1. 1 Stimuli Responsive Materials Derived from Poly(acrylamides) Greg Sorenson April 15, 2010 Mahanthappa Group University of Wisconsin - Madison

2. Motivation Nature Proteins – Temperature/pH responsive – Specific monomer interactions lead to structure ‘Smart’ Materials Drug/gene delivery Tissue scaffolds Implantable devices 2 Ober, C. K. et. Al. Macromolecules 2009, 42 (2), 465-471. Stuart, M. A. C. et. al. Nature Materials 2010, 9, 101-113.

3. Temperature – Hydrogen Bonding – Hydrophobic interactions pH – Weak electrolyte – Degree of ionization – Electrostatic interactions Potential Triggers 3 Lui, F.; Urban, M. W.. Progress in Polymer Science 2010, 35, 3-23.

4. 1968 Heskins and Guillet – Soluble only in solvents capable of hydrogen bonding – Dilute aqueous solutions became turbid above 31°C – What is going on? An Interesting Observation 4 NIPAM Poly(NIPAM) Heskins, M.; Guillet, J. E.. Journal of Macromolecular Science, Chemistry 1968, 2 (8), 1441-1455.

5. Polymers in Solution Three kinds of interactions to consider – Solvent-Solvent – Polymer-Polymer – Solvent-Polymer 5 Hiemenz, P. C.; Lodge, T. P., Polymer Chemistry. 2 ed.; CRC Press: Boca Raton, 2007..

6. Polymers in Solution Polymer-Polymer interactions dominate Globule formation Two phase system Polymer-solvent interactions dominate The polymer is soluble One phase 6 Poor Solvent Good Solvent Hiemenz, P. C.; Lodge, T. P., Polymer Chemistry. 2 ed.; CRC Press: Boca Raton, 2007

7. Polymers in Solution – Lower Critical Solution Temperature (LCST) – Upper Critical Solution Temperature (UCST) 7  Temperature Fractional Composition Two phase region Two phase region One phase  Rubinstein, M.; Colby, R. H., Polymer Physics. Oxford University Press Inc.: New York, 2003

8. Characterizing the Transition UV-Vis spectroscopy – Transmittance vs. Temperature Differential Scanning Calorimetry (DSC) – Heat flux vs. temperature Dynamic Light Scattering (DLS) 8

9. Advantages of Acrylamides Acrylamides Easily tuned Controllable architecture – Molecular weight – Molecular weight distribution 9 Hydrophilicity/ hydrophobicity Hydrogen bonding

10. Molecular Weight Effects SampleM n,NMR (kDa) PDI (M w /M n ) LCST (°C) a2.81.0743.0 b6.51.0936.3 c10.91.1135.5 d26.51.1633.3 e28.92.0031.2 10 Xia, Y. et. al. Macromolecules 2005, 38 (14), 5937-5943.

11. Tailoring a Material Monomer Choice – Easily accessible – Hydrophobic Vs. Hydrophilic Architectural control – Controlled Polymerization Molecular weight and distribution PDI – Co-polymers Random co-polymers Blocky architectures 11

12. Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization 12 Initiation: Chain Transfer: Reinitiation: Termination: Equilibrium: Hiemenz, P. C.; Lodge, T. P., Polymer Chemistry. 2 ed.; CRC Press: Boca Raton, 2007; p 587.

13. Simple Alkyl Polyacrylamides 13 M n ~ 10 kDa, 1g/L solution in water Cao, Y.; et. al. Macromolecules 2007, 40 (18), 6481-6488.

14. What about more complex systems? Acrylamides derived from amino acids – Multiple kinds of functional groups – Easily accessible – Potentially Biocompatible 14

15. Proline Based Acrylamides Amino acid derivatives – Protein mimic – Connective tissue – Multiple hydrogen bonding points Potential for a dual responsive nature 15 A-Pro-OH soluble pH ~ 9 A-Pro-OMe LCST = 17.5 °C A-Hyp-OH Water soluble A-Hyp-OMe LCST = 49.5 °C Mori, H. et. al. Macromolecules 2008, 41 (15), 5604-5615

16. Proline Based Acrylamides 16 A-Pro-OMe A-Hyp-OMe M n = 12.2 kDa. PDI = 1.26 M n = 11.0 kDa. PDI = 1.29 Mori, H. et. al. Macromolecules 2008, 41 (15), 5604-5615. Mori, H. et. al. Chemical Communications 2005, (38), 4872-4874.

17. Random copolymerization Random co-polymer – M n = 5.5-8.3 kDa. – PDI = 1.15-1.28 – LCST from 17 - 43 °C – LCST is lost for x< 50% 17 A-Pro-OMe Mori, H. et. al. Chemical Communications 2005, (38), 4872-4874. DMA

18. Globules Micelles Polymersomes Complex Architectures 18

19. Block Copolymers Block copolymer – M n = 25.0 kDa. (PDI = 1.58) – m:n = 27:73 – 2 mg/mL in water – pH = 2 – No transition in the random copolymer 19 Mori, H. et. al. Macromolecules 2010, 43 (3), 1289-1298.

20. What’s going on? 20 Mori, H. et. al. Macromolecules 2010, 43 (3), 1289-1298. Loosely H-bonded A-pro-OMe H-bonded diblock complex Dehydrated A-pro-OMe Low Temperature High Temperature

21. Dual-Responsive Material Block copolymer – M n = 14.7 kDa. (PDI = 1.34) – m:n = 22:78 – 2 mg/mL in water – LCST is dependent on pH 21 Mori, H. Macromolecules 2009, 42 (14), 4985-4992.

22. Dual-Responsive Material Composition dependence – M n = 8.5 - 24.8 kDa. – PDI = 1.25 - 1.37 – 2 mg/mL in water – pH behavior dominates at large m. 22 pH= 10 pH= 11 Mori, H. Macromolecules 2009, 42 (14), 4985-4992.

23. Block and Random Combined 23 Lokitz, B. S. et. al. Macromolecules 2007, 40 (18), 6473-6480. NIPAM AVAL M n (DEA) = 11.6 kDa. V-044 =

24. Summary and Outlook Amino acid based acrylamides – Modular platform – Wide range of temperature response – Easily controlled architectures – Complex architectures What’s Next – Further structural characterization – Biocompatibility – Extensions into other macromolecular assemblies 24

25. Acknowledgments Professor Mahesh Mahanthappa The Mahanthappa Group: Dr. Andy Schmitt Corinne Lipscomb Joan Widin Ryan Weber Milton Repollet-Pedrosa Glen Thomas Adam Schmitt Beau Monnot Steve Banik 25

26. Good SolventTheta SolventPoor Solvent Polymers in Solution 26 = the interaction parameter

27. 27 = the interaction parameter

28. Globules Micelles Polymersomes Structures in Solution 28

29. Temperature Fractional Composition Two phase region Two phase region One phase 29