Dendrimers, Dendrons, and Dendritic Polymers

Transcription

1 Dendrimers, Dendrons, and Dendritic Polymers Dendrimer science has exploded onto the polymer science scene as the fourth major class of polymer architecture after the three traditional categories of: (I) linear, (II) crosslinked, and (III) branched types. Capturing the history of dendrimer discovery to the present day with a special focus on developments in the past decade, this book addresses all the essential information for a newcomer, as well as those experienced in the field. Special issues covered include: Fundamental theory, chemistry, and physics of the dendritic state Synthetic strategies for dendrons and dendrimers including click chemistry, selfassembly, etc. Dendron/dendrimer characterization techniques Architecturally driven dendritic effects Developments in scientific and commercial applications Convergence with nanotechnology including dendrimer-based nanodevices, nanomaterials, nanotoxicology, and nanomedicine Dendrimers as a window to a systematic framework for unifying and defining nanoscience The emergence of dendrimer-based, Mendeleev-like nano-periodic property patterns The future of the dendritic state This is the ideal book for researchers in both academia and industry who wish to gain a complete introduction to the dendritic state with a special focus on dendrimer and dendron polymer science. Donald A. Tomalia is Director of the National Dendrimer & Nanotechnology Center and Founder/CEO of NanoSynthons, LLC. He is internationally recognized as a pioneer in dendrimers, dendritic polymers, dendrimer-based nanomedicine, and a new nano-periodic system for defining and unifying nanoscience. Active in both academia and industry, Tomalia is an Associate Editor of Nanomedicine (Elsevier), and the founder of several dendrimer-related companies including, most recently, NanoSynthons, LLC (2010) and Dendritic Nanotechnologies, Inc. (2001), a subsidiary of Starpharma, Melbourne, Australia. Jørn B. Christensen is an Associate Professor in the Department of Chemistry at the University of Copenhagen. He has a background in organic chemistry and has worked in many different areas ranging from organic superconductors to non-antibiotics. Ulrik Boas is an Associate Professor in the National Veterinary Institute at the Technical University of Denmark. He received his Ph.D. in Organic and Macromolecular Chemistry in 2002, prior to which he gained several years of experience working in the biotechnology industry. in this web service

2 A brilliant and exciting book co-authored by the pioneer of the dendrimer field. With a focus on dendrons/dendrimers, it provides a unique perspective on the history, current status and anticipated future developments of these precise nanostructures. This book is packed with critical information for academic, governmental and private sector scientists with in-depth commentary on the theory, synthesis, characterization and applications of dendrimers. A must have reference source for all students and scientists interested in this rapidly growing area of soft particle nanoscience. Anil K. Patri, Frederick National Laboratory for Cancer Research, USA in this web service

3 Dendrimers, Dendrons, and Dendritic Polymers Discovery, Applications, and the Future Donald A. Tomalia NanoSynthons, LLC Jørn B. Christensen University of Copenhagen Ulrik Boas Technical University of Denmark in this web service

4 c a m b r i d g e u n i v e r s i t y p r e s s Cambridge, New York, Melbourne, Madrid, Cape Town Singapore, São Paulo, Delhi, Mexico City The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by, New York Information on this title: / D. Tomalia, J. Christensen, U. Boas 2012 This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of. First published 2012 Printed in the United Kingdom at the University Press, Cambridge A catalog record for this publication is available from the British Library Library of Congress Cataloging in Publication data Tomalia, Donald A. Dendrimers, dendrons, and dendritic polymers : discovery, applications, and the future / Donald A. Tomalia, Jørn B. Christensen, Ulrik Boas. pages cm Includes bibliographical references and index. ISBN Dendrimers. 2. Dendritic cells. I. Christensen, J. B. (Jørn Bolstad) II. Boas, U. III. Title. TP1180.D45T dc ISBN Hardback Additional resources for this publication at / has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. in this web service

5 Contents Foreword page ix 1 Introduction Background/historical Birth of a new macromolecular chemistry concept Dendritic polymer subclasses International academic/commercial interest and activity 16 References 20 2 The dendritic state Introduction Dendrons, dendrimers, and megamers Advances in dendron and dendrimer internal complexity Supramacromolecular assembly of dendrons Supramacromolecular self-assembly of dendrimers Dendritic supramolecular networks Hierarchical Aufbau: picoscale to micron sized dendritic lattices 98 References 99 3 Synthetic methodologies Synthesis of dendritic polymers a fourth major new architectural class Dendrons and dendrimers Statistical, divergent growth Controlled, convergent growth Supramolecular self-assembly 149 References Characterization methodologies The challenges of defining structures in a new, unprecedented polymer architecture Determination of composition and chemical functionality 164 in this web service

6 vi Contents 4.3 Characterization of dendritic architectural structures Homogeneity and molecular weight Determination of size/dimensions Determination of thermal properties Determination of encapsulation properties 179 References Nanomedical and advanced materials Diagnostics Advanced imaging Dendrimers as vectors for genetic material delivery Dendrimer-based nanopharmaceuticals Advanced materials Summary 245 References Toxicology of dendrimers and dendrons Introduction Methods for measurement of toxicity in vitro and in vivo Effects of charge and functionality Toxicity effects of size, shape, and polarity Modulation of toxicity Bio-permeability and biodistribution Immunogenicity of dendrimers Summary 272 References The dendritic effect Introduction/definitions Architecture driven properties: dendritic versus linear macromolecular architecture Architecture driven intrinsic dendrimer properties Interdependence of critical nanoscale design parameters (CNDPs) in a typical dendrimer family Relationship of CNDPs to dendritic effects Conservation of critical hierarchical design parameters (CHDPs) 286 References A quantized building block concept leading to a new nano-periodic system Introduction First principles and central dogma for traditional chemistry 293 in this web service

7 Contents vii 8.3 Heuristic atom mimicry of dendrimers Chemical bonding, valency and stoichiometric binding ratios to form (dendrimer)n-type nano-compounds/assemblies Proposed nano-periodic system for unifying and defining nanoscience Structural control in dendrimers: CNDPs Use of first principles to create a new nano-periodic system Elemental periodic property patterns leading to Mendeleev s periodic table Nano-periodic physico-chemical property patterns Predictive nano-periodic property patterns of importance to nano-medicine: discrete in vivo excretion and permeability First steps toward a central dogma for synthetic nano-chemistry: dendrimer-based nano-chemistry First nano-periodic tables for predicting amphiphilic dendron self-assembly to supramolecular dendrimers based on the CNDPs: (a) size, (b) shape, (c) surface chemistry, and (d) flexibility Overview of Aufbau intermediates involved in the dimensional enhancement of soft nano-element; [S-1] category complexity Conclusions 366 References The past, present, and future for dendrons and dendrimers Historical overview of dendron/dendrimer structural and process development Dendrimer applications and products Summary Conclusion 392 References 393 Index 407 in this web service

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9 Foreword While scanning through this book, you can sense the leadership of the inventor of the word that defines this field: the visionary pioneer who bridged the discovery of dendrimers, their first technological applications, the early merger of the fields of medicine and nanoscience into nanomedicine, and the grand vision of a uniform classification of the chemical sciences on all levels and length scales, in a systematic nano-periodic framewok for unifying and defining nanoscience. In spite of numerous excellent books in this exciting field, bordering the interface between the most creative science of complex chemical synthesis by covalent and supramolecular bonds, and science fiction, a book like the current one could not have been written by anybody but Donald A. Tomalia, strongly aided and supported by two more recent practitioners in this field, Jørn B. Christensen and Ulrik Boas. Reading through this book, you can feel the dedication and imagination of D. A. Tomalia in the same way that you feel it in his lectures, trying to reach the minds and dreams of the young generation of scientists from the beginning of this new century. This is not a book for those solely interested in having yet another updated and comprehensive list of publications from this field on their desk. This is a book which has been constructed based on almost a lifetime of dedication to the development of this field. This book provides an in-depth analysis of the state-of-the-art of the most advanced conceptual developments in the field, for those creative contributors or newcomers who want to master the field directly from one of its most creative inventors and visionaries, and who are interested in listening to the authors views on its future, and its possible evolution into other new multidisciplinary fields. In order to provide this transfer of unwavering intellectual belief in the scientific importance and utility of dendrimers, the authors have selected a range of topics, from the discovery and development of the dendritic architecture and dendritic state as a new macromolecular concepts, followed by the discussion of synthetic and characterization challenges, biopharmaceutical applications, toxicology issues, the dendritic effect, the concept of dendrimers as quantized building blocks leading to a new nano-periodic system, and concluding with discussion of the past, present and future of dendrimers and dendrons. This very enjoyable book is as a must for the desk of every chemist including inorganic, organic, supramolecular, polymer and physical chemists as well as nanoscientists, soft condensed matter scientists, and medical practitioners, regardless if they are in academia or industry. Virgil Percec University of Pennsylvania, Philadelphia in this web service