Copolymerization NIPAM

After investigating the effect of comonomer composition on the chain association as well as the effect of comonomer distribution on the chain folding, Siu et al. [141] extended their study to the effect of comonomer distribution on the chain association. They copolymerized NIPAM and vinyl pyrroli-done (VP) at temperatures, respectively, higher and lower than the LCST, which resulted in segmented and random VP distributions on the PNIPAM chain backbone. The synthesis characterization of these PNIPAM-co-VP amphiphilic copolymers with a similar chain length and comonomer composition, but different comonomer distributions, were described in previous sections. 

The copolymer can be further fractionated by precipitation from acetone solution to n-hexanc at room temperature. In each case, only the first fraction should be used to obtain narrowly distributed high molar mass copolymer chains for LLS measurement, ll NMR can be used to characterize the copolymer composition. The ratio of the peak areas of the methine proton of the isopropyl group in NIPAM and the two protons neighboring the carbonyl group in VP can be used to determine the VP content. The composition of each NIPAM-co-VP copolymer was found to be close to the feeding monomer ratio prior to the copolymerization. The nomenclature used hereafter for these copolymers is NIPAM-co-VP/x/y, where x andy are the copolymerization temperature (°C) and the VP content (mol%), respectively. The solution with a concentration of as low as 3.0 x 10-6 g/mL can be clarified with a 0.45 cm Millipore Millex-LCR filter to remove dust before the LLS measurement. The resistivity of deionized water used should be close to 18 M 2 cm. The chemical structure of poly(NIPAM-co-VP) is as follows (Scheme 2). 

MACA as a hydrophobic comonomer can be used to modify PNIPAM. Copolymers, PNIPAM-co-MACA with different amounts of MACA can be synthesized by free-radical copolymerization of NIPAM and MACA in a mixture of methanol and chloroform with AIBN as the initiator. The resulting copolymers after purification can be dried in vacuum at 40 °C for 24 h. Hereafter, these copolymers are denoted as PNIPAM-co-x-MACA, where x denotes the molar percent of MACA. As expected, their solubility in water decreases as the MACA content or the solution temperature increases. It is also expected that the copolymer chains with a higher MACA content would have a lower LCST in comparison with PNIPAM homopolymer chains. In order to prepare a true solution, one has to dissolve these copolymers in water at low temperatures. The chemical structure of PNIPAM-co-MACA is as follows (Scheme 7). 

Linear NIPAM-co-VP copolymers As discussed in the Experimental Section, hydrophilic comonomer, vinyl pyrrolidone (VP), can be purposely copolymerized into PNIPAM at two different temperatures, 30 °C and 60 °C, respectively, below and above the LCST of PNIPAM homopolymer. At each temperature, the copolymers with two different VP/NIPAM ratios (5 and 10 mol%) were prepared. A proper fractionation of resultant copolymers led to narrowly-distributed long NIPAM-co-VP copolymer chains with a similar length and VP/NIPAM ratio, but different comonomer distributions. 

Temperature- and pH-sensitive core-shell microgels consisting of a PNIPAAm core crosslinked with BIS and a polyvinylamine (PVAm) shell were synthesized by graft copolymerization in the absence of surfactant and stabilizer [106] The core-shell morphology of the microgels was confirmed by TEM and zeta-potential measurements. Other examples of core-shell microgel systems are PNIPAAm-g-P(NIPAM-co-styrene) colloids [107] or PS(core)-g-PNIPAAm (shell) particles [108],... 

These polymers were selected owing to their ability to promptly transit from hydrated coil to dehydrated globule conformation when temperature increases above their lower critical solution temperature (LCST). Homopolymers of NIPAM have a LCST in aqueous media around 32°C, which is not compatible with physiological conditions. Thus, to be exploitable for in vivo drug delivery, this temperature must be increased by copolymerization with other hydrophilic monomers. When these monomers have ioniz-able moieties such as methacrylic acid (MAA, pKa=5.4), the increase in LCST is dependent on ionization, and therefore the polymers acquire pH-dependent physiological solubility (2). 

The macromonomers were then copolymerized with styrene in ethanol. The resulting microspheres, with a PS core and poly(NIPAM) brushes, were thermosensitive [264-267]. 

The poly(vinylpyridine) chloride was then copolymerized with NIPAM in the presence of N,N -mclhylcncbisacrylamide to obtain graft copolymer gels. These gels were found to be temperature- and pH-dependent. But above 33 °C, the authors showed aggregation of the poly(NIPAM) phase and a pH > 5.5 leads to aggregation of the poly(vinylpyridine). However, the pH effect remains minor compared with that of temperature. 

With the purpose of conferring thermosensitivity to chitosan-based hydrogels. Park et al. proposed the grafting of carboxylic acid-terminated poly(ethylene oxide-h-propylene oxide) block copolymer (Pluronic) onto the primary amine of chitosan, mediated by EDC coupling agent [102]. With the same purpose, Wang et al. grafted poly(N-isopropyl acrylamide) (NiPAM) chains onto chitosan by the copolymerization of acrylic acid-derivatized chitosan and N-isopropylacrylamide (NIPAAm) in aqueous solution [103]. 

By radical copolymerization of poly(A/-isopropylacrylamide-co-N,iV-dime-thylaminoethyl methacrylate) [poly(NIPAM-co-DMAEMA)] macromonomer with the monomers NIPAM and DMAEMA, comb-type cationic hydrogels with poly(NIPAM-co-DMAEMA) backbone networks and grafted poly(NIPAM-co-DMAEMA) side chains can be successfully prepared. Within the comb-type hydrogels the grafted chains have freely mobile ends, which are distinct from typical network structures of normal-type crosslinked hydrogels, as shown in Figure 5.7. The obtained hydrogels show both temperature and pH sensitivity. They all deswell with an increase of temperature and/or pH, and exhibit a lower critical solution temperature (LCST) at about 34 °C and a p a value at about pH 7.3. 

Different ionic monomers were copolymerized with NIPAM or VCL to obtain pH- and T-sensitive miaogels. Snowden et reported the preparation of aqueous microgels by... 

The copolymerization of different functional monomas during precipitation polymerization can be used for the design of amphoteric aqueous microgels." " Amphoteric miaogels wae prepared by copolymerization of NIPAM with AAc and vinylimidazole (VIm)." Alternatively, Tan and co-workas prepared amphoteric colloids by copolymerization of AAc, 2-(diethylamino)ethyl methacrylate, and poly( ethylene... 

Much of the work reported in the academic literature is based upon microgels prepared from poly(NIPAM), but there are, however, a number of microgels that have been prepared from other monomers. These include methyl methacrylate with other copolymers such as ethylene glycol dimethacrylate (17,18), methyl methacrylate with p-divinylbenzene (19), and methyl methacrylate with methacrylic acid (20). Other microgel particles have been prepared from poly(allylamine hydrochloride) (21), vinylpyrrolidinone and acrylic acid (22), acrylamide and acrylamide with methacrylamidopropyltrimethylammonium chloride (23), and acrylamide copolymerized with 2-acrylamido-2-methylpropanesulfonic acid (24). 

Influence of Comonomers on Microgel Properties. The overall physicochemical properties of a microgel depend not only on the cross-linker concentration, but also on the concentration of monomer/comonomers used in the synthesis. The addition of a small amount of comonomer (typically 1-5 wt% monomer) can have a dramatic effect on the overall properties of the resultant microgel particles. For example, a pH- and temperature-sensitive microgel can be prepared by copolymerizing poly(NIPAM) with acrylic acid. These spherical particles undergo... 

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