N-Alkyl chitosan

Uragami, T., Kato, S., and Miyata, T. 1997. Structure of N-alkyl chitosan membranes on water-permselectivity for aqueous ethanol solutions, J. Membr. Sci., 124 203-211. 

A series of N-alkyl chitosans has been recently reported their potential usefulness for medical applications has still to be evaluated. 

Dong Y Sakurai K, Wu Y, Kondo Y Mnltiple crystalline morphologies of N-alkyl chitosan solution cast films. Polym Bull 2002 49 189. 

Recent progress of basic and application studies in chitin chemistry was reviewed by Kurita (2001) with emphasis on the controlled modification reactions for the preparation of chitin derivatives. The reactions discussed include hydrolysis of main chain, deacetylation, acylation, M-phthaloylation, tosylation, alkylation, Schiff base formation, reductive alkylation, 0-carboxymethylation, N-carboxyalkylation, silylation, and graft copolymerization. For conducting modification reactions in a facile and controlled manner, some soluble chitin derivatives are convenient. Among soluble precursors, N-phthaloyl chitosan is particularly useful and made possible a series of regioselective and quantitative substitutions that was otherwise difficult. One of the important achievements based on this organosoluble precursor is the synthesis of nonnatural branched polysaccharides that have sugar branches at a specific site of the linear chitin or chitosan backbone [89]. 

The Schiff reaction between chitosan and aldehydes or ketones yields the corresponding aldimines and ketimines, which are converted to N-alkyl derivatives upon hydrogenation with borohydride. Chitosan acetate salt can be converted into chitin upon heating [130]. The following are important examples of modified chitosans that currently have niche markets or prominent places in advanced research. 

Zhang C, Ding Y et al (2007) Polymeric micelle systems of hydroxycamptothecin based on amphiphilic N-alkyl-N-trimethyl chitosan derivatives. Colloids Surf B 55 192-199... 

Zhang C, Ping Q et al (2003) Preparation of N-alkyl-O-sulfate chitosan derivatives and micellar solubilization of taxol. Carbohydr Polym 54 137-141... 

Chitin is an abundant natural biopolymer and exhibits excellent antimicrobial properties. To obtain enhanced antimicrobial properties, deacetylated products of chitin—chitosan (CS) have to be synthesised, which includes the introduction of alkyl groups to the amine groups to produce quaternised N-alkyl CS derivatives, the introduction of extra quaternary ammonium grafts to CS and modification with phenolic hydroxyl moieties. 

N-alkylation as shown in Fignre 13.4. Their inclusion ability was examined by the use of />-nitrophe-nol and 3-methyl-4-nitrophenol as model compounds. The potent inclusion ability was observed on a-CD-grafted chitosan beads toward p-nitrophenol while 3-methyl-4-nitrophenol was not adsorbed on the beads. Controlled release study suggested that p-nitrophenol entrapped with a-CD-grafted chitosan beads was released slowly into the buffer and that equilibrium was reached after 15 h. In contrast to these results, chitosan beads, which have little ability to form inclusion complexes, released almost all of the p-nitrophenol within several hours. 

Sashiwa, H. and Shigemasa, Y. 1999. Chemical modification of chitin and chitosan. 2 Preparation and water soluble property of N-acylated or N-alkylated partially deacetylated chitins. Carbohydr. Polym. 39 127-138. 

Chemical. A large number of chitin and chitosan derivatives have been synthesized through modification of the primary (C-6) and secondary (C-3) hydroxyl groups present on each repeat imit, including amine (C-2) functionality existing on deacetylated imits (31). Reactions typical of hydroxyl and amine groups (such as acylations with acid chlorides and anhydrides) including urethane and urea formation respectively, are feasible with isocyanates. The primary amine can be quatemized by alkyl iodides or converted to an imine with a variety of aldehydes and ketones that can subsequently be reduced to an N-alkylated derivative. Chitin and chitosan are reactive with a variety of alkyl chlorides after treatment with concentrated NaOH. Important derivatives such as carboxymethylated chitin and chitosan are commonly produced in this manner with the addition of sodium chloroacetate. 

Figure 1. Some chemical reactions for the molecular design of chitin and chitosan. [1], chitin [2], chitosan [3], alkoxide (alkali chitin) [4] salt (carboxyl-ate) [5], chelation [6] Schiff s base [7], N-acylation [8], halogenation [9], N-alkylation [10], 0-alkylation [11], oxido-deaminative cleavage [12], 0-acylation [13], sulfonation [14], sulfation, phosphorylation and nitration.

N-Trimethyl chitosan chloride (TMC) with introduced quaternary amino groups on the chitosan chain has been synthesized using iodomethane in an alkaline solution of N-methyl pyrrolidinone (NMP). Quaternization is based on the nucleophilic alkylation of the primary amino group at the C-2 position of chitosan [41]. TMC... 

Ngimhuang, J., Furukawa, J., Satoh, T., Furuike, X, Sakairi, N. Synthesis of a novel polymeric surfactant by reductive N-alkylation of chitosan with 3-O-dodecyl-glu-... 

A usual approach to increase chitosan s solubility at neutral pH values is the substitution of the primary amine. Whereas N-substitution with alkyl groups (i.e. -CH3 groups) can increase the aqueous solubility without affecting its cationic character, substitution with moieties bearing carboxyl groups can yield polymers with polyampholytic properties (Muzzarelli et al. 1982). Mono-carboxymethylated chitosan (MCC) was synthesized and further... 

Tokura, S. and Nishi, N. (1982) Preparation and properties of alkyl-chitin fibers, in Chitin Chitosan (eds S. Hirano and S. Tokura), Proceedings of the Second International Conference on Chitin and Chitosan, Japanese Society of Chitin Chitosan, Tattori, Japan, pp. 244-247. 

Ramos, V. M., Rodriguez, N. M., Rodriguez, M. S. et al. 2003. Modified chitosan carrying phosphonic and alkyl groups. Carbohydr. Polym. 51 425 29. 

Introducing small functional groups to the chitosan structure, such as alkyl or carboxymethyl groups (<9-/N-carboxyalkylation), can drastically increase the solubility of chitosan at neutral and alkaline pHs without affecting its cationic character. The conversion of chitosan to a variety of iV-alkylated derivatives can be achieved by treatment with aldehydes or ketones leading to formation of Schiff... 

Eventually, alkyl radicals can be randomly produced along the polymer chain after its exposure to irradiations (electron beam or °Co y-ray irradiation). This was demonstrated with a N-phthaloylchitosan (the soluble intermediate for the modification of chitosan) followed by the grafting of either S or Ss s 9.59o stmcture and/or the location of the aminoxyl function was, however, unclear. Holmberg et irradiated poly(vinylidene fluoride) (PVDF) in the presence of TEMPO. The macroinitiator was then used to graft styrene or a styrene/ N-phenylmaleimide mixture onto the PVDF membranes. Such a result was surprising since the alkoxyamine formed should be very stable and not prone to decomposition. 

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