Hydrophobic methacrylamides

This chapter will discuss hydrophobic associations in random copolymers of AMPS and some hydrophobic methacrylamide and methacrylate comonomers with a focus on the intra- versus interpolymer self-association in connection witih the type of hydrophobes, their content in the polymers, and spacer bonding. A particular emphasis will be placed on intrapolymer association of hydrophobes which leads to single-molecular self-assemblies. Functionalization of the single-macromolecular assemblies with some photoactive chromophores will also be presented briefly. 

Free-radical copolymerizations of 2-acrylamido-2-methylpropanesulfonate (AMPS) and methacrylamides A -substituted with bulky hydrophobes of cyclic structures yields random copolymers (see Scheme 1) that form unimer micelles in aqueous solution independent of the concentration [22], Such hydrophobic methacrylamides include Y-cyclododecylmethacrylamide (CdMAm) [24], A -(l-adamantyl)methacrylamide (AdMAm) [24], and A -(l-naphthylmethyl)methacrylamide (1-NpMAm) [25]. 

A practical problem that is often encountered in the synthesis of copolymers of electrolyte and hydrophobic monomers is the choice of solvent that dissolves the two monomer types and resulting copolymers. Dimethylfor-mamide (DMF) is a suitable solvent to be used for the copolymerizations of AMPS with these hydrophobic methacrylamides [24,25]. 

The copolymerizations of AMPS and the hydrophobic methacrylamides are characterized as an ideal copolymerization in which the monomer reactivity ratios are practically unity, resulting in copolymer compositions equal to monomer feed compositions and the completely random distribution of the monomer units along the polymer chain [24,25]. Thus, the copolymer compositions can be determined by the molar ratios of the monomers in feed, allowing one to prepare copolymers with well-defined compositions and a completely random distribution of the monomer units in the polymer chain. This is a structural requirement for polymers to form unimer micelles [22]. The copolymers with 40-70 mol% AMPS unit and 30-60 mol% hy-... 

For spectroscopic characterization these copolymers can be labeled with fluorescent probe molecules, such as pyrene and naphthalene. This can be easily achieved by terpolymerization of AMPS, a hydrophobic methacrylamide, and a small amount of A -(l-pyrenylmethyl)methacrylamide (PyMAm) [24] or A -(2-naphthylmethyl)methacrylamide (2-NpMAm) [22], respectively. The terpolymerizations and their purification can be performed in a manner analogous with the copolymerization procedures described earlier. The fluorescent label content in the terpolymers can be determined by UV-visible absorption spectroscopy. 

Hydrophobic polymers with some hydrophilic groups can be obtained with an emulsion polymerization technique. Suitable monomers are nitrogen-containing acrylics and methacrylics allyl monomers such as dimethylamino-ethyl methacrylate, dimethylaminopropyl methacrylamide, diethylamino-ethyl methacrylate, dimethylaminoethyl acrylate, diethylaminoethyl acrylate and nitrogen-containing allyl monomers (e.g., diallylamine and N,N-diallyl-cyclohexylamine) [225,226]. 

Methoxy poly(ethyleneglycol) (mPEG) was the most frequently used semitelechelic polymer for over 2 decades. It has been successfully used for the modification of various proteins, biomedical surfaces and hydrophobic anticancer drugs (for reviews see References [3,9,10]. Recently, a number of new semitelechelic (ST) polymers, such as ST-poly(A -isopropylacry-lamide) (ST-PNIPAAM) [11-15], ST-poly(4-acryloylmorpholine) (ST-PAcM) [16], ST-poly(A-vinylpyrrolidone) (ST-PVP) [17], and ST-poly[A-(2-hydroxypropyl)methacrylamide] (ST-PHPMA) [18-21] have been prepared and shown to be effective in the modification of proteins or biomedical surfaces. 

In contrast, the phase transition of polymeric liposomes is retained if the polymer chain is more flexible or located on the surface of the vesicles instead within the hydrophobic core. Polymerized vesicles of methacrylamide (29) show a phase transition temperature which is slightly lower than the one for the corresponding monomeric vesicles (Fig. 26). This can be explained by a disordering influence of the polymer chain on the head group packing 15). 

Several other studies have also been made in an attempt to account theoretically for the phase transition in terms different from those of the Flory-Huggins theory. Otake et al. [55] thus proposed a theoretical model that takes hydrophobic interaction into account in explaining the thermally induced discontinuous volume collapse of hydrogels. In addition, Prausnitz et al. [56] proposed a lattice model, an improvement of which was made to explain the swelling curves of gels consisting of /V,/V -methylenebis(acrylamide) (MBA)-crosslinked copolymers of AAm with [(methacrylamide)propyl]trimethyl-ammonium chloride (MAPTAC) [57],... 

Morishima, Y., et al. (1995), Characterization of unimolecular micelles of random copolymers of sodium 2-(acrylamido)-2-methylpropanesulfonate and methacrylamides bearing bulky hydrophobic substituents, Macromolecules, 28, 2874-2881. 

By far the most used systems are matrices based on methacrylate, methacrylamide and styrene and the most common crosslinkers are ethyleneglycol dimethacrylate and divinylbenzene. Methacrylamide based species are the most hydrophilic and styrene ones the most hydrophobic, with the methacrylate systems falling in between. This therefore provides quite a wide choice and imprinted polymers with high mechanical stability and chemical inertness, suitable for example in HPLC applications, are readily achievable. To some extent the chemical nature of the matrix is of less importance than its morphology, and in this respect the type and level of crosslinker used, together with the nature and proportion of the porogen are more crucial (see later). All of these experimental parameters are of course inter-dependent. 

Nonionic, anionic, and cationic VP copolymers are all available commercially to enhance the hydrophilic, hydrophobic, and ionic properties of PVP for specihc applications. Important comonomers include vinyl acetate (VA), acrylic acid (AA), vinyl alcohol, dimethy-laminoethylmethacrylate (DMAEMA), styrene, maleic anhydride, acrylamide, methyl methacrylate, lauryl methacrylate (LM), a-olelins, methacrylamido-propyltrimethyl ammonium chloride (MAPTAC), vinyl caprolactam (VCL), and dimethylaminopropyl-methacrylamide (DMAPMA). 

The absolute control over the genes that encode for the proteins readily allows the introduction of different functionalities that can be attached to synthetic polymers. Kopecek et al. [88,89] used this methodology to produce coiled-coil peptide sequences, e.g. (VSSLESK)n containing a histidine tag on the end. The hydrophobic interaction between the side groups of the valines and leucines in the sequence causes the protein to as-siune a helical or coil type structure. These hydrophobic interactions then cause several coils to further aggregate to form so called coiled coils. This coiled coil aggregation can be disrupted by temperature, pH and solvent. A copolymer of poly[N-(2-hydroxy-propyl) methacrylamide- co-(N, N"-dicarboxymethylaminopropyl)methacrylamide], (p[HPMA-co-DAMA]) with... 

Other related co-monomers were also studied. These included 7V-(hydroxy-methyl)acrylamide (HMA), methacrylamide, and iV,A/-dimethylacrylamide. The copolymerization of styrene with HMA led to less water-soluble polymer in the serum than in the case of copolymers of acrylamide and styrene. This may be attributable to differences in the hydrophilic-hydrophobic properties of acrylamide and HMA. Some monodisperse latices were prepared from styrene-HMA-water systems by procedures similar to Procedure 12-2. At a ratio of HMA to styrene of 0.2 to 1.0 the reported particle diameter was 0.3 /im with good size uniformity. It was projected that even better uniformity would be obtained when the ratio of HMA to styrene is 0.09 to 1.0. Either potassium persulfate or Af,A -azobisisopropylamidine hydrochloride has been used as initiators with similar results. Latices were generally purified by repetitive centrifiigation-decantation-redispersion cycles. 

Methacrylamide monomers were chosen due to their hydrolytic stability, structural similarity to amino acids found in naturally occurring AMP, incorporation of hydrophobic and hydrophilic moieties, and pKa values. APMA was chosen due to its similarity to lysine. While ionic bonding facilitates initial polymer-cell interactions, it is the hydrophobic substituents that act to disrupt the lipid membrane of bacteria. DMAPMA and DEAPMA were chosen due to their hydrophobic dimethyl and diethyl amino groups, respectively. Copolymers were formed by copolymerising APMA with DMAPMA and APMA with DEAPMA at varying ratios. 

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