Dendrimers

Anne-Marie Caminade is Director of Research at the Centre National de la Recherche Scientifique (CNRS) in the Laboratoire de Chimie de Coordination in Toulouse (France), where she has been head of the Molecular, Macromolecular, and Supramolecular Main Group Chemistry team (15 to 20 researchers) since 2006. Having received two Ph.Ds (1984 and 1988 in Toulouse) and two Post-docs, in industry (Institut Français du Pétrole, France, 1984) and as an Alexander von Humboldt Fellow at the University of Saarbrücken (Germany, 1988), she has been working since 1985 at the CNRS in Toulouse. Her current research interest is on the synthesis, reactivity and study of properties and applications of dendrimers and dendritic macromolecules in three main fields: Catalysis, Biology-Medicine, and Materials. She is the co-author of 278 publications and 25 patents. She is the coordinator or "scientist in charge" of several French and European projects, and received the bronze medal of the CNRS in 1989, and the Organic Chemistry Prize of the French Chemical Society in 2006.Co-authors for the book will be members of her research team including: Dr Cédric-Olivier Turrin (biology), Dr Régis Laurent and Dr Armelle Ouali (catalysis), Dr Béatrice Delavaux-Nicot (materials).

• Preface xv Part 1 Generalities, Syntheses, Characterizations, and Physicochemical Properties 11 Syntheses of Dendrimers and Dendrons 3Anne-Marie Caminade1.1 Introduction: What Are Dendrimers and Dendrons? 31.2 Syntheses of Poly(propyleneimine) Dendrimers (PPI) 51.3 Synthesis of Poly(amidoamine) Dendrimers (PAMAM) 51.4 Syntheses of Poly(ether) Dendrimers 71.5 Syntheses of Poly(ester) Dendrimers 101.6 Synthesis of Poly(lysine) Dendrimers 141.7 Syntheses of Silicon-Containing Dendrimers 151.8 Syntheses of Phosphorus-Containing Dendrimers 161.9 Syntheses of Carbon-Based Dendrimers 171.10 Syntheses of Dendrimers Constituted of Nitrogen Heterocycles 191.11 Syntheses by Self-Assembly 211.12 Accelerated Syntheses 261.13 Conclusion 30References 302 Methods of Characterization of Dendrimers 35Anne-Marie Caminade2.1 Introduction 352.2 Spectroscopy and Spectrometry 362.2.1 Nuclear Magnetic Resonance (NMR) 362.2.2 Mass Spectrometry 402.2.3 X-ray Diffraction 412.2.4 Infrared (IR) and Raman Spectroscopy 422.2.5 Ultraviolet–Visible (UV–vis) Spectroscopy 432.2.6 Fluorescence 442.2.7 Chirality, Optical Rotation, and Circular Dichroism (CD) 452.2.8 Electron Paramagnetic Resonance (EPR) 452.2.9 Electrochemistry 462.2.10 Magnetometry 462.2.11 Mössbauer Spectroscopy 462.2.12 X-ray Spectroscopies 472.3 Scattering Techniques 472.3.1 Laser Light Scattering (LLS) 472.3.2 Small-Angle Neutron Scattering (SANS) 472.3.3 Small-Angle X-ray Scattering (SAXS) andWide-Angle X-ray Scattering (WAXS) 482.4 Microscopy 482.4.1 Transmission Electron Microscopy (TEM) 492.4.2 Atomic Force Microscopy (AFM) 492.4.3 Polarizing Optical Microscopy (POM) 502.5 Rheology and Physical Characterizations 502.5.1 Intrinsic Viscosity 502.5.2 Differential Scanning Calorimetry (DSC) 502.5.3 Dielectric Spectroscopy (DS) 512.5.4 Dipole Moments 512.6 Separation Techniques 522.6.1 Size Exclusion Chromatography 522.6.2 Electrophoresis 532.7 Conclusion 53References 543 Luminescent Dendrimers 67Anne-Marie Caminade3.1 Introduction 673.2 Dendrimers with Fluorescent Terminal Groups 683.2.1 Fully Substituted Dendrimers 683.2.2 Partially Substituted Dendrimers 693.3 Luminescent Group at the Core of Dendrimers and Energy/Light-Harvesting Properties 743.3.1 Organic Fluorophores as Cores 743.3.2 Porphyrins and Phthalocyanines as Cores 773.3.3 Metallic Cores 783.4 Fluorescent Groups inside the Structure of Dendrimers 793.5 Intrinsically Fluorescent Dendrimers 813.5.1 Fluorescent Groups throughout the Dendrimeric Structure 813.5.2 Fluorescence of Dendrimers without Known Fluorophores 863.6 Two-Photon-Excited Fluorescence of Dendrimers 863.7 Conclusion 89References 904 Stimuli-Responsive Dendrimers 99Anne-Marie Caminade4.1 Introduction 994.2 Photoresponsive Dendrimeric Structures 1004.2.1 Azobenzene-Containing Dendrimers and Dendrons 1014.2.2 Other Types of Photoresponsive Dendrimers 1084.3 Thermoresponsive Dendrimeric Structures 1104.3.1 Thermoresponsive Properties of Dendrimers 1104.3.2 Thermoresponsive Properties of Dendrons and Dendronized Polymers 1124.4 Dendrimers Responsive to Solution Media Changes 1144.4.1 pH-Responsive Dendrimers 1144.4.2 Dendrimers Disassembly 1154.5 Conclusion 117References 1185 Liquid Crystalline Dendrimers 125Anne-Marie Caminade5.1 Introduction 1255.2 Mesogenic Groups as Terminal Functions of Dendrons 1265.3 Mesogenic Groups as Terminal Functions of Dendrimers 1315.4 Mesogenic Groups as Branches of Dendrimers 1345.5 Conclusion 135References 1366 Dendrimers and Nanoparticles 141Cédric-Olivier Turrin and Anne-Marie Caminade6.1 Introduction 1416.2 Dendrimers or Dendrons for Coating Nanoparticles 1426.2.1 Dendronization of Nanoparticles by Ligand Exchange 1426.2.2 Direct Synthesis of Dendronized Nanoparticles 1476.2.3 Dendrimer Coated Nanoparticles 1496.2.4 Nanocomposites with Interdendrimer Nanoparticles 1516.3 Dendrimers as Templates for the Synthesis ofDendrimer-Encapsulated Nanoparticles (DENs) 1526.3.1 Catalysis with Dendrimer-Encapsulated Nanoparticles 1536.3.2 Other Uses of Dendrimer-Encapsulated Nanoparticles 1546.4 Conclusion and Perspectives 154References 155Part 2 Applications in Catalysis 1637 Terminal Groups of Dendrimers as Catalysts for Homogeneous Catalysis 165Armelle Ouali and Anne-Marie Caminade7.1 General Introduction 1657.1.1 The “Dendrimer Effect” 1657.1.2 Recycling the Catalysts 1667.2 Catalytic Organometallic Sites as Catalysts for Homogeneous Catalysis 1677.2.1 Formation of C–X Bonds (X = C, N, O) 1677.2.2 Addition Reactions on a C=X Double Bond (X = C, O) 1757.2.3 Oxidation Reactions 1777.3 Organocatalysis with Dendrimers 1787.4 Conclusion 178References 1798 Catalytic Sites inside the Dendrimeric Structure for Homogeneous Catalysis 183Armelle Ouali and Anne-Marie Caminade8.1 Introduction 1838.2 Catalytic Sites as the Core of Dendrimers 1848.2.1 Dendrimers Bearing a Transition-Metal-Based Complex at the Core 1848.2.2 Dendrimers Bearing an Organocatalyst at the Core 1888.3 Catalytic Sites inside the Branches of Dendrimers 1918.3.1 Formation of C–X Bonds (X = C, N, O) 1918.3.2 Addition Reactions on a C=C Double Bond: Olefi n Hydrogenation 1928.4 Conclusion 192References 1939 Dendrimers as Homogeneous Enantioselective Catalysts 197Armelle Ouali and Anne-Marie Caminade9.1 Introduction 1979.2 Catalytic Organometallic Sites as Catalysts for Homogeneous Catalysis 1989.2.1 Formation of C–X Bonds (X = C, N, O) 1989.2.2 Addition Reactions on a C=X Double Bond (X = C, O) 2049.3 Organocatalysis with Dendrimers 2099.3.1 Aldolizations 2099.3.2 Aza–Morita–Baylis–Hillmann Reactions 2099.3.3 Transaminations 2109.4 Conclusion 210References 21010 Catalysis with Dendrimers in Particular Media 215Régis Laurent and Anne-Marie Caminade10.1 Introduction 21510.2 Two-Phase (Liquid–Liquid) Media 21610.3 Catalysis in Ionic Liquids 21910.4 Catalysis in Supercritical Media 22010.5 Catalysis in Aqueous Media 22110.6 Conclusion 234References 23411 Heterogeneous Catalysis with Dendrimers 239Régis Laurent and Anne-Marie Caminade11.1 Introduction 23911.2 Catalysis with Dendrons Synthesized from a Solid Material 24011.2.1 Silica as an Inorganic Support 24011.2.2 Polymers and Resins as Organic Supports 24811.3 Catalysis with Dendrons or Dendrimers Grafted on to a Solid Surface 25411.4 Catalysis with Insoluble Dendrimers 25711.5 Conclusion 260References 261Part 3 Applications for the Elaboration or Modification of Materials 26712 Dendrimers inside Materials 269Régis Laurent and Anne-Marie Caminade12.1 Introduction 26912.2 Dendrimers for the Elaboration of Gels 27012.2.1 Dendrimers for the Elaboration of Supramolecular Hygrogels 27012.2.2 Dendrimers for the Elaboration of Polymer-Type Hygrogels 27312.2.3 Dendrimers for the Elaboration of Organogels 27612.3 Dendrimers inside Silica Gels 28012.4 Dendrimers inside Other Types of Materials 28512.5 Dendrimers for the Elaboration of OLEDs 28812.5.1 Fluorescent Dendrimers for the Elaboration of OLEDs 29012.5.2 Phosphorescent Dendrimers for the Elaboration of OLEDs 29512.6 Conclusion 298References 29913 Self-Assembly of Dendrimers in Layers 313Béatrice Delavaux-Nicot and Anne-Marie Caminade13.1 Introduction 31313.2 Langmuir–Blodgett Films of Dendrons and Dendrimers 31413.2.1 Poly(benzyl ether) Derivatives 31613.2.2. Poly(amidoamine) and Poly(propyleneimine) Derivatives 31913.2.3 Azobenzene Derivatives 32013.2.4 Poly(carbosilane) Dendrimer Derivatives 32113.2.5 Fullerene C60 Derivatives 32213.2.6 Other Examples 32513.3 Assemblies of Dendrons and Dendrimers on Solid Surfaces 32613.3.1 Assembly of Dendrons and Dendrimers on Gold Surfaces 32713.3.2 Assembly of Dendrons and Dendrimers on Silicon Substrates or Related Substrates 33013.4 Several Routes for the Formation of Dendron or Dendrimer Multilayers 33413.5 Nanoimprinting with Dendrons and Dendrimers on Solid Surfaces 34213.5.1 Dendrimer-Based Self-Assembled Monolayers as Resists for Scanning Probe Lithography 34213.5.2 Microprinting, Transfer Printing, and Dip-Pen Nanolithography with Dendrimers 34413.6 Conclusion 350References 35114 Dendrimers as Chemical Sensors 361Anne-Marie Caminade14.1 Introduction 36114.2 Dendrimers as Chemical Sensors in Solution 36214.2.1 Porphyrins and Other Macrocyclic Derivatives as the Core or Branches of Dendrimeric Sensors 36214.2.2 Terminal Groups of Dendrimers as Sensors in Solution 36314.3 Dendrimers as Electrochemical Sensors 36514.4 Dendrimers on Modifi ed Surfaces as Chemical Sensors 36714.4.1 Dendrimers on Surfaces at the Interface with a Solution 36714.4.2 Dendrimers on Surfaces at the Interface with a Vapor 36814.5 Conclusion 370References 37015 Dendrimers as Biological Sensors 375Anne-Marie Caminade15.1 Introduction 37515.2 Dendrimers as Sensors in Solutions of Biological Media 37515.3 Detection by Electrochemical Methods 37815.4 Dendrimers or Dendrons for DNA Microarrays 38015.5 Dendrimers for Other Types of Biomicroarrays 38315.6 Dendrimers on Other Types of Support 38415.7 Dendrimers as Multiply Labeled Entities Connected to the Target 38515.8 Conclusion 386References 387Part 4 Applications in Biology/Medicine 39316 Dendrimers for Imaging 395Cédric-Olivier Turrin and Anne-Marie Caminade16.1 Introduction 39516.2 Magnetic Resonance Imaging with Dendrimers 39516.2.1 Paramagnetic Dendrimer-Based Contrast Agents 39816.2.2 PARACEST Dendrimer-Based Contrast Agents 40216.2.3 Superparamagnetic Dendrimer-Based Contrast Agents 40216.2.4 Dendrimer-Based 129Xe HYPER-CEST MRI Contrast Agents 40316.2.5 19F Dendrimer-Based MRI Contrast Agents 40316.3 Other Types of Imaging with Dendrimers 40316.3.1 Dendrimers for Optical Imaging 40316.3.2 Dendrimers for Nuclear Medicine (NM) Imaging and Computed Tomography X-Ray Imaging (CT) 40516.4 Conclusion and Perspectives 407References 40717 Dendrimers as Transfection Agents 413Cédric-Olivier Turrin and Anne-Marie Caminade17.1 Introduction 41317.2 Gene Transfection with PAMAM Dendrimers 41517.2.1 Pioneering Results 41517.2.2 Gene Transfection with Surface-Modifi ed PAMAM 41617.2.3 Gene Transfection with Core-Modifi ed PAMAM 41817.2.4 Gene Transfection with PAMAM-Functionalized Nanoparticles 41917.2.5 Gene Transfection with PAMAM-Like Hyperbranched Polymers 42017.3 Gene Transfection with Other Dendrimers 42117.3.1 Gene Transfection with PPI Dendrimers 42117.3.2 Gene Transfection with Peptide-Based Dendrimers 42217.3.3 Gene Transfection with Phosphorus-Based Dendrimers 42317.3.4 Gene Transfection with Silane-Based Dendrimers 42417.4 Conclusion and Perspective 426References 42618 Dendrimer Conjugates for Drug Delivery 437Cédric-Olivier Turrin and Anne-Marie Caminade18.1 Introduction 43718.2 Improving Bioavailability with Dendrimers 43818.3 Passive Targeting in Tumors with Dendrimer–Drug Conjugates 44018.3.1 Dendrimer–Drug Bioconjugates and the EPR Effect 44018.3.2 PEGylated Dendrimeric Scaffolds 44218.4 Active Targeting with Site-Specifi c Dendrimer–Drug Conjugates 44618.4.1 Addressing with Folic Acid (FA) 44618.4.2 Addressing with Tumor-Homing Peptides 44818.4.3 Addressing with Monoclonal Antibodies 44918.5 Dendrimers for Photodynamic Therapy (PDT) 44918.6 Dendrimers for Boron Neutron Capture Therapy (BNCT) 45118.7 Conclusion and Perspectives 452References 45319 Encapsulation of Drugs inside Dendrimers 463Cédric-Olivier Turrin and Anne-Marie Caminade19.1 Introduction 46319.2 From Dendritic Boxes to Dendrimer-Based Formulations 46419.3 Improving Bioavailability with Dendrimers? 46419.4 Toxicological Issues 46519.5 Dendrimer-Based Formulations for Drug Delivery 46619.5.1 Nontargeted Formulations 46619.5.2 Supramolecular Assemblies Involving Surface Ionic Interactions 47319.5.3 Targeted Formulations 47519.6 Conclusion and Perspectives 477References 47720 Unexpected Biological Applications of Dendrimers and Specifi c Multivalency Activities 485Cédric-Olivier Turrin and Anne-Marie Caminade20.1 Introduction 48520.2 Dendrimers and Multivalency 48620.2.1 Multivalent Effects and Dendrimeric Effects 48620.2.2 Glycodendrimers 48720.3 Antimicrobial Dendrimers 48820.3.1 Polycationic Dendrimers 48920.3.2 Polyanionic Dendrimers 49120.4 From Immunomodulation to Regenerative Medicine 49420.4.1 Immunomodulation and Anti-Inflammation 49420.4.2 Dendrimers and Regenerative Medicine 49820.5 Conclusion and Perspectives 501References 50221 General Conclusions and Perspectives 511Anne-Marie CaminadeIndex 515

“The book is of high quality and recommended reading for anyone working with dendrimers or wanting to have a good reference book; rich in information, clearly organized and thoroughly referenced with topical primary publications.”  (Angewandte Chemie, 2012)