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ENGINEEREDCARBOHYDRATE-BASEDMATERIALS FORBIOMEDICALAPPLICATIONSPolymers, Surfaces, Dendrimers,Nanoparticles, and Hydrogels

Edited by

RAVIN NARAINUniversity of AlbertaEdmonton, Alberta, Canada

A JOHN WILEY & SONS, INC., PUBLICATION

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ENGINEEREDCARBOHYDRATE-BASEDMATERIALS FOR BIOMEDICALAPPLICATIONS

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ENGINEEREDCARBOHYDRATE-BASEDMATERIALS FORBIOMEDICALAPPLICATIONSPolymers, Surfaces, Dendrimers,Nanoparticles, and Hydrogels

Edited by

RAVIN NARAINUniversity of AlbertaEdmonton, Alberta, Canada

A JOHN WILEY & SONS, INC., PUBLICATION

iii


Copyright C© 2011 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Engineered carbohydrate-based materials for biomedical applications : polymers, surfaces,dendrimers, nanoparticles, and hydrogels / edited by Ravin Narain.

p. ; cm.Includes bibliographical references and index.ISBN 978-0-470-47235-4 (cloth)

1. Carbohydrates–Biotechnology. I. Narain, Ravin.[DNLM: 1. Biopolymers–physiology. 2. Biocompatible Materials. 3. Biomedical

Engineering–methods. 4. Dendrimers. 5. Hydrogels. 6. Polysaccharides–chemistry.QT 37.5.P7]

TP248.65.P64E54 2011660.6–dc22 2010039787

Printed in the United States of America

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CONTENTS

PREFACE vii

CONTRIBUTORS xi

1 SYNTHESIS OF GLYCOPOLYMERS 1Samuel Pearson, Gaojian Chen, and Martina H. Stenzel

2 BLOCK GLYCOPOLYMERS AND THEIR SELF-ASSEMBLYPROPERTIES 119Qian Yang

3 CATIONIC GLYCOPOLYMERS 143Marya Ahmed and Ravin Narain

4 GLYCOPOLYMER BIOCONJUGATES 167Marya Ahmed and Ravin Narain

5 GLYCOPOLYMER-FUNCTIONALIZED CARBONNANOTUBES 189Marya Ahmed and Ravin Narain

6 GLYCONANOPARTICLES: NEW NANOMATERIALS FORBIOLOGICAL APPLICATIONS 213Isabel Garcıa, Juan Gallo, Marco Marradi, and Soledad Penades

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vi CONTENTS

7 GLYCODENDRIMERS AND THEIR BIOLOGICALAPPLICATIONS 261Elizabeth R. Gillies

8 GLYCOSURFACES 307Anca Mateescu and Maria Vamvakaki

9 CARBOHYDRATE-DERIVED HYDROGELSAND MICROGELS 337Mitsuhiro Ebara

10 MODIFIED NATURAL POLYSACCHARIDES ASNANOPARTICULATE DRUG DELIVERY DEVICES 355Archana Bhaw-Luximon

INDEX 397


PREFACE

Carbohydrates are the most abundant, easily accessible and cheap biomolecules in na-ture. Besides their potential uses as key chemical raw materials and energy production,they have been recognized to play a key role in a wide variety of complex biologicalprocesses. They are involved to a large extent in mediating recognition processesthrough their interactions with proteins and other biological entities. They have beenrecognized to play a significant role in many important cellular recognition processesincluding cell growth regulation, differentiation, adhesion, cancer cell metastasis,cellular trafficking, inflammation by bacteria and viruses, and immune response. In-dividual carbohydrate–protein interactions are generally weak, and multivalent formsof carbohydrate ligands are usually involved in those biological processes.

This book has been conceived in order to provide an up-to-date account of themajor developments on the biomedical applications of synthetic carbohydrate-basedmaterials. This book is organized into five main themes such as polymers, nanopar-ticles, surfaces, dendrimers, and hydrogels.

Synthetic glycopolymers are essential macromolecules that display many struc-tural and functional features. With functions similar to those of natural carbohydrates,synthetic glycopolymers with specific pendant saccharide moieties can play a sig-nificant role in pathological and biological processes via multivalent carbohydrate–protein interactions. With recent progress in organic and polymer chemistry, func-tional glycopolymers have been prepared with remarkable ease. Carbohydrate-basedpolymers with different properties were also synthesized, including biodegradable,thermosensitive, and acid-degradable core-crosslinked glyconanoparticles, with neu-roactivity and with chiroptical properties. Chapter 1 provides a comprehensive re-view on the synthesis of glycomonomers and their corresponding glycopolymers viaa wide range of organic and polymerization synthesis approach. Some biological

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viii PREFACE

interaction studies and applications of glycopolymers, such as in antivirus/bacteriaand gene delivery, are also described. Chapter 2 discusses the solution properties ofblock glycopolymers and their biological relevance. The synthesis of smart blockglycopolymers using various polymerization techniques has been discussed. The us-age of these smart glycopolymers in tissue engineering, drug delivery, and pathogeninteractions is discussed. One of the well-studied types of block glycopolymers iscationic glycopolymers. The use of cationic polymers for gene delivery purposes isa facile technique that is extensively studied as a possible source of noninvasive andefficient gene delivery. Chapter 3 discusses the role and importance of cationic gly-copolymers for gene delivery purposes. The brief overview of synthesis of cationicglycopolymers by different polymerization techniques is provided. The detailed studyof cationic glycopolymer for gene delivery purposes is specifically discussed.

The incorporation of glycopolymers or their corresponding copolymers to macro-molecules of choice can further enhance their physiological impact for biologicalapplications. The major challenge in this regard is the synthesis of glycopolymerbioconjugates of controlled dimensions to explore their uses for biomedical appli-cations. Chapter 4 describes the synthetic techniques used in the literature for theproduction glycopolymer bioconjugates and their importance in biological applica-tions. The facile approaches to synthesize glycopolymer bioconjugates of controlleddimensions are highlighted and their role in biological assays, diagnostics, and in thestudy of carbohydrate- and protein-based interactions is elaborated.

The synthesis of glycoclusters is an important aspect of synthetic carbohydrate-based materials under study to understand their interactions with macromoleculessuch as pathogens and several proteins. These interactions of glycoclusters with liv-ing organisms or macromolecules make the basics of most biological phenomena,including invasion, metastasis, and infections. Nanotechnology is a rapidly growingfield of materials science that has also extensively been explored in biological ap-plications, owing to the facile introduction of functional groups on the surface ofnanomaterials. The introduction of glycopolymer-based moieties on the surface ofnanomaterials are found to produce glycoclusters with enhanced biological signifi-cance compared to glycopolymers alone, due to the multivalent effect of functionalgroups present on the surface of nanomaterials. These nanomaterials are largely stud-ied in literature as a function of their structure, nature of materials, surface function-alization properties, and morphology-dependent interactions with living organisms.Chapter 5 discusses the various strategies to synthesize glycopolymer-functionalizedcarbon nanotubes and their interactions in vitro and in vivo. The inherent propertiesof carbon nanotubes toward cellular uptake and their toxicity issues are discussed.Moreover, the uses of glycopolymer-functionalized nanotubes for biomedical ap-plications, including gene and drug delivery, and tissue engineering is described.Chapter 6 provides a brief overview about the synthesis and surface functionalizationof another type of nanomaterial, namely metallic nanoparticles. The synthesis andsurface functionalization of gold and magnetic nanoparticles and of quantum dotswith biocompatible carbohydrate-based polymers has opened various possibilities fortheir uses in biotechnology and biomedicines. This chapter describes a review of fewbiomedical applications of these glyconanoparticles, including their use in pathogen


PREFACE ix

inhibition, fluorescent probes, magnetic resonance imaging, and cancer metastasis.Another approach to obtain multivalency and to enhance the function of glycopoly-mers is the synthesis of glycodendrimers, which compared to their correspondingpolymers are of controlled molecular weight and architecture. Chapter 7 describesthe synthesis of glycodendrimers using various strategies and their interactions withproteins are studied. The interactions of glycodendrimers with various proteins atphysiological and pathological levels are the discussed.

In addition to the surface functionalization of nanoscaffolds in colloidal form,the synthesis of glycopolymer-coated macroscaffolds are found to be an attractiveplatform for the tissue engineering purposes. These glycopolymer-modified surfacesprovide not only biocompatibility but are also shown to possess the potential toprovide the selectivity in cellular growth and proliferation. Chapter 8 provides adetailed overview of the synthetic techniques involved in the functionalization ofmacroscaffolds with glycopolymers or their corresponding copolymers. Moreover,the characterization of these surfaces and their role in tissue engineering and asnonfouling surfaces for the inhibition of pathogens is discussed. Chapter 9 providesa different synthetic route to produce biomaterials for tissue engineering and genedelivery. The chapter focuses on the synthesis of glycopolymer-functionalized hy-drogels by various techniques. The use of these hydrogels in tissue engineering anddrug delivery is discussed. Chapter 10 mainly focuses on the modification of naturalcarbohydrate-based scaffolds for drug delivery purposes via various administrationroutes. These modifications are thought to increase the efficacy of drug delivery, inaddition to eliminating the hypersensitivity reactions associated with various drugtreatments.

Ravin Narain


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CONTRIBUTORS

Marya Ahmed, Department of Chemical and Materials Engineering and AlbertaIngenuity Centre for Carbohydrate Science, University of Alberta, Edmonton, AB,Canada

Archana Bhaw-Luximon, Department of Chemistry, University of Mauritius,Reduit, Mauritius

Gaojian Chen, Centre for Advanced Macromolecular Design, University of NewSouth Wales, Sydney, Australia

Mitsuhiro Ebara, Smart Biomaterials Group, Biomaterials Center, National Insti-tute for Materials Science, Tsukuba, Japan

Juan Gallo, Laboratory of Glyconanotechnology, Biofunctional NanomaterialsUnit, CIC biomaGUNE/CIBER-BBN, San Sebastian, Spain

Isabel Garcıa, Laboratory of Glyconanotechnology, Biofunctional NanomaterialsUnit, CIC biomaGUNE/CIBER-BBN, San Sebastian, Spain

Elizabeth R. Gillies, Department of Chemistry, Department of Chemical andBiochemical Engineering, The University of Western Ontario, London, Canada

Marco Marradi, Laboratory of Glyconanotechnology, Biofunctional Nanomateri-als Unit, CIC biomaGUNE/CIBER-BBN, San Sebastian, Spain

Anca Mateescu, Institute of Electronic Structure and Laser, Foundation for Re-search and Technology—Hellas Heraklion, Crete, Greece, Department of Chem-istry, University of Crete, Heraklion, Crete, Greece

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xii CONTRIBUTORS

Ravin Narain, Department of Chemical and Materials Engineering and AlbertaIngenuity Centre for Carbohydrate Science, University of Alberta, Edmonton,AB, Canada

Samuel Pearson, Centre for Advanced Macromolecular Design, University of NewSouth Wales, Sydney, Australia

Soledad Penades, Laboratory of Glyconanotechnology, Biofunctional Nanomate-rials Unit, CIC biomaGUNE/CIBER-BBN, San Sebastian, Spain

Martina H. Stenzel, Centre for Advanced Macromolecular Design, University ofNew South Wales, Sydney, Australia

Maria Vamvakaki, Institute of Electronic Structure and Laser, Foundation forResearch and Technology—Hellas, Heraklion, Crete, Greece, Department of Ma-terials Science and Technology, University of Crete, Heraklion, Crete, Greece

Qian Yang, Lehrstuhl fur Technische Chemie II, Universitat Duisburg-Essen,Essen, Germany

P1: OTA/XYZ P2: ABCc01 JWBS056-Narain December 3, 2010 16:11 Printer Name: Yet to Come

CHAPTER 1

SYNTHESIS OF GLYCOPOLYMERSSAMUEL PEARSON, GAOJIAN CHEN, and MARTINA H. STENZELCentre for Advanced Macromolecular Design, University of New South Wales,Sydney, Australia

1.1 Introduction 21.2 Synthesis of Vinyl-Containing Glycomonomers 2

1.2.1 Monomers from Protected Carbohydrates 21.2.2 Monomers from Unprotected Sugars 4

1.3 Conventional Free Radical Polymerization 51.3.1 Acrylamide Monomers 61.3.2 (Meth)acrylate Monomers 61.3.3 Styrene-Based Monomers 181.3.4 Other Vinyl-Containing Glycomonomers 19

1.4 Controlled/Living Radical Polymerization 201.4.1 Stable Free Radical Polymerization 201.4.2 Atom Transfer Radical Polymerization 33

1.4.3 Reversible Addition–Fragmentation Chain Transfer Polymerization 501.5 Ring-Opening Polymerization 711.6 Ionic Chain Polymerization 74

1.6.1 Anionic Chain Polymerization 741.6.2 Cationic Chain Polymerization 80

1.7 Ring-Opening Metathesis Polymerization (ROMP) 821.8 Postfunctionalization of Preformed Polymers Using Sugar Moieties 90

1.8.1 Amide Linkage 981.8.2 Click Approach 1011.8.3 Other Nonclick Approaches 103

1.9 Conclusions 104References 104

Engineered Carbohydrate-Based Materials for Biomedical Applications: Polymers, Surfaces,Dendrimers, Nanoparticles, and Hydrogels, Edited by Ravin NarainCopyright C© 2011 John Wiley & Sons, Inc.

1


2 SYNTHESIS OF GLYCOPOLYMERS

1.1 INTRODUCTION

Glycopolymers—synthetic polymers with pendant carbohydrates—have receivedconsiderable attention in the fields of polymer chemistry, material science, andbiomedicine due to their biocompatibility and their bioactivity. From humble be-ginnings where glycopolymers were synthesized from vinyl-functionalized sugarsvia free radical polymerization with little control over the resulting polymer char-acteristics, glycopolymer synthesis has now developed into a mature area where thecontrol over molecular weight and polymer architecture is routinely sought and in-deed achieved. Glycopolymer synthesis has now infiltrated most known techniquesof polymer synthesis and is not restricted to controlled radical processes; ionic tech-niques also provide feasible means to polymerize glycomonomers in a controlledmanner.

The aim of this chapter is to provide a comprehensive review of all the techniquesthat have been utilized for the synthesis of glycopolymers; however, greater em-phasis will be placed on the techniques that supercede free radical polymerization.After highlighting the important achievements in the synthesis of glycopolymers viafree radical polymerization, focus will turn toward glycopolymer synthesis via thecontrolled/living radical polymerization processes known as nitroxide-mediated poly-merization (NMP), cyanoxyl-mediated polymerization, atom transfer radical poly-merization (ATRP), and reversible addition–fragmentation chain transfer (RAFT)polymerization. Glycopolymer synthesis by ring-opening polymerization (ROP), an-ionic polymerization and cationic polymerization will detail the progress made inthe area of ionic polymerization, and a discussion of the work carried out usingring-opening metathesis polymerization (ROMP) will conclude the section on thesynthesis of glycopolymers by polymerizing sugar-containing monomers. The func-tionalization of reactive polymer scaffolds with carbohydrate species will then bediscussed as an alternative strategy for synthesizing glycopolymers.

1.2 SYNTHESIS OF VINYL-CONTAINING GLYCOMONOMERS

1.2.1 Monomers from Protected Carbohydrates

The commercial availability of a range of carbohydrates provides access to a widearray of different glycomonomers, and significant efforts have been dedicated to thesynthesis of polymerizable vinyl sugars. In an early feature article, Wulff et al. [1]highlighted possible avenues for generating glycomonomers in which an importantdistinction must be made between protected and unprotected carbohydrates. Thechoice of employing protected or unprotected sugars is dependent on the ease ofstereospecific functionalization of the sugar, the solubility of the monomer and poly-mer, the potential incompleteness of the removal of the protective group, and the easeof purification. The most common synthetic approaches are outlined below, but theyare discussed in more detail elsewhere [1].


SYNTHESIS OF VINYL-CONTAINING GLYCOMONOMERS 3

1.2.1.1 Reactions Using Isopropylidene-Protected Sugars Many sugarscan easily be protected using acetone to form isopropylidene derivatives. This ap-proach, which is suitable for a range of sugars including glucose, galactose, fructose,and sorbose, allows easy functionalization of the remaining hydroxyl functionalitywith acrylate [2], methacrylate [3], and 4-vinylbenzyl groups [4].

1.2.1.2 Glycosides from Halogeno Sugars Glycoside monomer synthesisvia the reaction between halogeno sugars and hydroxyl groups of vinyl-containingspecies has been explored in detailed with varying degrees of success. The startingmaterials, typically acetylated 1-halogeno sugars, can be expensive or difficult toobtain, but the technique is especially useful for inserting longer spacers between thepolymerizable moiety and the sugar. The cleavage of the acetyl protecting groups inalkaline media does not affect the glycoside bond [5].

1.2.1.3 Grignard Reactions The aldehyde functionality of a sugar moleculecan be targeted by Grignard reagents [6]. Prior protection of the remaining hydroxylgroups is essential.



1.2.2 Monomers from Unprotected Sugars

1.2.2.1 Enzymatic trans-esterification Enzyme-catalysed trans-esterification reactions present a highly efficient and regioselective avenue forobtaining glycomonomers that would otherwise be inaccessible without utilizingprotecting groups. The reaction of sugars with vinyl-containing esters in organicsolvents is catalyzed by lipases such as Candida antarctica, usually yieldingderivatives functionalized in 6-position [7], although efficient functionalization inthe 1-position has also been reported [8].

1.2.2.2 Fischer Glycoside Synthesis Direct monosubstitution in theanomeric (C-1) position without the recourse to protective chemistry can be achievedby the reaction of an excess of hydroxyl groups, such as in hydroxyethyl acrylate,with the sugar in the presence of phosphomolybdic acid as catalyst [9].

β

1.2.2.3 Synthesis via Barbituratic Acid Barbituratic acid reacts readily withthe C-1 position of the unprotected sugar to generate a reactive salt. Subsequent reac-tion with bromides such as 4-vinyl benzyl bromide leads to polymerizable monomers.Conversion of the barbituratic acid ring to a diamide further improves water solubility[10].

1.2.2.4 Conversion of Aminosugars A popular route to glycomonomers isthe fast reaction between aminosugars and acyl halides or anhydrides. The highreactivity of the amine group ensures its preferential reaction even in the presenceof unprotected hydroxyl groups. Reactions of acryloyl chloride and methacryloyl


CONVENTIONAL FREE RADICAL POLYMERIZATION 5

chloride [11] and also isocyanates [12] and epoxides with various aminosugars havebeen explored to confer the glycomonomers in high yields.

1.2.2.5 Reaction between Oxidized Sugars and Amines A range ofamide-linked glycomonomers are accessible from sugars that have been oxidized totheir corresponding lactones and can therefore be reacted with vinyl-functionalizedamines [13].

While these are the most common strategies used for glycomonomer synthesis, otherpathways have emerged in recent years such as Cu(I) click chemistry [14]. Some ofthese approaches are highlighted in this chapter.

1.3 CONVENTIONAL FREE RADICAL POLYMERIZATION

Free radical polymerization is one of the most widely used techniques for makingpolymers. The polymerization reaction is initiated by free radical initiators and hasbeen used to synthesize linear vinyl saccharide polymers since the 1960s. Despite itsdisadvantages, such as high polydispersities of the resulting polymers and difficultiesin controlling terminal functionalities, the robustness of free radical polymerizationhas encouraged its widespread use. Indeed, a large number of reports have emergedon the synthesis of glycopolymers via free radical polymerization in both aqueousand nonaqueous media.

Glycopolymers, polymers with pendant sugar groups, were first reported in 1961when Kimura et al. [15] and Whistler et al. [11a, 11c] reported the free radicalhomo- and copolymerization of glycomonomers. Significant activity in the field offree radical polymerization of glycomonomers emerged in the following years, whichonly declined in the late 1990s with the birth of living free radical polymerization



techniques. The feature article by Wulff et al. [1] highlighted the body of work andthe array of structures. Here, we only highlight some of the latest achievements inthis area, mainly publications after 1990.

1.3.1 Acrylamide Monomers

Roy et al. copolymerized 4-acrylamidophenyl-�-lactoside (Table 1.1, entry 1)and acrylamide in water at 90◦C in the presence of ammonium persulfate(APS) and tetramethylethylenediamine (TMEDA) [16]. The antigenicity of theresulting carbohydrate copolymer was then demonstrated by agar gel diffusionwith peanut and castor bean lectins. Nishimura et al. outlined the synthesisof 3-(N-acryloylamino)propyl 2-acetamido-2-deoxy-�-d-glucopyranoside [17] (Ta-ble 1.1, entry 2) and 3-(N-acryloylamino)propyl O-(�-d-galactopyranosyl)-(l-4)-2-acetamido-2-deoxy-�-d-glucopyranoside [18] (Table 1.1, entry 3) and polymerizedthem in a similar manner to Roy et al. [16].

Methacrylamide-functionalized mannose monomers (Table 1.1, entries 4–5) werepolymerized by Tagawa et al. using a lipophilic azo-initiator containing two longalkyl chains per initiating fragment [19]. Incorporation of the amphiphiles into li-posomes generated structures that were able to recognize Concanavalin A (Con A)with little difference observed between the species with varying spacer lengths be-tween the polymer backbone and the sugar residue. Also starting with protectedsugars, Carpino et al. reported the synthesis of 2,3,4,6-tetra-O-acetyl-1-O-(4-methacryloylaminophenyl)-�-d-glucopyranoside (Table 1.1, entry 6) and 1-O-(4-methacryloylaminophenyl)-�-d-glucopyranoside (Table 1.1, entry 7), and homopoly-merized them with 2,2′-azobisisobutyronitrile (AIBN) as initiator in dimethylfor-mamide (DMF) to afford polymers that were then deprotected with sodium methoxideto give water-soluble glycopolymers [20].

1.3.2 (Meth)acrylate Monomers

Novel (meth)acrylic monomers (Table 1.1, entry 9) bearing a monosaccharide residuewere developed by Kitazawa et al. by reacting methyl glycosides with 2-hydroxyethylacrylate or methacrylate in the presence of heteropoly acid. The monomers were thenpolymerized in aqueous solution with potassium persulfate as initiator [9].

A galactose-based monomer containing a galactopyranose unit attached throughan ester linkage to a vinyl group (Table 1.1, entry 10) was synthesized by Fortesand co-workers and was then copolymerized with ethyl acrylate in DMF under freeradical conditions [22].

The protected monomers 2-(2′,3′,4′,6′-tetra-O-acetyl-�-d-glucosyloxy)ethylmethacrylate (Table 1.1, entry 11) and 2-(2′,3′,4′,6′-tetra-O-acetyl-�-d-galactosyloxy)ethyl methacrylate (Table 1.1, entry 12) were polymerized by Cameronet al. in chloroform, and the polymers deacetylated in a mixture of dichloromethaneand methanol [23]. The alternative approach for obtaining deprotected polymers wasalso adopted; entries 11 and 12 were deprotected to give the corresponding monomers2-(�-d-glucosyloxy)ethyl methacrylate (GlcEMA; Table 1.1, entry 13) and


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MSO

60◦ C

AIB

N29

O

HO

HO

OH

O

OH

O

HO

OH

OH

H N

O

Lac

tosa

min

e26

DM

SO60

◦ CA

IBN

29

O

HO

HO

AcH

NO

OH

O

HO

AcH

N

OH

H N

O

(con

tinu

ed)

13


TA

BL

E1.

1G

lyco

mon

omer

sSy

nthe

size

dvi

aF

ree

Rad

ical

Pol

ymer

izat

ion

(Con

tinue

d)

Car

bohy

drat

eE

ntry

Mon

omer

Solv

enta

Tem

pera

ture

Initi

ator

bR

efer

ence

Glu

cose

27D

MSO

60◦ C

AIB

N30

Glu

curo

nam

ide

28D

MSO

60◦ C

AIB

N30

Gal

acto

se/

gluc

onam

ide

29D

MSO

60◦ C

AIB

N30

HO

OH

HO

OH

NH

O

O

O

HO

HO

HO

OH

14


�,�

-Gal

acto

treh

alos

e30

DM

SO,H

2O

60◦ C

AA

PD31

OO

H

OH

HO

NHO

HN

O

HN

O

O

HO

HO

HO

OH O

�,�

-Gal

acto

treh

alos

e31

DM

SO,H

2O

60◦ C

AA

PD31

OO

H

OH

O

O

HO

HO

HO

OH H

O

NHO

HN

O

H N

O

Glu

cosa

min

e32

H2O

RT

APS

32

OH

O HO

NH

AcO

OH

n

n =

1 o

r 2

or 3

or

9

(con

tinu

ed)

15


TA

BL

E1.

1G

lyco

mon

omer

sSy

nthe

size

dvi

aF

ree

Rad

ical

Pol

ymer

izat

ion

(Con

tinue

d)

Car

bohy

drat

eE

ntry

Mon

omer

Solv

enta

Tem

pera

ture

Initi

ator

bR

efer

ence

Lac

tosa

min

e33

H2O

RT

APS

32

Chi

tobi

ose

34H

2O

RT

APS

32

OH

O HO

AcH

NO

OH

O

HO

AcH

NO

OH

Lac

tosa

min

e35

H2O

RT

APS

33

O

HO

HO

OH

O

OH

O

ON

HA

cO

OH

OO

H

HO

HO

Me

Gal

acto

se36

Cop

olym

eriz

atio

nin

diff

eren

tso

lven

ts

65◦ C

AIB

N34

OO O

OO

O

16

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ENGINEERED CARBOHYDRATE-BASED MATERIALS FOR BIOMEDICAL …download.e-bookshelf.de/download/0000/5820/48/L-G... · · 2013-07-23Engineered carbohydrate-based materials for biomedical