氏名　CHE KU MOHAMMAD FAIZAL
学位の種類　博士（工学）
学位記番号　博甲第503号
学位授与の日付　平成21年3月25日
学位論文題目　Study of separation membrane adsorbents prepared by scaffold molecular imprinting　（スキャフォルド分子インプリント法を用いた分離用膜吸着材に関する研究）
論文審査委員
　主査　教授　小林　高臣
　副査　教授　野坂　芳雄
　副査　教授　梅田　実
　副査　長岡工業高等専門学校教授　丸山　一典
　副査　産学融合特任講師　于　海峰

• 論文目次
• 論文要旨
• 論文審査の結果の要旨

［平成20（2008）年度博士論文題名一覧］ ［博士論文題名一覧］に戻る．

Contents
Abbreviaation list
Chapter 1.　General Introduction　p.1
　1.1　Molecular imprinting technique　p.1
　1.1.1　General principle of molecular imprinting　p.2
　1.2　Approaches to molecular imprinting　p.4
　1.3　Scaffolding molecular imprinting　p.8
　1.4　Molecular impronted membranes　p.12
　1.5　Targeted Tocopherol by imprinting separation methodology　p.15
　1.6　Scope of present investigation　p.17
　1.7　Reference　p.19
Chapter 2.　Tocopherol-Targeted membrane Adsorbents Prepared by Hybrid Molecular Imprinting
　2.1　Introduction　p.26
　2.2　Experimental　p.28
　2.2.1　Materials　p.28
　2.2.2　Preparation of a-Toc imprinted monomer　p.30
　2.2.3　Preparation of a-Toc imprinted and non-imprinted polymers　p.32
　2.2.4　Preparation of a-TMA-HMIP membranes　p.32
　2.2.5　Uptake of substrates by HMIP membranes　p.34
　2.2.6　Determination of the equilibrium binding constant by Scatchard analysis　p.35
　2.3　Result and discussion　p.36
　2.3.1　Characteristics of the imprinted monomer and imprinted polymer　p.36
　2.3.2　Selective binding of P（a-TMA-co-DVB）H and HMIP　p.44
　2.2.3　Selective binding of a-Toc to the imprinted membranes　p.52
　2.4　Conclusion　p.56
　2.5　Reference　p.56
Chapter 3.　Tocopherol targeted membrane adsorbents containing imprinting cross-linked copolymers prepared by surfactant-free dispersion technique
　3.1　Introduction　p.58
　3.2　Experimental　p.61
　3.2.1　Materials　p.61
　3.2.2　Preparation of a-tocopherol-imprinted monomer and MIP microparticles using high-shear dispersion method　p.62
　3.2.3　Prepartion of membranes adsorbents containing P（a-TMA-co-DVB）　p.63
　3.2.4　Equilibrium binding experiments of substrate　p.64
　3.2.5　Permselective binding of substrates to PSf-P（α-TMA-co-DVB）　p.66
　3.3　Results and discussion　p.67
　3.3.1　Characteristics of the imprinted polymer beads and hybridized membranes　p.67
　3.3.2　Selective binding of a-Toc to molecular-imprinted membrane in batch system　p.78
　3.3.3　Separation of a-Toc and other analogs by a-Toc imprinted membrane　p.81
　3.4　Conclusion　p.85
　3.5　Reference　p.85
Chapter 4.　Scaffold membranes for selective adsorption of a-tocopherol by phase inversion covalently imprinting technique
　4.1　Introduction　p.88
　4.2　Experimental　p.92
　4.2.1　Materials　p.92
　4.2.2　Preparation of a-tocopherol imprinted monomer　p.92
　4.2.3　Copolymerization and preparation of P（a-TMA-co-AN） membranes　p.92
　4.2.4　Copolymer characterization　p.93
　4.2.5　Permeation experiments through molecular imprinted membrane　p.96
　4.3　Results and discussion　p.97
　4.3.1　Preparation of the imprinted membranes　p.97
　4.3.2　Selective binding of a-Toc to molecular imprinted membrane in batch system　p.102
　4.3.3　Selective binding of a-Toc and other analogs by a-Toc imprinted membrane　p.110
　Conclusion　p.113
　Reference　p.114
Chapter 5.　Molecular imprinting targeted for a-tocopherol by using calix［4］resorcarenes scaffold in phase inversion membrane
　5.1　Introduction　p.116
　5.2　Experimental　p.121
　5.2.1　Materials　p.121
　5.2.2　Synthesis of Calix［4］resorcarene host　p.121
　5.2.3　Preparation of imprinted membranes　p.122
　5.2.4　Membrane properties and binding experiments　p.122
　5.3　Results and discussion　p.124
　5.3.1　Characterization of a-Toc imprinted membranes　p.124
　5.3.2　Selective binding of imprinted membranes　p.130
　5.3.3　Separation of a-Toc and other analogs by a-Toc imprinted membrane　p.137
　5.4　Conclusion　p.140
　5.5　Reference　p.140
Chapter 6.　Summary　p.142
List of Publications　p.145
Presentation in Conferences and Symposiums　p.146

Molecular imprinting technique is a technology that allows for creation of molecular recognition sites in synthetic polymers via the use of templates. Imprinted materials have been used in various applications, including stationary phase for chromatography, recognition elements in sensors, or solid phase extraction. As widely recognized, effective performance of imprinted polymers is caused by highly cross-linked polymernetworks for retaining shape of the template molecule. After the removal of the template, resultant cavities in the imprinted polymer show the molecule selectivity. However, the highly cross-linked imprinted polymer only can be obtained in powder shape. This character restrictspractical uses for several applications. Moreover, the development of artificial membrane that rivals biological membranes in selectivity isan important current goal in bioorganic, pharmaceutical and environmental chemistry. Therefore, imprinted membranes provide meaningful tools in these fields. This present thesis relates to new molecularly imprinting membranes having selective separation behavior to targeted template. Three new preparation techniques are proposed; covalent approach by phase inversion imprinting, multiple non-covalent scaffolds in imprintedmembranes, and hybrid imprinted membranes.
For the first system, preparations and properties of hybrid molecular imprinted membranes was constructed from covalently imprinted polymer powder having memory sites in membrane scaffolding. Firstly, template containing MIP were synthesized by copolymerization of α-TMA with DVB usedas crosslinker. To identify the solvent effect on hydrolysis reaction, MIP was prepared with various type of solvent in different loading composition. It was found that the solvent had significant influence to the resultant MIP porosity as well as hydrolysis efficiency. In conclusion,it was observed the resultant HMIP membranes showed ability to selectively bind and transport the template molecule, and such materials could have great potential to be applied for selective membrane separation.
The second system was based on preparation of hybrid imprinted membranes （HMIP） containing cross-linked MIP particles, which were synthesizedwith different particles size by high-sheared dispersion polymerization. Then, the MIP particles were followed to fix in the scaffold membrane formed by phase inversion method. In the study, copolymerization of functional monomer with crosslinker was carried out by dispersion techniqueunder high shear condition. It was observed that agitation speed promoted the resultant MIP powder to be nano size and increased the surface areaespecially in 13500 rpm. The increasing effective surface area of resultant MIP particles enabled efficient template removal by hydrolysis ofmethacryloyl tocopherol bond under acid-alcoholic solution. Beside, the polymer particles size greatly affected the morphology and performance ofimprinted membrane. It was noted that smaller size particles enhanced imprinted membrane porosity and then, adsorption of the targeted template increased. Evidence of the separation of the mixture showed separation factor of α-Toc and 4-Chr with 17.3 was achieved for PSf-HMIP membrane.
Alternatively, a molecular imprinted membrane utilizing the multiple non-covalent interactions was studied as comparison for the above systems.
In this technique, the supramolecular host, calix［4］resorcarene, was used in order to gain relatively strong multi-interaction with template. Due to the encoded template information in membrane, procedure was involved by fixing host-guest complex in a scaffold polymer membrane during phase inversion of the polymer solution containing the host- guest in water. Then, the template removal was easily achieved by wash with acid-alcoholicsolution. It was apparent in the non-covalent technique that the imprinted membrane showed good binding selectivity by permselective experiments.
In conclusion, it was found that the system became to be new potential for molecular imprinting technique related to scaffold method.

　本論文は「Study of Separation Membrane Adsorbents Prepared by Scaffold Molecular Imprinting （スキャフォルド分子インプリント法を用いた分離用吸着材に関する研究）」と題し、全6章から構成されており、スキャフォルド分子インプリント法という新規インプリント概念を提唱し、この手法で作製できた分子認識分離膜の透過特性、分子吸着特性を述べている。
　第1章「General Introduction」では、分子インプリント法について概説し、膜状分子インプリント材料のこれまでの経緯と、スキャフォルド分子インプリント法の新規性とその技術的位置づけについて解説し、本論文の目的を述べている。
　第2章「Tocopherol Targeted Membrane Adsorbents Prepared by Hybrid Molecular Imprinting」では、α-Tocopherol （α-Toc）に対して分子認識・吸着特性を持つ粉末状の分子インプリントポリマー（MIP）を合成し、そのα-Toc選択特性について説明し、更に、ハイブリッドインプリントにより、ポリスルホン、ナイロン6、セルロースアセテートを足場として固定した分離膜を作製し、その膜特性を述べている。
　第3章「Tocopherol Targeted Membrane Adsorbents Containing Imprinting Cross-linked Copolymers prepared by Surfactant-free Dispersion Technique」では、合成したα-Toc メタアクリレート（α-TMA）をジビニルベンゼンと架橋したスフェア状のMIP粉末を用い、種々の膜材とハイブリッド分子インプリント膜を作製している。ポリスルホン等とのハイブリッド化により、これらの膜材がMIP粉末の足場として作用し、両者の協働吸着作用により、Tocの膜吸着能力が増加することを述べている。また、Toc誘導体の膜分離実験において高い選択性を持つ分離挙動を示す事を説明している。
　第4章「Scaffold Membranes for Selective Adsorption of α-Tocopherol by Phase Inversion Covalently Imprinting Technique」ではα-TMAとアクリロニトリルとの共重合体を合成し、相転換法にて分離膜を作製した後に、そのToc残基を酸性にて加水分解し、新規分子インプリント膜とする、共有結合タイプの相転換インプリント法を始めて提案し、α-Tocの分離特性を評価するとともに、膜分離に応用できる事を述べている。
　第5章「Molecular Imprinting Targeted for α-Tocopherol by Using Calix［4］　resorcarenes Scaffold in Phase Inversion Membrane」では、α-Toc-Calix［4］resorcarene錯体をポリスルホンに埋め込んだ膜は、鋳型分子除去後でもそのインプリント部位をCalix［4］ resorcareneホストに保持できており、α-Tocに対する認識性が高く、効率の良い吸着特性を発現することを初めて見出し、新たなスキャフォルド分子インプリントのアプローチを提案している。
　第6章では、本論文で得られた結果と考察を要約している。
　以上の内容より、本論文は工学上および工業上貢献するところが大きく、博士（工学）の学位論文として十分な価値を有するものと認める。