Review
Chitosan-modifications and applications: Opportunities galore

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Abstract

Of late, the most bountiful natural biopolymer chitin and chitosan have become cynosure of all party because of an unusual combination of biological activities plus mechanical and physical properties. However applications of chitin are limited due to its inherent insoluble and intractable nature. Chitosan, alkaline hydrolytic derivative of chitin has better solubility profile, less crystallinity and is amenable to chemical modifications due to presence of functional groups as hydroxyl, acetamido, and amine. The chemical modification of chitosan is of interest because the modification would not change the fundamental skeleton of chitosan, would keep the original physicochemical and biochemical properties and finally would bring new or improved properties. In view of rapidly growing interest in chitosan its chemical aspects and chemical modification studies is reviewed. The several chemical modifications such as oligomerization, alkylation, acylation, quternization, hydroxyalkylation, carboxyalkylation, thiolation, sulfation, phosphorylation, enzymatic modifications and graft copolymerization along with many assorted modifications have been carried out. The chemical modification affords a wide range of derivatives with modified properties for specific end use applications in diversified areas mainly of pharmaceutical, biomedical and biotechnological fields. Assorted modifications including chitosan hybrids with sugars, cyclodextrin, dendrimers, and crown ethers have also emerged as interesting multifunctional macromolecules. The versatility in possible modifications and applications of chitosan derivatives presents a great challenge to scientific community and to industry. The successful acceptance of this challenge will change the role of chitosan from being a molecule in waiting to a lead player.

Introduction

Chitin and chitosan are aminoglucopyrans composed of N-acetylglucosamine (GlcNAc) and glucosamine (GlcN) residues. These polysaccharides are renewable resources which are currently being explored intensively for their applications in pharmaceutical, cosmetics, biomedical, biotechnological, agricultural, food, and non-food industries as well (water treatment, paper, and textile) [1]. These unique polymers have emerged as a new class of physiological materials of highly sophisticated functions due to their versatile biological activity, excellent biocompatibility, and complete biodegradability in combination with low toxicity [2], [3], [4]. To exploit the unique properties and to realize full potential of these versatile polysaccharides, attempts are being made to derivatize them.

Section snippets

Chemistry

Chitin is the second most abundant natural biopolymer derived from exoskeletons of crustaceans and also from cell walls of fungi and insect [5]. Chitin is a linear cationic heteropolymer of randomly distributed GlcNAc and GlcN residues with β-1,4-linkage. Chitobiose, 4-O-(2-amino-2-deoxy-β-d-glucopyranosyl)-(1  4)-2-amino-2-deoxy-d-glucose, is the structural unit of native chitin [6]. Bound water is also a part of the structure. The degree of deacetylation in chitin can be as low as <10% and the

Chemical characteristics

Although the molecular structures of chitin and chitosan seem quite similar, the physical characteristics and the chemical reactions they undergo are often surprisingly distinct. Both polymers possess reactive hydroxyl and amino groups, but chitosan is usually less crystalline than chitin, which presumably makes chitosan more accessible to reagents. After heating, they decompose prior to melting, thus these polymers have no melt points. Probably the most striking difference between chitin and

Chemical modifications of chitin

Chitin is a chemically stable biopolymer. The existence in its solid state of both intra- and inter-molecular hydrogen bonds, additionally pose problems inherent to the operating difficulties. α-Chitin because of its insolubility is rarely subjected to chemical reactions, except for the preparation of chitosan by deacetylation. β-Chitin has relatively high reactivity [15].

According to Noishiki et al. β-chitin can be converted to thermodynamically stable α-chitin by treatment with 20% NaOH

Chitosan and chemical modifications of chitosan

Production of chitosan from chitin by removal of the acetyl group involves a harsh treatment with concentrated aqueous or alcoholic NaOH solution with care to protect reaction mixture from oxygen, with a nitrogen purge or by addition of sodium borohydride in order to avoid undesirable reactions such as depolymerization and generation of reactive species. The attempts/efforts have been made to minimize the amount of NaOH required for the reaction [48].

Chitosan oligomers

The very high molecular weight and therefore a very high viscosity of chitosan precluded its use in several biological applications. Being a polymer it can be subjected to depolymerization (chitonolysis) producing low-molecular-weight chitosan, oligosaccharide (chitooligomers) and monomers (Fig. 5). Because of the excellent solubility of chitosan oligomers, their applications are numerous and varied [49], [50], [51]. Several methods viz. chemical, physical and enzymatic have been suggested for

Chitosan derivatives of importance

Chitosan is an amenable molecule. Without disturbing DP of chitosan, one can chemically modify this acquiescent polymer since it provides functional groups as primary amine and primary as well as a secondary hydroxyl groups in its monomers (Fig. 6). The important examples of modified chitosans that hold prominent places in research are listed in Table 2.

Enzymatic modification of chitosan

The enzymatic grafting of phenolic compounds onto chitosan to confer water solubility under basic conditions has been reported (Fig. 25) [339]. The method takes help of tyrosinase which converts a wide range of phenolic substrates into electrophilic o-quinones which undergo two different subsequent non-enzymatic reactions with chitosan to yield either Shiff bases or Michael type adducts. With tyrosinase chitosan in slightly acidic media the natural phenolic chlorogenic acid could be modified

Graft copolymers of chitosan

Graft copolymerization is an attractive technique of modifying the chemical and physical properties of chitin and chitosan for widening their practical use. The properties of the resulting graft copolymers are broadly controlled by the characteristics of the side chains, including molecular structure, length, and number. Till today, a number of research works has been done to study the effects of these variables on the grafting parameters and the properties of grafted chitosan polymers (Table 3

Chitosan–dendrimer hybrid

Dendrimer-like hyperbranched polymers, a new class of topological macromolecules, have recently been grafted onto chitosan. Tsubokawa and Takayama [450] 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: (i) Micheal addition of methyl acrylate to the surface amino groups and (ii) amidation of the resulting esters with

Cyclic-host bound chitosan

Crown ethers have particular molecular structures and good complexing selectivity for metal ions. These crown-ether-bound chitosans will have a stronger complexing capacity and better selectivity for metal ions because of the synergistic effect of high molecular weight. Tang et al. [460] prepared the crown-ether bound chitosan with Schiff’s-base-type and its reduced form (Fig. 38). Crown ether-bound chitosans had not only good adsorption capacities for metal ions Pd2+, Au3+, and Ag+, but also

Conclusion

Chitosan is almost the only cationic polysaccharide in nature. Its unique physicochemical and biological properties make it worthy in regard to pharmaceutical and biomedical applications. However, since chitosan does not dissolve in neutral and basic aqueous media, its use is limited. Chemical modifications of chitosan provide derivatives that are soluble at neutral and basic pH. Moreover, chemical modifications can be used to attach various functional groups and to control hydrophobic,

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