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Synthesis of Cleavable Amphiphilic Block Copolymers
Deepak Vishnu Dharmangadan, Liying Wang, Qiuying Zhang, Mario
*
Gauthier
Institute for Polymer Research, Department of Chemistry, University of Waterloo
Introduction
Synthesis of Novel Redox-Sensitive Initiator
Synthesis of Redox Sensitive Block Copolymers
(PLA-b-PEG)
b
Amphiphilic block copolymers in solution can self-assemble into different
nanostructures such as micelles, wormlike structures, and polymeric vesicles
(polymersomes).1 One important potential application of amphiphilic block
copolymers is as drug carriers,2,3 to help prevent the deactivation of therapeutic
drugs such as proteins, antibodies and nucleic acids during their travel in the
blood stream.4 Depending on the types of functional groups used and the
external stimuli present, different response mechanisms may come into play
including pH-sensitive, thermosensitive, redox-sensitive, enzyme-sensitive,
photosensitive, and so on.5 Herewith we describe the synthesis of a novel
redox-sensitive initiator for the metal-free ring opening polymerization (ROP) of
lactide. A series of redox-sensitive amphiphilic block copolymers of polylactide
(PLA) with polylysine (PLys) or poly(ethylene glycol) (PEG) segments were also
obtained using the PLA macroinitiator.
c
d *e
f
a
OH
c',d'
e'
b'
*
9
8
a'
OH
7
6
5
NH
ppm 4
3
2
1
0
Synthesis of Redox-Sensitive Block Copolymers
(PLA-b-PLys)
PEG-OH
PEG-COOH
PEG-b-PLA
Why Lactide, Lysine and Poly(ethylene glycol)?
a
b
 Lactide: Serves as monomer for the hydrophobic block. Polylactide (PLA)based materials are highly biocompatible, biodegradable by enzymes, can
hydrolyze under physiological conditions.
a
 Lysine: Serves as monomer for the hydrophilic block. Lysine is an amino
acid that the human body does not produce on its own, but it plays a key role in
the makeup of body proteins.
b
8
a
 Poly(ethylene glycol): Is highly soluble in organic solvents and, therefore,
end-group modifications are relatively easy. PEG is also soluble in water and
has a low intrinsic toxicity making it ideally suited for biological applications.
d
Why Metal-Free Ring Opening Polymerization?
 Conventional ROP uses metal complexes with organic ligands
 Drawbacks: High PDI, metal ions cannot be removed completely, high price
8
d e,f
f
a
NH3 Br
c
6
*
5
Normalized intensity
Allows the synthesis of PLA with low PDI and targeted molecular weights
2
1
0
0.6
Polymer
Target Mn
[g/mol]
Mn [g/mol]
PDI
PLA-Boc
2500
2800
1.08
PLA-Boc
5000
5600
1.05
PLA(2.5K)-b-PLys
(1:2)
20300
22500
1.18
0.4
MW Data from NMR
0.2
0.0
5
10
15
20
Retention time (min)
25
2
1
0
30
 Mn determined from 1H NMR and GPC are close to the target Mn
 Prepared redox sensitive PLA-b-PLyz and PLA-b-PEO block
copolymers with low polydispersity indices
0.8
0
ppm 3
 Synthesized polylactide with low polydispersity index by metal-free
ring-opening polymerization using the novel redox-sensitive initiator
b,e
*
MW Data from GPC
PLA-b-PLys
PLA-Boc
PLA-NH2
1.0
4
 Successfully synthesized a novel redox-sensitive initiator
*
b,e
4 ppm 3
1.2
System6
d
d
c
a
7
5
Conclusions
b
c
-
6
e,f
a
+
7
g
c
Ph
The DBU/BA
b
d
c
Polymer
Target Mn [g/mol]
Measured Mn
[g/mol]
PLA-Boc
2500
2480
PLA-Boc
5000
4500
PLA(2.5K)-b-PLys (1:2)
20300
22100
References
1. Li, X.; Chen, G. Polym. Chem. 2015, 6, 1417–1430. 2. Chen, H.;
He, S. Mol. Pharm. 2015,12, 1885–1892. 3. Bensaid, F. et al.
Biomacromolecules 2013, 14, 1189–1198. 4. Ge, Z.; Liu, S. Chem.
Soc. Rev. 2013, 42, 7289–7325. 5. Tong, R. et al. J. Chem. Soc. Rev.
2014, 43, 6982–7012. 6. Coady, D. J. et al. Chem. Commun. 2011, 47,
3105–3107.