (2)

where k_B is the Boltzmann constant, T is the absolute temperature and η is the solvent viscosity. The polydispersity factor of micelles is represented as μ₂/Γ², where μ₂ is the second cumulant of the decay function and Γ² is the average characteristic line width.

Zeta-potential measurements

The electrophoretic mobility (EPM) was measured by an Otsuka ELS Z zeta-potential and particle analyzer. The zeta-potential (ζ) was calculated from the EPM using the Smoluchowski equation:

μ_E = ζε/η (3)

where μ_E is the EPM, ε is the permittivity of the solvent, and η is the solvent viscosity.

Transmission electron microscopy

The TEM measurements were carried out using a JEOL JEM-1210 electron microscope at an accelerating voltage of 80 kV. To prepare the samples for the TEM measurements, the nanospheres were dispersed in water followed by casting on a copper grid. The excess solution was removed by soaking with a blotting paper. The samples were then dried in air for one day. For the preparation of a polymeric micelles sample, 0.1 wt% phosphotungstic acid solution is used to improve the contrast.¹⁸

XRD analysis

Phase identification of the hollow nanospheres was carried out using a Shimadzu-7000 X-ray diffractometer at 40 kV, 30 mA, and with CuKα radiation (1.5406 Å). Data were collected in the scan range of 20–70° in the continuous scan mode at a scanning speed of 2° min⁻¹ using 0.15 mm receiving slits.

Thermal analysis

A simultaneous thermogravimetric analysis (TGA) and a differential thermal analysis (DTA) were carried out using a SEIKO-6300 TG/DTA instrument at the heating rate of 10 °C min⁻¹ in air.

Fourier transform infrared absorption spectroscopy

The Fourier transform infrared (FTIR) absorption spectra were measured by a JASCO FT/IR-7300 spectrometer at room temperature. The samples were prepared by the KBr method.

Results and discussion

Characterization of polymeric micelles

The polymeric micelles obtained were characterized by DLS and TEM measurements. The D_h of the polymeric micelles is about 70 nm (Fig. S2, ESI†) at pH 8. The D_h ranges from 50 to 70 nm as the pH is increased from 3.5 to 6.0 and becomes almost constant after that. This is explained by the conformational change of the PAA block. At low pH (pH < 4) the PAA block is protonated, and has a shrunken conformation resulting in the minimum value of D_h. At high pH (pH > 5.5), the PAA block swells considerably in water because the carboxylic acid groups are converted to carboxylate ions¹⁹ leading to a larger D_h value. The polymeric micelles were stained with phosphotungstic acid and observed by TEM. The TEM image shown in Fig. 1 revealed that the micelle has a spherical structure. The white sphere of around 25 nm average diameter corresponds to the hard PS core, because the phosphotungstic acid preferentially stains the PS core. The TEM image provides the clear evidence for the micelles formation.

Fig. 1 TEM image of the PS-b-PAA-b-PEG micelles. The micelles were stained with phosphotungstic acid.

Interaction of Ba²⁺ ions with micelles

When Ba²⁺ ions are introduced into PS-b-PAA-b-PEG solutions at pH 8, the PAA block will be bound to the Ba²⁺ ions, which leads to the formation of bidentate metal–polymer chelated particles.²⁰ In these chelated particles, metal ions are bound to PAA segments via electrostatic interaction, forming an insoluble hydrophobic shell that is stabilized by a PEG corona. In order to confirm the interaction of Ba²⁺ ions with the PAA shell, we titrated PS-b-PAA-b-PEG with BaCl₂ solutions, and examined the particle size, zeta-potential, and shape of the particles. Fig. 2a shows the dependence of D_h on DN. In the absence of metal ions almost all carboxylic acid groups are deprotonated at pH 9 as their pK_a value is 4.5²¹ and the PAA chains are fully extended to produce the maximum size of the micelles. The average D_h of the particles varies from 73 to 43 nm depending on DN. There is a sharp decrease in D_h above 60% DN and the limiting value above 100%. The polydispersity factor, μ₂/Γ², of D_h lies between 0.07 and 0.14 over all DN, indicating that the size distribution of the Ba²⁺/PS-b-PAA-b-PEG chelated particles is fairly mono-disperse. The added Ba²⁺ ions cancel the charges of the carboxylate anions. The electrostatic repulsion among the anionic shells, therefore, is weakened and the blocks are shrunken, resulting in the decrease of the total micellar size. The binding of Ba²⁺ ions to PS-b-PAA-b-PEG was checked by zeta-potential measurement. Fig. 2b shows the dependence of zeta-potential of Ba²⁺/PS-b-PAA-b-PEG chelated particles on DN. The successive addition of Ba²⁺ ions increases the zeta-potential. Above 100% DN the value of zeta-potential is not increased. This fact shows that the complex formation is triggered essentially by electrostatic interactions. But the zeta-potential values do not reach zero when DN exceeds 100%. This implies that all the carboxylate groups in PAA are not available for binding of Ba²⁺ ions; it is due to the complicated structure of the polymer and steric hinderance.²²

Fig. 2 (a) Hydrodynamic diameter (D_h) and (b) zeta-potential (ζ) of Ba²⁺/PS-b-PAA-b-PEG chelated particles as a function of DN.

The TEM image of the Ba²⁺/PS-b-PAA-b-PEG nanocomposites is shown in Fig. 3a. The image clearly shows the effective binding of Ba²⁺ ions to the polymer. The dark periphery is the PAA block of PS-b-PAA-b-PEG stained with Ba²⁺ ions. The spheres observed by TEM basically correspond to a glassy PS core surrounded by a compact Ba²⁺/PAA layer, because the PEG corona seems to be less stained compared to the PAA shell. Therefore, the observed diameter (35 nm) is smaller than the D_h (ca. 40 nm) in DLS measurements.

Fig. 3 TEM pictures of (a) Ba²⁺/PS-b-PAA-b-PEG chelated particles and (b) hollow BaSO₄ nanospheres.

Fabrication of hollow BaSO₄ nanospheres

The attractive interaction between the anionic PAA block and Ba²⁺ ions induces the formation of chelated particles of the copolymer and the metal ions, which act as a soft template for the synthesis of hollow BaSO₄ nanospheres. The Ba²⁺/PS-b-PAA-b-PEG chelated particles were used for mineralization of BaSO₄ by adding sulfate ions in the form of Na₂SO₄. Hollow BaSO₄ nanospheres were obtained after removing the polymeric template by calcination at 500 °C. Fig. 3b illustrates a TEM image of hollow BaSO₄ nanospheres. The hollow BaSO₄ nanospheres have a uniform size. The outer diameter is ∼25 nm, and the void space diameter is ∼16 nm. In our method the PS core acts as a template to form cavities of hollow BaSO₄ nanospheres. But the void space diameter is less than the core size of the polymeric template shown in Fig. 1. It has been reported by several groups²³ that the cavity size of the hollow inorganic particles becomes smaller than the size of the template polymers, which is ascribed to the shrinking of the particles during the calcination. Therefore, the difference between the cavity size of hollow BaSO₄ nanospheres and the core size of the polymeric template seems to be due to shrinking during the calcination. The nanospheres are somewhat aggregated as seen in Fig. 3b. It is probably due to calcination.²⁴ The BaSO₄/PS-b-PAA-b-PEG nanocomposite particles, prior to calcination, are well dispersed and no agglomeration is seen in aqueous solution (Fig. S3, ESI†). Removal of the polymeric template was confirmed by FTIR measurements. Fig. S4 (ESI†) shows the FTIR spectra of the polymer and hollow BaSO₄ nanospheres after calcination of the BaSO₄/PS-b-PAA-b-PEG composite particles. The disappearance of the PEG band (around 2900 cm⁻¹) and the carbonyl stretching band (around 1720 cm⁻¹) after calcination indicates the removal of the polymeric template.

The crystalline characteristics of the obtained hollow BaSO₄ nanospheres were investigated by XRD analysis. The XRD pattern is shown in Fig. S5 (ESI†). It is clearly shown that the nanospheres are crystallized in an orthorhombic structure (ICDD No. 001-1229).

The thermal behavior of BaSO₄/PS-b-PAA-b-PEG composite particles was studied by TG-DTA in the temperature range 20–1000 °C. The TG-DTA curves for the BaSO₄/PS-b-PAA-b-PEG composites are shown in Fig. 4. The initial parts of the TG curves slightly decline. This implies desorption of absorbed water molecules. The decomposition of the polymer is the main step of the weight loss. The strong exothermic peak on DTA curves around 350 °C and 450 °C shows decomposition of the template polymer. The thermogravimetric analysis of the dried powder samples shows about a 16% weight loss in air for the BaSO₄/PS-b-PAA-b-PEG composites. This weight loss corresponds to decomposition of the polymer.

Fig. 4 TG (—)/DTA (⋯) graphs of BaSO₄/PS-b-PAA-b-PEG nanocomposites.

Conclusions

Complexation of Ba²⁺ ions with the PS-b-PAA-b-PEG micelles was induced under basic conditions. This is based on the electrostatic interaction between cationic Ba²⁺ ions and an anionic (deprotonated) PAA block. The mono-dispersed Ba²⁺/PS-b-PAA-b-PEG chelated particles were successfully used as a template for the synthesis of well-defined hollow BaSO₄ nanospheres. The obtained nanospheres have a uniform cavity size and wall thickness. This synthesis strategy is potentially expandable to other inorganic materials which undergo crystal growth too fast to be obtained by other methods.

Acknowledgements

The authors thank Mr Toshimi Tabata for his help in the TEM measurements, and Professor Takanori Watari and Dr Hom Nath Luitel for the XRD and TG-DTA measurements. The present study was supported by a Grant-in-Aid for Scientific Research (20310054) from the Japan Society for the Promotion of Science (JSPS).

References

1. (a) H. Bala, W. Fu, Y. Guo, J. Zhao, Y. Jiang, X. Ding, K. Li, M. Yu and Z. Wang, Colloids Surf., A, 2006, 274, 71–76; (b) B. M. Nagaraja, H. Abimanyu, K. D. Jung and K. S. Yoo, J. Colloid Interface Sci., 2007, 316, 645–651; (c) J. P. Barraud, Encyclopedia of Diagnostic Imaging, ed. A. A. Baert, Springer-Verlag, vol. 2, pp. 2485–2488; (d) H. Leng, Micro-computed Tomography of Microdamage in Cortical Bone, PhD dissertation, University of Notredum, 2006.
2. (a) J. Xiao, A. T. Kan and M. B. Tomson, Langmuir, 2001, 17, 4668–4673; (b) A. E. Murdaugh and S. Mann, Langmuir, 2009, 25, 9792–9796; (c) A. W. Xu, Y. Ma and H. Colfen, J. Mater. Chem., 2007, 17, 415–449; (d) M. Uchida, A. Sue, T. Yoshioka and A. Okuwaki, CrystEngComm, 2001, 3, 21–26.
3. H. Zhang, Y. Liu, J. Zhang, H. Sun, J. Wu and B. Yang, Langmuir, 2008, 24, 12730–12733.
4. S. N. Black, L. A. Bromley, D. Cottier, R. J. Davey, B. Dobbs and J. E. Rout, J. Chem. Soc., Faraday Trans., 1991, 87, 3409–3414.
5. (a) M. Li, H. Schnablegger and S. Mann, Nature, 1999, 402, 393–395; (b) G. Wu, H. Zhou and S. Zhu, Mater. Lett., 2007, 61, 168–170.
6. (a) R. I. C. Ibara, G. R. Gattorno, M. F. G. Sanchez, A. S. Solis and O. Manero, Langmuir, 2010, 26, 6954–6959; (b) A. Gupta, P. Singh and C. Shivakumara, Solid State Commun., 2010, 150, 386–388.
7. M. Li and S. Mann, Langmuir, 2000, 16, 7088–7094.
8. L. Qi, H. Cölfen and M. Antonietti, Angew. Chem., Int. Ed., 2000, 39, 604–607.
9. L. Qi, H. Cölfen, M. Antonietti, M. Li, J. D. Hopwood, A. J. Ashley and S. Mann, Chem.–Eur. J., 2001, 7, 3526–3532.
10. M. Li, H. Colfen and S. Mann, J. Mater. Chem., 2004, 14, 2269–2276.
11. (a) X. W. Lou, L. A. Archer and Z. C. Yang, Adv. Mater., 2008, 20, 3987–4019; (b) Y. Wang, A. S. Angelatos and F. Caruso, Chem. Mater., 2008, 20, 848–858; (c) W. J. Tong and C. Y. Gao, J. Mater. Chem., 2008, 18, 3799–3812; (d) S. J. Son, X. Bai and S. B. Lee, Drug Discovery Today, 2007, 12, 650–656.
12. (a) Y. Chen, H. Chen, D. Zeng, Y. Tian, F. Chen, J. Feng and J. Shi, ACS Nano, 2010, 4, 6001–6013; (b) H. B. Na, I. C. Song and T. Hyeon, Adv. Mater., 2009, 21, 2133–2148.
13. (a) A. Khanal, Y. Inoue, M. Yada and K. Nakashima, J. Am. Chem. Soc., 2007, 129, 1534–1535; (b) J. Yang, J. U. Lind and W. C. Trogler, Chem. Mater., 2008, 20, 2875–2877; (c) K. K. Perkin, J. L. Turner, K. L. Wooley and S. Mann, Nano Lett., 2005, 5, 1457–1461.
14. H. Lee and K. Char, ACS Appl. Mater. Interfaces, 2009, 1, 913–920.
15. D. Liu, A. Khanal, Y. Inoue, M. Yada and K. Nakashima, Chem. Lett., 2009, 38, 130–131.
16. S. Yusa, Y. Yokoyama and Y. Morishima, Macromolecules, 2009, 42, 376–383.
17. B. P. Bastakoti, S. Guragain, Y. Yokoyama, S. Yusa and K. Nakashima, Langmuir, 2011, 27, 379–384.
18. S. O. Obare, N. R. Jana and C. J. Murphy, Nano Lett., 2001, 1, 601–603.
19. S. Ludwigs, K. Schmidt and G. Krausch, Macromolecules, 2005, 38, 2376–2382.
20. I. Pochard, P. Couchot and A. Foissy, Colloid Polym. Sci., 1998, 276, 1088–1097.
21. D. G. Leaist, J. Solution Chem., 1989, 18, 421–435.
22. Y. An, T. Ushida, M. Susuki, T. Koyama, K. Hanabusa and H. Shirai, Polymer, 1996, 37, 3097–3100.
23. (a) A. Syoufian, Y. Inoue, M. Yada and K. Nakashima, Mater. Lett., 2007, 61, 1572–1575; (b) K. G. Li and Z. C. Zhang, Mater. Lett., 2004, 58, 2768–2771.
24. N. L. Wu, S. Y. Wang and I. A. Rusakova, Science, 1999, 285, 1375–1377.

---

Footnote

† Electronic supplementary information (ESI) available: NMR spectra, DLS data, FTIR spectra, XRD and TEM images. See DOI: 10.1039/c1nj20671k

---