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