Functional polymer silicon hybrids via surface initiated living radical polymerizations

FUNCTIONAL POLYMER-SILICON HYBRIDS VIA SURFACEINITIATED LIVING RADICAL POLYMERIZATIONS XU FUJIAN (M. ENG, CAS) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMICAL AND BIOMOLECULAR ENGINEERING NATIONAL UNIVERSITY OF SINGAPORE 2006 ACKNOWLEDGEMENTS First of all, I wish to express my cordial gratitude to my supervisors, Prof. Kang En-Tang and Prof. Neoh Koon-Gee, for their continuous guidance, profound discussion, enlightening comments, valuable suggestions, and warm encouragement throughout this research work. The invaluable knowledge I have learnt from them on how to research work and how to enjoy research paves my way for this thesis and my future research career. I would like to thank Mr. Zhong Shaoping, Mr. Song Yan, Mr. Yuan Shaojun, Assistant Prof. Yung Lin-Yue, Lanry, Assistant Prof. Tong Yen Wah, and Assistant Prof. Zhu Chunxiang for their generous assistance and cooperation. I am also grateful to my seniors, Ms. Li Yali, Mr. Cai Qinjia, Dr. Zhai Guangquan, Dr. Ling Qidan, and Ms. Cen Lian, for their kind help and sharing with me their invaluable research experiences. I am deeply grateful to the financial support from the Singapore Millennium Foundation (in the form of PhD Scholarship) and the National University of Singapore (in the form of Research Scholarship and President’s Graduate Fellowship). Finally, but not least, I would like to give my special thanks to my wife and my parents for their continuous love, support, and encouragements. I TABLE OF CONTENTS Chapter 1.1 1.2 Chapter 2.1 2.2 2.3 Chapter 3.1 3.2 3.3 3.4 Chapter 4.1 4.2 4.3 4.4 Chapter Acknowledgement I Table of Contents II Summary IV Nomenclatures VI List of Figures VII List of Tables XIII Introduction Background of Research Research Objectives and Scopes Literature Survey Surface Functionalization of Silicon Substrates via SelfAssembly of Monolayers “Polymer Brushes” Functionalized Surfaces Polymer Brushes in Biotechnology 13 24 Surface-Active and Stimuli-Responsive Polymer-Si(100) Hybrids from Surface-Initiated Atom Transfer Radical Polymerization (ATRP) for Control of Cell Adhesion 31 Introduction Experimental Section Results and Discussion Conclusions 32 33 40 59 Thermo-Responsive Comb-Shaped Copolymer-Si(100) Hybrids from Surface-Initiated ATRP for Accelerated Temperature-Dependent Cell Detachment 60 Introduction Experimental Section Results and Discussion Conclusions 61 63 67 82 Glucose Oxidase (GOD) Immobilization on Poly(glycidyl methacrylate)-Si(111) Hybrids from Surface-Initiated 83 II ATRP 5.1 5.2 5.3 5.4 Introduction Experimental Section Results and Discussion Conclusions 84 86 90 105 Collagen Immobilization on Poly(2-hydroxyethyl meth acrylate)-Si(111) Hybrids from Surface-Initiated ATRP for Cell Adhesion 106 Introduction Experimental Section Results and Discussion Conclusions 107 109 113 129 Heparin Immobilization on Poly(poly(ethylene glycol) methacrylate)-Si(111) Hybrids from Surface-Initiated ATRP for Blood Compatible Surfaces 130 Introduction Experimental Section Results and Discussion Conclusions 131 133 138 156 Chapter Controlled Micropatterning of a Si(100) Surface via Surface-Initiated Living Radical Polymerizations 157 8.1 Controlled Micropatterning of a Si(100) Surface by a Combination of Surface-Initiated Nitroxide-Mediated Radical Polymerization (NMRP) and ATRP 158 8.2 Resist-Free Micropatterning of Binary Polymer Brushes on a Si(100) Surface via Consecutive Surface-Initiated ATRP and Reversible Addition-Fragmentation ChainTransfer Polymerization (RAFTP) 172 Conclusions and Recommendations for Future Work 183 References 187 List of Publications 204 Chapter 6.1 6.2 6.3 6.4 Chapter 7.1 7.2 7.3 7.4 Chapter III SUMMARY Surface-initiated atom transfer radical polymerization (ATRP) is a versatile tool for surface functionalization and allows the preparation of well-defined polymer brushes with dormant chain ends on various types of substrates. The aims of this work were to develop simple methods for immobilizing the Si-C bonded ATRP initiators and to prepare a series of well-defined and patterned functional polymer-silicon hybrids via surface-initiated ATRP. These well-defined polymer-silicon hybrids could be explored as biomaterials to control cell adhesion and to couple different biomacromolecules. Initially, a two-step method for immobilizing ATRP initiators on the hydrogen-terminated Si(100) surface (the Si(100)-H surface) via UV-induced hydrosilylation of 4-vinylaniline (VAn) with the Si(100)-H surface and the reaction of the amine group of the Si-C bonded VAn with 2-bromoisobutyrate bromide was developed. Poly(poly(ethylene glycol) monomethacrylate)-Si(100), or P(PEGMA)-Si(100), and poly(N-isopropylacrylamide)Si(100), or P(NIPAAm)-Si(100), hybrids were prepared via surface-initiated ATRP. The P(PEGMA)-Si(100) hybrids were very effective in preventing cell attachment and growth. The cell adhesion on the P(NIPAAm)-Si(100) hybrids was controllable by temperature. In addition, a simple one-step process for coupling a Si-C bonded ATRP initiator, 4vinylbenzyl chloride (VBC), via UV-induced hydrosilylation was developed. From the SiC bonded VBC surfaces (the Si-VBC surfaces), thermoresponsive comb-shaped copolymer-Si(100) hybrids were prepared via successive surface-initiated ATRPs of glycidyl methacrylate (GMA) and NIPAAm. The temperature-responsive hybrids can facilitate cell recovery without restraining cell attachment and proliferation. IV An alternative one-step method is also used to covalently attach VBC via radical-initiated hydrosilylation with the Si(111)-H surface. From the attached VBC monolayer, GMA polymer-Si(111), or P(GMA)-Si(111), hybrids were prepared via surface-initiated ATRP for subsequent immobilization of glucose oxidase (GOD). An equivalent enzyme activity (EA) of above1.6 units/cm2 and a relative activity (RA) of about 55-65% were achieved for the immobilized GOD. The developed one-step coupling of VBC via UV-induced hydrosilylation was also extended to the preparation of poly(2-hydroxyethyl methacrylate)-Si(111), or P(HEMA)-Si(111), and P(PEGMA)-Si(111) hybrids via surface-initiated ATRP. The active chloride end groups (preserved throughout the ATRP process) and the chloride groups (converted from the hydroxyl pendant groups of the P(HEMA)-Si(111) or P(PEGMA)-Si(111) hybrid surfaces) were used as leaving groups to immobilize collagen or heparin to produce the collagen-coupled P(HEMA)-Si(111) or heparin-coupled P(PEGMA)-Si(111) hybrids. The collagen-coupled P(HEMA)-Si(111) hybrid surfaces exhibited good cell adhesion and growth characteristics. The heparincoupled P(PEGMA)-Si(111) hybrid surfaces exhibited significantly improved antithrombogenicity with a plasma recalcification time (PRT) of about 150 min. Finally, surface-initiated ATRP was combined with nitroxide-mediated radical polymerization (NMRP), or reversible addition-fragmentation chain transfer polymerization (RAFTP), to prepare micropatterned and binary polymer brushes on a Si(100) surface. The combination of surface-initiated NMRP and ATRP was carried out on photoresist-patterned silicon surfaces, while the combination of surface-initiated ATRP and RAFTP for the preparation of micropatterned binary brushes was carried out in a resist-free process with the aid of a photomask. V NOMENCLATURES AFM Atomic force microscopy ATRP Atom transfer radical polymerization NMRP Nitroxide-mediated radical polymerization Bpy 2,2’-Bipyridine BSA Bovine serum albumin DMAEMA (N,N-Dimethylamino)ethyl methacrylate HEMA 2-Hydroethyl methacrylate HF Hydrofluoric acid HMTETA 1,1,4,7,10,10,-Hexamethyltriethyenetetramine GMA Glycidyl methacrylate GOD Glucose oxidase NIPAAm N-Isopropylacrylamide PEGMA Poly(ethylene glycol) monomethacrylate PRT Plasma recalcification time RAFTP Reversible addition-fragmentation chain transfer polymerization SEM Scanning electron microscopy Si(100) (100)-Oriented single crystal silicon Si(111) (111)-Oriented single crystal silicon Si-H Hydrogen-terminated silicon UV Ultraviolet VBC 4-Vinyl benzyl chloride XPS X-ray photoelectron spectroscopy VI LIST OF FIGURES Chapter Figure 2.1 Fluoride-based etching methods for preparing hydrogen-terminated silicon (Si-H) surfaces (Buriak, 2002). Figure 2.2 Mechanism for radical initiated hydrosilylation (Buriak, 2002). Figure 2.3 Mechanism for UV-induced hydrosilylation (Boukherroub et al., 1999). Figure 2.4 Preparation of polymer brushes by ‘physisorption’, ‘grafting to’ and ‘grafting from’ methods (Zhao and Brittain, 1999). Figure 2.5 (a) NMRP mechanism (Hawker et al., 1996) and (b) preparation of polystyrene brushes by surface-initiated NMRP (Husseman et al., 1999). Figure 2.6 (a) ATRP mechanism (Matyjaszewski and Xia, 2001) and (b) preparation of polymer brushes by surface-initiated ATRP of methacrylate-based monomers (Senaratne et al., 2005). Figure 2.7 Preparation of Si-C bonded polymer brushes by surface-initiated ATRP from Si-H surfaces (Yu et al., 2004). Chapter Figure 3.1 Schematic diagram illustrating the processes of UV-induced coupling of VAn on the Si-H surface to give rise to the Si-VAn surface, reaction of the Si-VAn surface with 2-bromoisobutyrate bromide to give rise to the Si-VAn-Br surface, and surface-initiated ATRP on the Si-VAn-Br surface. Figure 3.2 (a, b) Si 2p core-level and wide scan spectra of the Si-H surfaces, (c, d) N1s core-level and wide scan spectra of the Si-VAn surface, and (e, f) Br 3d core-level and wide scan spectra of the Si-VAn-Br surface. Inset (a’) shows the Si 2p core-level spectra of the pristine Si(100). Figure 3.3 C 1s and N 1s core-level spectra of the (a, b) Si-g-P(PEGMA) and (c, b) Si-g-P(NIPAAm) surfaces from ATRP of h. Figure 3.4 Dependence of the thickness of the grafted P(PEGMA) layer for (a) the Si-g-P(PEGMA) surface and of the grafted P(NIPAAm) layer for (b) the Si-g-P(NIPAAm) surface on the polymerization time during the surfaceinitiated ATRP. Figure 3.5 Optical micrographs of 3T3 fibroblasts cultured for days on the pristine Si(100) surface ((a) at 37oC, (a’) at 20oC), the Si-VAn surface ((b) at 37oC, (b’) at 20oC), the Si-VAn-Br surface ((c) at 37oC, (c’) at 20oC), the VII Si-g-P(PEGMA) surfaces (d, e and f, corresponding to increasing thickness, as in Samples i, ii and iii in Table 2.1), and the Si-gP(NIPAAm) surfaces (((g, h and i) at 37oC, (g’, h’ and i’) at 20oC), corresponding to increasing thickness, as in Samples iv, v and vi in Table 3.1). Figure 3.6 C 1s and N 1s core-level spectra of the (a, b) Si-g-P(NIPAAm)(0.5% PEGMA) and (c, b) Si-g-P(NIPAAm)(1.0% PEGMA) surfaces. Figure 3.7 Optical micrographs of the Si-g-P(NIPAAm) surface ((a) at 37oC, (a’, a”) at 20oC), the Si-g-P(NIPAAm)(0.5% PEGMA) surface ((b) at 37oC, (b’, b”) at 20oC) and the Si-g-P(NIPAAm)(1.0% PEGMA) surface ((c) at 37oC, (c’, c”) at 20oC). The surfaces correspond to those described in Table 3.2. Figure 3.8 AFM images of (a) the Si-H surface, (b) the Si-VAn-Br surface, (c) the Si-g-P(PEGMA) surface obtained at ATRP time of h, (d) the Si-gP(NIPAAm) surfaces obtained at ATRP time of h, (e) the Si-gP(NIPAAm)(0.5% PEGMA) surface corresponding to that described in Figure 3.6(a), and (f) the Si-g-P(NIPAAm)(1.0% PEGMA) surface corresponding to that described in Figure 3.6(c). Figure 3.9 C 1s and N 1s core-level spectra of (a, b) the Si-g-P(PEGMA)-bP(NIPAAm) surface ([NIPAAm]:[CuBr]:[CuBr2]:[HMTETA] = 100: 1:0.2:2 in DMSO at 40oC for 10 h), and (c, d) the Si-g-P(NIPAAm)-bP(PEGMA) surface ([PEGMA]:[CuBr]:[CuBr2]:[HMTETA] = 100:1: 0.2:2 in deionized water at 40oC for 10 h), Their starting Si-g-P(PEGMA) and Si-g-P(NIPAAm) surfaces corresponded to those described in Figure 3.3. Figure 3.10 Optical micrographs of cell adhesion on the Si-g-P(PEGMA)-bP(NIPAAm) surface ((a) at 37oC, (a’) at 20oC), and the Si-g-P(NIPAAm) -b-P(PEGMA) surface ((b) at 37oC). The surfaces correspond to those described in Table 3.3. Chapter Figure 4.1 Figure 4.2 Schematic diagram illustrating the processes of UV-induced hydrosilylation of VBC with the Si-H surface to produce the Si-VBC surface, surface-initiated ATRP of GMA from the Si-VBC surface (the Si-g-P(GMA) surface), CPA coupling via a ring-opening reaction of the epoxy groups on the Si-g-P(GMA) surface (the Si-g-P(GMA)-Cl surface), and surface-initiated ATRP of NIPAAm from the Si-gP(GMA)-Cl surface. C 1s and Cl 2p core-level spectra of (a, b) the Si-VBC surface, (c, d) the Si-g-P(GMA) surface, and (e, f) the Si-g-P(GMA)-Cl surface. Inset (a’) shows the Si 2p core-level spectra of the Si-VBC surface. VIII Figure 4.3 Dependence of the (a) thickness and (b) degree of polymerization (DP) of the grafted P(GMA) chains of the Si-g-P(GMA) surface on the surfaceinitiated ATRP time. Figure 4.4 Wide scan and N 1s core-level spectra of the (a, b) Si-g-P(GMA)-bP(NIPAAm) surface, (c, d) Si-g- P(GMA)-cb-P(NIPAAm)1 surface, and (e, f) Si-g-P(GMA)-cb-P(NIPAAm)2 surfaces. The surfaces correspond to those described in Table 4.1. Figure 4.5 Optical micrographs of the adhesion and detachment characteristics of 3T3 fibroblasts of the Si-g-P(GMA) ((a) at 37oC, (a’, a”) at 20oC), Si-gP(GMA)-b-P(NIPAAm) ((b) at 37oC, (b’, b”) at 20oC), Si-g-P(GMA)-cbP(NIPAAm)1 ((c) at 37oC, (c’, c”) at 20oC), and Si-g-P(GMA)-cbP(NIPAAm)2 ((d) at 37oC, (d’, d”) at 20oC) surfaces. The surfaces correspond to those described in Table 4.1. Figure 4.6 Time-dependent cell detachment from the graft-modified silicon surfaces upon reducing the culture temperature to 20oC, which is well below the LCST of P(NIPAAm) at about 32oC. 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Immobilization of Biomacromolecules onto Aminolyzed Poly(L-lactic acid) toward Acceleration of Endothelium Regeneration, Tissue Eng., 10, pp.53-61. 2004. 203 Appendix List of Publications Chapter 3: (1) Xu, F.J., S.P. Zhong, L.Y.L. Yung, E.T. Kang and K.G. Neoh. Surface-Active and Stimuli-Responsive Polymer-Si(100) Hybrids from Surface-Initiated Atom Transfer Radical Polymerization for Control of Cell Adhesion, Biomacromolecules, 5, pp.2392-2403. 2004. Chapter 4: (2) Xu, F.J., E.T. Kang and K.G. Neoh. UV-Induced Coupling of 4-Vinylbenzyl Chloride on Hydrogen-Terminated Si(100) Surfaces for the Preparation of Well-Defined Polymer-Si Hybrids via Surface-Initiated ATRP, Macromolecules, 38, pp.1573-1580. 2005. (3) Xu, F.J., S.P. Zhong, L.Y.L. Yung, Y.W. Tong, E.T. Kang and K.G. Neoh. ThermoResponsive Comb-Shaped Copolymer-Si(100) Hybrids for Accelerated Temperature Dependent Cell Detachment. Biomaterials, 27, pp.1236-1245. 2006. Chapter 5: (3) Xu, F.J., Q.J. Cai, Y.L. Li, E.T. Kang and K.G. Neoh. Covalent Immobilization of Glucose Oxidase on Well-defined Poly(glycidyl methacrylate)-Si(111) Hybrids from Surface-Initiated Atom Transfer Radical Polymerization, Biomacromolecules, 6, pp.1012-1020. 2005. Chapter 6: (5) Xu, F.J., S.P. Zhong, L.Y.L. Yung, Y.W. Tong, E.T. Kang and K.G. Neoh. CollagenCoupled Poly(2-hydroxyethyl methacrylate)-Si(111) Hybrid Surfaces for Cell Immobilization. Tissue Eng., 11, pp.1736-1748. 2005. Chapter 7: (6) Xu, F.J., Y.L. Li, E.T. Kang and K.G. Neoh. Heparin-Coupled Poly(poly(ethylene glycol) monomethacrylate)-Si(111) Hybrids and Their Blood Compatible Surfaces. Biomacromolecules, 6, pp.1759-1768. 2005. Chapter 8: (7) Xu, F.J., Y. Song, Z.P. Cheng, X.L. Zhu, C.X. Zhu, E.T. Kang and K.G. Neoh. Controlled Micropatterning of a Si(100) Surface by Combined Nitroxide-Mediated and Atom Transfer Radical Polymerizations, Macromolecules, 38, pp.6254-6258. 2005. (8) Xu, F.J., E.T. Kang and K.G. Neoh. Resist-Free Micropatterning of Binary Polymer Brushes on Si(100) via Surface-Initiated Living Radical Polymerizations, J. Mater. Chem., 16, pp.2948-2952. 2006. Other Publications not Included in This Thesis: (9) Xu, F.J., E.T. Kang and K.G. Neoh. pH- and Temperature-Responsive Hydrogels from Crosslinked Triblock Copolymers Prepared via Consecutive Atom Transfer Radical Polymerizations, Biomaterials, pp.2787-2797. 2006. 204 [...]... P(PEGMA)-Si(111), hybrids are prepared via surface4 Chapter 1 initiated ATRP These hybrids are utilized to couple heparin for the preparation of blood compatible surfaces In Chapter 8, surface- initiated nitroxide-mediated radical polymerization (NMRP) and reversible addition-fragmentation chain transfer polymerization (RAFTP) are combined with surface- initiated ATRP in the preparation of micropatterned binary polymer. .. 2004) For the case of functionalized silicon surface, most studies of polymer brushes prepared via surfaceinitiated ATRP focus on the native oxide-terminated silicon surfaces The generalized scheme of surface- initiated ATRP from silicon surfaces is shown in Figure 2.6(b) (Senaratne et al., 2005) Ejaz et al (1998) immobilized 2-(4-chlorosulfonylphenyl) ethyltrimethoxylsilane onto a silicon wafer and prepared... on the Si-H surfaces will be investigated; A series of well-defined polymer- silicon hybrids with appropriate chemical and physical functionalities will be prepared via surface- initiated ATRP from the Si-C bonded ATRP initiators; These polymer- silicon hybrids are to be explored as biomaterials for controlling cell adhesion and coupling of different biomacromolecules; 3 Chapter 1 Surface- initiated ATRP... (Yu et al., 2004) Relatively few studies have applied the functional polymer brushes prepared from surface- initiated ATRP to the fields of biomaterial and biomedical devices In addition, combination of surface- initiated ATRP with other living radical polymerization techniques to prepare micropatterned polymer brushes and binary brushes on silicon surfaces remains to be explored Based on these interesting... of the diblock copolymer brushes grafted the hydrogen-terminated silicon surfaces Chapter 4 Table 4.1 Chapter 5 Table 5.1 Chapter 6 Table 6.1 Chapter 7 Table 7.1 Layer thickness and static water contact angle of the polymer- Si(100) hybrids prepared via surface- initiated ATRP Static water contact angle, amount of immobilized GOD, and enzyme activity of the GOD-functionalized silicon surfaces Static water... brushes on silicon surfaces Finally, the summary and recommendation for further work are given in Chapter 9 With the inherent advantage of the electronic properties of silicon substrates, the well-defined (and patterned) functional polymer brushes, together with the functionalities of coupled biomacromolecules, the functional polymer- silicon hybrids are potentially useful for the fabrication of siliconbased... reactive silicon radical on the surface The surface reaction then propagates as a chain reaction along the Si-H surface Figure 2.2 Mechanism for radical initiated hydrosilylation (Buriak, 2002) Linford and Chidsey (1993) demonstrated for the first time that densely packed alkyl monolayers, directly bonded to silicon surfaces via Si-C bonds, can be prepared in the presence of a diacyl peroxide radical. .. surface- initiated ATRP These hybrids are further functionalized with thermo-responsive polymers for accelerated cell detachment In Chapter 5, an alternative one-step method for the covalent attachment of VBC via radical -initiated hydrosilylation of the Si(111) surfaces is described From the attached VBC monolayer, P(GMA)-Si(111) hybrids are prepared by surface- initiated ATRP The hybrid surfaces are used for... is highly desirable With the progress in polymerization methods, it is possible to prepare well-defined polymer graft chains on various substrates by living or controlled polymerization strategies, such as surfaceinitiated living cationic polymerization (Jordan and UIman, 1998), anionic polymerization (Ingall et al., 1999; Jordan et al., 1999), ring opening polymerization (Choi and Langer, 2001), reversible... can help control the polymerization Polystyrene cleaved from the surfaces has a polydispersity of about 1.14, very close to that of the “free” polymer formed in the solution Andruzzi et al (2004) prepared flurorinated poly(styrene)-based block copolymer brushes on the silicon wafer by TEMPO-mediated radical polymerizations The obtained polymer brushes were very stable towards surface reconstruction . FUNCTIONAL POLYMER-SILICON HYBRIDS VIA SURFACE- INITIATED LIVING RADICAL POLYMERIZATIONS XU FUJIAN (M. ENG,. Si(100) Surface via Surface-Initiated Living Radical Polymerizations Controlled Micropatterning of a Si(100) Surface by a Combination of Surface-Initiated Nitroxide-Mediated Radical Polymerization. prepare a series of well-defined and patterned functional polymer-silicon hybrids via surface-initiated ATRP. These well-defined polymer-silicon hybrids could be explored as biomaterials to control