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Preparation of Porous Polysaccharides Templated by Coordination Polymer with Three-dimensional Nanochannels Yuichiro Kobayashi, Kayako Honjo, Susumu Kitagawa, and Takashi Uemura ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b15936 • Publication Date (Web): 07 Feb 2017 Downloaded from http://pubs.acs.org on February 9, 2017
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ACS Applied Materials & Interfaces
Preparation of Porous Polysaccharides Templated by Coordination Polymer with Three-dimensional Nanochannels Yuichiro Kobayashi,† Kayako Honjo,† Susumu Kitagawa,*,†,‡ and Takashi Uemura*,†,§ †
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan ‡
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan §
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan Key word: Porous coordination polymers / Metal-organic frameworks / Glucose / Polysaccharide / Ring-opening polymerization / Porous materials
ABSTRACT: Polymerization of monosaccharide monomers usually suffers from the production of polysaccharides with illdefined structures because of the uncontrolled random reactions among many reactive hydroxyl groups on saccharide monomers. In particular, rational synthesis of polysaccharides with porosity approximating molecular dimensions is still in its infancy, despite their usefulness as drug carriers. Here, we disclose an efficient synthetic methodology for the preparation of polysaccharides with controllable mesoporosity in the structure, utilizing [Cu3(benzene-1,3,5-tricarboxylate)]n (HKUST-1; 1) as templates. Cationic ring-opening polymerization of 1,6-anhydro glucose was performed in nanochannels of 1, followed by removal of the host frameworks, giving polysaccharide particles as replicas of the original molds. Nitrogen adsorption measurement revealed that the obtained polysaccharide particles contained high mesoporosity in the structure, which could be controlled systematically depending on the polymerization conditions. Owing to the large specific surface area, tunable porosity and particle size, we could also demonstrate the capabilities of our polysaccharides for loading and releasing of a drug molecule and protein.
Introduction Polysaccharides are widely used as practical materials for separation, bioplastics, functional foods, and pharmaceuticals because of their chirality, chemical reactivity, characteristic structures, and biocompatibility.1-4 Among the most generally accepted approaches to preparing polysaccharide-based materials are the modification reactions of naturally abundant polysaccharides. In fact, chemical and physical cross-linking reactions of naturally abundant polysaccharides, such as amylose and dextran, can afford macroporous polysaccharides that can be utilized for tissue engineering.5-7 In this regard, preparation of functional polysaccharides with nanoporous void structures allows opportunities for their application as drug carriers.8,9 A rational synthetic strategy for designing highly porous polysaccharides with controlled pore and
particle sizes is a requisite for creating smart drug carriers with characteristics of high drug loading and their targeted release. For example, preparation of nanosized polysaccharide hydrogels via formation of cross-linkings has emerged as a successful strategy, offering important features that are attractive for drug delivery.10-15 In recent years, various demands for polysaccharide-based materials have also prompted the development of controlled polymerizations from monosaccharides to produce polysaccharides with well-defined structures.16-22 However, reliable and efficient methodologies for the preparation of polysaccharides with permanent nanoprosity have yet to be established because of the difficulties in regulating the random reactions among many hydroxyl groups on saccharide monomers.
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Figure 1. Schematic image for template synthesis of porous PGlc using three-dimensional nanochannels of 1 as a host matrix. View of three-dimensional nanochannels of 1 displayed using a space-filling model (O, red: C, gray: Cu, blue).
One of the most promising methods for producing porous polymeric materials with controlled size and morphology is the templating technique, in which many host matrices, such as zeolite and mesoporous silica, have been used as templates.23-27 In these systems, restructuring of the polymer chains often results in the collapse of the porous structures during the isolation process because removal of these hard hosts containing covalent bonds requires relatively harsh conditions.28-32 To overcome this problem, we employ porous coordination polymers/metal-organic frameworks (PCPs/MOFs) with noncovalent framework structures based on metal ions and bridging organic ligands.33-35 In recent years, they have developed rapidly as a particular class of functional solid materials for applications in storage, exchange, and conversion.36-38 Utilization of the designable nanochannels for polymerization can control the structure and assembly of the resulting polymers.39,40 From the viewpoint of templating, polymers accommodated in PCPs can be recovered under mild conditions, preventing unfavorable re-structuring of polymers.41 As the framework structures are finely tunable, use of these host materials as templates can allow for the precise control of not only the porosity but also the morphology of the resulting polymers.42,43 In this paper, we report a feasible method for providing porous polyglucose (PGlc) particles via polymerization of monosaccharide in three-dimensional channels of a PCP and subsequent removal of the host framework (Figure 1). The obtained PGlc represented an exact morphological replica of the pristine PCPs microcrystals. In addition, obvious mesoporosity was observed in the PGlc, where the size and distribution of the pores could be systematically controlled at the nanometer scale. Because of the high porosity and tunable particle size, this material has a capability of loading and releasing several biologically important molecules and proteins efficiently, manifesting promise as a drug carrier.
Experimental Section Materials. All of the reagents and chemicals used were obtained from commercial sources, unless otherwise noted. [Cu3(benzene-1,3,5-tricarboxylate)]n (HKUST-1; 1) was prepared according to previously described methods.44 Synthesis of PGlc using 1. The host compound 1 (0.40 g) was dried by heating at 130 °C under vacuum (0.3 kPa) for 4 h. The dried host was immersed in a dry MeOH solution (1.0 mL) of 1,6-anhydro-β-D-glucose (AGlc) (0.12 g, 0.74 mmol) and monochloroacetic acid (3.6 mg, 39 µmol) at room temperature. The solvent was removed under vacuum (10 kPa) for 8 h at room temperature to obtain a composite with AGlc. Subsequently, the composite was heated at 150 °C for a predetermined time under N2 atmosphere. The resulting product was washed with MeOH repeatedly to remove any unreacted AGlc and analyze it using 1H NMR spectroscopy for the calculation of monomer conversion. The obtained composite was then dried under reduced pressure (0.3 kPa) at room temperature. To isolate the PGlc inside the channels, the resulting product was stirred in a 0.5 M aqueous sodium ethylenediaminetetraacetate (Na-EDTA) solution (10 mL) for one day for the complete dissolution of the host framework. Polymeric product (PGlc) was released and collected by centrifugation. The collected PGlc was washed with water and dried under reduced pressure (0.3 kPa) at room temperature. Synthesis of PGlc in solution. AGlc (1.0 g, 6.2 mmol) and monochloroacetic acid (31 mg, 0.32 mmol) were dissolved in dry DMF (5 mL), and then the solution was heated at 150 °C for 48 h under N2 atmosphere. The resulting PGlc was washed repeatedly with water, and dried under reduced pressure (0.3 kPa) at room temperature. Loading with ib. PGlc (50 mg) was soaked in an EtOH solution (1 mL) containing ibuprofen (ib, 30 mg), and then the solvent was removed under vacuum (0.3 kPa) for 12 h at room temperature. Excess ib external to the PGlc
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Figure 2. XRPD patterns of 1, AGlc, 1⊃AGlc, 1⊃PGlc, and PGlc recovered from 1.
was completely removed under vacuum (0.3 kPa) at 60 °C for 6 h. We compared the values of weight loss corresponding to adsorbed ib in PGlc before and after the drug loading to determine the loading amount of ib. Loading with BSA. PGlc (100 mg) was soaked in a 10 mM phosphate-buffered saline (PBS) solution (pH 7.4) (1 mL) containing bovine serum albumin (BSA, 600 mg), and then the suspension was stirred for 24 h. The vial was sealed to avoid evaporation of the solvent. The obtained precipitate was separated from the solution by vacuum filtration, washed with PBS solution (pH 7.4) (1 mL) to remove excess BSA external to the PGlc, and dried under reduced pressure (0.3 kPa) at room temperature. To extract BSA from the PGlc–BSA composite, PGlc–BSA composite was soaked in 10 mM PBS solution (pH 7.4) for one day. The supernatant was filtered, and we performed UV–vis measurement of the filtrate to determine the amount of extracted BSA. Guest releasing. PGlc–ib composite was placed in a dialysis bag with 8 kDa molecular weight cutoff, which was soaked in 10 mM PBS solution (pH 7.4) at 37 °C. At predetermined time intervals, 3 mL of the solution was filtered to monitor using UV–vis spectroscopy. In the case of PGlc–BSA composite, we performed the same experiment without using a dialysis bag. PGlc–BSA composite was soaked in 10 mM PBS solution (pH 7.4) at 37 °C. At predetermined time intervals, the supernatant (3 mL) was filtered to monitor using UV–vis spectroscopy. Measurement. We used a porous PGlc with particle and pore sizes of 8.2 µm and 7.4 nm, respectively (Table 1, entry 4) for most of the analyses, unless otherwise noted. X-ray powder diffraction (XRPD) data were collected using a Rigaku SmartLab X-ray diffractometer employing CuKα radiation. IR spectra were measured using a Thermo Scientific Nicolet iS5. Thermogravimetric analysis
Figure 3. (a) Conversions of AGlc versus polymerization time of AGlc in 1. (b) Nitrogen adsorption (filled circle) and desorption (open circle) isotherms at 77 K on solutionsynthesized PGlc (black) and PGlc isolated from 1 with different monomer conversions (46%, green; 62%, blue; and 83%, red). (c) Pore-size distribution of PGlc isolated from 1 with different monomer conversion (46%, green; 62%, blue; and 83%, red), determined from the nitrogen adsorption profile using the BJH method. (d) Surface areas calculated using BET equation (open circle) and pore widths (filled circle) of the PGlc isolated from 1 versus conversion of AGlc.
(TGA) was carried out from room temperature to 500 °C at a heating rate of 10 °C min–1 using a Rigaku Instrument Thermo Plus TG8120 in N2 atmosphere. Differential scanning calorimetry (DSC) was carried out with a Seiko Instruments DSC 6220 under a N2 atmosphere and 10 K min–1 heating rate. The scanning electron microscopyenergy-dispersive X-ray (SEM–EDX) measurements were performed using a JEOL JED-2300 detector in a JEOL JSM5600 at an accelerating voltage of 30 kV. Samples were placed on a conducting carbon tape attached to a SEM grid, and then coated with platinum. Particle size distributions of dry powder samples were measured using a HORIBA Partica LA-950 laser diffraction particle size analyzer. UV–vis spectra were recorded on a JASCO V-670 spectrometer. The X-ray fluorescence (XRF) spectroscopy was performed using a Rigaku EDXL300. The adsorption isotherms of N2 at 77 K were measured using BELSORPmini equipment. Before the adsorption measurements, the sample was treated under reduced pressure (
