(57f) Tacticity Control Over Hyperbranched Poly(N-isopropylacrylamide) and Its Effects On Thermal Transition Temperature

Tacticity control over hyperbranched poly(N-isopropylacrylamide) and its effects on thermal transition
temperature

Kai Chang, Nathan C. Rubright, Lakeshia J. Taite.

Chemical
and Biomolecular Engineering, Georgia Institute of
Technology.

Background:
Hyperbranched polymers are a
class of polymers with very interesting properties, especially in the field of
drug delivery.  They have many similar
properties with dendrimers including globular
structure with many end groups as well as internal cavities that can be used to
encapsulate drugs. Hyperbranched systems are usually
not as well defined as dendritic systems; however,
they are far less labor intensive to synthesize.  Hyperbranched poly(N-isopropylacrylamide) (pNIPAAm)
synthesis has been reported previously by Vogt et. al and Carter et. al.;
however, the effect of branching on the ability to control tacticity
is as yet unknown. 

pNIPAAm is a
well-studied thermally responsive polymer that is often associated with
biological applications due to its sharp aqueous lower critical solution
temperature (LCST) of ~32°C.
In a hyperbranched system, the additional
complexity of the architecture naturally decreases the LCST, a phenomenon that
is likely due to the steric hindrance of the
formation of water structures resulting from the hydrogen bonding of the water
molecules to the acrylamide sidechain.  Ordering the polymer in its tacticity, therefore, may have a synergistic effect in
allowing additional order in the system and reducing the amount of LCST
reduction.

In previous studies, Reversible
Addition-Fragmentation Chain Transfer (RAFT) polymerization, a controlled
?living? radical polymerization scheme was used with hyperbranch
inducing chain transfer agents (CTAs) in order to create these hyperbranched polymers.
RAFT polymerization lends itself easily to copolymerization; therefore,
the inclusion of copolymers was also studied; specifically copolymerization
with acrylic acid (AAc).  pNIPAAm-AAc
is often used in biological systems due to the increased LCST of such a system
and a hyperbranched pNIPAAm-AAc
with a sufficiently high LCST (~45°C) has potential
drug delivery applications.

Methods: Synthesis of 4-Vinylbenzyl-imidazole Dithioate (1)
was done according to the procedure set forth by Carter et al.

Polymerization was conducted as follows.  A 90:10:2:1 ratio of NIPAAm:AAc:1: Azobisisobutyronitrile was placed in a
sealed 100 mL roundbottom
flask equipped with a magnetic stir bar.
In the case of syndiotactic polymerization,
3-methyl-3-pentanol was included in the reaction flask.  The mixture was purged with Nitrogen and
Nitrogen purged Dioxane was added.  The solution was reacted at 65^oC
for 48 hours and was quenched by exposure to air.  The pNIPAAm-co-AAc was precipitated into ether, filtered and dried under
vacuum.  The resulting solid was resuspended in nanopure water (18
MΩ) and dialyzed using 2500 MWCO cassettes (Pierce) overnight.  The solution was then lyophilized to obtain
the product.

Results: Characterization
of polymer was conducted using NMR spectrometry and gel permeation
chromatography.  LCST was determined
using UV-Visible Spectrometry.

As expected
for RAFT polymerization, the polydispersity index for
the polymers were low, on the order of 1.1, and indicative of living
polymerization.  LCST data is shown in
Fig. 1.

Fig.1:  LCST curves of pNIPAAm-co-AAc at 10% AAc.  Syndiotactic and atactic data are shown as well as a hyperbranched
pNIPAAm control.

While the hyperbranched pNIPAAm
control point and the atactic pNIPAAm-co-AAc showed
expected results of a below 32°C and far above 32°C LCST
respectively, the syndiotactic data shows a contrary
effect.  Previous studies into the
effects of tacticity on LCST linear pNIPAAm demonstrated that increased syndiotacticity
increases the LCST.  The opposite trend
seen in this case indicates that increased order in tacticity
indeed has an effect on the LCST of hyperbranched pNIPAAm; however, the effect is not to allow for more
hydrogen bonding of water, but rather less, possibly as a result of increased
packing density of the ordered polymer.

Conclusions:  Highly
branched systems behave differently from their linear counterparts in many
ways.  In the case of hyperbranched
pNIPAAm, increasing syndiotacticity
has the opposite effect from its linear counterpart.  Further investigation is necessary to
definitively provide an explanation.

References: 

Vogt AP. Macromolecules. 2008;41:7368-7373

Carter S. Macromolecular Bioscience. 2005;5:373-378

Hirano
T. J. Polym Sci.
Part A: Polym. Chem. 2006;44:4450-4460