University of Groningen Synthesis and Properties of Starch Based
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University of Groningen Synthesis and properties of starch based biomaterials Sugih, Asaf Kleopas IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2008 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Sugih, A. K. (2008). Synthesis and properties of starch based biomaterials. s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 26-09-2021 Chapter 2 Experimental Studies on the Ring Opening Polymerization of p‐dioxanone using an Al(OiPr)3‐Monosaccharide Initiator System Abstract The ring opening polymerization (ROP) of p‐dioxanone using a protected i monosaccharide (1,2;3,4‐di‐O‐isopropylidene‐α‐D‐galactopyranose)/Al(O Pr)3 initiator system to yield polydioxanone with a protected monosaccharide end‐ group is described. The products were synthesized at 60‐100°C and characterized by 1H‐ and 13C‐NMR, and MALDI‐TOF mass spectrometry. Besides the desired polydioxanone functionalised with a monosaccharide end‐group, also polydioxanone with an OiPr end‐group was formed (20‐30 %). Systematic studies showed that the polymer yield is a function of the reaction temperature and the reaction time, with higher temperatures (100°C) leading to lower yields. The average chain length of the polymers is between 7 and 58 repeating units and may be tuned by the monomer to monosaccharide ratio (at constant Al(OiPr)3 intake). A statistical model has been developed that successfully describes the experimentally observed relation between the average chain length of the functionalized polymer and reaction parameters. Keywords: biodegradable, polyesters, ring‐opening polymerization Chapter 2 2.1. Introduction Aliphatic polyesters, such as polycaprolactone, polyglycolide, and polylactides, are interesting polymers because of their good product performance and biodegradability [1]. Polydioxanone (poly(p‐dioxanone) or poly(1,4‐dioxan‐2‐ one)), accessible by the polymerization of p‐dioxanone (1), has interesting product properties compared to other aliphatic polyesters. Its melting temperature is close to 110 oC, which is a unique compromise between application and processing temperature. This melting point is considerably higher than typically found for polycaprolactone (60 oC) and lower than that of polylactides (at least 175°C). The relatively low melting point of polycaprolactone limits its applicability, whereas the high temperature for polylactides results in thermal degradation and undesirable transfer reactions during synthesis and processing steps [2]. Polydioxanone has a tensile strength close to 48.3 MPa and an elongation at break of 500‐600%, and is tougher than polylactides and even HDPE [3]. From a biodegradability point of view, polydioxanone also shows good performance. It is fully degraded in the body within a period of 180 days [4]. Nishida et al [5] reported that polydioxanone decomposes to non‐toxic gases (CO2 and H2O) by microorganisms. Despite its good properties, only limited information about the synthesis and properties of polydioxanone is available in the open literature, probably because the p‐dioxanone monomer has become commercially available only recently [1]. Biodegradable aliphatic polyesters end‐capped with sugar molecules have been studied extensively for use in biomedical applications, particularly for nano‐ encapsulation systems for drug delivery [6]. The synthesis of protected monosaccharide end‐capped biodegradable polymers is usually performed via Ring Opening Polymerization (ROP). The catalysts are metal alkoxides with Lewis acidic character [8, 9]. The ring‐opening polymerization (ROP) of p‐dioxanone i using metal catalysts such as aluminum isopropoxide [Al(O Pr)3], stannous octoate [Sn(Oct)2], or zinc lactate has been reported. The alkoxide group will end up as an ester end‐group in the polymer and in this way at least one of the end‐groups may be easily controlled and varied. Exchange of the alkoxide group by e.g. reaction of the metal‐alkoxide with an appropriate alcohol allows the synthesis of end‐capped poly‐lactones. Several polymers with bioactive alcoholic and phenolic end‐groups of interest for drug‐related applications were synthesized (for example geraniol, quinine, tocopherol, testosterone, pregnenolone, stigmasterol and ergocalciferol) [10] and also with protected monosaccharides (galactopyranose/ glucofuranose) [6‐7]. This chapter describes experimental studies on the catalytic ROP of p‐ dioxanone in the presence of a protected glucose molecule (1,2;3,4‐di‐O‐ isopropylidene‐α‐D‐galactopyranose, 2), which to the best of our knowledge is the first study to functionalise polydioxanone with a monosaccharide. Besides 26 Ring Opening Polymerization of p‐dioxanone using an Al(OiPr)3‐Monosaccharide Initiator System potential applications in biomedical products, the results of this study are also of interest for the preparation of starch/polydioxanone polymers using ROP. Particularly interesting in this field are starch polymers grafted with polydioxanone. However, grafting efficiencies are difficult to determine in this system by standard analytical techniques (e.g. NMR) due to the poor solubility of the products in standard organic solvents. As such, the synthetic pathways and the soluble, relatively low molecular weight compounds reported in this study may be viewed as model systems for more complex, poorly soluble heterogeneous systems. 2.2. Materials and Methods 2.2.1. Materials p‐Dioxanone monomer (1, Boehringer Ingelheim, Germany) was purified according to the procedure described by Raquez et al [2, 3]. Toluene (Labscan) was dried and stored on molecular sieves 3 Å (Labscan) under nitrogen. 1,2;3,4‐di‐O‐ isopropylidene‐α‐D‐galactopyranose (2), 97% (Sigma) and aluminum isopropoxide, 98+% (Aldrich) were used as received. Analytical grade dichloroethane (Labscan), heptane (Acros), and diethylether (Labscan) were used as received. CDCl3 was obtained from Sigma and was used as received. 2.2.2. Methods All polymerization experiments were carried out under a protective nitrogen atmosphere using standard Schlenk‐ and glovebox techniques. 2.2.2.1. Typical example for the synthesis of polydioxanone end‐capped with 1,2;3,4‐di‐O‐ isopropylidene‐α‐D‐galactopyranose (2) 2 (1.44 g, 5.5 mmol) was dissolved in toluene (1 ml) at 50 oC. To this solution, 0.8 ml of a solution of an aluminum isopropoxide stock solution was added. This stock solution was prepared by adding 4.07 g, (20 mmol) of aluminum isopropoxide to 20 ml of toluene. The resulting clear solution was stirred for 2 h at 50 oC. Subsequently, part of this solution (350 µl, containing 0.55 mmol of 2 and 0.08 mmol aluminum isopropoxide) was added to pure 1 (0.8 g, 8 mmol), which was pre‐heated till about 60°C to obtain it in a liquid state. The polymerization was allowed to proceed for 16 h at 100 oC. The reaction mixture was clear and colorless during the reaction. After the pre‐determined reaction time, the mixture was brought to room temperature and several drops of HCl (1 N) were added to stop the reaction. Next, hot dichloroethane (20‐25 ml) was added to completely dissolve the partly solid polymer at room temperature. The hot solution was 27 Chapter 2 precipitated in a heptane/ ether mixture (300‐400 ml, 4:1 by volume) at 4‐8 oC. The white solid was finally separated from the liquid by decantation and dried in a vacuum oven (5 mbar, 40 oC) until constant weight. The isolated yield at this condition was 68%. 2.2.3. Product Analyses 1 13 NMR analyses were performed in CDCl3. H‐ and C‐NMR spectra were recorded on a Varian AMX 400 NMR. 2D‐NMR spectra were recorded on a Varian Unity 500 NMR. Processing of the raw data was performed using VNMR software. MALDI‐TOF spectra were recorded on an Applied Biosystems Voyager DE‐PRO machine using dithranol/ NaI as the matrix (linear mode). 2.2.4. Calculation of Average Degree of Polymerization theo The Theoretical Average Degree of Polymerization, X n in terms of number of monomer units is calculated as follows [6]: theo [monomer]0 X n = monomer conversion × [total initiator] (2.1.) [monomer]0 = monomer conversion× i 3[Al(O Pr)3 ] + [sugar]0 Here, it is assumed that all available initiator is used effectively. If the amount of sugar is in excess with respect to the aluminum catalyst, the above equation simplifies to theo [monomer]0 X n = monomer conversion× (2.2.) [sugar]0 1H‐NMR was applied to determine the experimental average degree of exp polymerization, X n of the product. exp X n is calculated by comparing the peak area of characteristic end‐group protons with that of a proton of the repeating unit in the polymer (A H‐polymer). As will be shown later, two polymers with different end‐groups are present, one initiated on a galactopyranose molecule and the other on an isopropoxide group. This leads to the following equation: exp A H-repeating unit X n = (2.3.) A H-galactopyranose end group + A H-isopropoxide end group 28 Ring Opening Polymerization of p‐dioxanone using an Al(OiPr)3‐Monosaccharide Initiator System The NMR peaks of the repeating unit overlap partially with those of the galactopyranose end group.