1. Click chemistry for chitosan nanocarriers and biomaterials Ph.D. Student: Ingólfur Magnússon Instructor: Már Másson 7. June 2013 Research day

2. Click chemistry Chemical philosophy from 2001 Refers to synthesis that links together complex compounds Click reactions are – Fast – Simple to use – Easy to purify – Versatile – Regiospecific – High yields Huisgen 1,3-dipolar cycloaddition

3. Thiol based click reactions Have attracted attention in the last 5 years Preparation of thiol sugars often more demanding than azide sugars Thiol maleimide based click chemistry – Thiols are highly selective for maleimides – Has been utilized for many years in bioconjugate chemistry – May open doors to external control to tailor biological molecules for example in peptide synthesizes

4. Aims One pot synthesizes of water soluble chitosan, functioned with photosensitizer and maleimide spacer

5. Aims

6. Results

7. Maleimide functionalized chitosan

8. 1 H NMR 1 1 2 3 4 5 6 5 6 4 3 6 2 CDCl3

9. 1 H NMR CDCl3 H-1 H-2 H-3 H-4 H-5 H-6 H-1 H-2H-5 H-3 H-4 H-6 TBDMS Spacer and water peak A A A Chitosan part Maleimide peak

10. One Pot Synthesis

11. 1 H NMR H-1 H-2 H-3 H-4 H-5 H-6 7 8 8 8 8 H-1 D2OD2O 7 9 10 11 12 13 TBDMS redidues 13 11 10 12 9 H2-H6

12. Deprotection

13. 1 H NMR H-1 H-2 H-3 H-4 H-5 H-6 9 10 11 12 13 TBDMS redidues D2OD2O H-1 13 11 10 12 9 H2-H6

14. Conclusion Synthesis of TBDMS chitosan with maleimide was achieved Maleimide double bond does not survive deprotection of TBDMS protection group The results shows that the one pot synthesis of chitosan derivatives is still possible The only threshold in this work is the stability of the maleimide double bond

15. Future work Protect the maleimide double bond by dimethylfuran protection Try the one pot synthesis of chitosan derivatives with protected maleimide

16. Thank you for listening Questions