Designing Hydrogels by ATRP - In-Situ Gelling Polymers: For Biomedical Applications - page 77

significantly decrease the kinetic chain length of a propagating radical during
one activation/deactivation cycle.
Although intra-molecular cyclization has been well documented as the
probable reason for delayed experimental gelation, it remains a challenge to
quantify the degree of cyclization, primary due to the complicated structure
of the branched polymers and the multiple pathways in the kinetics. However,
very recently, two reports partially addressed this issue by designing a spe-
cific crosslinker [ 93 ] and/or polymerization system [ 94 ]. A disulfide-based
divinyl crosslinker was used for RAFT copolymerization with methyl meth-
acrylate (MMA). The interesting observation was that the disulfide crosslinker
that participated in primary cyclization reactions showed different NMR shifts
from the crosslinkers that reacted in inter-molecular reactions. The distin-
guished NMR shifts resolved in the spectrum was used to quantify the amount
of primary intra-molecular reactions, although secondary cyclization are still
elusive.
4 ATRP in Water and Formation of Water Soluble
Polymers
Water is a safe, inexpensive and environmentally benign solvent that has been
broadly used in industrial scale processes for conventional solution RP of hydro-
philic monomers and for biphasic heterogeneous-mediated polymerizations of
hydrophobic monomers (oil-in-water) and hydrophilic monomers (water-in-oil).
Therefore it was highly desirable to develop conditions that allowed conducting
ATRP in aqueous media [ 95 - 100 ].
4.1 Homogeneous Aqueous ATRP
Several groups have reported the ATRP of hydrophilic monomers (Scheme 3 )
in aqueous systems [ 24 , 95 , 97 , 100 - 109 ]. However, in many cases, the level
of control over the ATRP reactions was limited, leading to production of
materials with broad MWD, significant tailing to low molecular weight, low
initiation efficiency and loss of chain-end initiating groups [ 102 , 103 , 107 ].
There are several challenges associated with conducting an ATRP in water.
First, the larger ATRP equilibrium constant in aqueous media generates a
high concentration of radicals and consequently increases the rate of termina-
tion reactions. Second, the partial dissociation of halide ion from deactivator
complex leads to loss of deactivator and inefficient deactivation of propa-
gating radicals. Third, certain Cu(I)/L complexes disproportionate in water.
Fourth, the potential hydrolysis of carbon-halogen bond diminishes chain-end
functionality.