Advances in Chitin and Chitosan Modification Through Graft Copolymerization: A Comprehensive Review

Iranian Polymer Journal
14 (3), 2005, 235-265
Advances in Chitin and Chitosan Modification

through Graft Copolymerization:
A Comprehensive Review
M. Jalal Zohuriaan-Mehr*
Superabsorbent Hydrogel Division, Iran Polymer and Petrochemical Institute
P.O. Box: 14965-115, Tehran, I.R. Iran
Received 22 April 2004; accepted 14 September 2004
ABSTRACT
iopolymer chitin, the most abundant natural amino polysaccharide, and its most
important derivative, chitosan, are recently considered as the subjects for extensive worldwide academic and industrial research. In spite of potential applications
of chitin and chitosan, it is necessary to establish efficient appropriate modifications to
explore fully their high potential. A variety of chemical modifications are employed to modify these carbohydrate polymers. The present article provides a comprehensive review on
one of the most promising approaches to modify chitin and chitosan, i.e., graft copolymerization, with an emphasis on the synthetic aspects. Both chemically- and radiation-initiated graft copolymerization of various vinyl monomers onto the trunk polymers are investigated. Meanwhile, the limited cases of polycondensation and oxidative coupling are presented as the non-vinyl graft copolymerization methods. Then, the ring-opening graft
copolymerization is described and the cases of the cyclic monomers -aminoacid N-carboxy anhydrides and -caprolactone are investigated. An extensive description of the
grafting onto approach is provided. The preformed polymers discussed here for grafting
onto chitin/chitosan include living poly(2-alkyl oxazolines), poly(ethylene glycol)s, block
polyethers, poly(ethylene imine)s, poly(2-hydroxyalkanoate)s, polyurethanes, poly
(dimethylsiloxane)s, and dendrimer-like hyperbranched polymers. Chitin/chitosan multiple modification including graft copolymerization is also investigated. Regioselective
grafting using derivatives such as 6-iodo-, mercapto-, deoxy(thiosulphato)-chitins, and Ntrichloroacetyl chitosan are described as suitable approaches to achieve chitin/chitosan
graft copolymers with well-known structures.
Key Words:
chitin;
chitosan;
polysaccharide;
graft copolymerization;
modification.
CONTENTS
INTRODUCTION
GRAFT COPOLYMER SYNTHESIS
Vinyl Graft Copolymerization
(a) Chemically Initiated Vinyl Polymerization
(b) Radiation-initiated Vinyl Polymerization
Non-Vinyl Graft Copolymerization
(*) To whom correspondence should be addressed.
E-mail: m.zohuriaan@ippi.ac.ir
(a) Graft Copolymerization via Polycondensation
Zohuriaan-Mehr M.J.
Advances in Chitin and Chitosan Modification ...

(b) Graft Copolymerization via Oxidative Coupling
Cyclic Monomer Graft Copolymerization: Ring-Opening
Method Preformed Polymer Grafting:
Grafting Onto
Method
Multiple Modification of Chitin/Chitosan

(a) Further Modification of the Graft Copolymers
(b) Grafting onto Pre-modified Chitin/Chitosan
CONCLUSION
ACKNOWLEDGEMENTS
REFERENCES
INTRODUCTION
Cellulose and chitin as biopolymers are the most abundant organic compounds in Nature and estimated to be
at levels approaching 1011 tons annually [1]. Chitin has
been a major structural component of animal exoskeleton since the Cambrian Period, more than 550 million
years ago. The total amount of chitin harvestable without imbalancing the marine ecosystem is estimated to
be 1.5*108 kg/year [2], mostly from the shells of crustaceans such as crab, shrimp and krill. Although cellu-
Figure 1. Annual number of chitin/chitosan related reports;

(a) patents, 1966-2000 [7], (b) scientific research articles in
the 1990s as obtained from ScienceDirect [3].
236
lose has been studied extensively, only limited attention

has been paid to chitin, principally from its biological
properties [1,3]. Despite its huge annual production and
easy accessibility, chitin still remains an unutilized biomass resource primarily because of its intractable bulk
structure [1]. However, as Khor has stated [3], the 21st
century can be the century of chitin taking a place as an
extraordinary material, because chitin and its derivatives have exhibited high potential in a wide variety of
fields including medical, pharmaceutical, cosmetics,
bio-related science and technology, food industry, agriculture, and environmental protection [4-9]. Ravi
Kumar has emphasized on the pharmaceutical applications of these biopolymers in his recent reviews [9-11].
Some reviews are published on fibre- and film-forming
capabilities of chitin and chitosan [12,13]. In a very
fascinating field i.e., gene therapy, chitosan and its
appropriate derivatives are recently found to be excellent candidates for controlled gene delivery [14-18].
Overall, as exhibited in Figure 1, either scientific [3] or
patent [7] literatures reveal a considerable growing in
the field of chitin/chitosan science and technology from
mid 1980s.
Chitin is structurally similar to cellulose, but it has
acetamide groups at the C-2 positions instead of
hydroxyl groups. So it is a nitrogen (amido/amino) containing polysaccharide, with repeating units of 2acetamido/amino-2-deoxy-(1
4)--D-glucopyranose (Scheme I). In addition to its unique polysaccharide architecture, the presence of a little amino groups
(5-15%) in chitin [4,19] is highly advantageous for providing distinctive biological functions and for conducting modification reactions [7,20,21]. Chitosan is the Ndeacetylated derivative of chitin, though this Ndeacetylation is almost never complete [20,21]. Actually, the names chitin and chitosan correspond to a
family of polymers varying in the acetyl content.
Scheme I. Structural repeating units of chitin (DD= 5-15%)

and its deacetylated product, chitosan (DD 40%).
Iranian Polymer Journal / Volume 14 Number 3 (2005)
Zohuriaan-Mehr M.J.
Therefore, the degree of acetylation (DA) determines

whether the biopolymer is chitin or chitosan. Chitosan is the term used for the considerably deacetylated chitin that is soluble in dilute acetic acid (degree of
deacetylation, DD 70%) [1].
In spite of potential applications of chitin and chitosan, it is necessary to establish efficient appropriate
modifications to explore fully the high potential of
these biomacromolecules. Chemical modifications of
chitin are generally difficult owing to the lack of solubility, and the reactions under heterogeneous conditions
are accompanied by various problems such as the poor
extent of reaction, difficulty in selective substitution,
structural ambiguity of the products, and partial degradation due to severe reaction conditions. Therefore,
with regard to developing advanced functions, much
attention had been paid to modification of chitosan
rather than chitin.
Chitin and chitosan have been modified via a variety of chemical modifications. Some authors have
reviewed the methods [1,4] and Roberts have explained
the modification reactions in his source-book Chitin
Chemistry [20]. Of the various possible modifications
(e.g., nitration, phosphorylation, sulphation, xanthation
[14], acylation, hydroxyalkylation [4], Schiffs base
formation and alkylation [4,20-22]), graft copolymerization is expected to be one of the most promising
approaches to a wide variety of molecular designs leading to novel types of hybrid materials, which are composed of bio- and synthetic-polymers [23]. This modification technique, as foreseen by Kurita [1], will likely find new applications in some fields including water
treatment, metal cation adsorption, toileries, medicine,
agriculture, food processing and separation. This
method has not been explored extensively, so that the
Roberts famous sourcebook comprises only less than
one page on this topic. A literature review showed that,
except a very short article published in 1996 by Kurita
in the Polymeric Materials Encyclopedia [24], there is
no review article on the graft polymerization onto
chitin and chitosan.
During recent years, various research-teams as well
as the author and coworkers [25-33] have focused
remarkably on graft copolymerization as a versatile
method of chitin and chitosan modification. This fascinating technique may be considered as an approach to
achieve novel chitin/chitosan-based materials with
improved properties including all the expected usefulness of these biomaterials [4-11]. As concluded in the
present article, chitin will not be a biomaterial in waiting any more.
GRAFT COPOLYMER SYNTHESIS
A graft copolymer is a macromolecular chain with one
or more species of block connected to the main chain as
side chain(s) [34]. Thus, it can be described as having
the general structure shown in Scheme II, where the
main polymer backbone poly(A), commonly referred
to as the trunk polymer, has branches of polymer chain
poly(B) emanating from different points along its
length. The common nomenclature used to describe
this structure, where poly(A) is grafted with poly(B), is
poly(A)-graft-poly(B), which can be further abbreviated as poly(A)-g-poly(B).
Grafting of synthetic polymer is a convenient
Scheme II. General free radical mechanism of graft copolymerization of vinyl monomer B onto trunk polymer poly(A) to
form the graft copolymer poly(A)-g-poly(B).
237
Zohuriaan-Mehr M.J.
method to add new properties to a natural polymer with

minimum loss of the initial properties of the substrate.
Chitin and chitosan possess aforesaid useful properties
that render them interesting starting materials for the
synthesis of graft copolymers. Most of the copolymers
are prepared through graft polymerization of vinyl
monomers onto the biopolymer backbone [31]. But this
is not the only approach for synthesizing a grafted
product. Because the chemistry of grafting vinyl
monomers is quite different from that of grafting other
monomers (or performed side chains), this section is
divided into two subsections, the first dealing with
grafting of vinyl monomers, the second reviewing other
types of grafting methods.
Vinyl Graft Copolymerization
Grafting of polyvinylic and polyacrylic synthetic materials on the polysaccharides are mainly achieved by
radical polymerization. Graft copolymers are prepared
by first generating free radicals on the biopolymer
backbone and then allowing these radicals to serve as
macroinitiators for the vinyl (or acrylic) monomer
(Scheme II). Mino and Kaizerman firstly reported this
approach in 1958 for graft copolymer preparation using
a ceric ion redox initiating system [36]. Then, the
chemistry and technology of the radical graft copolymerization technique [23,37] was developed especially
in the case of cellulose [38] and starch [34,39]. Generally, free radical initiated graft copolymers have medium to high molecular weight branches that are infrequently spaced along the polysaccharide backbone
[38]. The copolymerizations can also be initiated
anionically by allowing monomer to react with an alkali-metal alkoxide derivative of polysaccharide. However, this method has not been progressed due to difficulty of the process and the low molecular weight of the
grafted branches [39]. The properties of the resulting
graft copolymers may be controlled widely by the characteristics of the side chains including molecular structures, length, number, and frequency.
One of the most important features of graft polymerization is unwanted formation of homopolymer,
homopoly(B), that is not chemically bonded to the substrate poly(A). Homopolymer can result if the initiator
used is one that produces free radicals in solution (in
the presence of vinyl monomer B initiating homopolymerization) before creating the macroradicals. Once a
238
grafted chain has been initiated and begins to propagate, chain transfer from the growing grafted chain end
can occur with some species in the medium to yield
free radicals that could initiate the growth of
homopoly(B) chains [23].
To evaluate the efficiency of the graft copolymerization, the homopolymer is extracted with an appropriate solvent. Then, the homopolymer percentage (Hp%)
and other various grafting compositional parameters
are calculated. Although there are no unified definitions
for calculating the parameters, the most frequently
reported expressions for all kinds of graft copolymerizations are as follows [23,34,40]:
Graft yield (G%) = 100 (W3-W0) / W0
(1)
Add-on (Ad%) = 100 (W3-W0) / W3
(2)
Hp% = 100 (W2-W3) / W2

Hp% = 100 W4/ W1
(3)
or,
where W0, W1, W2, W3 and W4 designate the weight of

the original substrate, monomer charged, total product
(i.e., copolymer and homopolymer), pure graft copolymer, and homopolymer, respectively.
The various initiating systems employed to graft
copolymerize different vinyl monomers onto chitin or
chitosan can be categorized to two main classes, i.e.
chemical initiation and radiation initiation that are
investigated in the next sections.
(a) Chemically-initiated Vinyl Polymerization
Among the variety of chemical reagents reported for

initiating the vinyl monomer graft copolymerization
onto chitin/chitosan, ceric ion initiation and Fentons
initiation are the most important systems.
Cerium in its tetravalent state is a versatile oxidizing agent used most frequently in the graft copolymerization of vinyl monomers onto cellulose and starch
[34-40]. It forms a redox pair with the anhydroglucose
units of the polysaccharide to yield the macroradicals
under slightly acidic conditions. As with cellulose and
starch, the ceric ion has been a useful initiation method
for graft copolymerizing chitin and chitosan with typical vinyl monomers [27-32] due to the similarities in
the chemical structures of these polysaccharides.
The mechanism of initiation for chitosan is
Zohuriaan-Mehr M.J.
Scheme III. General mechanism for ceric-initiated graft

copolymerization of a typical vinyl monomer, acrylonitrile
(AN), onto chitosan [28]. The opening of the pyranose ring
shown above is very rarely occurred along a chitosan chain,
so the initial structure of the trunk polymer is not actually
destroyed.
believed to begin with a complex formation of Ce4+

with the primary amine and the hydroxyl groups at the
C-2 and C-3 positions, respectively. The radicals
responsible for the initiation of grafted copolymer
chains using vinyl monomer are produced from the
complex dissociation. A general mechanism for the
reaction proposed recently by the author and coworkers
[28] is shown in Scheme III. At higher temperatures
(e.g., 90oC), it is proposed that the imine moiety shown
in Scheme III is further hydrolyzed in the aqueous
acidic conditions to the corresponding aldehyde,
whereby oxidation to an acyl radical gives another site
capable of initiating a grafted polymer chain [23].

Moderate to excellent yields accompanied various
amounts of homopolymer are reported. Table 1 provides the grafting conditions and compositional parameters of the synthetic polymer grafted chitin/chitosan
prepared using the ceric-saccharide initiating system.
According to the recent study by the author and
coworkers [27,28], acrylonitrile was optimally graft
copolymerized onto chitosan in a homogeneous phase
while a very low level of homopolyacrylonitrile (2 %)
was formed (the first row of Table 1). Based upon the
study, the optimum conditions for achieving the maximum grafting were determined to be as: chitosan
amount 0.20 g, acetic acid 2% w/w, reaction temperature 50oC; AN 1.60 g, ceric ammonium nitrate (CAN)
concentration 0.006 M, time 2 h. The grafting efficiency was recognized to remain almost unchanged with
the reaction time. The grafting-time independence can
be attributed to a decrease in concentration for both initiator and monomer and also to a reduction of the number of sites on the chitosan backbone accessible for
grafting as the reaction proceeds. Empirical rate of the
polymerization showed a first-order dependence on the
monomer concentration and a half-order dependence
on the initiator concentration. An overall activation
energy of 44.9 kJ/mol was determined for this graft
polymerization reaction [28]. The hydrophobically
modified chitosan exhibited higher thermal stability
than chitosan itself [30].
Kim et al. [41] reported the ceric-induced graft
copolymerization of N-isopropylacrylamide (NIPAM)
onto chitosan at 25oC to prevent a high level of
homopolymer formation (Table 1). The maximum
grafting yield (48%) was obtained at 0.5 M of
monomer concentration, 0.002 M of CAN initiator and
2 h of the reaction time. They found a decreased percent of grafting when the initiator concentration was
higher than 0.002 M. The grafting loss was attributed to
lower macroradical formation at the expense of producing more homopoly(NIPAM). The excessive CAN may
also be consumed for oxidation of the polysaccharide
backbone leading to decreased molecular weight of the
graft copolymer product.
Vinyl acetate (VAc), a less reactive monomer than
acrylates, was also recently graft copolymerized onto
chitosan by CAN in dispersion medium at 60oC
[42,43]. With an addition of 0.5-7.5 g of chitosan based
239
Zohuriaan-Mehr M.J.
Table 1. Preparative reaction conditions and grafting parameters of synthetic polymer grafted chitin/chitosan synthesized via cericinduced graft copolymerization.
Grafting parameters
Substrate
Copolymerization conditions
Monomer
Ce
(mM)
Monomer concentration
Temp.
(oC)
Time (h)
Ad
Hp
Chitosan
ANa
6.6 wt%
50
NQb
81
27,28
Chitosan
NIPAMc
0.5 M
25
48
NQ
41
2.16
9.6 wt%
60
236
NQ
NQ
42,43
87
1.22 M
70
331
76.8
NQ
44
VAc
Chitosan
Chitosan
4VP
Chitosan
AAf
h
NGg
NG
50-55
57
NQ
10
45
50-55
NQ
NQ
10
45
Chitosan
MAA
NG
NG
Chitosan
DMSAi
18.2
0.1434 M
60
50
NQ
NQ
46
Chitin
AA
8.0
1.17 M
60
200
NQ
NQ
47
Chitin
AA
3.45
0.959 M
60
45
31.3
NQ
48
Chitin
AMj
8.8
0.42 M
60
243
70.8
NQ
47
4.25
0.0199 M
40
~300
NQ
NQ
49
MMA
Chitin
(a)
Ref.
(%)
4+
Acrylonitrile,
(b)
Not quantified,
(c)
N-Isopropylacrylamide,
methacryloxyethyl-N-(3-sulphopropyl) ammonium,
(j)
(d)
Vinyl acetate,
Acrylamide,
(k)
(e)
(f)
Acrylic acid,
(g)
Not given,
(h)
Methacrylic acid,
(i)
N,N-Dimethyl-N-
Methyl methacrylate.
on 50 g VAc, the monomer conversion was found to be

between 70 and 80% after 2 h of reaction. The experimental results indicated that the chitosan macromolecules not only took part in the copolymerization, but
also served as a surfactant providing the stability of the
dispersion particles. The particulate membrane chitosan-g-PVAc formed after drying exhibited higher
toughness and lower water-absorption compared to
non-grafted chitosan. The copper ion adsorption by the
poly(VAc) grafted chitosan was also studied [43].
The monomer 4-vinylpyridine (4VP) is another
non-acrylic monomer graft polymerized onto chitosan
[44] under homogeneous conditions. Percent grafting
was increased with the amount of the monomer, showing a tendency to level off at a 4VP concentration of
0.53 M. As given in Table 1, maximum graft yield
(331%) was achieved in lieu of a very high CAN consumption (0.087 M). According to the authors, their
used system has a drawback since it requires the precipitation of the obtained product in a basic medium,
resulting in the coprecipitation of the excess cerium
salts that cannot be separated from the grafted product.
The purified graft copolymers showed swellability
behaviour in 1:1 and 1:2 acetic acid:ethanol solvent
mixtures and insolubility in ethanol, dimethylfor240
4-Vinyl pyridine,
mamide (DMF), dimethylsulphoxide (DMSO) and

tetrahydrofurane (THF).
Acrylic and methacrylic acids were graft polymerized onto chitosan by Shantha et al. [45] to tailor drug
carriers. They have reported an ambiguous procedure
of polymerization without giving the CAN concentration used. Although they did not achieve a high grafting percent (Table 1), they utilized graft copolymers for
preparing functionalized chitosan beads by a polymer
dispersion technique. The drug sulphadiazine was
entrapped in the microspheres and the in vitro drug
release profiles were established in either simulated
gastric and intestinal fluids. A sulphobetain methacrylic
monomer, N,N-dimethyl-N-methacryloxyethyl-N-(3sulphopropyl) ammonium, was recently reported to be
graft polymerized onto chitosan by ceric ion initiation
[46]. A maximum percentage of grafting about 50%
was obtained under an optimized condition (0.5 g chitosan in 50 mL of 2 wt% acetic acid aqueous solution,
CAN 0.0182 M, monomer 0.1434 M, 60oC, 2 h). Thermal properties of the graft copolymer were found to be
slightly different from the original chitosan.
Chemically modified chitosan microspheres were
synthesized by graft copolymerization of a bifunctional macromolecular monomer, poly(ethylene glycole)
Zohuriaan-Mehr M.J.
diacrylate onto chitosan backbone using CAN [47].

The products were fully characterized by spectral, thermal and morphological techniques. Since the preparative reaction resulted in cross-linked networks, the
grafting parameters could not be determined.
Regarding chitin, limited reports have been published about the ceric initiated grafing. Kurita et al. [48]
have reported an efficient and reproducible procedure
for graft copolymerization of acrylamide (AM) and
acrylic acid (AA) onto powdery chitin. As a solvent,
water proved to be superior to conventional nitric acid
solution (except the reactions with a small amount of
the initiator CAN). In spite of the heterogeneous conditions, under optimized conditions (0.10 g chitin, 10 mL
water, 0.8-1.6 g CAN, 0.30-0.43 g monomer, 60oC, 2h),
around 240% and 200% graft yields were achieved for
AM and AA, respectively. The resulting graft copolymers showed improved affinity for solvents and hygroscopicity compared to the original chitin.
Acrylic acid was graft copolymerized onto chitin
using CAN by other workers as well [49]. They
achieved a low grafting (45%) under conventionally
acidified (1 M nitric acid) reaction conditions (chitin
1.00 g, water 45 mL, CAN 0.00345 M, AA 0.959 M,
60oC, 1 h). The chitin-g-poly(AA) was used to study
the effect of carboxylic group of the graft copolymer on
the metal binding ability of calcium ions in aqueous
medium as a function of pH, contact time and the metal
concentration. The maximum adsorption of the graft
copolymer and the original chitin were found to be 0.50
and 0.19 mmol Ca2+ g-1, respectively.
Ren et al. [50] modified chitin via graft polymerization of methyl methacrylate (MMA) by CAN. They
found the optimized grafting conditions to be: chitin
0.50 g, water 220 mL, nitric acid 0.0383 M, CAN
0.0425 M, monomer 0.0199 M, 40oC, 5 h. Grafting percentage of about 300% was obtained under the condi-
Scheme IV. Mechanism for hydroxy radical formation by

means of Fentonss reagent in aqueous media.
tions. Solubility of the highly poly(MMA) grafted

chitins in various organic solvents showed significant
changes, and a gel-like mass swelling was resulted.
Fine films could be made from the gel-like material
especially in DMF or dimethylacetamide, when a small
amount of lithium chloride was used. Complementary
studies revealed that the amphiphilic comb-like chitin
derivatives containing PMMA side chains were able to
form stable monolayers with high collapse pressure
[51].
Fenton s reagent is another frequently used initiator
for graft copolymerizing vinyl monomers onto
chitin/chitosan [52,53]. The reagent involves a redox
reaction between the ferrous ion and hydrogen peroxide, providing hydroxyl radicals (Scheme IV). These
radicals are believed to be responsible for creating the
macroradicals on the polysaccharide backbone, by
means of hydrogen abstraction, that initiate the growth
of grafted chains with various monomers. Although
H2O2 alone could be an adequate initiator for the
copolymerization, there are reasons why reducing
agents such as Fe2+ are used for grafting onto chitosan.
In addition to the higher yield of radical production at
much lower temperatures via the redox reaction, the
chelating properties of chitosan with metal ions tend to
promote OH radical formation in the vicinity of the chitosan in order to increase macroradical yields rather
than homopolymer formation initiation.
MMA was graft copolymerizaed onto chitosan with
grafting pecentages of 400-500% with homopolymer
yields of around 20-30% [52]. Methyl acrylate (MA)
has also been grafted with yields of 250-300% while
homopoly(MA) was produced in the range of 15-20%
[53].
Scheme V. Mechanism for macroradical formation on the

backbone of chitin by means of ferrous ion-persulphate redox
system in aqueous media.
241
Zohuriaan-Mehr M.J.
Since chitin in less reactive than chitosan, its

chelating properties may be enhanced through the addition of thiocarbonate sites along the chitin backbone
via the xanthate process, i.e. treatment with concentrated aqueous sodium hydroxide and carbon disulphide
[54]. After treating the chitin thiocarbonate derivative
with ferrous ion, the complex (Chitin-O-CS2-)2Fe2+ is
formed. The decomposition of the complex leads to
free Fe2+, which is believed to react with hydrogen peroxide as shown in Scheme IV to produce OH radicals
that subsequently create chitin macroradicals upon
hydrogen abstraction. Grafting percentages on the
order of 80 and 40% were obtained with this process
using acrylonitrile and acrylic acid, respectively. In
both cases, homopolymer was obtained but not quantified.
As an alternative method for grafting, a variation of
Fentons reagent has been investigated. Thus, potassium persulphate (KPS) and ferrous ammonium sulphate
are combined in a redox reaction that ultimately produces hydroxy radicals being able to form chitin
macroradicals (Scheme V). MMA was graft polymerized onto chitin with this system at grafting percentages
of 300-500%, where 40-50% of the monomer was
homopolymerized [55]. Potassium persulphate alone
was only able to achieve around 80-90% grafting while
producing similar yields of homopoly(MMA).
When a non-acrylic monomer, i.e. N-vinyl pyrrolidone, was employed to graft copolymerize onto chitosan using KPS alone, graft yields of 200-300% were
obtained accompanied by 10-20% homopolymer yields
[56]. After the grafting, the solubility of chitosan was
markedly reduced either in common organic solvents
or in dilute organic or inorganic acids. However, the
solubility of the grafted chitosan substantially
improved after adsorption of copper ions, becoming
completely soluble in dilute hydrochloric acid.
Chitosan has been subjected to graft copolymerization, comparatively with MA and MMA monomers
using KPS alone and KPS coupled with various reducing agents [57]. The results are summarized in Table 2.
No reference was made to a mechanism where the persulphate reacts specifically with the chitosan, so it is
assumed the general mechanism proceeds as in Scheme
V, where the other reducing agents (MnCl2, ammonium
tartrate, etc.) may be substituted for the ferrous ion.
Hsu et al. [58] found that chitosan was degraded by
242
KPS in aqueous media via a free-radical mechanism.

This is an important point that should be taken into
account in all the persulphate containing initiating systems. The same authors reported recently the synthesis
of chitosan-modified PMMA by emulsion polymerizaTable 2. Various initiating systems employed for graft copolymerization of different vinyl monomers onto chitosan. This
table does not include the ceric- and Fenton's-based initiating
systems.
Monomer
Initiator system
G (%)
Hp (%)
Ref.
268
37
57
MMA
KPS
MMA
KPS-FASa
300-350
40-50
55
MMA
KPS-CuCl2
497
29
57
MMA
KPS-MnCl2
489
16
57
MMA
KPS-AOX
397
29
57
MMA
KPS-ATA
388
31
57
MA
KPS
281
63
57
MA
KPS-FAS
80-90
40-50
55
MA
KPS-CuCl2
48
87
57
MA
KPS-MnCl2
335
22
57
MA
KPS-AOX
511
57
MA
KPS-ATA
339
40
57
VP
KPS
200-300
10-20
56
MMA
KPS
276
60
AN
KPS
249
60
AM
KPS
220
61
AA
KPS-FAS
52
62
AMPS
KPS
180
63
650
64
MA
DPIC
VAc
AIBN
10
65
MA
AIBN
20
65
MMA
AIBN
65
65
AN
AIBN
10
65
MMA
APS
300
50
23
MMA
H2O2
300
50
23
MMA
TBBe
40
50
66
(a)
Ferrous ammonium sulphate, (b) Ammonium oxalate, (c) Ammonium tartrate,
(d)
Potassium diperiodatocuprate (III),
(e)
Tributyl borane.
Zohuriaan-Mehr M.J.
tion [59]. They verified that chitosan played multiple

roles in the emulsion. In addition to a surfactant role,
KPS can appreciably be deactivated by low molecular
weight chitosans produced by the persulphate-induced
degradation. Therefore, long reaction times will not
favour the formation of high copolymers when they are
initiated by a persulphate system.
Most recently, KPS-initiated graft copolymerization of acrylonitrile (AN) and MMA onto chitosan was
reported [60]. Maximum graft yield of chitosan-g-PAN
(249%) was obtained with 0.12 M of AN and 0.00074
M of KPS at 65oC for 2 h for 1% chitosan solution. For
chitosan-g-PMMA, 0.14 M of MMA at 65oC gave
maximum grafting (276%). No residual monomers
were found by HPLC in the graft copolymers. Thin
membranous films could be prepared by thermopressing the modified chitosans.
Yazdani-Pedram et al. have recently studied the
effect of reaction variables on KPS-initiated graft
copolymerization of acrylamide onto chitosan in the
presence of N,N-methylenebisacrylamide (MBA)
cross-linker [61]. They found the optimum reaction
conditions (0.8 g chitosan, 50 mL acetic acid 2%, 2.4 g
AM, 0.25% MBA, 0.002 M potassium persulphate,
60oC, 30 min.) to achieve high grafting percentage
(~220%). Acrylic acid has also been graft copolymerized onto chitosan by the same research group [62].
They employed KPS-ferrous ammonium sulphate
(FAS) redox initiating system to achieve low efficiency
of grafting (52%) under optimized conditions (chitosan
0.3 g, water 50 mL, acrylic acid 2 mL, KPS 0.01 M,
FAS 0.00006 M, 70oC, 2 h). All the grafted products
were insoluble in water and in dilute acid solutions.
The insolubility is the main difference between the
graft copolymers and the chitosan itself which readily
dissolves in slightly acidic media. The grafted chitosan
samples, however, were swelled in these media. The
swelling properties of the highly swollen poly(acrylic
acid) grafted chitosan hydrogels were also studied [62].
Optimized synthesis of a graft copolymer based on
chitosan and 2-acrylamido-2-methylpropane sulphonic
acid (AMPS) was reported by Najjar et al. [63] using
KPS in homogeneous solution. The maximum percentage of grafting of ~180% was achieved under the optimum conditions (1% v/v acetic acid, 50oC reaction
temperature, 10 min. chitosan-KPS mixing period, 0.37
mmol of KPS, and 28.96 mmol AMPS).
Scheme VI. Single electron transfer mechanism for initiating

graft copolymerization of vinyl monomers onto chitosan using
(a) Cu(III) and (b) Ni(IV) proposed recently by Liu et al.
[64,65].
Most recently, a novel redox system, Cu(III)-chitosan, was employed to initiate the graft copolymerization of MA onto chitosan in alkali aqueous media [64].
A maximum grafting of around 650% was achieved
under the optimum conditions concluded: 0.3 g chitosan
(DD 0.82, mesh 60), 2.6 mL MA, pH 11.6 (by adding
KOH solution), Cu(III) 0.00192 M, 35oC, 1 h. According to a proposal of the authors, a single electron transfer from -NH2 of chitosan to Cu(III) occurs to produce
a radical-cation converted subsequently to -NH radical
in alkaline medium. The -NH radical is thought to initiate the graft copolymerization (Scheme VI(a)). The
trivalent copper, as the salt potassium diperiodatocuprate (III), was easily prepared from the cheap copper salt, CuSO4.5H2O. Since the grafting reaction can
be carried out at a mild temperature of 35oC using a
cheap initiator, the initiating system was recognized to
be superior to conventional initiators [64].
A redox system based on a supernormal valence
transition metal, i.e. Ni(IV)-chitosan, was recently
reported in the Chemical Journal on Internet [65].
Thus, acrylonitrile was graft polymerized onto chitosan
(MW 2-3*105, DD>0.82) using potassium diperiodatonickelate (IV). Under the optimized copolymeriza-
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Zohuriaan-Mehr M.J.
tion conditions (Ni(IV) 2.25 mM, monomer/chitosan

wt. ratio 5.3, 32oC, 2 h) for treating 0.3 g of chitosan, a
grafting percentage of 110% was achieved. Based on
the FTIR spectral N-H zigzag bands and the previous
reports, the authors verified the process involving a
two-step single electron transfer mechanism for the initiation of the polymerization (Scheme VI(b)).
Azobisisobutyronitrile (AIBN), ammonium persulphate (APS), and hydrogen peroxide (H2O2) are commonly employed to graft copolymerize vinyl
monomers onto chitin and chitosan [23,66]. Under
heating (or irradiation), the first radicals produced by
these systems occur from homolytic bond scissions of
the initiator, whereby these radicals subsequently react
with the monomer to initiate the polymerization. For
typical graft copolymerization, these radicals provided
by the initiator, in addition to reacting directly with
vinyl monomer, abstract hydrogens from chitin or chitosan creating macroradicals that are capable of initiating a grafted chain with vinyl monomers. Vinyl acetate,
AN, MA, and MMA are graft polymerized onto chitosan using this kind of initiation system. The typical
results are summarized in Table 2.
Tributylborane (TBB) was also utilized for initiating the grafting onto chitosan. According to Kojima et
al. [67], the alkylborane-initiated polymerizations of
various vinyl monomers in the presence of oxygen
occur by means of a free-radical mechanism, prompting the investigation of the initiator for the grafting of
chitin with MMA. Based on the proposed mechanism,
a solvated chitin-TBB complex produces radicals on
the chitin backbone that in turn, initiate the graft polymerization. The system produces homopoly(MMA)
value as high as 50% and low level of graft yield (about
40%).
(b) Radiation-initiated Vinyl Polymerization
Both high- and low-energy radiation may be used for

graft copolymerization of vinyl monomers onto polysaccharides. The radiation-induced grafting onto cellulosics has been discussed in the chapter 3 of the sourcebook of Hebeish and Guthrie [38].
Employing high-energy radiation (e.g., , , X-ray)
is an efficient basic method for initiating radical graft
polymerization onto polysaccharides. The initiation
method with the highest graft efficiency seems to be
pre-irradiated of the polysaccharides with -radiation
244
followed by the activated polysaccharide with vinyl

monomers under suitable reaction conditions [35,38].
Grafting efficiency means in this connection not only a
high number of grafted branches with high molecular
weights, it means in particular a low level of
homopolymer formed. Although the radiation-based
grafting is cleaner and more efficient in this regard
than chemical initiation methods, they are harder to
handle under technical conditions [35]. This is why the
number of researches on irradiation methods have
been considerably smaller that that of the chemical
methods.
Irradiation of -ray on powdery chitin initiates the
graft polymerization of styrene, as in the case of cellulose, but the grafting percentage is low (i.e., 64%).
Styrene was also graft copolymerized onto chitosan
powders or films. Water was recognized to be essential
for the both grafting reactions. The chitosan-g-polystyrene adsorbed bromine better than chitosan, and the
copolymer films showed less swelling and higher elongation in water than what the chitosan films did [1,68].
Pengfei et al. [69] recently reported the -radiationinduced graft copolymerization of styrene onto chitin
and chitosan powder. The reaction was promoted in the
presence of methanol, and atmospheric oxygen delayed
the reaction but did not inhibit it completely. Molecular
weight of the grafted polystyrene did not change obviously with the dose of radiation, but it was increased
with the increase of the concentration of the monomer
charged. The polydispersity index of the grafted chains
was measured to be basically between 1 and 2.
Singh and Ray graft copolymerized 2-hydroxyethylmethacrylate (HEMA) onto chitosan films using
60Co gamma radiation to improve their blood compatibility [70]. They found that the level of grafting could
be controlled by the grafting conditions, namely solvent composition, monomer concentration, dose rate,
and total dose. They achieved a maximum graft yield of
108% under the conditions of solvent water-methanol
volume ratio 1:1, HEMA concentration 20 vol%, dose
rate 90 rad/s and total dose 0.216 Mrad. The swelling
of this PHEMA-grafted film in phosphate buffer (pH
7.4, 0.1 M) at 37oC was 58% compared to that of the
original chitosan film, i.e. 110%.
Chitosan films have also been subjected to gamma
radiation-induced graft copolymerization of the vinyl
monomer N,N-dimethylaminoethyl methacrylate [71].
Zohuriaan-Mehr M.J.
The reaction variables affecting on the grafting percentage have been studied. The grafting of 70% is being
achieved under the conditions of solvent watermethanol volume ratio 1:1, the monomer concentration
15 vol%, dose rate 90 rad/s and total dose 0.216 Mrad,
and irradiation time 80 min. The garfted chitosan was
fully characterized by swelling and tensile measurements, and FTIR, DSC, TGA and XRD methods. The
degree of swelling, crystallinity, and tensile strength
were decreased by 51, 43, and 37%, respectively, at a
graft level 54%, whereas the modified films showed
improved thermal stability [71].
Low energy photons may also initiate the polymerization of a vinyl or acrylic monomer if the irradiation
is carried out in the presence of an activator (photosensitizer). Such a sensitizer must become active on exposure to the particular wavelength range of the incident
radiation [38]. Irradiation with low energy radiation,
i.e. visible or ultraviolet (UV) lights, usually in the
presence of a photosensitizer such as benzophenone or
azo compounds, is a rarely used method for grafting
onto chitin/chitosan. UV-initiated graft copolymerization of MMA onto chitosan has been reported [23,72].
The grafting percentage was decreased in order:
Photo-initiation (by the light of 253 nm) without a
catalyst (G 300%, Hp 30-40%) > photoinduced method
with photosensitizer AIBN (G 150%, Hp 60%) > photoinduced method with photosensitizer benzophenon
(G 140%, Hp 40%).
Under the noncatalytic photoinduced initiation conditions (i.e., the irradiation of only chitosan, solvent
and monomer), it was proposed that the amine group of
chitosan be removed by the photolysis [23]. When a
mixture of acrylonitrile and styrene was used, almost
alternation copolymers were introduced [24].
Photo-induced initiation was also applied to the
graft copolymerization of MMA onto chitin or oxychitin (oxidized chitin). A small amount of dimethylformamide reduced the induction period and increased
either the grafting percentage or the apparent number
of grafted chains. Non-catalytic photo-induced graft
polymerization was smooth and obtained higher graft
yield (G 150%, Hp 50%), compared to the grafting
photo-sensitized with H2O2 (G 70%, Hp 50%) or AIBN
(G 60%, Hp 90%) [23,72].
Some pre-designated chitin/chitosan derivatives
have also been subjected to irradiation-induced graft
copolymerization to yield indirectly the corresponding

grafted products. They are explained in the next section
entitled grafting onto pre-modified chitin/chitosan .
Non-vinyl Graft Copolymerization
(a) Graft Copolymerization via Polycondensation
Condensation polymerization has not been widely used

for preparing graft copolymers of polysaccharides usually due to susceptibility of the saccharide backbone to
high temperature and harsh conditions of the typical
polycondensation reactions.
However, lactic acid (LA) was successfully graft
copolymerized onto chitosan through condensation
polymerization of D,L-lactic acid in absence of a catalyst [73]. So, the bio-active and compatible polymer
polylactic acid (PLA) is conjugated with the biopolymer chitosan through an amide linkage.
The degrees of substitution (DS) ranged from 6 to
18 were measured using both elemental analysis and
salicylaldehyde methods. Degree of polymerization
(DP) of the PLA side chains was determined, by 1H
NMR analysis, to be in the range of 0.9-4.4. The graft
copolymers were found to be physically cross-linked
during the polymerization leading to pH-sensitive chitosan-PLA hydrogels. Water uptake of the hydrogels
was investigated as a function of values of DP, DS, pH
and salt concentration. The structural change and
swelling mechanism of the hydrogels were also investigated [74]. A study on cytocompatibe chitosan-g-PLA
copolymer film has recently been reported [75]. The
results showed that the cell growth rate on the film was
obviously faster than chitosan itself.
(b) Graft Copolymerization via Oxidative Coupling
With a view to prepare conductive polymers, polyaniline was grafted onto chitosan [24]. On the treatment of
chitosan in aqueous acetic acid solution with aniline in
the presence of APS, polyaniline side chains were
introduced at the amino groups. Chitosan-g-polyaniline
was fabricated into films and fibres, but the properties
varied according to the ratio of amino group to aniline
in the grafting reaction. With a ratio of 1/1 to 1/5, the
products were sturdy and flexible, while those with a
1/6 to 1/10 ratio were brittle. Optical microscopic
observations indicated that the products prepared at a
ratio below 1/5 were homogeneous, but those of 1/6
ratio had crystalline regions. The graft copolymers
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Zohuriaan-Mehr M.J.
were deep blue and became dark green when treated

with hydrochloric acid. The conductivity could be
raised from less than 10-7 to 0.01 S/cm upon protonic
doping with HCl [1,24].
Cyclic Monomer Graft Copolymerization: Ringopening Method
In general, four groups of cyclic monomers have been
mainly used for graft copolymerization onto polysaccharides: oxiranes (epoxides), lactons, -aminoacid Ncarboxy anhydrides (NCAs) and 2-alkyl oxazolines
[35]. However, the various NCAs have been the main
type of cyclic monomer used to graft onto chitin and
chitosan.
Chitin-g-oligo(caprolactone) was recently reported
to be synthesized via ring opening graft polymerization
of -caprolactone (CL) to partially deacetylated chitin
catalyzed by tin(II) 2-ethylhexanoate in the presence of
water as a swelling agent [76]. Thus, N-substituted
graft copolymer with 40 wt% oligo(CL) (average
degree of polymerization ~4) was obtained by the reaction conditions: 0.20 g chitin (DD 0.51), catalyst 0.17
mol%, water 130 mol%, 100oC, 20 h. The structure of
Scheme VII. Synthesis of chitin/chitosan-polypeptide bioconjugates via ring-opening graft copolymerization of aminoacid N-carboxy anhydrides (NCAs) onto partially
deacetylated chitin [24,78].
246
the copolymer was fully characterized by IR, NMR and

XRD methods.
Partially deacetylated chitin have been grafted with
D,L-alanine NCA, -methyl L-glutamate NCA, and Lalanine NCA [23,24,77]. NCA ring can undergo nucleophilic attack to open and polymerize with evolution of
CO2 to yield a polypeptide chain [78]. As shown in
Scheme VII, the free amine of the deacetylated chitin is
believed to initiate the graft copolymerization by
means of attack upon carbonyl, ultimately creating the
grafted chitin derivative. The advantages of this
method are low level of homopolymer formation and
the possibility of the side chain length control by the
regulation of the NCA concentration under proper conditions. Degree of polymerization (DP), however, is not
usually higher than 20 [23]. The resulting copolymers
are new types of hybrid materials composed of both a
polysaccharide and polypeptides.
Chitosan or water-soluble chitin failed to initiate
these reactions in organic solvents due to low extents of
swelling and rapid hydrolysis of NCAs [1]. A watersoluble chitin (50% deacetylated chitin), however,
exhibited high reactivity in aqueous solution. It was
treated with an ethyl acetate solution of -methyl L-glutamate NCA [24]. The ring-opening graft polymerization of the NCA proceeded smoothly at 0oC to give
chitin-g-poly(-methyl L-glutamate). Although NCAs
are very susceptible to hydrolysis, the grafting efficiency was surprisingly high, up to 91%, and no homopolymerization was observed. On alkaline hydrolysis, side
chain ester groups were transformed into carboxylate
groups. Graft copolymerization of NCAs onto partially
deacetylated chitins is also possible in DMSO, but the
grafting efficiency was moderate because of the heterogeneous reaction conditions [1]. Chitin-g-poly(methyl L-glutamate) copolymers have shown varying
degrees of solubility in common polar solvents depending on the side chain length [1,24].
Poly(L-alanine) side chains were also introduced to
chitin in a similar manner [77]. The grafted poly(L-alanine) chains could be regarded as spacer arms having a
terminal free amino group which can be used for further modifications. They were utilized to immobilize
dihydronicotinamide groups (the active site of coenzyme NDAH) (Scheme VIII). The resulting bioconjugates were utilized for asymmetric reduction of a
ketone while the peptide spacer arms regulated the
Zohuriaan-Mehr M.J.
Scheme IX. General representation of the garfting onto

method for modification of trunk polymer poly(A) with preformed reactive (telechelic) polymer, poly(B) [79]. Reaction of
functional group x with y leads to a covalent linkage.
Scheme VIII. Immobilization of dehydronicotinamide group
(coenzyme NADH active site) on partially deacetylated chitin
[77,78].
reduction process [78].

Preformed Polymer Grafting: Grafting Onto
Method
Grafting with telechelic polymers provides an alternative method, commonly referred to as grafting onto ,
for synthesizing hybrid branched architectures [79].
Telechelic polymers have been defined as those containing one or more functional end groups that have the
capacity for selective reaction to form bonds with
another molecule [80]. Unlike the classic grafting
techniques where the grafted chain is grown from the
trunk polymer by the continual addition of monomer to
Scheme X. Synthesis of living poly(2-alkyl-2-oxazoline),

PAO, followed by its use to graft onto partially deacetylated
chitin [81].
247
Zohuriaan-Mehr M.J.
the growing chain end, grafting onto connects a preformed polymer chains (poly(B)) and the trunk polymer (poly(A)) by covalently bonding the chain end of
the poly(B) with a particular site on poly(A)s backbone
(Scheme IX).
Living poly(2-alkyl oxazolines) telechelic polymers have been grafted onto partially deacetylated
chitins by Aoi et al. [81] in DMSO. In this solvent, the
water-soluble chitin swells to some extent, thus the
amino group was used to terminate the living polyoxazolines synthesized by cationic ring-opening polymerization of the corresponding oxazolines with methyl trifluoromethanesulphonate (Scheme X). Full degrees of
N-substitution of available amine groups have been
obtained with grafted chain DPs ranging from 8 to 33
units [82]. The number of side chains was controlled by
the amount of living polymers employed. This method
enabled the introduction of monodispersed side chains.
The grafted derivatives were miscible with PVC to

varying degrees [83,84]. They were soluble in water,
DMF, and DMSO, and partially soluble in chloroform,
acetonitrile, and methanol. Living poly(2-methyl-2oxazoline) and poly(isobutylvinyl ether) cation was
successfully terminated by surface amino groups on
chitosan powder to give the corresponding polymergrafted chitosan [85].
According to a pioneering report published in 1999,
the same research group [86] synthesized chitin derivatives with well-defined block copolymer side chains.
In fact, they reported the first example of introduction
of living block copolymer to a polysaccharide. The
graft copolymers having monodisperse amphiphilic
poly(2-oxazoline) block copolymer side chains exhibited associative behaviour and complexation with
hydrophobic substances depending on the chemical
structure. Among the derivatives, chitin-graft-[poly(2-
Scheme XI. Approaches for PEGylating chitosan, an outstanding case of grafting of a preformed polymer onto chitosan. The chitosan-g-PEG graft copolymer is often referred to as PEGylated chitosan. mPEG= methoxyterminated PEG, PNP= paranitrophenyl, WSC= water-soluble carbodiimide, BtOH= hydroxybenzotriazole.
248
Zohuriaan-Mehr M.J.
methyl-2-oxazoline)-block-poly(2-phenyl-2-oxazoline)] formed cylindrical aggregates (diameter 40 nm,

length 80-200 nm) in aqueous solution.
Poly(ethylene glycol) (PEG) have appeared to be a
very important synthetic macromolecule in bio-science
and technology [87,88]. The term PEGylation is usually referred to a process involving the conjugation of
PEG with a substrate. The conjugation of PEG to drugs,
especially protein drugs, is well known to enhance the
solubility and stability of the protein in solution, to alter
bioavailability, pharmacokinetics, immunogenic properties, and biological activities, and also to protect it
from recognition by the immune system, prolonging its
circulation time and efficacy in vivo [89]. Several
methods have been reported on the PEGylation of
chitn/chitosan using PEGs with various terminal reactive groups (Scheme XI). Harris et al. [90] have reported the synthesis and characterization of various functional PEGs useful for PEGylation.
PEGylated chitosans may be especially suitable as
carriers for delivery of anionic drugs, such as proteins,
glycosaminoglycans, and DNA plasmides or oligonucleotides [89]. Methoxy PEG p-nitrophenol carbonate
(MW 5000) was used to link PEG to chitosan through
a urethane linkage [89]. The synthetic route including
the reaction of the chitosan free amine groups with
methoxy PEG p-nitrophenol carbonate is shown in
Scheme XI. Grafting yields were 80-90% based on the
weight of chitosan, where grafted derivatives were soluble in aqueous solutions at pH 6.5, contrary to highly
deacetylated chitosan.
Methoxy PEG acid (Mn = 5000) was activated with
a carbodiimide/hydroxylbenzotriazole technique used
in peptide synthesis, to subsequently acylate chitosan
free amine groups [91]. The product PEGylated chitosan chains were obtained with degrees of N-substitution (DS) ranging from 0.02 to 0.55, where the copolymers having DS greater than 0.10 were observed to be
water-soluble after ultrasonication. Other workers [92]
reported another approach for immobilization of proteins with PEG tresylates and chitosan tresylates. They
found that the tresylate reacts by an unexpected mechanism with this regard, however, to give a sulphonateamide linkage as the major product rather than simple
N-alkylation. PEG tresylate also PEGylates the thiols
[88], and this may sometimes be a disadvantage.
PEGylation of chitosan via reductive alkylation of
the amine group of the chitosan was firstly reported in

1984 by Harris et al. [90]. This facile one-pot synthetic
method includes the reaction of the -NH2 with -CHO of
an aldehyde-terminated PEG to form a Schiff-base. The
imine unsaturation (-CH=N-) is then reduced by sodium cyanoborohydride (NaBH3CN) to produce a stable
N-PEGylated chitosan (Scheme XI). This approach was
then employed by other workers to efficiently prepare
the chitosan-PEG copolymeric hybrids [90,91,93].
Sugimoto et al. [92,93] optimized the process to obtain
purified chitosan-PEG hybrids with DS values substantially higher than those reported by the pioneers (DS
0.74 s. 0.06). They then treated the hybrids with acetic
anhydride to prepare chitin-PEG hybrids. The solubility of the graft copolymers in water was reported to be
dependent on the PEG molecular weight, the weight
ratio of PEG in the hybrids, DS, and degree of acetylation [93]. The modification with the higher molecular
weight PEG improved water-solubility of chitosan
keeping the main skeleton intact. The bioactivities of
the PEGylated chitosans were studied as well [94,95].
PEG side chains with very low molecular weight (i.e.,
oligo(ethylene glycol) pendant chains) were also prepared via the same way to achieve comb-shaped chitosan derivatives [96]. The tri- and tetra(ethylene glycol) monosubstituted derivatives were characterized by
high affinity for organic solvents as well as water in
sharp contrast to the original chitosan. They showed
significant adsorption capacity toward metal cations. It
should be pointed out that the above-described reductive amination is also a potentially useful method for
conjugation of any NH2 containing drugs to PEG.
The reductive amination is also possible by using
PEG propionaldehyde or PEG acetaldehyde [97] to
provide a direct amine link to PEG with retention of
basic properties. However, the ease of polymerization
of the PEG acetaldehyde in preparation has presented
problems in application of these methods [98]. It has
also been found that air oxidation of PEG acetaldehyde
occurs readily and low-temperature storage under an
inert atmosphere is thus necessary [99]. Bentley et al.
came over these problems using a simple and reliable
method for preparation and use in reductive amination
of PEG acetaldehyde hydrate generated in situ by
hydrolysis of PEG acetaldehyde diethylacetal. They
demonstrated the application of their approach in
PEGylation of lysozyme and chitosan (Scheme XI) to
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Zohuriaan-Mehr M.J.
form water-soluble methoxy PEG (mPEG) derivatives

and PEG-chitosan hydrogels [99].
In a three-step synthetic approach for chitosan
PEGylation reported by Ouchi et al. [91], the C-6
hydroxyl group of chitosan was firstly protected by
means of triphenylmethylation. The 6-O-triphenylmethyl chitosan derivative was then coupled with
mPEG acid (Mn 5000) in the presence of a water-soluble carbodiimide and a hydroxybenzotriazole. The protected hydroxyl group was finally deprotected by treating with acetic acid solution to yield chitosan-g-PEG in
which the PEG has been grafted onto chitosan via an
amide linkage (Scheme XI). The degree of PEG introduction was estimated by colloidal titration to be 25%.
The article has focused on the aggregation phenomenon of the PEG-grafted chitosan in aqueous solution
[91].
To control the elastic modulus of chitosan for
applying in resorbable small diameter vascular grafts,
polyethylene glycol was grafted onto chitosan using
succinimidyl-propionate-PEG to produce PEG-chitosan graft copolymer [100] (Scheme XI). The grafting
of PEG chains increased the distance between the polymer chains, thus reducing the crystallinity and resulting
in a lower elastic modulus.
Triblock polyethers PEO-PPO-PEO, known as
Pluronic polyols or poloxamers, were grafted onto chitosan and poly(acrylic acid) by A.S. Hoffman et al.
[101]. They first activated one OH end group of the
polyol with p-nitrophenyl (pNP) chloroformate and
then conjugated directly with chitosan (MW 750000,
DD 0.8) (Scheme XII) at various pHs. Dilute solutions
(2-3 wt%) of the hybrid product, chitosan-g-[poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene
oxide)], formed gels upon warming from 4 to 34oC.
The viscosity buildup increased significantly with the
degree of grafting and decreases sharply with increasing shear rates.
Poly(ethylene imine) (PEI), a branched or linear
commercially available polyamine, has also been grafted onto chitosan (Scheme XII). Kawamura et al. [102]
cross-linked chitosan beads with ethylene diglycidyl
ether and then reacted the derivative with epichlorohydrin. The epoxidized chitosan beads were finally reacted with PEI to achieve polyaminated highly porous chitosan chelating resin useful for meat ion adsorption.
The authors investigated the adsorption of mercury (II)
250
on the resin in detail [103]. Another approach was followed by Ruiz et al. [104] to prepare highly aminated
chitosan-based chelating resins. Chitosan beads (from
specially controlled coagulation of a chitosan solution
in a NaOH solution) were brought into contact in
dimethylacetamide and then rinsed PEI-impregnated
particles were reacted with glutaraldehyde. The crosslinked imine unsaturation-containing material was
hydrogenated by sodium borohydride to stabilize the
resin. Sorption of platinum and palladium [104], and
osmium and iridium [105] has been studied by these
PEI-grafted chitosans. It was shown that the secondary
and tertiary amine functions increased the reactivity of
the sorbent for metal ions. After re-hydration, the PEI
grafts maintained the structure of the polymer and prevented the collapse of the porous network and
improved diffusion properties.
Poly(-hydroxyalkanoate)s, PHAs, the highly crystalline, optically active, biocompatible aliphatic polyesters elaborated by a wide variety of microorganisms,
have also been conjugated with carbohydrate polymers
through the grafting onto method. The microbial polyester poly(-hydroxybutyrate), PHB, was grafted onto
chitosan firstly by Yalpani et al. [106]. Thus, the chitosan solution in dilute acetic acid was treated with
reduced molecular weight PHB (in the presence of
dimethylsulphoxide at ambient temperature for 1-5
days) to afford the corresponding amide conjugates
(Scheme XII). The degree of substitution of the chitosan amine functions in the bioconjugate was very low
(DS 0.02-0.03), varying insignificantly over the range
of PHB-chitosan ratios examined. The molecular
weight of the PHB branches was around 10000.
Most recently, the synthesis of a polyurethanegrafted chitosan was reported by Silva et al. [107].
They firstly prepared the urethane prepolymer by condensation reactions of PEG of two different molar
masses and isophorone diisocyanate. In a DMF/acetic
acid (1:1) medium, the NCO terminated prepolymer
was then grafted with chitosan backbone through a urea
linkage (Scheme XII). The DS values varied from 0.03
to 0.6 depending on the reaction conditions.
Poly(dimethylsiloxane) (PDMS)-grafted chitosan
was prepared and characterized [108]. Thus, PDMS
prepolymer was synthesized by ionic ring-opening
polymerization of octamethylcyclotrisiloxane using nbutyl lithium. The tensile strength and elongation of
Zohuriaan-Mehr M.J.
Scheme XII. Various synthetic routes to chitosans conjugated with different macromolecular pendant groups through grafting
onto method. PEI= polyethyleneimine, PHB= poly(3-hydroxybutyrate), PEO= poly(ethylene oxide). PPO= poly(propylene oxide),
pNP= para-nitrophenyl, G-APG= Gluadin APG (a partially hydrolyzed wheat gluten protein, MW ~5000), PPG= poly(propylene glycol), BPA= bisphenol A residue, PDMS=poly(dimethyl siloxane), PEG= poly(ethylene glycol), IPDI= isophorone diisocyanate (3isocynatomethyl-3,5,5-trimethyl-cyclohexyl isocyanate).
chitosan-g-PDMS copolymer were mostly constant

regardless of the grafting percentage. While critical
surface energy of chitosan is about 0.032 N/m, that of
the copolymer was a little decreased to 0.025-0.029
N/m by grafting PDMS onto chitosan.
Epoxy-terminated PDMS was grafted onto chitosan
using UV irradiation at room temperature without
using a catalyst. The product was a pH-sensitive hydrogel without a chemical cross-linking occurrence. In
fact, the PDMS substituents provided the basis for
hydrophobic interactions that contribute the formation
of the hydrogel network. The hydrogels exhibited high
equilibrium water content in the range of 82-92%
[109].
Chitosan miniemulsions were used for the synthesis of epoxy particles by polyaddition. As chitosan
bears amine and alcohol functions, it can react with the
epoxide and can be grafted onto the particles, which are
obtained by polyaddition reaction. This turned out to be
a convenient technique to modify or graft the water-soluble chitosan with water-insoluble reaction partners,
thus resulting in new and not accessible chitosan derivatives [110]. Here, also other biodegradable polymer
(i.e., a protein) was added for hybrid formation
(Scheme XII). Finally, nanocapsules consisting of
hybrid polyaddition polymers as shell and a hydropho-
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Zohuriaan-Mehr M.J.
bic part as core were elaborated. These biocompatible

and biodegradable capsules promise applications in
drug delivery.
In the course of the reaction for grafting a preformed polymer onto a substrate, the preformed polymer may be converted to another polymer with totally
different, but desirable, properties. Most recently,

Zohuriaan-Mehr and coworkers have achieved a onestep reaction to prepare lightly cross-linked poly(sodium acrylate-co-acrylamide) grafted chitosans through
hydrolytic treatment of chitosan/polyacrylonitrile
blends. According to FTIR spectroscopy, no cyanide
Scheme XIII. Chitosan modification via dendronization [112,113]. TEG= triethylene glycol, R=H.
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Zohuriaan-Mehr M.J.
functional group was detected in the grafted chitosan.

This chitosan-based copolymeric hydrogel exhibited
super-swelling properties and ampholytic behaviour
[111].
Dendrimer-like hyperbranched polymers, a new
class of topological macromolecules, have recently
been grafted onto chitosan. Tsubokawa et al. [112]
reported the surface modification of chitosan powder by
grafting of hyperbranched dendritic polyamidoamine.
They found that the polyamidoamine was propagated
from the surface of chitosan by repetition of two
processes: (1) Micheal addition of methyl acrylate to the
surface amino groups and (2) amidation of the resulting
esters with ethylenediamine to give polyamidoamine
dendrimer grafted chitosan powder (Scheme XIII).
Sashiwa et al. [113] synthesized a dendronized chitosan-sialic acid hybrid using convergent grafting of
pre-assembled dendrons built on gallic acid and tri(ethylene glycol) (TEG) backbone. Thus, sialic acid dendrons bearing a focal aldehyde end group were synthesized by a reiterative amide bond strategy. Polyamineending trivalent (1st generation: G1) and nona-valent
(2nd generation: G2) dendrons having gallic acid as
branching unit and TEG as spacer arm were prepared
and initially attached to a sialic acid p-phenylisothiocyanate derivative. The focal aldehyde sialodendrons
were then convergently grafted onto chitosan by reductive amination in 76-80% yields. The DS of the sialodendrimer in the hybrid were 0.13 (G1) and 0.06 (G2).
The water solubility of these novel hybrids was further
improved by N-succinylation of the remaining amine
functionality.
During recent years, Sashiwa and Aiba (from the
Green Biotechnology Research Group of The Special
Division for Human Life Technology, National Inst.
Adv. Ind. Sci. Tech., Osaka, Japan) have started extensive research on chitin and chitosan with collaboration
of other academic/industrial centers. They often publish their results as original papers under continued
titles: studies on chitin and chitosan and chemical
modification of chitosan . Several articles among these
series (including the parts 3, 6, and 8-11) have been
focused on chitosan-dendrimer hybrids (CDHs). In the
sixteenth part of the latter title, for example, the synthesis of polypropyleneimine dendrimer-chitosan hybrid
has been reported [114]. The hybrids were prepared in
80-90% yield and DS of 0.11 (G1), 0.042 (G3), and
0.037 (G4). CDHs having carboxyl, ester, and PEG and

various generations were also prepared using dendrimer acetal by reductive N-alkylation. The synthetic
procedure could be accomplished by one-step reaction
without organic solvent [115]. The DS of the dendrimers was 0.13-0.18. Perfectly or partially water-soluble CDHs could be obtained. Good biodegradation
was observed in these hybrids.
Multiple Modification of Chitin/Chitosan
There are some cases in which: (i) the reactivity of
chitin/chitosan itself is insufficient to participate in the
desired reaction, (ii) the modified chitin/chitosan does
not possess the desired properties or (iii) some site(s) of
chitin/chitosan must be protected (and finally deprotected) to sustain during the modification reaction(s). In
such instants, there are two general approaches via
chemical modification when the graft polymerization is
a certain pathway to achieve desired characteristics: (a)
in-situ- and/or post-treatment of the graft copolymer,
(b) graft copolymerization onto a previously modified
chitin/chitosan. So, the products may generally be
referred to as multiply modified materials.
(a) Further Modification of the Graft Copolymers
Recently, a hydrophobically modified chitosan, chitosan-g-polyacrylonitrile copolymer prepared through

a ceric-induced graft polymerization [28,29], was posttreated under alkaline conditions to achieve novel
polyampholytic smart superabsorbing hydrogels with
pH-reversibility and on-off switching behaviour
[30,31]. The superabsorbents so called as to H-chitoPAN, showed low salt sensitivity when the add-on
value of the initial chitosan-polyacrylonitrile graft
coplymer was low [31]. The both modified chitosans
exhibited enhanced thermal stability over chitosan
itself [30]. According to the authors, the sharp pHresponsiveness behaviour of the hydrogels is expected
to be a promising factor of their possible application in
many technologies such as controlled delivery of
bioactive agents.
Another case is an in situ modification of
poly(NIPAM) grafted chitosan in the course of the synthetic reaction. When the grafting reaction was conducted in the presence of glutaraldehyde (GA) as a
cross-linker, thermo- and pH-sensitive interpenetrating
polymer network (IPN) hydrogels were obtained. The
253
Zohuriaan-Mehr M.J.
hydrogels were comparatively studied with some chitosan/poly(NIPAM) blend IPHs with the same composition ratios [41]. The equilibrium water content of all
the IPN samples dropped sharply at pH 6 and temperature higher than 30oC. Therefore, the IPN hydrogels
exhibited swelling/deswelling changes in response to
external stimuli such as pH and temperature were recognized to be useful as modulation systems in biomedical fields.
A similar approach was reported recently by Don et
al. [43] in the case of graft copolymerization of VAc
onto chitosan in the presence of GA. They obtained
particulate membranes of chitosan-g-PVAc formed
after drying the suspension mixture of the polymerization reaction [42]. The membranes were then subjected
to copper ion adsorption experiments. The mechanical
strength of the wet membranes was improved by the insitu cross-linking with GA. The copper ion adsorption
quantity of the membranes, however, was disfavoured
by the strengthening [43].
Recently, microspheres of chitosan-g-polyacrylamide cross-linked with GA were prepared to use for
encapsulating indomethacin, a nonstreoidal antiinflammatory drug [116]. The microspheres were characterized for drug entrapment efficiency, particle size,
and water transport into the polymeric matrix as well as
for the drug-release kinetics.
(b) Grafting onto Pre-modified Chitin/Chitosan
A few chitosan derivatives are reported to be graft

copolymerized with some vinyl monomers via the conventional vinyl graft copolymerization. Hyroxypropyl
chitosan was prepared, characterized, and subjected to
graft copolymerization with methacrylic acid (MAA)
using APS as an initiator [117]. The same monomer
was recently graft copolymerized onto carboxymethyl
chitosan (CMCTS) by APS. An optimized grafting conditions (for CMCTS 8 g/L) was reported to be APS 8
mmol/L, MAA 2.4 mol/L, 60-70oC, 2h. Grafting percentage as high as 1500% was reported under the optimal conditions [118].
Sodium salts of acrylic acid (AA) and MAA were
graft polymerized onto carboxymethyl chitosan using
APS initiator [119]. Under a tentative conditions
(CMCTS 0.02 g, monomer 1.2 M, APS 0.4 mM, 70oC,
2 h), grafting percentages 875 and 933% were achieved
for CMCTS-g-PAA and CMCTS-g-PMAA, respective-
254
Scheme XIV. Thiocarbonation-bromate redox initiation [121]

of graft polymerization of a vinyl monomer onto chitosan (X=
NH or O).
ly. The antibacterial activity of the doubly modified

chitosans against S. aureus and E. coli was explored by
the viable cell counting method.
O-Acetyl-chitin was synthesized and subjected to
graft copolymerization with MMA via a photo-induced
grafting by Morita et al. [120]. They conducted the
non-catalytic reaction in a rotary photochemical reactor
irradiating UV light with a 160 W low-pressure mercury lamp at distance of 75 mm. A grafting percentage
~490% was achieved under optimized conditions: Oacetyl-chitin (DS 0.81) 0.15 g, H2O 10 mL, MMA
2 mL, 50oC, irradiation time 4 h.
As mentioned before, since chitin is less reactive
than chitosan, its reactivity may be enhanced through
the addition of thiocarbonate sites along the chitin
backbone via the xanthate process, i.e. treatment with
concentrated aqueous sodium hydroxide and carbon
disulphide [54]. After treating the chitin thiocarbonate
derivative with ferrous ion, the complex chitin xanthate-Fe(II) is formed. The decomposition of the complex leads to free Fe(II), which is believed to react with
hydrogen peroxide as shown in Scheme IV to produce
OH radicals that subsequently create chitin macroradicals upon hydrogen abstraction. Grafting percentages
on the order of 80 and 40% were obtained with this
process using acrylonitrile and acrylic acid, respectively.
Chitosan was graft copolymerized with hydroxyethyl methacrylate (HEMA) via a thiocarbonated chitosan-potassium bromate redox initiation approach
[121] (Scheme XIV). For a chitosan thiocarbonated
under the optimized conditions NaOH 1%, CS2 2%,
material-to-liquor (M/L) ratio 1:20, 30oC, and 1 h, total
conversion of the monomer ranged up to 75% and a
maximum grafting of 38% was achieved under the
Zohuriaan-Mehr M.J.
optimized grafting conditions (KBrO3 0.6 mmol/g chitosan, formic acid 2 g/g chitosan, HEMA 75%, M/L
ratio 1:30, 40oC, 2 h). The polymerization composite
product (including the graft copolymer, homopoly

(HEMA) and unreacted chitosan) was easily cast as
films which were featureless in the scanning electron
Scheme XV. Macromolecular architecture of graft copolymeric chitins with well-known structures from tosyl-, iodo-, mercapto-, and
deoxy(thiosulphato)-chitin derivatives [122-126]. Ac= acetyl, Me= methyl, Ph= phenyl, DMSO= dimethylsulfoxide.
255
Zohuriaan-Mehr M.J.
Scheme XVI. Mechanism for graft copolymerization of chitosan (R-NH2) with methyl acrylate using a newly reported
trichloroacetyl-manganese carbonyl co-initiator photoactivated system [127]. Trichloroacetyl chitosan derivative (R-NHCOCCl3) is necessarily used in this system.
microscopy.
Most of the vinyl graft copolymerizations (e.g., the
above case, pesulphate- and ceric-intiating systems) are
comprised a simple manner, but the initiating site and
hence the structures of the resulting copolymers are not
well-defined. Kurita et al. showed that with iodo-, tosyl-,
and mercapto-chitin derivatives, graft copolymers having well-defined structures could be prepared, because it
would produce initiating species only at the position
carrying the certain functional group [1, 122-125].
Tosylation (treatment with excess p-toluene
sulphonyl chloride) was carried out on alkali chitin. 6Tosylated chitins were then treated with sodium iodide
in DMSO. The reaction proceeded smoothly to give 6iodo-chitins that exhibited good solubility in the solvent [122]. On addition of a Lewis acid such as SnCl4
to iodo-chitin in nitrobenzene, reactive carbenium
species were formed, and styrene was efficiently graft
copolymerized by a cationic mechanism in a swollen
state (Scheme XV). The grafting percentage (G%) was
reported to be up to 800%. The Mn and PDI of the
grafted polystyrene were measured to be 58000 and
1.5, respectively. Irradiation of UV light on iodo-chitin
in DMSO solutions gave rise to the homolysis of the CI bonds to form carbon free radicals, and styrene was
graft copolymerized by a radical mechanism. The grafting percentage is low, however, no appreciable amount
of homopolymer was detected [1].
6-Mercapto-chitin is another candidate for the
macroradical initiator to prepare well-defined graft
copolymers. Altough mercapto-chitin is insoluble, it is
expected to efficiently graft copolymerization owing to
the presence of the readily dissociating mercapto
groups and to swelling in organic solvents. Actually,
256
styrene was graft copolymerized onto chitin efficiently

in DMSO at 80oC, and the resulting G% reached almost
1000 [123]. The Mn and PDI of the grafted polystyrene
were measured to be 974000 and 2.62, respectively.
The G% and Mn values indicated that 4% of the mrcapto groups were used for the graft copolymerization, and
a polystyrene chain was attached on average to every
45 pyranose units. MMA was also graft polymerized
onto mercapto-chitin under similar conditions to
achieve chitin-g-PMMA copolymers [124] (Scheme
XV). The G% value was enhanced with the amount of
the monomer and reached above 1200 under appropriate conditions. The resulting graft copolymers exhibited remarkable affinity for various common organic solvents.
Tosyl-chitin and iodo-chitin can also serve as polymeric initiators for ring-opening polymerization of 2methyl-oxazolines to give poly(N-acetylethyleneimine)s in dimethylacetamide solution at 80oC
[125] (Scheme XV). Tosyl-chitin was recognized to be
more suitable than iodo-chitin judging from the G%
values [1, 125]. Mn of the side chains isolated from the
copolymer of 160% grafting was 2700, indicating that
18% of the tosylate groups were actually utilized for
initiating the graft copolymerization.
6-Deoxy(thiosulphato)chitin (S2O3-chitin, DS
0.49) was synthesized and introduced as a precursor for
non-catalytic photo-induced graft copolymerization of
MMA, AN, AA, and AM [126] (Scheme XV). Chitin
was first tosylated and subsequently transformed into
S2O3-chitin. UV irradiation (at a fixed temperature
50oC) easily proceeded the polymerization. The photolysis of the S2O3 groups (confirmed by IR spectra) carried only in quartz, not in a Pyrex tube. The monomer
MMA and AN showed good activities. In the case of
MMA, under optimized conditions (S2O3-chitin 0.15 g,
water 10 mL, MMA 2 mL, 1h), G% value reached
around 600.
Chitosan powder was grafted with methyl acrylate
(MA) utilizing the trichloroacetyl/Mn2(CO)10 photoinitiating system by Jenkins and Hudson [127]. First,
highly deacetylated chitosan was N-trichloroacetylated
by trichloroacetic anthydride. The trichloroacetyl chitosan powder was then graft copolymerized heterogeneously with MA using the manganese carbonyl co-initiator photoactivated with 436 nm light at room temperature (Scheme XVI). Graft percentages greater than
Zohuriaan-Mehr M.J.
Scheme XVII. A 6-step synthetic strategy for synthesizing a chitosan-g-polystyrene copolymer with well-known structure having
amphiphilic properties [129]. DCC= dicyclohexylcarbodiimide, DMF= dimethylformamide, Py= pyridine, Ph= phenyl.
600% were obtained, while 20-30% of the poly(MA)

formed was homopolymer.
In a multi-step synthetic approach for PEGylating
chitosan [91], the C-6 hydroxyl group of chitosan was
firstly protected be means of triphenylmethylation. The
6-O-triphenylmethyl chitosan derivative was then coupled with mPEG acid (Mn 5000) in the presence a
water-soluble carbodiimide and a hydroxybenzotriazole. The protected hydroxyl group was finally deprotected by treating with acetic acid solution to yield chitosan-g-PEG in which the PEG has been grafted onto
chitosan via an amide linkage (Scheme XI). The degree
of PEG introduction was estimated by colloidal titration to be 25%.
Unlike the most of approaches to PEGylate chitosan leading to N-substituted chitosan-PEG graft
copolymer as illustrated in Scheme XI, most recently,

chitosan-O-PEG graft copolymers were synthesized via
etherification of N-phthaloyl chitosan by PEG
monomethyl ether (mPEG) iodide in DMF in the presence of silver oxide, and finally, deprotection of the Nphthaloylated chitosan amino group [128]. Varying the
ratio of mPEG iodide to chitosan, different degree of
O-substitution of mPEG to monosaccharide residue of
chitosan (5-197%) was obtained. The graft copolymers
were soluble in water and aqueous solutions of wide
pH range. Reduced viscosity of aqueous solutions of
the copolymers was extremely low and similar to that
of mPEG 2000.
Ohya et al. [129] reported a novel 6-step synthetic
strategy (Scheme XVII) to tailor a new chitosan-gpolystyrene with well-known structure and amphiphilic
257
Zohuriaan-Mehr M.J.
Scheme XVIII. The synthetic pathway to a novel gene delivery agent; galatosylated chitosan-graft-poly(vinyl pyrrolidone) [133].
Ac= acetyl, EDC= 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, NHS= N-hydroxysuccinimide.
properties. Thus, the amino group of chitosan was firstly protected by phthalic anhydride. The primary alcohol group of the N-phthaloylchitosan was protected by
tritylchloride. 6-O-tritylchitosan was then prepared
using hydrazine-deprotection of the amino group. 6-Otritylchitosan was coupled with 4-4-azobis(4-cyanovaleric acid) (ACVA). Graft polymerization of styrene
258
onto the 6-O-tritylchitosan was carried out in DMF

employing the pendant ACVA moiety as an initiator.
After deprotection of trityl groups of the polymerization products, chitosan-g-polystyrene graft copolymer
was obtained. Under the reported conditions (6-Otritylchitosan (DS 24 mol%) 0.2 g, styrene-to-ACVA
mole ratio 810, 60oC, 8 h), the weight percentage and
Zohuriaan-Mehr M.J.
Mn of polystyrene content of the copolymer was measured to be around 96% and 51000, respectively. The
graft copolymer showed a micro-phase separated morphology.
In another approach to modification, a polymerizable group is firstly introduced to the chitosan backbone and the reactive derivative is then (co)polymerized. For example, treatment of chitosan with maleic
anhydride led to O- and N-maleinated chitosan. This
fully substituted derivative was then copolymerized
with acrylamide by APS initiator to yield cross-linked
copolymers. The products were characterized by
remarkable swelling in water with a volume increase of
20-150 times [130]. Using NIPAM, a similar strategy
was followed to prepare pH/temperature-sensitive
hydrogels [131].
Most recently, Tanodekaew et al. [132] reported the
preparation of acrylic grafted chitin for wound dressing
application. Acrylic acid (AA) was first linked to chitin
via esterification (H2SO4, 70oC, 1 h). The acrylic double bonds acted as the active grafting sites on the substrate that was further polymerized with AA monomer
(KPS, 65oC, 4 h) to form a network structure. The
swelling behaviour and gel strength were found to
depend upon the monomer feed content. Chitinpoly(AA) 1:4 yielded optimal swelling and gel
strength. The overall results of the cellular behaviour
on the modified chitin film suggested that the material
has a potential for biomedical applications particularly
as temporary skin substitute.
In the field of gene delivery, a galactosylated chitosan-g-poly(vinyl pyrrolidone) was recently prepared
to employ as hepatocyte-targeting DNA carrier [133].
Chitosan was coupled with lactobionic acid via an
active ester intermediate using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC).
Through a grafting onto method, a preformed synthetic water-soluble polymer, i.e. monocarboxylic terminated poly(vinyl pyrrolidone) (PVP), was then
chemically conjugated with galactosylated chitosan
(GC) utilizing EDC and N-hydroxysuccinimide (NHS)
as an activator (Scheme XVIII). The complex formation of GC-g-PVP/DNA complexes was confirmed by
agarose gel electrophoresis. The morphology of the
complex that observed by atomic force microscopy had
a compact and spherical shape, around 40 nm particle
sizes at a charge ratio of 3. The DNA-binding property
of the graft copolymer mainly depended on the molecular weight of chitosan and composition of the synthetic part of the bioconjugate.
CONCLUSION
The science and technology of chitin and chitosan are
advancing quite rapidly as a result of expanding interest in these biopolymers, which have unique characteristics. With regard to developing advanced functions,
much attention has been paid to modification of chitin
and chitosan. Graft copolymerization is considered to
be one of the most promising approaches to a wide
variety of molecular designs leading to novel type of
tailored hybrid materials.
The present review deals with the chemistry of
modification of chitin and chitosan via graft copolymerization with an emphasis on synthetic approaches.
The article includes the majority of published papers in
the field. Overall, the main concluding remarks may be
summarized as follows:
- Direct grafting of vinyl monomers onto the substrate via radical copolymerization, being a simple and
useful method of modification, have classically been
plagued by a lack of control over the mechanism. Here,
there are many different reactions occurring simultaneously, namely, initiation, propagation, etc. This complicated reaction system results in ill-defined structures
and non-desired homopolymer. Major efforts to reduce
homopolymer formation have been attempted; however, it is still generated more or less.
- Graft copolymerization of vinyl monomers onto
the substrate activated by high-energy radiation (preirradiation technique) can solve the homopolymer formation problem in some extent.
- Living polymerization systems may be considered
as a good solution of the homopolymer problem, as
mentioned in the case of grafting of living poly(2-alkyl
oxazolines) or living poly(isobutylvinyl ether) onto
partially deactylated chitin.
- Grafting onto special derivatives of the biopolymers (e.g. tosyl-, iodo- or mercapto-chitin) is a certain
approach to achieve graft copolymers with welldefined structures.
- By employing the grafting onto method, a high
level of control on the macromolecular structure is pos-
259
Zohuriaan-Mehr M.J.
sible without suffering from the above mentioned problems. This multi-step approach, however, is time consuming and cost non-effective, especially when a certain functional group of the trunk polymer is necessary
to be protected (and then deprotected).
- While the unique structure and properties of chitosan (e.g., biological and cationic polymer characteristics) are mainly originated from its free amino group,
the most modification strategy lead to N-substituted chitosan copolymers, in which the majority of the amino
groups are blocked. Therefore, retaining these functional groups is an important challenge for preserving the
intrinsic properties of the biopolymer in the hybrid
material. Protection of the NH2 group, usually as
phthaloyl group, grafting treatment(s), and deprotection
of the amino groups may be considered as an appropriate sequence result in desirable regioselectivity.
- Chitosan and partially deacetylated chitin have
been more frequently subjected to the grafting rather
than chitin itself. The reason is mainly related to insolubility of natural chitin in most of possible reaction
media. Therefore, the intractability of chitin has yet
remained as a challenge for the researchers who insist
to modify chitin. Anyhow, it should be pointed out that
the harsher the reaction conditions, the higher the polysaccharide molecular weight loss will be.
This contribution is also intended to stimulate further research on chitin and chitosan modification in
order to use these precious renewable biomaterials
instead of the fossil-based materials used in bio-science
and technology. Fast-growing academic/industrial
activities in this regard, as obviously exhibited in Figure 1, ensures that chitin will not be a biomaterial in
waiting any more.
ACKNOWLEGEMENTS
The author is very grateful to Professor A. Pourjavadi
and the PhD students G.R. Mahdavinia and H. Hosseinzadeh from Chemistry Department of Sharif University. Technology, for their main role in our chitin/chitosan-related collaborations. The authors special
thanks are due to the IPPI Director, Professor H.
Mirzadeh, for his continued support of the Superabsorbent Hydrogel Division and its recent orientation
toward the biopolymer-based hydrogels. His moral
support was a major driving force to write this paper.
260
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Iranian Polymer Journal

14 (3), 2005, 235-265

Advances in Chitin and Chitosan Modification

(a) Graft Copolymerization via Polycondensation

Advances in Chitin and Chitosan Modification ...

Multiple Modification of Chitin/Chitosan

Figure 1. Annual number of chitin/chitosan related reports;

lose has been studied extensively, only limited attention

Scheme I. Structural repeating units of chitin (DD= 5-15%)

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

Therefore, the degree of acetylation (DA) determines

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

method to add new properties to a natural polymer with

Add-on (Ad%) = 100 (W3-W0) / W3

Hp% = 100 (W2-W3) / W2

where W0, W1, W2, W3 and W4 designate the weight of

Among the variety of chemical reagents reported for

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

Scheme III. General mechanism for ceric-initiated graft

believed to begin with a complex formation of Ce4+

capable of initiating a grafted polymer chain [23].

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

on 50 g VAc, the monomer conversion was found to be

mamide (DMF), dimethylsulphoxide (DMSO) and

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

diacrylate onto chitosan backbone using CAN [47].

Scheme IV. Mechanism for hydroxy radical formation by

tions. Solubility of the highly poly(MMA) grafted

Scheme V. Mechanism for macroradical formation on the

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

Since chitin in less reactive than chitosan, its

KPS in aqueous media via a free-radical mechanism.

Ferrous ammonium sulphate, (b) Ammonium oxalate, (c) Ammonium tartrate,

Potassium diperiodatocuprate (III),

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

tion [59]. They verified that chitosan played multiple

Scheme VI. Single electron transfer mechanism for initiating

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

tion conditions (Ni(IV) 2.25 mM, monomer/chitosan

Both high- and low-energy radiation may be used for

followed by the activated polysaccharide with vinyl

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

copolymerization to yield indirectly the corresponding

Condensation polymerization has not been widely used

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

were deep blue and became dark green when treated

the copolymer was fully characterized by IR, NMR and

Iranian Polymer Journal / Volume 14 Number 3 (2005)

Advances in Chitin and Chitosan Modification ...

Scheme IX. General representation of the garfting onto

reduction process [78].

Scheme X. Synthesis of living poly(2-alkyl-2-oxazoline),

Iranian Polymer Journal / Volume 14 Number 3 (2005)