1. Ingólfur Magnússon 12. May 2014
Click chemistry for synthesis of chitosan nanocarriers and biomaterials
Ingólfur Magnússon
12. May 2014

2. 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
The main focus is on synthesis
Initially the focus was on reducing end of chitosan

3. My PhD committee Margrét Þorsteinsdóttir, University of Iceland
Ólafur Eysteinn Sigurjónsson, Univeristy of Reykjavik, Blood Bank of Iceland
Knud J. Jensen, University of Denmark
Stefán Jónsson, Actavis

4. PhD requirements Publish 3 articles
Take minimum 24 ECTS units in courses at the University of Iceland
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

5. Conferences CLINAM-European Foundation for Clinical Nanomedicine
Basel, Switzerland, 23-26th of June 2013
EFNÍS- The Icelandic Chemical Society
Reykjavík, Iceland, 28th of October 2013
Conference about researches in life and health science-University of Iceland
Reykjavík, Iceland, 3rd of January
Translational nanomedicine-University of Angers
Angers, France, 27-29th of August 2014

6. Some of the work I have been doing

7. Maleimide chitosan

8. Chitosan with photo crosslinking agents

9. Project work plan

10. Article 1

11. 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

12. 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.

13. 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

14. Article 2

15. Photo crosslinking reagents – article 2
Compound
DS (%) A 1 2 5
10-15 B C
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.

16. 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

17. Article 3

18. Sulfhydryl derivatives of Chitosan
Recently started this work
Click reactions with maleimide
Casting membranes

19. 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.

20. 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

21. Article 4

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

23. Target molecules for Denmark

24. 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.

25. 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

26. Thank you for listening
Any questions?