2. www.helsinki.fi/yliopisto
• Purpose of study
• Biomedical properties of hbPG
• Anionic ring-opening polymerization
• Steps of the study
• Monomer synthesis
• Polymerizations
• Multibranching
• Analysis methods
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Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Contents
3. www.helsinki.fi/yliopisto
• Synthesis of hyperbranched polyethers as modules for
attachment onto hyaluronic acid
• Anionic ring-opening polymerization
• Good control over MW and PDI
• Glycidol is easily available and cheap
• water-soluble, biocompatible, non-degradable…
• Clickable end-group
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Purpose of the study
4. www.helsinki.fi/yliopisto 26.6.2014 4
Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Purpose of the study
• Synthesis of hbPG with:
• low PDI (< 1.2)
• controlled Mn of up to 6500 g/mol
• high degree of branching
• ”clickable” focal point
5. www.helsinki.fi/yliopisto
• Low toxicity Biocompatible
• High water solubility
• Functionalizable hydroxyl-groups
• Control over PDI and MW are essential for
biomedical applications
• Biocompatibility dependant on MW, hyperbranched
structure is less sensitive
‒ High MW polymers with long lifetime in living systems
• Hyperbranched molecules in solution behave more
like proteins than linear polymers
26.6.2014 5
Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Biomedical properties of hbPG
6. www.helsinki.fi/yliopisto
• Much lower PDI than via polycondensation or self-
condensing vinyl polymerization
Controlled preparation of hyperbranched structures
• Control obtained by
• low number of active alkoxides
• high amount of hydroxyl-groups in initiator
• slow addition of monomer
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Anionic ring-opening
multibranching polymerization
7. www.helsinki.fi/yliopisto
• Alkoxides are active polymerization sites
• Low amount inhibits reaction similarly to controlled
radical chain polymerization
• Hydroxyl-groups are dormant sites
• High concentration constrains the reaction
26.6.2014 7
Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Anionic ring-opening
multibranching polymerization
8. www.helsinki.fi/yliopisto
• Slow addition of monomers prevents cyclization
reactions that occur in high monomer/initiator ratios
Branching only to the core unit
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Anionic ring-opening
multibranching polymerization
9. www.helsinki.fi/yliopisto
1. Synthesis of multifunctional initiator
• Synthesis of “backbone”-monomer (done)
• Polymerization of “backbone” (done)
• Deprotection of “backbone” (in progress)
2. Hyperbranching (pending)
26.6.2014 9
Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Steps of the study
10. www.helsinki.fi/yliopisto
• Commercially available solketal and epichlorohydrin
• Phase-transfer reaction
• Purification via column chromatography
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Synthesis of “backbone”-
monomer
12. www.helsinki.fi/yliopisto
• Also via ring-opening polymerization
26.6.2014 12
Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Polymerization of “backbone”
15. www.helsinki.fi/yliopisto
Sample
Code
Polymer
[monomer]
[mol/L]
[i-Bu3Al] /
[NBu4N3]
Init. Temp.
[°C]
Pol. Temp.
[°C]
Time
[h]
Conv.a
[%]
DPth
Mn,th
b
[g/mol]
Mn,GPC
c
[g/mol]
Mw/Mn
c
AK 02 PIGG 0.5 1.5 -30 RT 4 0 20 - - -
AK 03 PIGG 0.5 1.5 RT 80 48.25 20 20 750 - -
AK 05 PIGG 0.5 5.0 -30 RT 68.67 65 20 2400 - -
AK06 PIGG 1.0 5.0 -30 RT 24 46 20 1700 - -
AK07 PIGG 2.0 5.0 -30 RT 24 100 20 3800 4199 1,334
AK08 PIGG 1.0 5.0 -30 80 24 100 20 3800 1552 1,075
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Results of polymerization
(so far…)
aDetermined by 1H-NMR (CDCl3) of crude polymerization mixture after termination with 1 drop of MeOH. bCalculated by
DPth×(Conv./100)×M(IGG: 188.22 g/mol). cGPC in THF containing 1 % toluene as internal standard with polyethylene oxide standards.
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• Not yet realized
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Ring opening multibranching
polymerization (ROMBP)
17. www.helsinki.fi/yliopisto
• NMR
• Chemical structure of intermediate products
• Determination of reaction kinetics
• End group analysis of final product
‒ Click reaction to azide-group with detectable agent
• IR
• Chemical structure of intermediate and final products
• End group analysis of final product
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Analysis methods
Phenyl acetylene
18. www.helsinki.fi/yliopisto
• SEC
• MW and PDI of intermediates and final product
• MALDI
• Quantification of clickable azide-group
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Analysis methods
19. www.helsinki.fi/yliopisto
• Sunder, A.; Hanselmann, R.; Frey, H.; Mülhaupt, R. Macromolecules
1999, 32, 4240-4246.
• Schömer, M.; Schüll, C.; Frey, H. J. Polym. Sci. Part Polym. Chem. 2013,
51, 995-1019.
• Schüll, C.; Nuhn, L.; Mangold, C.; Christ, E.; Zentel, R.; Frey, H.
Macromolecules 2012, 45, 5901-5910.
• Zill, A.; Rutz, A.L.; Kohman, R.E.; Alkilany, A.M.; Murphy, C.J.; Kong, H.;
Zimmerman, S.C. Chem Commun. 2011, 47, 1279-1281.
• Kainthan, R.K.; Gnanamani, M.; Ganguli, M.; Ghosh, T.; Brooks, D.E.;
Maiti, S.; Kizhakkedathu, J.N. Biomaterials 2006, 27, 5377-5390.
• Gervais, M.; Labbé, A.; Carlotti, S.; Deffieux, A. Macromolecules 2009,
42, 2395–2400.
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Department of Polymer Chemistry /
Antti Korpi / Hyperbranched Polyglycerols (hbPG)
Literature