title: Impact of chain length on antibacterial activity and hemocompatibility of quaternary N-alkyl and n,n-dialkyl chitosan derivatives.
abstract: A highly efficient method for chemical modification of chitosan biopolymers by reductive amination to yield N,N-dialkyl chitosan derivatives was developed. The use of 3,6-O-di-tert-butyldimethylsilylchitosan as a precursor enabled the first 100% disubstitution of the amino groups with long alkyl chains. The corresponding mono N-alkyl derivatives were also synthesized, and all the alkyl compounds were then quaternized using an optimized procedure. These well-defined derivatives were studied for antibacterial activity against Gram positive S. aureus, E. faecalis, and Gram negative E. coli, P. aeruginosa, which could be correlated to the length of the alkyl chain, but the order was dependent on the bacterial strain. Toxicity against human red blood cells and human epithelial Caco-2 cells was found to be proportional to the length of the alkyl chain. The most active chitosan derivatives were found to be more selective for killing bacteria than the quaternary ammonium disinfectants cetylpyridinium chloride and benzalkonium chloride, as well as the antimicrobial peptides melittin and LL-37.
authors.affiliation: †Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sahariah
authors.affiliation: †Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Berglind E
authors.initials: BE
authors.lastname: Benediktssdóttir
authors.affiliation: ‡Department of Biomedical Science, Faculty of Medicine, University of Iceland, Stapi, Hringbraut 31, 101 Reykjavik, Iceland.
authors.forename: Martha Á
authors.initials: MÁ
authors.lastname: Hjálmarsdóttir
authors.affiliation: §The REModeL Lab, The Blood Bank, Landspitali University Hospital, Snorrabraut 60, 105 Reykjavik, Iceland.|∥Institute of Biomedical and Neural Engineering, Reykjavik University, Menntavegur 1, 101, Reykjavik, Iceland.
authors.forename: Olafur E
authors.initials: OE
authors.lastname: Sigurjonsson
authors.affiliation: ⊥Department of Chemistry, Faculty of Science, Centre for Carbohydrate Recognition and Signalling, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Fredriksberg C, Copenhagen, Denmark.
authors.forename: Kasper K
authors.initials: KK
authors.lastname: Sørensen
authors.affiliation: ⊥Department of Chemistry, Faculty of Science, Centre for Carbohydrate Recognition and Signalling, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Fredriksberg C, Copenhagen, Denmark.
authors.forename: Mikkel B
authors.initials: MB
authors.lastname: Thygesen
authors.affiliation: ⊥Department of Chemistry, Faculty of Science, Centre for Carbohydrate Recognition and Signalling, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Fredriksberg C, Copenhagen, Denmark.
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
authors.affiliation: †Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Már
authors.initials: M
authors.lastname: Másson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001704:Biopolymers / Q000737:chemistry* / Q000494:pharmacology; D018938:Caco-2 Cells; D048271:Chitosan / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001704:Biopolymers; D048271:Chitosan