This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Review pubs.acs.org/CR
Copper-Mediated Living Radical Polymerization (Atom Transfer Radical Polymerization and Copper(0) Mediated Polymerization): From Fundamentals to Bioapplications Cyrille Boyer,*,†,‡ Nathaniel Alan Corrigan,‡ Kenward Jung,‡ Diep Nguyen,‡ Thuy-Khanh Nguyen,‡ Nik Nik M. Adnan,†,‡ Susan Oliver,†,‡ Sivaprakash Shanmugam,‡ and Jonathan Yeow†,‡ †
Australian Centre for Nanomedicine, and ‡Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney 2052, Australia 2.3.2. Photoinduced ATRP 2.3.3. ATRP Using Biological Systems 3. Building Soft Nanomaterials via Copper-Mediated Polymerization 3.1. Multiblock Copolymers Synthesized by Copper-Mediated Polymerization 3.2. Postmodification of Polymers Synthesized by Copper-Mediated Polymerization 3.3. Amphiphilic Multiblock Copolymers 3.4. Biological Applications of Self-Assembled Block Copolymers 3.5. Stimuli-Responsive Self-Assembled Systems 3.5.1. pH-Responsive Self-Assembled Systems 3.5.2. Temperature-Responsive Self-Assembled Systems 3.5.3. Light-Responsive Self-Assembled Systems 3.5.4. Biologically Sensitive Self-Assembled Systems 3.5.5. Multiresponsive Self-Assembled Systems 3.6. Star Polymer, Nanogels and Microgels 3.6.1. Synthesis of Star Polymers 3.6.2. Biological Applications of Star Polymers 3.7. Synthesis and Applications of Nanogels and Microgels 3.8. Bottlebrushes 3.8.1. Synthetic Approaches to Bottlebrush Polymers 3.8.2. Biological Applications of Bottlebrush Polymers 3.9. Cyclic Polymers 3.9.1. Synthetic Approaches to Cyclic Polymers 3.9.2. Biological Applications of Cyclic Polymers 3.10. Hyperbranched Polymers 3.10.1. Synthetic Approaches to Hyperbranched Polymers 3.10.2. Biological Applications of Hyperbranched Polymers
CONTENTS 1. Introduction 1.1. Emergence of Living Radical Polymerization 1.2. Scope of This Review 2. Outset and Evolution of Copper-Mediated Polymerization 2.1. Atom Transfer Radical Polymerization (ATRP) 2.1.1. Normal ATRP 2.1.2. Reverse Atom Transfer Radical Polymerization 2.1.3. Simultaneous Reverse and Normally Initiated (SR&NI) ATRP 2.1.4. Activators Generated by Electron Transfer (AGET) ATRP 2.1.5. Activators Regenerated by Electron Transfer (ARGET) ATRP 2.1.6. Initiators for Continuous Activator Regeneration (ICAR) ATRP 2.2. Copper(0)-Mediated Polymerization 2.2.1. Supplemental Activators and Reducing Agents (SARA) ATRP 2.2.2. Single Electron Transfer-Degenerative Transfer Living Radical Polymerization (SET-DTLRP) and Single Electron Transfer-Living Radical Polymerization (SETLRP) 2.2.3. Controversy: SARA ATRP and SET-LRP 2.2.4. Applications of Copper(0)-Mediated Polymerization 2.3. Advances in Copper-Mediated Polymerizations 2.3.1. Electrochemically Mediated ATRP (eATRP) © 2015 American Chemical Society
1804 1804 1804 1805 1805 1806 1807 1808 1808 1808 1809 1809 1809
1810 1812
1814 1815 1816 1816 1817 1818 1819 1820 1821 1826 1828 1831 1834 1837 1838 1840 1846 1847 1847 1849 1850 1850 1851 1851 1851 1853
1812 Special Issue: Frontiers in Macromolecular and Supramolecular Science
1813
Received: July 6, 2015 Published: November 4, 2015
1814 1803
DOI: 10.1021/acs.chemrev.5b00396 Chem. Rev. 2016, 116, 1803−1949
Chemical Reviews 3.11. Combinatorial Polymerization Approaches for Various Architectures 4. Protein, SiRNA/DNA Polymer Conjugates, and Glycopolymers 4.1. Protein Polymer Bioconjugates 4.1.1. Grafting to Proteins 4.1.2. Grafting from Proteins 4.2. Nucleic Acid Bioconjugates 4.2.1. DNA−Polymer Conjugates 4.2.2. DNA−Polymer Conjugates in Solution 4.2.3. DNA−Polymer Conjugates from a Solid Support 4.2.4. RNA−Polymer Conjugates in Solution 4.3. Copper-Mediated Synthesis of Glycopolymers 4.3.1. Synthesis of Glycopolymers 4.3.2. Applications of Copper-Mediated Glycopolymer Synthesis 5. Modification of Polysaccharides by CopperMediated Polymerization 5.1. Copolymers Using Polysaccharide as Building Block via Copper-Mediated Polymerization in Homogeneous Systems 5.1.1. Graft Copolymers Using Polysaccharide as Backbone 5.1.2. Block Copolymers Using Polysaccharide as One Block 5.2. Surface-Initiated Copper-Mediated Polymerization of Polysaccharides 5.2.1. Surface-Initiated Copper-Mediated Modification of Cellulose Surfaces 5.2.2. Other Polysaccharides Surfaces Modified by Surface-Initiated Copper-Mediated Polymerization 6. Functionalization of Inorganic Nanomaterial Surfaces 6.1. Iron Oxide Nanoparticles (IONPs) 6.1.1. Contrast Agent for Imaging 6.1.2. Drug and Gene Delivery 6.1.3. Biocidal Magnetic Nanoparticles 6.2. Gold Nanoparticles (AuNPs) 6.3. Mesoporous Silica Core/Shell Particles 6.4. Miscellaneous Nanoparticles 7. Copper-Mediated Synthesis of Polymer Brushes from Flat Surfaces 7.1. Flat Surface Modification 7.2. Comparison between ATRP and Cu(0)Mediated Polymerization Approach 7.3. Antifouling Surfaces 7.4. Antibacterial Surfaces 7.5. Stimuli-Responsive Bioactive Surfaces 7.6. Active Surfaces for Covalent Coupling of Biomolecules 7.7. Patterned Surfaces for Biomedical Applications 8. Conclusions and Future Trends Author Information Corresponding Author Notes Biography Acknowledgments Abbreviations References
Review
1. INTRODUCTION 1855
1.1. Emergence of Living Radical Polymerization
The discovery of the first “living” radical polymerization by Otsu and co-workers1 in 1982 heralded the start of a very exciting time for polymer chemists. Since then, a plethora of living radical polymerization techniques have been developed, including nitroxide-mediated polymerization (NMP),2−5 metalmediated living polymerization,6−8 atom transfer radical polymerization (ATRP),9 iodine degenerative transfer polymerization,10 reversible addition−fragmentation chain transfer polymerization (RAFT),11 single electron transfer-degenerative chain transfer living radical polymerization (SET-DTLRP),12 single electron transfer-living radical polymerization (SETLRP),13 as well as new efficient coupling reactions, including copper-mediated azide−alkyne cycloaddition (CuAAc).14 The living radical polymerization techniques have allowed the rational design of functional polymeric materials with a high level of control over molecular weight and molecular weight distribution, traditionally only achievable by ionic polymerizations.15−24 More importantly, living radical polymerizations have dramatically simplified the reaction setup for the synthesis of complex polymer structures as living radical polymerizations are less experimentally demanding in comparison with ionic polymerizations.25 Ionic polymerization requires specific equipment due to its high sensitivity to impurities (including water) and temperature. Although such reaction setups can be readily found in most chemistry laboratories, this is not necessarily the case for biology, pharmacy, and bioengineering departments. Furthermore, living radical polymerization techniques have broadly expanded the scope of functional monomers and compatible solvents. Over the past 10−15 years, the mechanism and reaction conditions of living radical polymerization techniques have been thoroughly investigated, resulting in the ability to produce a large variety of polymeric materials with various architectures, and greater control over molecular weight and molecular weight distributions.26 Copper-mediated polymerization techniques, including ATRP and copper(0)-mediated polymerization, have emerged as very powerful tools for the preparation of functional materials. Furthermore, the commercial availability of the initiators used in these techniques has significantly improved their accessibility, empowering a wider gamut of researchers in their ability to prepare the materials of the future. Typical polymerizations can be carried out in a variety of solvents and conditions, including water at room temperature, and demonstrate control over a broad range of nonfunctional and functional monomer families, including (meth)acrylates, (meth)acrylamides, and styrene derivatives. Because of its versatility, copper-mediated polymerization has been utilized for the synthesis of functional materials finding extensive applications in medicine and bioengineering over the last 10 years. Initially, early research in the field focused strongly on reaction modeling and establishing feasibility but has rapidly progressed to include highly specialized applications, particularly in a biological context. Moreover, the simplicity of copper-mediated polymerizations has even enabled nonpolymer chemists to readily use such approaches to create new functional materials.
1858 1858 1858 1860 1863 1863 1864 1865 1865 1866 1867 1867 1871
1872 1872 1879 1879 1879
1880 1880 1883 1883 1885 1886 1886 1891 1894 1896 1896 1899 1899 1901 1905 1906 1909 1909 1910 1910 1910 1910 1911 1911 1914
1.2. Scope of This Review
The intention of this Review is to highlight the use of coppermediated living radical polymerization as an efficient macromolecular engineering tool for the production of functional 1804
DOI: 10.1021/acs.chemrev.5b00396 Chem. Rev. 2016, 116, 1803−1949
Chemical Reviews
Review
Table 1. Evolution of Copper Concentrations in ATRPa technique
year
[Cu] (ppm)
normal ATRP reverse ATRP SR&NI AGET ARGET ICAR SARA SET-DTLRP SET-LRP eATRP photo-ATRP photo-SET-LRP
19959 199530 200131 200532 200633 200634 199735 200212 2006 201136 201037 201338
∼5000 ∼5000 ∼2000
Review pubs.acs.org/CR
Copper-Mediated Living Radical Polymerization (Atom Transfer Radical Polymerization and Copper(0) Mediated Polymerization): From Fundamentals to Bioapplications Cyrille Boyer,*,†,‡ Nathaniel Alan Corrigan,‡ Kenward Jung,‡ Diep Nguyen,‡ Thuy-Khanh Nguyen,‡ Nik Nik M. Adnan,†,‡ Susan Oliver,†,‡ Sivaprakash Shanmugam,‡ and Jonathan Yeow†,‡ †
Australian Centre for Nanomedicine, and ‡Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney 2052, Australia 2.3.2. Photoinduced ATRP 2.3.3. ATRP Using Biological Systems 3. Building Soft Nanomaterials via Copper-Mediated Polymerization 3.1. Multiblock Copolymers Synthesized by Copper-Mediated Polymerization 3.2. Postmodification of Polymers Synthesized by Copper-Mediated Polymerization 3.3. Amphiphilic Multiblock Copolymers 3.4. Biological Applications of Self-Assembled Block Copolymers 3.5. Stimuli-Responsive Self-Assembled Systems 3.5.1. pH-Responsive Self-Assembled Systems 3.5.2. Temperature-Responsive Self-Assembled Systems 3.5.3. Light-Responsive Self-Assembled Systems 3.5.4. Biologically Sensitive Self-Assembled Systems 3.5.5. Multiresponsive Self-Assembled Systems 3.6. Star Polymer, Nanogels and Microgels 3.6.1. Synthesis of Star Polymers 3.6.2. Biological Applications of Star Polymers 3.7. Synthesis and Applications of Nanogels and Microgels 3.8. Bottlebrushes 3.8.1. Synthetic Approaches to Bottlebrush Polymers 3.8.2. Biological Applications of Bottlebrush Polymers 3.9. Cyclic Polymers 3.9.1. Synthetic Approaches to Cyclic Polymers 3.9.2. Biological Applications of Cyclic Polymers 3.10. Hyperbranched Polymers 3.10.1. Synthetic Approaches to Hyperbranched Polymers 3.10.2. Biological Applications of Hyperbranched Polymers
CONTENTS 1. Introduction 1.1. Emergence of Living Radical Polymerization 1.2. Scope of This Review 2. Outset and Evolution of Copper-Mediated Polymerization 2.1. Atom Transfer Radical Polymerization (ATRP) 2.1.1. Normal ATRP 2.1.2. Reverse Atom Transfer Radical Polymerization 2.1.3. Simultaneous Reverse and Normally Initiated (SR&NI) ATRP 2.1.4. Activators Generated by Electron Transfer (AGET) ATRP 2.1.5. Activators Regenerated by Electron Transfer (ARGET) ATRP 2.1.6. Initiators for Continuous Activator Regeneration (ICAR) ATRP 2.2. Copper(0)-Mediated Polymerization 2.2.1. Supplemental Activators and Reducing Agents (SARA) ATRP 2.2.2. Single Electron Transfer-Degenerative Transfer Living Radical Polymerization (SET-DTLRP) and Single Electron Transfer-Living Radical Polymerization (SETLRP) 2.2.3. Controversy: SARA ATRP and SET-LRP 2.2.4. Applications of Copper(0)-Mediated Polymerization 2.3. Advances in Copper-Mediated Polymerizations 2.3.1. Electrochemically Mediated ATRP (eATRP) © 2015 American Chemical Society
1804 1804 1804 1805 1805 1806 1807 1808 1808 1808 1809 1809 1809
1810 1812
1814 1815 1816 1816 1817 1818 1819 1820 1821 1826 1828 1831 1834 1837 1838 1840 1846 1847 1847 1849 1850 1850 1851 1851 1851 1853
1812 Special Issue: Frontiers in Macromolecular and Supramolecular Science
1813
Received: July 6, 2015 Published: November 4, 2015
1814 1803
DOI: 10.1021/acs.chemrev.5b00396 Chem. Rev. 2016, 116, 1803−1949
Chemical Reviews 3.11. Combinatorial Polymerization Approaches for Various Architectures 4. Protein, SiRNA/DNA Polymer Conjugates, and Glycopolymers 4.1. Protein Polymer Bioconjugates 4.1.1. Grafting to Proteins 4.1.2. Grafting from Proteins 4.2. Nucleic Acid Bioconjugates 4.2.1. DNA−Polymer Conjugates 4.2.2. DNA−Polymer Conjugates in Solution 4.2.3. DNA−Polymer Conjugates from a Solid Support 4.2.4. RNA−Polymer Conjugates in Solution 4.3. Copper-Mediated Synthesis of Glycopolymers 4.3.1. Synthesis of Glycopolymers 4.3.2. Applications of Copper-Mediated Glycopolymer Synthesis 5. Modification of Polysaccharides by CopperMediated Polymerization 5.1. Copolymers Using Polysaccharide as Building Block via Copper-Mediated Polymerization in Homogeneous Systems 5.1.1. Graft Copolymers Using Polysaccharide as Backbone 5.1.2. Block Copolymers Using Polysaccharide as One Block 5.2. Surface-Initiated Copper-Mediated Polymerization of Polysaccharides 5.2.1. Surface-Initiated Copper-Mediated Modification of Cellulose Surfaces 5.2.2. Other Polysaccharides Surfaces Modified by Surface-Initiated Copper-Mediated Polymerization 6. Functionalization of Inorganic Nanomaterial Surfaces 6.1. Iron Oxide Nanoparticles (IONPs) 6.1.1. Contrast Agent for Imaging 6.1.2. Drug and Gene Delivery 6.1.3. Biocidal Magnetic Nanoparticles 6.2. Gold Nanoparticles (AuNPs) 6.3. Mesoporous Silica Core/Shell Particles 6.4. Miscellaneous Nanoparticles 7. Copper-Mediated Synthesis of Polymer Brushes from Flat Surfaces 7.1. Flat Surface Modification 7.2. Comparison between ATRP and Cu(0)Mediated Polymerization Approach 7.3. Antifouling Surfaces 7.4. Antibacterial Surfaces 7.5. Stimuli-Responsive Bioactive Surfaces 7.6. Active Surfaces for Covalent Coupling of Biomolecules 7.7. Patterned Surfaces for Biomedical Applications 8. Conclusions and Future Trends Author Information Corresponding Author Notes Biography Acknowledgments Abbreviations References
Review
1. INTRODUCTION 1855
1.1. Emergence of Living Radical Polymerization
The discovery of the first “living” radical polymerization by Otsu and co-workers1 in 1982 heralded the start of a very exciting time for polymer chemists. Since then, a plethora of living radical polymerization techniques have been developed, including nitroxide-mediated polymerization (NMP),2−5 metalmediated living polymerization,6−8 atom transfer radical polymerization (ATRP),9 iodine degenerative transfer polymerization,10 reversible addition−fragmentation chain transfer polymerization (RAFT),11 single electron transfer-degenerative chain transfer living radical polymerization (SET-DTLRP),12 single electron transfer-living radical polymerization (SETLRP),13 as well as new efficient coupling reactions, including copper-mediated azide−alkyne cycloaddition (CuAAc).14 The living radical polymerization techniques have allowed the rational design of functional polymeric materials with a high level of control over molecular weight and molecular weight distribution, traditionally only achievable by ionic polymerizations.15−24 More importantly, living radical polymerizations have dramatically simplified the reaction setup for the synthesis of complex polymer structures as living radical polymerizations are less experimentally demanding in comparison with ionic polymerizations.25 Ionic polymerization requires specific equipment due to its high sensitivity to impurities (including water) and temperature. Although such reaction setups can be readily found in most chemistry laboratories, this is not necessarily the case for biology, pharmacy, and bioengineering departments. Furthermore, living radical polymerization techniques have broadly expanded the scope of functional monomers and compatible solvents. Over the past 10−15 years, the mechanism and reaction conditions of living radical polymerization techniques have been thoroughly investigated, resulting in the ability to produce a large variety of polymeric materials with various architectures, and greater control over molecular weight and molecular weight distributions.26 Copper-mediated polymerization techniques, including ATRP and copper(0)-mediated polymerization, have emerged as very powerful tools for the preparation of functional materials. Furthermore, the commercial availability of the initiators used in these techniques has significantly improved their accessibility, empowering a wider gamut of researchers in their ability to prepare the materials of the future. Typical polymerizations can be carried out in a variety of solvents and conditions, including water at room temperature, and demonstrate control over a broad range of nonfunctional and functional monomer families, including (meth)acrylates, (meth)acrylamides, and styrene derivatives. Because of its versatility, copper-mediated polymerization has been utilized for the synthesis of functional materials finding extensive applications in medicine and bioengineering over the last 10 years. Initially, early research in the field focused strongly on reaction modeling and establishing feasibility but has rapidly progressed to include highly specialized applications, particularly in a biological context. Moreover, the simplicity of copper-mediated polymerizations has even enabled nonpolymer chemists to readily use such approaches to create new functional materials.
1858 1858 1858 1860 1863 1863 1864 1865 1865 1866 1867 1867 1871
1872 1872 1879 1879 1879
1880 1880 1883 1883 1885 1886 1886 1891 1894 1896 1896 1899 1899 1901 1905 1906 1909 1909 1910 1910 1910 1910 1911 1911 1914
1.2. Scope of This Review
The intention of this Review is to highlight the use of coppermediated living radical polymerization as an efficient macromolecular engineering tool for the production of functional 1804
DOI: 10.1021/acs.chemrev.5b00396 Chem. Rev. 2016, 116, 1803−1949
Chemical Reviews
Review
Table 1. Evolution of Copper Concentrations in ATRPa technique
year
[Cu] (ppm)
normal ATRP reverse ATRP SR&NI AGET ARGET ICAR SARA SET-DTLRP SET-LRP eATRP photo-ATRP photo-SET-LRP
19959 199530 200131 200532 200633 200634 199735 200212 2006 201136 201037 201338
∼5000 ∼5000 ∼2000
