Stimuli Responsive Materials Derived from
Poly(acrylamides)
Greg Sorenson
April 15, 2010
Mahanthappa Group
University of Wisconsin - Madison
1
Motivation
Nature
• Proteins
– Temperature/pH responsive
– Specific monomer
interactions lead to structure
Ober, C. K. et. Al. Macromolecules 2009, 42 (2), 465-471.
Stuart, M. A. C. et. al. Nature Materials 2010, 9, 101-113.
‘Smart’ Materials
• Drug/gene delivery
• Tissue scaffolds
• Implantable devices
2
Potential Triggers
• Temperature
– Hydrogen Bonding
– Hydrophobic interactions
• pH
– Weak electrolyte
– Degree of ionization
– Electrostatic interactions
Lui, F.; Urban, M. W.. Progress in Polymer Science 2010, 35, 3-23.
3
An Interesting Observation
• 1968 Heskins and Guillet
NIPAM
Poly(NIPAM)
– Soluble only in solvents capable of hydrogen bonding
– Dilute aqueous solutions became turbid above 31°C
– What is going on?
Heskins, M.; Guillet, J. E.. Journal of Macromolecular Science, Chemistry 1968, 2 (8), 1441-1455.
4
Polymers in Solution
• Three kinds of interactions to consider
– Solvent-Solvent
– Polymer-Polymer
– Solvent-Polymer
Hiemenz, P. C.; Lodge, T. P., Polymer Chemistry. 2 ed.; CRC Press: Boca Raton, 2007..
5
Polymers in Solution
Poor Solvent
Good Solvent
• Polymer-Polymer
interactions dominate
• Globule formation
• Two phase system
• Polymer-solvent
interactions dominate
• The polymer is soluble
• One phase
Hiemenz, P. C.; Lodge, T. P., Polymer Chemistry. 2 ed.; CRC Press: Boca Raton, 2007
6
Polymers in Solution
– Lower Critical Solution
Temperature (LCST)
D
Temperature
– Upper Critical Solution
Temperature (UCST)
Two phase
region
One phase
D
Two phase
region
Fractional Composition
Rubinstein, M.; Colby, R. H., Polymer Physics. Oxford University Press Inc.: New York, 2003
7
Characterizing the Transition
• UV-Vis spectroscopy
– Transmittance vs. Temperature
• Differential Scanning Calorimetry (DSC)
– Heat flux vs. temperature
• Dynamic Light Scattering (DLS)
8
Advantages of Acrylamides
• Acrylamides
• Easily tuned
Hydrophilicity/
hydrophobicity
Hydrogen
bonding
• Controllable architecture
– Molecular weight
– Molecular weight distribution
9
Molecular Weight Effects
Sample
Mn,NMR
(kDa)
PDI
(Mw/Mn)
LCST (°C)
a
2.8
1.07
43.0
b
6.5
1.09
36.3
c
10.9
1.11
35.5
d
26.5
1.16
33.3
e
28.9
2.00
31.2
Xia, Y. et. al. Macromolecules 2005, 38 (14), 5937-5943.
10
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
Reversible Addition-Fragmentation Chain
Transfer (RAFT) Polymerization
Initiation:
Chain Transfer:
Reinitiation:
Equilibrium:
Termination:
Hiemenz, P. C.; Lodge, T. P., Polymer Chemistry. 2 ed.; CRC Press: Boca Raton, 2007; p 587.
12
Simple Alkyl Polyacrylamides
Polymer
R1
R2
LCST (°C)
Poly(N,N-dimethylacrylamide)
Me
Me
soluble
Poly(N,N-ethylmethylacrylamide)
Me
Et
70
Poly(N,N-diethylacrylamide)
Et
Et
32
Poly(N-isopropylacrylamide)
H
iPr
36
Poly(N-n-propylacrylamide)
H
nPr
25
Poly(N-n-butylacrylamide)
H
nBu
Insoluble
Mn ~ 10 kDa, 1g/L solution in water
Cao, Y.; et. al. Macromolecules 2007, 40 (18), 6481-6488.
13
What about more complex systems?
• Acrylamides derived from amino acids
– Multiple kinds of functional groups
– Easily accessible
– Potentially Biocompatible
14
Proline Based Acrylamides
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
• Amino acid derivatives
– Protein mimic
– Connective tissue
– Multiple hydrogen bonding points
• Potential for a dual responsive nature
Mori, H. et. al. Macromolecules 2008, 41 (15), 5604-5615
15
Proline Based Acrylamides
A-Pro-OMe
Mn= 12.2 kDa.
PDI = 1.26
A-Hyp-OMe
Mn= 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.
16
Random copolymerization
A-Pro-OMe
DMA
• Random co-polymer
– Mn= 5.5-8.3 kDa.
– PDI = 1.15-1.28
– LCST from 17 - 43 °C
– LCST is lost for
x< 50%
Mori, H. et. al. Chemical Communications 2005, (38), 4872-4874.
17
Complex Architectures
• Globules
• Micelles
• Polymersomes
18
Block Copolymers
• Block copolymer
–
–
–
–
–
Mn= 25.0 kDa. (PDI = 1.58)
m:n = 27:73
2 mg/mL in water
pH = 2
No transition in the random
copolymer
Mori, H. et. al. Macromolecules 2010, 43 (3), 1289-1298.
19
What’s going on?
Low Temperature
High Temperature
𝛥
Loosely H-bonded
A-pro-OMe
Mori, H. et. al. Macromolecules 2010, 43 (3), 1289-1298.
𝛥
H-bonded diblock
complex
Dehydrated
A-pro-OMe
20
Dual-Responsive Material
• Block copolymer
–
–
–
–
Mn= 14.7 kDa. (PDI = 1.34)
m:n = 22:78
2 mg/mL in water
LCST is dependent on pH
Mori, H. Macromolecules 2009, 42 (14), 4985-4992.
21
Dual-Responsive Material
pH= 10
pH= 11
• Composition dependence
–
–
–
–
Mori, H. Macromolecules 2009, 42 (14), 4985-4992.
Mn= 8.5 - 24.8 kDa.
PDI = 1.25 - 1.37
2 mg/mL in water
pH behavior dominates at
large m.
22
Block and Random Combined
NIPAM
Polymer
AVAL
NIPAM/AVAL
(mol %)
Mn
PDI
(kDa.)
LCST (°C)
(pH = 2)
(pH = 4)
(pH = 8)
1
100/0
39.9
1.18
35
36
36
2
88/12
38.8
1.19
23
32
--
3
79/21
39.9
1.15
14
30
--
4
71/29
41.0
1.13
11
28
--
5
62/38
39.9
1.16
9
29
--
Mn (DEA) = 11.6 kDa.
Lokitz, B. S. et. al. Macromolecules 2007, 40 (18), 6473-6480.
V-044 =
23
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
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
Polymers in Solution
Good Solvent
Theta Solvent
Poor Solvent
𝜒 = the interaction parameter
26
𝜒 = the interaction parameter
27
Structures in Solution
• Globules
• Micelles
• Polymersomes
28
Temperature
Two phase
region
One phase
Two phase
region
Fractional Composition
29