Water-Soluble Quaternary and Protonable Basic Chitotriazolans: Synthesis by Click Chemistry Conversion of Chitosan Azides and Investigation of Antibacterial Activity.

The azide transfer reaction and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) can be used to convert the amino groups in chitosan to triazole 1,2,3-moieties. The resulting polymer has been named chitotriazolan. This synthesis was performed with six different quaternary ammonium alkynes and three amine alkynes to obtain a series of nine water-soluble chitotriazolan derivatives. The structure and complete conversion of the azide were confirmed by FT-IR and proton NMR spectroscopy. The derivatives were investigated for antibacterial activity against S. aureus, E. faecalis, E. coli, and P. aeruginosa. The activity of the quaternized chitotriazolan derivatives varied depending on the structure of the quaternary moiety and the species of bacteria. The basic protonable derivatives were less active or inactive against the bacteria.

Chitotriazolan (poly(ß(1-4)-2-(1H-1,2,3-triazol-1-yl)-2-deoxy-d-glucose)) derivatives: Synthesis, characterization, and evaluation of antibacterial activity.

Here we describe the first synthesis of a new type of polysaccharides derived from chitosan. In these structures, the 2-amino group on the pyranose ring was quantitively replaced by an aromatic 1,2,3-triazole moiety. The 2-amino group of chitosan and di-TBDMS chitosan was converted into an azide by diazo transfer reaction. The chitosan azide and TBDMS-chitosan azide were poorly soluble but could be fully converted to triazoles by "copper-catalysed Huisgen cycloaddition" in DMF or DMSO. The reaction could be done with different alkynes but derivatives lacking cationic or anionic groups were poorly soluble or insoluble in tested aqueous and organic solvents. Derivatives with N,N-dimethylaminomethyl, N,N,N-trimethylammoniummethyl, sulfonmethyl, and phosphomethyl groups linked to the 4-position of the triazole moiety were soluble in water at neutral or basic conditions and could be analyzed by 1H, 13C APT, COSY, and HSQC NMR. The quaternized cationic chitotriazolan's had high activity against S. aureus and E. coli, whereas the anionic chitotriazolan's lacked activity.

The antibacterial structure-activity relationship for common chitosan derivatives.

The relationship between the degree of substitution and antibacterial activity was studied for six common chitosan derivatives N, N,N-trimethyl chitosan (TMCNH2/TM and TMCTM/DM) N-(2-(N,N,N-trimethylammoniumyl)acetyl)-chitin (TACin), N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan (HTC), hydroxypropyl chitosan (HPC), thioglycolic chitosan (TGC) and carboxymethyl chitosan (CMC). The degree of substitution (DS) in the 36 studied samples ranged from 0.02 to 1.1 as determined by 1H NMR. The activity was determined as the minimum inhibitory concentration (MIC) against S. aureus and E. coli at pH 7.2 and 5.5. The antibacterial effect of TMC and TACin increased with DS. Samples of these derivatives with high DS were more active than chitosan at pH 7.2. HTC was more active than chitosan against S. aureus, but this activity was not affected by DS. In other cases, the activity of HTC decreased with an increase in DS. The DS for the TGC was very low and the activity was similar to unmodified chitosan. The activity of HPC decreased with DS. CMC was not active in this study.

Selective synthesis of N,N,N-trimethylated chitosan derivatives at different degree of substitution and investigation of structure-activity relationship for activity against P. aeruginosa and MRSA.

Two new cationic chitosan derivatives were synthesized using a combination of Boc and TBDMS protection strategies. This included a series of six samples of the TMCNH2/TM derivative, where some of the amino groups were N,N,N-trimethylated and the remaining was in the primary state. A series of six samples of the TACin derivative, where some of the amino groups were N-acetylated with quaternary 2-(N,N,N-trimethylammoniumyl) acetyl group and the remaining fully N-acetylated, were also synthesized. The degree of substitution (DS) for quaternary amino groups in these series ranged from 0.06-0.89. TMCDM/TM derivatives with a mix of N,N,N-trimethylated and N,N-dimethylated groups were also synthesized according to a published procedure but in this case, it was more difficult to control the DS than with the TBDMS protection strategy. Broth microdilution assay revealed a markedly different structure-activity relationship (SAR) for the two derivatives. The activity for the TMC derivatives reached a plateau above 0.2-0.3 DS whereas the activity increased continuously with DS for TACin. The highest DS TMCNH2/TM was more active than the highest DS, TACin, against Gram-positive MRSA but less active against the Gram-negative P. aeruginosa.