Designing Hydrogels by ATRP - In-Situ Gelling Polymers: For Biomedical Applications - page 75

Conventional RP

(Dilute) Polymeric nanogel Nanogel clusters Gel (concentrated)

Monomer conversion
Polymer concentration

ATRP

(Dilute) Branched copolymer Gel (concentrated)

Scheme 2 Different gelation processes in conventional RP and ATRP. Reprinted with permis-
sion from Elsevier [ 59 ]

intramolecular cyclization reactions could be enhanced by performing the
copolymerization under dilute conditions [ 69 ] in a selective solvent and/or in a
confined space [ 70 ] e.g., emulsion, which usually delays and prevents macro-
scopic gelation and produces microgels.
Highly branched polymers and/or gels with inhomogeneous structures are
formed during most conventional RP reactions due to the intrinsic limitations of
the RP method, which include slow initiation, fast chain propagation, and exclu-
sive radical termination reactions [ 5 , 8 , 71 - 73 ]. Due to the slow initiation, pri-
mary radicals are slowly but continuously generated in the system, resulting in
formation of a very dilute polymer solution at the beginning ([PC] t ~ ʼ M). Thus,
based on Eq. 1 , a conventional RP reaction with bulk condition ([M] 0 = 10 M),
1 mol% of crosslinker ([X] 0 = 0.1 M) and M w /M n = 2 for the primary chains
should gel at very low conversion, e.g., p c = 0.16 %,. However, the experimen-
tal gel point based on monomer conversion in conventional RP is typically 1 or
2 orders of magnitude larger than the predicted value. This is mainly due to an
excluded volume effect of polymer chains in dilute conditions and a significant
contribution of intramolecular cyclization reactions (Scheme 2 ) [ 5 , 8 , 74 ]. At the
beginning of the polymerization, the polymer chains formed in the reaction con-
tain numerous pendent vinyl groups, but seldom overlap with each other because
of the extremely low polymer concentration. Consequently, most of the pendent
vinyl groups are consumed via intramolecular cyclization reactions, producing a
less-swollen nanogel with highly crosslinked domains. As the reaction proceeds,
the number of these nanogels increases and radicals generated later in the reaction
connect these preformed overlapping nanogels into a macroscopic heterogeneous
network [ 5 , 8 , 59 ].