poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · dr....
TRANSCRIPT
![Page 1: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/1.jpg)
Poly(glycidyl methacrylate): a
versatile polymeric building
block for functional materials*
*Polymer Chemistry, 2013, 4, 124-132 / Patent Filed
M. Benaglia, A. Alberti, F. Magnoni, S. Tozzi
ISOF - Bologna
Coffee talk@ISOF 6 November 2012
L. Giorgini - Bologna University
![Page 2: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/2.jpg)
A
B
M
n
Results achieved with the advent of controlled
polymerization techniques
Controlled MW with narrow distribution
Control of the chemical composition of the polymer by selecting the appropriate monomer
Introduction of functional groups at the chain ends
Moreover
Unprecedented control on the polymer architecture
Spatial self-organization
![Page 3: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/3.jpg)
R
S Z
S
M
The RAFT technique in particular…
The RAFT group permits conjugation reactions that involve either the dithio carbonyl group or the forming thiol function
Introduction of special functionalities by choosing the appropriate RAFT agent
R
S
M
n
Z
S
Disadvantage:
polymerization conditions must be optimized for each monomer
•Hetero Diels-Alder reaction •Thiol-ene click reaction •Disulfide bridge formation •Thiol anchoring
![Page 4: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/4.jpg)
Poly(glycidyl methacrylate)
Reactive epoxy function
Hydrogels Methacrylic epoxy resins as coatings and adhesives
Glycidyl methacrylate
industrially widely employed
Radical Polymerization
![Page 5: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/5.jpg)
Poly(glycidyl methacrylate) by RAFT
Ring-opening reactions induced by nucleophiles
PGMA obtained with:
•controlled MW •determined architecture •functionalized ends
The treatment investigated enables maximum control of the chemical composition for a pre-synthesized polymer
![Page 6: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/6.jpg)
Nucleophilic ring-opening of the epoxy groups
A
B
n
OO
O
A
B
n
OO
OH
Nu
:Nu
Nucleophiles:
•Amines •Thiols •Phenols •Azide
![Page 7: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/7.jpg)
Treatment with amines
Cross-linked polymer
Linear polymer
Primary amines
Secondary amines
![Page 8: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/8.jpg)
Easy access to a library of polymers
Morpholine
N-methylpiperazine
Piperidine
4-Hydroxypiperidine
3-Hydroxypiperidine
Diethylamine
Diethanolamine
Methylethanolamine
Imidazole
Benzimidazole
![Page 9: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/9.jpg)
pH tunable sensitive materials
and the
solubility can be varied from
hydrophilic to lipophilic
Materials obtained with amines as nucleophiles are:
![Page 10: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/10.jpg)
R
S*
OO
n
OH
N
O
By NMR the ring-opening reaction is quantitative
00.511.522.533.544.55
ppm
H2O
DMSO
R
SC(S)Z
OO
n
O
![Page 11: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/11.jpg)
2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5
GPC analysis: the linearity of the PGMA is maintained
mL THF
R
SC(S)Z
OO
n
O
Mn 10900 g mol-1
PDI 1.14
2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5
R
S*
OO
n
OH
N
OMn 14000 g mol-1
PDI 1.15
molecular weight <50 KDa for renal excretion
![Page 12: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/12.jpg)
Possible cross-linking mechanisms
2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5
PGMA Treatment in aprotic polar solvents like:
DMSO or
N-Methylpyrrolidone
-speeds up the process
-cross-linking is avoided
mL
Trans-esterification
![Page 13: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/13.jpg)
Other class of nucleophiles
Thiols
OO
n
OH
S
HO
SH
OH
0123456
ppm
DMSO
H2O
![Page 14: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/14.jpg)
OH
OO
n
O
OH
Aromatic alcohols
Other class of nucleophiles
012345678
ppm
DMSO
H2O
![Page 15: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/15.jpg)
pH insensitive
and
can be
hydrophilic or lipophilic materials
Materials obtained with mercaptanes or
aromatic alcohols as nucleophiles are:
![Page 16: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/16.jpg)
Treatment with sodium azide
C=O
O
O
C=O
n
O
HO
N
m
C=O
O
O
n+m
O
NHO C=O
O
C=O
n
O
HO
N
HO
N3
NaN3
m
O
-N3
2104 cm-1
Azide functionalized polymers
for click reactions with
alkynyl-substrates
![Page 17: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/17.jpg)
Amphiphilic block-copolymer
PHMPMA-b-PMMA PHMPMA-b-PSt PHMPMA-b-PBA
Spatial self-organization into micelles
![Page 18: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/18.jpg)
Polymeric micelles
CO CO CO
O O O
OH
N
O
CO
O
OH
N
O
OH
N
O
OH
N
O
Lipophilic block
Hydrophilic block Hydrated shell
H2O Self-assembling
Amphiphilic block-copolymer
= Nile Red
Loaded core
Intracellular Delivery of
Lipophilic Substances
![Page 19: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/19.jpg)
Cellular uptake of polymeric micelles
Human colon carcinoma cells LS-174T
![Page 20: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/20.jpg)
Post post-polymerization processes enables for
further chemical and structural modifications
012345678910
ppm
H2O DMSO
![Page 21: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/21.jpg)
Pre post-polymerization functionalizations
Maleimide-functionalized substrates
R = Amino-terminated polymers
Fluorescent dyes
Maleimide - Not Reversible Linking
![Page 22: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/22.jpg)
Pre post-polymerization functionalizations
Suitable for (bio-)conjugation with thiol substrates
Suitable for conjugation with amine substrates
Disulfide Bridge - Reversible Linking
![Page 23: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/23.jpg)
Conclusions
The treatment of PGMA with nucleophilic reagents
enables a multitude of different materials specifically
functionalized to be synthesized from the same polymer.
This process provides polymeric materials for:
Diagnostic agents delivery
Therapeutic agents delivery
Gene delivery
Active and/or passive targeting
Anti non-specific protein absorption properties
} Theranostic approach
> Plasmids, siRNA
Moreover, photoactive as well as electron and proton conductive
materials are also accessible
![Page 24: Poly(glycidyl methacrylate): a versatile polymeric building block … · 2013. 9. 25. · Dr. Angelo Alberti Dr. Francesco Magnoni Dr. Silvia Tozzi Students Dr. Tommaso Tabanelli](https://reader035.vdocuments.site/reader035/viewer/2022071501/6120f6c5eeee0665d657f1be/html5/thumbnails/24.jpg)
Acknowledgements
ISOF
Dr. Angelo Alberti
Dr. Francesco Magnoni
Dr. Silvia Tozzi
Students
Dr. Tommaso Tabanelli
Alice Cognigni
Cristiano Luciani
Gaia Tombari
Emilio Iacoli
Thank you for your kind attention
University of Bologna
Dr. Loris Giorgini
DR. Enzo Spisni