Click chemistry for synthesis of chitosan nanocarriers and biomaterials Ingólfur Magnússon 17th. June 2014

Introduction of PhD work The aim is to develop click chemistry based procedures for versitle, efficient and chemoselective synthesis of chitosan derivatives TBDMS chitosan will be used to synthesize chitosan derivatives with substituents like terminal alkyne, azide and maleimide. – These are further modified by click chemistry – Reducing end functionalization – Grafting in polymers backbone Chitosan derivatives will be used in casting films (membranes) – With different N-acetylation – With photo-crosslinking agents – In collaboration with the Blood Bank of Iceland

Chitosan Chitosan is a polysaccharide made from shrimp shell Chitosan: – Biodegradable – Low toxicity – antimicrobial – mucoadhesive – Polycationic – Affinity for negatively charged biological membranes – Limited water solubility above pH 6 – Low solubility in organic solvents

PhD requirements in Iceland Publish 3 articles Take minimum 24 ECTS units in courses Teach at least 200 hours during the study period Status: – Started February 2012 – I have finished both the teaching and 24 ECTS units – No publication yet, that work is in process – Aim to finish before December 2015

Some of the work I have been doing

Maleimide chitosan

Chitosan with photo crosslinking agents

Project work plan

Article 1

Chitosan maleimde article Focus on publishing article on the synthesis part Last step in the synthesis has been problematic because of hydrolysis of the maleimide group at acidic conditions Develop method to deprotect the TBDMS groups with low degradation/changing of the maleimide group

Chitosan maleimide (article 1) Degree of substitution of maleimide will be 1%, 5% and 10 % Click reaction will be done with 7-mercapto-4-methylcoumarin (fluorescence agent) If time allows, maleimide grafted chitosan might be reacted to proteins/peptides and other fluorescence agents – and biological data will then be obtained from coworkers Publication in journal like: Carbohydrate Polymers, European Polymer Journal, Macromolecules etc.

Main results in Chitosan Maleimide article 1 Synthesis and characterization data – NMR, IR, Fluorescence, Mass, GPC etc. Microscopy studies Nanoparticle formation Chitosan maleimide-sulfhydryl click reaction with proteins Focus on the synthesis part in this article

Article 2

Photo crosslinking reagents – article 2 CompoundDS (%) A B125 C125 The casting ability to form membranes of these chitosan derivatives will be investigated Photoactivation of the membranes and the effects of that on their properties Cell culture studies in collaboration with the blood bank (Óli Eysteins) Publication in journals like: Biomaterials, Journal of Natural Products, Journal of Medicinal Chemistry etc.

Results included in Article 2 (Photo crosslinking chitosan membranes) Synthesis and characterization data – NMR, IR, Mass, GPC etc. Casting in membranes Effects of photoactivation on membranes properties Coating implants with chitosan derivatives Cell studies in colloboration with the blood bank – Effects of chitosan on osteogenic differentiation – Microscopic studies

Article 3

Sulfhydryl derivatives of Chitosan Recently started this work before I went to Denmark Click reactions with maleimide Casting membranes

Sulfhydryl derivatives of Chitosan Properties that will be investigated – Muchoadesive – Adsorption – Toxicity – Microscopy Chitosan sulfhydryl membranes – Cell studies in collabaration with the blood bank Publication in journals like: Polymer Chemistry European Polymer journal, Journal of Sulfur Chemistry and etc.

Results included in Article 3 (Sulfhydryl chitosan) Synthesis and characterization data – NMR, IR, Mass, GPC etc. Click reactions with fluorescent maleimide Casting in membranes Membranes properties – Adsorption – Muchoadesive Cell studies

Article 4

Project in Denmark Focus on reducing end functionalization of chitosan – Fluorescent end-labeling of chitosan Grafting peptide or protein in chitosans backbone with click chemistry Nano particle formation (DLS) (Done in Iceland)

Oxime synthesis in Denmark

Denmark It is the aim that the work in Denmark will result in article I will focus on the synthesis and characterization of these compounds. This work will be published in synthetic chemistry journal. All biological test will be done in collaboration with coworkers (Blood Bank and PCI Biotech) Publication in journals like: Advances in Polymer Science, Pharmaceutical Research, International Journal of Nanomedicine and etc.

Results to be included in article 4 (Denmark) Synthesis and characterization data – NMR, IR, Fluorescence, Mass, GPC etc. Report peptide synthesis of chitosan – Click chemistry Oxime synthesis on chitosan reducing end Microscopy studies Nanoparticle formation

Thank you for listening Any questions?