Dendrimers E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1061

Veröffentlichungsjahr: 2011

Beschreibung

This book will be mainly focussed on the properties and uses of dendrimers and dendrons. The aim of this book is to be the reference book about dendrimers applications. It will not describe all details, but it will give the reader a unique overview of what has currently been done with dendrimers, with numerous references and illustrations. It will be divided in four main parts: Part 1) Generalities, syntheses, characterizations and properties; Part 2) Applications in catalysis; Part 3) Applications for the elaboration or modification of materials; and Part 4) Applications in biology/medicine. The role of the nanometric size and the multiple functions of dendrimers on the properties will be emphasized.

Leseprobe

Table of Contents

Cover

Title page

Copyright page

Dedication

Preface

Part 1: Generalities, Syntheses, Characterizations, and Physicochemical Properties

1 Syntheses of Dendrimers and Dendrons

1.1 Introduction: What Are Dendrimers and Dendrons?

1.2 Syntheses of Poly(propyleneimine) Dendrimers (PPI)

1.3 Synthesis of Poly(amidoamine) Dendrimers (PAMAM)

1.4 Syntheses of Poly(ether) Dendrimers

1.5 Syntheses of Poly(ester) Dendrimers

1.6 Synthesis of Poly(lysine) Dendrimers

1.7 Syntheses of Silicon-Containing Dendrimers

1.8 Syntheses of Phosphorus-Containing Dendrimers

1.9 Syntheses of Carbon-Based Dendrimers

1.10 Syntheses of Dendrimers Constituted of Nitrogen Heterocycles

1.11 Syntheses by Self-Assembly

1.12 Accelerated Syntheses

1.13 Conclusion

2 Methods of Characterization of Dendrimers

2.1 Introduction

2.2 Spectroscopy and Spectrometry

2.3 Scattering Techniques

2.4 Microscopy

2.5 Rheology and Physical Characterizations

2.6 Separation Techniques

2.7 Conclusion

3 Luminescent Dendrimers

3.1 Introduction

3.2 Dendrimers with Fluorescent Terminal Groups

3.3 Luminescent Group at the Core of Dendrimers and Energy/Light-Harvesting Properties

3.4 Fluorescent Groups inside the Structure of Dendrimers

3.5 Intrinsically Fluorescent Dendrimers

3.6 Two-Photon-Excited Fluorescence of Dendrimers

3.7 Conclusion

4 Stimuli-Responsive Dendrimers

4.1 Introduction

4.2 Photoresponsive Dendrimeric Structures

4.3 Thermoresponsive Dendrimeric Structures

4.4 Dendrimers Responsive to Solution Media Changes

4.5 Conclusion

5 Liquid Crystalline Dendrimers

5.1 Introduction

5.2 Mesogenic Groups as Terminal Functions of Dendrons

5.3 Mesogenic Groups as Terminal Functions of Dendrimers

5.4 Mesogenic Groups as Branches of Dendrimers

5.5 Conclusion

6 Dendrimers and Nanoparticles

6.1 Introduction

6.2 Dendrimers or Dendrons for Coating Nanoparticles

6.3 Dendrimers as Templates for the Synthesis of Dendrimer-Encapsulated Nanoparticles (DENs)

6.4 Conclusion and Perspectives

Part 2: Applications in Catalysis

7 Terminal Groups of Dendrimers as Catalysts for Homogeneous Catalysis

7.1 General Introduction

7.2 Catalytic Organometallic Sites as Catalysts for Homogeneous Catalysis

7.3 Organocatalysis with Dendrimers

7.4 Conclusion

8 Catalytic Sites inside the Dendrimeric Structure for Homogeneous Catalysis

8.1 Introduction

8.2 Catalytic Sites as the Core of Dendrimers

8.3 Catalytic Sites inside the Branches of Dendrimers

8.4 Conclusion

9 Dendrimers as Homogeneous Enantioselective Catalysts

9.1 Introduction

9.2 Catalytic Organometallic Sites as Catalysts for Homogeneous Catalysis

9.3 Organocatalysis with Dendrimers

9.4 Conclusion

10 Catalysis with Dendrimers in Particular Media

10.1 Introduction

10.2 Two-Phase (Liquid–Liquid) Media

10.3 Catalysis in Ionic Liquids

10.4 Catalysis in Supercritical Media

10.5 Catalysis in Aqueous Media

10.6 Conclusions

11 Heterogeneous Catalysis with Dendrimers

11.1 Introduction

11.2 Catalysis with Dendrons Synthesized from a Solid Material

11.3 Catalysis with Dendrons or Dendrimers Grafted on to a Solid Surface

11.4 Catalysis with Insoluble Dendrimers

11.5 Conclusion

Part 3: Applications for the Elaboration or Modifications of Materials

12 Dendrimers inside Materials

12.1 Introduction

12.2 Dendrimers for the Elaboration of Gels

12.3 Dendrimers inside Silica Gels

12.4 Dendrimers inside Other Types of Materials

12.5 Dendrimers for the Elaboration of OLEDs

12.6 Conclusion

13 Self-Assembly of Dendrimers in Layers

13.1 Introduction

13.2 Langmuir–Blodgett Films of Dendrons and Dendrimers

13.3 Assemblies of Dendrons and Dendrimers on Solid Surfaces

13.4 Several Routes for the Formation of Dendron or Dendrimer Multilayers

13.5 Nanoimprinting of Dendrons and Dendrimers on Solid Surfaces

13.6 Conclusion

14 Dendrimers as Chemical Sensors

14.1 Introduction

14.2 Dendrimers as Chemical Sensors in Solution

14.3 Dendrimers as Electrochemical Sensors

14.4 Dendrimers on Modified Surfaces as Chemical Sensors

14.5 Conclusion

15 Dendrimers as Biological Sensors

15.1 Introduction

15.2 Dendrimers as Sensors in Solutions of Biological Media

15.3 Detection by Electrochemical Methods

15.4 Dendrimers or Dendrons for DNA Microarrays

15.5 Dendrimers for Other Types of Biomicroarrays

15.6 Dendrimers on Other Types of Support

15.7 Dendrimers as Multiply Labeled Entities Connected to the Target

15.8 Conclusion

Part 4: Applications in Biology/Medicine

16 Dendrimers for Imaging

16.1 Introduction

16.2 Magnetic Resonance Imaging with Dendrimers

16.3 Other Types of Imaging with Dendrimers

16.4 Conclusion and Perspectives

17 Dendrimers as Transfection Agents

17.1 Introduction

17.2 Gene Transfection with PAMAM Dendrimers

17.3 Gene Transfection with Other Dendrimers

17.4 Conclusion and Perspectives

18 Dendrimer Conjugates for Drug Delivery

18.1 Introduction

18.2 Improving Bioavailability with Dendrimers

18.3 Passive Targeting in Tumors with Dendrimer–Drug Conjugates

18.4 Active Targeting with Site-Specific Dendrimer–Drug Conjugates

18.5 Dendrimers for Photodynamic Therapy (PDT)

18.6 Dendrimers for Boron Neutron Capture Therapy (BNCT)

18.7 Conclusion and Perspectives

19 Encapsulation of Drugs inside Dendrimers

19.1 Introduction

19.2 From Dendritic Boxes to Dendrimer-Based Formulations

19.3 Improving Bioavailability with Dendrimers?

19.4 Toxicological Issues

19.5 Dendrimer-Based Formulations for Drug Delivery

19.6 Conclusion and Perspectives

20 Unexpected Biological Applications of Dendrimers and Specific Multivalency Activities

20.1 Introduction

20.2 Dendrimers and Multivalency

20.3 Antimicrobial Dendrimers

20.4 From Immunomodulation to Regenerative Medicine

20.5 Conclusion and Perspectives

21 General Conclusions and Perspectives

Index

This edition first published 2011

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Library of Congress Cataloging-in-Publication Data

Dendrimers : towards catalytic, material, and biomedical uses / Anne-Marie Caminade ... [et al.].

p. cm.

 Includes bibliographical references and index.

 ISBN 978-0-470-74881-7 (cloth)

 1. Dendrimers. I. Caminade, Anne-Marie.

 TP1180.D45D47 2011

 668.92–dc23

2011014028

A catalogue record for this book is available from the British Library.

Print ISBN: 9780470748817

ePDF ISBN: 9781119976523

oBook ISBN: 9781119976530

ePub ISBN: 9781119977575

Mobi ISBN: 9781119977582

Dedicated to Jean-Pierre Majoral on the occasion of his 70th birthday

Preface

The tree-like architecture seems to be the structural solution that accompanies the increasing complexity of life. It appears that the dendritic structure, found within plant matter and other organic tissues, adapts to their development and is compatible with their metabolic requirements. Indeed, when a dimension characteristic of a living entity grows by a factor n, volume and mass are multiplied by n3, whereas an associated surface, if it is perfectly smooth, is multiplied only by n2. Thus, favoring exchanges which are essential for life necessitates multiplying the exchange surface, and nature seems to have chosen the branching solution. The dendritic structure is frequently found in nature on various scales: on the metre scale in the branches of trees, on the centimetre scale in the roots of these trees, on the millimetre scale in topologies of the circulatory system of the human anatomy (lungs, kidneys, or the liver), and finally on the micrometric scale in dendrites of the neurons of the brain or in dendritic cells. One can also find examples of natural dendritic-like supramolecular entities such as glycogen.

These natural tree-like structures are true sources of inspiration for chemists who reproduce the dendritic shape on a nanometric scale and who are able to synthesize macromolecules of well-defined ramified structure: the dendrimers. These compounds are chemical object fruits of two sister disciplines: the chemistry of polymers and organic synthesis.

This book is mainly focused on the properties and uses of dendrimers, dendrons, and dendrimerica species. After more than twenty years of research, the time has come to find some uses for these highly sophisticated macromolecules. This book is intended as a reference book about dendrimer applications and so does not cover all aspects of the topic, but it should give the reader a unique overview of what is currently being done with dendrimers, giving numerous references and illustrations. I hope you will appreciate the scientific content of this book, even if the field of dendrimers is now so large that some specialized works have been regretfully omitted. When necessary, a comparison with hyperbranched polymers will be given. This book is divided into four main parts: Part 1: Generalities, Syntheses, Characterizations, and Physicochemical Properties; Part 2: Applications in Catalysis; Part 3: Applications for the Elaboration or Modification of Materials; and Part 4: Applications in Biology/Medicine.

Part 1. This book begins with a description of the main dendrimer characteristics and the most popular methods of syntheses (Chapter 1). Then we discuss the main methods for characterizing these compounds, which pertain both to the molecular world and to the polymer world (Chapter 2). Following chapters emphasize some specific families of dendrimers which have generated an important body of work. These include fluorescent dendrimers (Chapter 3), stimuli-responsive dendrimers (Chapter 4), liquid crystalline dendrimers (Chapter 5), and dendrimers as templates for nanoparticles (Chapter 6). Chapter 6 concludes with catalytic uses of nanoparticles and serves as a link with the following series of chapters, which concern catalytic dendrimers.

Part 2. The first chapter of this series concerning catalysis describes homogeneous catalysis, which is the most important field of research about dendrimeric catalysts; examples given concern mainly organometallic catalysts, but also feature organic catalysts. Generally, the catalytically active entities constitute the terminal groups of dendrimers (Chapter 7), but they can also be included in the internal structure at the core or within the branches (Chapter 8). After these general chapters, we focus on some attractive special types of catalyses, in particular enantioselective catalyses (mostly asymmetric hydrogenations) (Chapter 9), catalyses in special media such as supercritical fluids or water (Chapter 10), and finally heterogeneous catalyses (Chapter 11), which will ensure the transition to the next series of chapters, concerning materials.

Part 3. This part of the book discusses some of the applications of dendrimers. Several types of dendrimers were used to elaborate diverse types of materials, such as organogels, hydrogels, and silica gels. One particular application concerns the elaboration of organic light emitting diodes (OLEDs) (Chapter 12). However, dendrimers can also be used to modify the surface of existing materials. This can be obtained from Langmuir–Blodgett films or by the direct assembly of a monolayer of dendrimers, linked either covalently or by electrostatic interaction to a solid surface. Some consequences of these works such as nanoimprinting and the elaboration of nano-objects are described in Chapter 13. Another consequence is the elaboration of sensitive sensors, explored in Chapter 14, which concerns chemical sensors with detection in particular by fluorescence or electrochemistry, while Chapter 15 discusses biological analyses, including DNA and protein microarrays, which are also based on surface modifications of materials. This chapter provides the transition to the last part of this book, about biological/medical uses of dendrimers.

Part 4. Numerous fields of research are related to biological/medical uses of dendrimers. A small part concerns medical imaging, for which one important activity provided by the dendrimer is a reduced clearance, due to their large size (Chapter 16). Most of the research related to biology concerns drug delivery in a broad sense. Numerous cationic dendrimers were used as transfection agents for various types of oligonucleotides, genes, or plasmid DNA or siRNA in various types of cell and these are covered in Chapter 17. Drug delivery has also been attempted using drugs covalently linked to the terminal groups of dendrimers, with the aim of producing an entity able to target precise cells such as an antibody, but the problem of drug release exists in the case of covalent grafting (Chapter 18). To try to overcome this problem, noncovalent encapsulation of drugs inside the structure of dendrimers has been attempted (Chapter 19). Some dendrimers were shown to possess biological properties by themselves, properties that the terminal functions they bear do not possess as monomers. This is a rare and unique property of dendrimers (Chapter 20). Finally, Chapter 21 offers conclusions and tentative perspectives about the applications of dendrimers.

I would like to add more personal reflections. Perhaps you are attracted to dendrimers because of their pleasant aesthetics. This was indeed the initial reason for my involvement in the field of dendrimers, when I saw for the first time in December 1992 a full page chemical structure of a fourth generation dendrimer. At first glance, it appeared to me to be a molecular crochet lace mat, before I realized it had a three-dimensional structure. In that instant, I decided to change the topic of my work, from macrocycles to dendrimers. After having convinced Jean-Pierre Majoral (the head of the research group at that time) of the appeal of this emerging topic, he offered constant scientific, material, and friendly help for years. If I gave the initial impulsion, there is no doubt that he greatly contributed with constancy to the expansion of this field worldwide. Without him, our contribution (about 250 publications in common to date) would never have been so large. This book is dedicated to him, with my deepest thanks.

With the passing of time, several researchers have gained a permanent position in our group: first Régis Laurent (since 1996), then Cédric-Olivier Turrin (since 2001), then Béatrice Delavaux-Nicot (since 2008), and finally Armelle Ouali (also since 2008). They are all authors of one to six chapters of this book; I am deeply indebted to them, not only for their contribution to this book but also for their enthusiasm in research. I also thank the numerous PhD students and post-docs who spent a few months or several years in our group. I also don’t forget all our colleagues in France or in foreign countries, with whom we have had friendly collaboration for years.

Anne-Marie Caminade, Toulouse, February 14, 2011

Note

a The dendrimer community (including ourselves) has adopted the adjective “dendritic”, which is confusing with regard to the field of biology, in particular in connection with the well-known “dendritic cells”. We have decided all along in this book to adopt the adjective “dendrimeric”, which is less confusing and was used in some cases in the literature.

Part 1: Generalities, Syntheses, Characterizations, and Physicochemical Properties

1

Syntheses of Dendrimers and Dendrons

Anne-Marie Caminade

1.1 Introduction: What Are Dendrimers and Dendrons?

The word “dendrimer” was created by D. A. Tomalia1 from two Greek words: dendros (tree) is associated with their shape and meros (part) is reminiscent of their chemical structure, constituted of associated monomers. Due to their repetitive structure, dendrimers pertain to the polymer world, even if they are never obtained by polymerization reactions. They have a perfectly defined structure, in contrast to classical polymers, as shown in Figure 1.1.

Figure 1.1 Different types of polymers. All are obtained by polymerization reactions, except the dendrimer

The synthesis of dendrimers is always carried out step by step, but two synthetic approaches can be used. The most intuitive, which was the first one proposed (by the group of F. Vögtle)2 and is currently the most widely used, is the divergent process. Starting from a multifunctional core possessing most generally two to six chemical functions, the first step is generally its activation or modification. Then, x equivalents (x is the number of functions of the core) of a branched monomer, which is generally of type AB2 (sometimes of type AB3), are coupled to the activated core and afford the first generation of the dendrimer. The next step is the deprotection or activation of the first generation. Then the activated dendrimer reacts with 2x equivalents of the AB2 branched monomer (or 3x equivalents with an AB3 monomer) to afford the second generation (Figure 1.2). Each time a new layer of branching units is created, a new generation is obtained; the number of the generation corresponds to the number of branched layers from the core. The surface is easily functionalized and modified at will at each step. The main drawback of the divergent process is the possible presence of defects for high generations, when the number of individual reactions required on a single molecule is high (several hundreds or even several thousands).

Figure 1.2 Comparison of divergent and convergent processes for the synthesis of dendrimers

The second type of method used for the synthesis of dendrimers is the convergent process, first proposed by the group of J. M. J. Fréchet.3 In this case, surface groups (generally two) are coupled to an AB2 monomer, in which A is protected or nonactive at this step. The surface groups will not be modified up to the end of the synthesis of the dendrimeric structure. After deprotection/activation of the core, this compound is coupled through its core with an AB2 monomer, to afford the first generation “dendron”, that is a dendrimeric wedge. The synthetic process can be repeated to give larger generation dendrons. These dendrons can be coupled in the final step to a multifunctional core to afford a “true” dendrimer (Figure 1.2). The advantage of the convergent process is that only a very small number of reactions occur at each step on each molecule (only one or two reactions depending on the synthetic step considered); thus the purity is easily controlled. There are two main drawbacks in this process; the first one is that very high generations are not attainable, due to the steric hindrance at the core when the dendrons become large (generally at the fifth generation), and the second one is the difficulty to modify the terminal groups. It must be noted that some dendrons are synthesized by a divergent process;4 in this case, the advantages and drawbacks are those of the divergent process.

In the next paragraphs of this chapter, we will display the pioneering and the most widely used methods of synthesis of dendrimers – those that have led to the various applications that will be emphasized in the other chapters. The chosen examples do not pretend to give an exhaustive overview of the synthesis of dendrimers but a flavor of what has been done in this topic; several other examples can be found in a recent review about the divergent processes.5

1.2 Syntheses of Poly(propyleneimine) Dendrimers (PPI)

The first synthetic compound having a true dendrimeric structure was obtained by the group of F. Vögtle in 1978, which named it a “cascade” structure.2 Starting from a diamine core, the first step of the divergent synthesis is a Michaël-type addition in the presence of acrylonitrile in excess. The second step is the reduction of the nitrile functions, which affords primary amines, suitable to repeat the synthetic process. Compounds were isolated in poor yields (for instance 24% in the reduction step); thus this synthesis was stopped at the second generation (Figure , upper part). Fifteen years after this pioneering work, this synthetic process was improved independently by the groups of E. W. Meijer and R. Mülhaupt (from a different core: ammoniac) to obtain these dendrimers in nearly quantitative yields, thus enabling the synthesis to be carried out up to higher generations (at least generation 5) and in a large scale (several kilograms) (Figure , lower part). This type of dendrimer can be found under different names, in particular PPI (for polypropyleneimine), DAB (for diaminobutane), and POPAM (for polypropylene amine). We will use PPI, which is the most used name for these dendrimers.