Quantitative structural analysis of graft copolymers by light scattering measurements in mixed solvents

Theoretical calculations have shown that it should be possible to determine the molar mass of the grafted chains of graft copolymers by light scattering measurements in suitable mixed solvents, and moreover, that this should be possible without the backbone having to be degraded, without the ungrafted backbone having to be isolated, and without the refractive index increment having to be determined after dialysis. Among the conditions that have to be met are the requirements that the mixed solvent must be isorefractive with respect to the backbone and that the preferential solvation of the grafted chains must be independent of their molar mass. The method is applied to fractions of graft copolymers with styrene or styreneacrylonitrile (SAN) being grafted onto ethylene/vinyl acetate copolymers, from which ungrafted polystyrene or SAN copolymer has been removed by solvent demixing. With this method the molar mass and the number of grafted chains, the coupling of backbone molecules via grafted chains, the shrinking and segregation of the individual grafted chains and the incompatibility of the grafted chains with the backbone polymer can be determined.     

Synthesis and characterization of poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) biodegradable micelles

A series of amphipathic graft copolymers composed of poly(L-lysine) (PLL) as the cationic polymer backbone and biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) as the grafting chains were synthesized and characterized. The terminal group of PLGA was activated and chemically conjugated to the primary epsilon-amine groups of PLL to produce PLL-g-PLGA copolymers. PLL-g-PLGA formed a self-assembling micelle structure in aqueous solution. The micelle size ranged from 69.4 to 149.6 nm in diameter, depending on the grafting percentage of PLGA. Upon increasing the number of PLGA chains grafted onto the PLL backbone, the size of the micelles gradually decreased, at the same time lowering their critical micelle concentration. The micelles were individually separated and had a spherical geometry, as observed by atomic force microscopy (AFM). These PLL-g-PLGA copolymers can be applied as cell adhesive surface coating materials for biodegradable tissue engineering scaffolds and can be used as non-viral DNA carriers for gene therapy.     

Über den aufbau von block- und pfropfcopolymeren

After briefly introducing the basic possibilities for the formation of graft and blockcopolymers, the important methods of the radical-initiated block and graft copolymerization are discussed on the basis of the characteristic examples, which are available in the literature. Thereafter the discussion is carried out on the few a t that time known syntheses in the field of the anionic block copolymerization, which then finally loads to the own work with polyfunctional macromolecular anionic initiators. Thus the addition of dialkylaluminium hydrides to macromolecules with C?C double bonds in side chains or at chain ends, and treating the products with transitionmetal halides (e.g. TiCl₄), macromolecular ZIEGLER -NATTA -Catalysts are formed. These initiate graft and block copolymerization of ethylene and α-olefines, whereby the poly-α-olefine molecules, which are already grown, can have a stereoregular structure. Macromolecules containing RC?NM linkages are formed on addition of organometallic compounds of lithium (LiR) or magnesium (MgRhal) to the N≡C triple bond in styrene-acrylonitrile copolymers, and they initiate anionic graft copolymerization of acrylonitrile (AN), methylmethacrylate (MMA), 2-vinylpyridine (2-VP), and 4-vinylpyridine (4-VP). Reactions of macromolecules containing O?C, N≡C, or C?C linkages in side chains with sodium or naphthalene sodium give macromolecular radical anions (e.g., high-polymeric ketyls in the case of poly-p-vinylbenzophenone) or dianions, formed by electron-transfer from the metal to the multiple bond. Both the radical anions and the dianions initiate anionic graft copolymerization of AN, MMA, 2-VP, 4-VP, butadiene, and styrene, and in this way pure graft copolymers are formed, free from “backbone molecules” and from homopolymers of the grafted monomer. Pure graft copolymers are formed also on use of macromolecular organometallic initiators, such as those formed by metallation of poly-4-chlorostyrene or 4-chlorostyrene styrene copolymers with stoichiometric amounts of naphthalene sodium. Since the anionic end groups of the growing side chains remain “living” during these processes, second and third monomers can be added to afford graft copolymers whose side chains are block copolymers. If the growing chains are terminated, e.g., by chlorosilanes containing functional groups, then reactive end groups are introduced into the side chains. Finally, graft and, in particular, block copolymers can be obtained when “finished” macromolecules containing very reactive silicon side or end groups (e.g., H? Si-, Cl? Si-, HO? Si-, CH₂?CH? CH₂? Si-groups) are joined together by chemical reactions. These methods open a route to block copolymers having stereoregular blocks. Macromolecules containing suitable functional groups attached to silicon atoms also provide a bridge to anionic processes. For instance, macromolecules containing p-vinyl-phenylsilicon end groups surprisingly react readily with sodium to radical anions which effect block copolymerization of vinyl monomers.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels are synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTs) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacryl amide-co-N,N-dimethylacrylamide) (poly(IPAAm-co-DMAAm)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37 degrees C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31 degrees C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36 degrees C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels arc synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTS) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (poly(IPAAm-(-o-DMAAiii)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37°C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31°C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36°C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.     

The effect of polymer composition on the gelation behavior of PLGA-g-PEG biodegradable thermoreversible gels

Graft copolymers consisting of a poly(D,L-lactic acid-co-glycolic acid) backbone grafted with polyethylene glycol side chains were synthesized and formed thermoreversible gels in aqueous solutions that exhibited solution behavior at low temperature and sol-to-gel transitions at higher temperature. The composition of the polymer and relative amounts of polylactic acid, glycolic acid, and ethylene glycol were varied by controlling the precursor concentrations and reaction temperature. The gelation temperature could be systematically tailored from 15 to 34 degrees C by increasing the concentration of polyethylene glycol in the graft copolymer. The gelation temperature also depended on the polymer molecular weight and concentration. This work has importance for the development of water soluble gels with tailored compositions and gelation temperatures for use in tissue engineering and as injectable depots for drug delivery.     

Thermo‐Responsive and Emulsifying Properties of Poly(N‐vinylcaprolactam) Based Graft Copolymers

Thermo‐responsive graft copolymers have been synthesized based on a poly(N‐vinylcaprolactam) (PVCL) backbone and either hydrophilic poly(ethylene oxide) (PEO) or hydrophobic poly(tetrahydrofuran) (PTHF) side chains. The phase separation behavior of the graft polymers in water was studied by transmittance measurements and compared to that of the corresponding swollen segmented polymer networks and aqueous solutions of both polymers. The influence of the concentration and length of the grafts on the cloud point temperature (T_CP) has been demonstrated. PVCL‐g‐PTHF copolymers have been synthesized by using the macromonomer technique, i.e. the radical copolymerization of VCL with a PTHF macromonomer. A special feature of these amphiphilic graft copolymers is their ability to stabilize aqueous emulsions below the T_CP and to suddenly break them above the T_CP. PVCL‐g‐PEO copolymers were prepared by a grafting onto method. First, succinimide groups were introduced in the backbone, to which amino terminated PEO chains were grafted in the second step. This leads to di‐hydrophilic copolymers that become amphiphilic after heating their aqueous solutions above the T_CP.

     

Poly(β-hydroxynonanoate) and polystyrene or poly(methyl methacrylate) graft copolymers: microstructure characteristics and mechanical and thermal behavior

Active polymers containing peroxide groups were synthesized via polymerization of styrene or methyl methacrylate with oligo(adipoyl 2,5-dimethylhexane-2,5-diyl peroxide) (OAHP) or oligo(2,5-dimethylhexane-2,5-diyl 4,4′-azobis(4-cyanoperoxyvalerate)) (LUAB). Poly(β-hydroxynonanoate) (PHN) and the active polymer were mixed, and free radical grafting reactions were carried out to optimize mechanical and viscoelastic properties of PHN. The “active” vinyl polymers polystyrene (PS) and poly(methyl methacrylate) (PMMA) were grafted onto PHN chains or cleaved them, depending on the PHN/active polymer mass ratio and the peroxygen content of the active polymer. The increase in tensile strength (f) and strain (ε) was observed to be maximum in graft copolymers having vinyl polymer contents less than 20 wt.-%. SEM micrographs showed surface topography. Phaseseparated graft copolymers reveal dispersed phase particles, micrometer and submicrometer sized particles, and holes in the micrographs. The SEM observations are also wholly consistent with the glass transition temperature behavior obtained from differential scanning calorimetric (DSC) measurements.     

Chemical structure of vinyl alcohol/acrylamide graft copolymers prepared by the cerium(IV) ion method

Graft copolymerization of acrylamide onto poly(vinyl alcohol) (PVA) samples with different 1,2-diol content was carried out by the Ce(IV) ion method. The poly(acrylamide) (PAAd) side chains were separated by oxidative degradation of the PVA backbone with nitric acid at which treatment the PAAd side chains reacted to poly(acrylic acid) (PAA) chains without a change of the degree of polymerization. The chemical structure of the graft copolymers was clarified on the basis of the number average molecular weights of the pure graft copolymer, of separated branches, and of the mother PVA molecules and the chemical composition of the graft copolymers. It was found that the number of branches per molecule was greater than one and increased with increasing content of 1,2-diol structures in the PVA mother molecule. A number of grafted branches as high as 12 caused the graft copolymer to be insoluble in water.     

Synthese und Charakterisierung von Copolymeren aus Azo-Initiatoren und Styrol

Copolymers with azoinitiator functions were prepared from styrene and different arylazoalkylmalonodinitriles by copolymerization in emulsion, using redox-initiators. This type of copolymer can be used for syntheses of graft copolymers. The concentration of azo-groups per polymer chain, the polymerization rate, and the molecular weight of the isolated copolymers were determined as a function of the composition of the starting monomer mixture and the structure of the azo-compounds. It was tried to separate the crude product of the grafting reaction into the ungrafted backbone, the graft-copolymer, and the homopolymer.     

Novel graft PLLA-based copolymers: potential of their application to particle technology

This study describes the synthesis of novel biodegradable graft copolymers based on a backbone of poly (L-lactic acid) (PLLA) on which short blocks of polyacrylamide (PAcr) were grafted. Preliminary results of their potential in the field of controlled-release technologies also have been reported. The copolymers have been synthesized through the radical polymerization of acrylamide initiated by a peroxide in the presence of PLLA. Two different methodologies of synthesis, namely, in solution and in emulsion, have been tested. The structure of the copolymers was studied by (1)H-NMR and infrared spectroscopy and by differential scanning calorimetry (DSC) and cytotoxicity tests were conducted to assess their biocompatibility. The copolymers were used to prepare particles by the emulsion-solvent evaporation technique. The shapes and dimensions of the particles were dependent on the polymer type and concentration used. The surfaces of the particles were modified by the presence of polyacrylamide residues, as demonstrated by zeta-potential measurements. The release behavior of the particles was assessed by encapsulating rhodamine B as the model compound. The release was faster for the particles prepared by the grafted polymer as a consequence of its increased hydrophilicity. Based on these novel biomaterials, preliminary results suggest a potential of the particles for peroral or parenteral drug delivery.     

Collagen-Poly(methyl methacrylate) graft copolymers: Effect of aqueous organic solvent system and salts on copolymer composition

Collagen-poly(methyl methacrylate) (PMMA) graft copolymers were prepared in a number of aqueous/organic solvent systems and in the presence of neutral salts using ceric ammonium nitrate as initiator. The composition of the collagen-methyl methacrylate graft copolymers was studied by hydrolyzing the collagen backbone and measuring the molecular weights of the grafted PMMA branches. In water/methanol grafting media the molecular weights of the PMMA branches showed a maximum at a methanol concentration of 25% and then decreased with further increase in methanol concentration. Even though the percent grafting registered a sharp fall with increasing concentration of methanol, the number of grafting sites remained more or less constant and was almost the same as that obtained in aqueous medium. Other aqueous/organic solvent systems gave more grafted chains than those prepared in water alone, and these were of lower molecular weight. Anions such as sulphate and chloride were found to have more influence than nitrate in decreasing the number of grafting sites.     

Synthesis and characterization of amphiphilic and microphase-separated graft copolymers, 1. Synthesis and bulk characterization of polystyrene-graft-ω-stearyl-poly(ethylene oxide)

Using the rigid and hydrophobic polystyrene (PS) chain as backbone, onto which flexible and hydrophilic stearyl-poly(ethylene oxide) (SPEO) chains are grafted, a new kind of amphiphilic, microphase-separated graft copolymer was synthesized using the macromonomer technique. Stearyl-poly(ethylene oxide) macromonomers with acryloyl end-group (SPEO-A) were prepared through an end-group exchange reaction of α-stearyl-ω-hydroxypoly(ethylene oxide) (SPEO-OH) and acryloyl chloride in the presence of triethylamine. The radical copolymerization of styrene with SPEO-A was carried out under various experimental conditions. Following a careful examination of their purity, the structure of the prepared copolymers was characterized by means of IR, ¹H NMR and GPC analyses. A new feasible method using first derivative UV spectrometry was developed for quantitative determination of the bulk composition of the graft copolymers. Copolymers with a wide range of bulk composition and satisfactory grafting degree were obtained.     

Grafting‐from Afforded Cyclic Graft Copolymers from Cyclic Anionic Macroinitiator via Lithiation of Tolyl Groups

Cyclic graft copolymers consisting of poly(p‐methylstyrene) backbone and polystyrene branches with relatively low molecular weight distribution are synthesized with grafting‐from approach by living anionic polymerization of styrene from lithiated cyclic poly(p‐methylstyrene)s as multifunctional anionic macroinitiators for vinyl polymerizations. Precursors of the macroinitiators are prepared by ring‐closing metathesis reaction of α,ω‐divinyl‐terminated telechelic polymers. Subsequently, selective lithiation of tolyl groups in the cyclic polymers is conducted by s‐BuLi in the presence of tetramethylethylenediamine in cyclohexane in order to prepare the macroinitiators. Addition of styrene monomer into the cyclic macroinitiators provides shift in SEC to higher molecular weight due to graft polymerization from the macroinitiators to form cyclic graft copolymers. The unique polymer architecture of the obtained cyclic graft copolymers is confirmed by unimolecular observation by using atomic force microscopy.     

Statistical treatment of the grafting reaction

Statistical calculations were performed for the fundamental quantities in the grafting reaction starting from a substrate polymer with a uniform and a most probable molar mass distribution: e.g., the number of branches in one graft copolymer, the number average degree of polymerization (P?_n) of the backbone of the graft copolymer, the fraction of the mother polymer grafted. It is shown that P?_n of the graft copolymer prepared from a mother polymer with a most probable molar mass distribution decreases at first with increasing number of grafted branches, reaches a minimum and then increases, if the P?_n of the grafted branch is lower than that of the mother polymer. This peculiar behavior is attributed to the fact that the mother polymer molecule with a higher molar mass has a higher probability to participate in the grafting. In addition, the calculation denotes that the synthesized, unfractionated graft copolymer is a polymolecular mixture of the copolymer having branches whose number distribution is remarkably broad.     

Scaling Laws for Polymer Chains Grafted onto Nanoparticles

An experimental approach is presented for identifying the scaling laws for polymer chains grafted onto gold nanoparticles. Poly(ethylene oxide) of various molecular weights are grafted onto gold nanoparticles via thiol end‐functional groups. The polymer‐grafted nanoparticles are self‐assembled into monolayers from solvents of different quality. Over a significant range of graft densities, nanoparticle monolayers deposited from good (athermal) solvent exhibit particle spacing that scales according to theoretical predictions for chains in dilute solution. This unexpected result for ordered nanoparticle monolayers is discussed in the context of the deposition process. In monolayers deposited from theta solvent, molecular weight scaling of particle spacing breaks down, possibly due to chain length dependence of solvent quality. In poor solvent, the structure of nanoparticle assemblies is not sufficiently ordered to obtain reliable measurements, possibly due to loss of nanoparticle dispersion. This approach opens up the possibility for accurate measurement of the effect of solvent on grafted chain scaling in nanoparticle assemblies.     

Bestimmung der Copolymerisationsparameter und Depolymerisationskonstanten von Methylmethacrylat-Acrylnitril-Copolymeren durch Protonenspinresonanz

It is shown how copolymerization parameters and constants of depolymerization can be obtained from NMR- or IR-spectra of copolymers if depolymerization reactions occur during the copolymerization. Relations are derived between these quantities and the concentrations of diads or longer sequences in the molecular chains which can be determined by spectroscopical measurements. The equations are valid for the general case that all growthreactions are reversible during the copolymerization. The applicability of the method was tested by NMR-measurements of methylmethacrylate-acrylonitrile-copolymers which were obtained via radical polymerization at temperatures between 50 and 180°C.     

Thermoassociative graft copolymers based on poly(N‐isopropylacrylamide): Relation between the chemical structure and the rheological properties

new family of thermoassociative graft copolymers has been recently synthesised using a two‐step procedure. Schematically, their structure combines a weak polyelectrolyte backbone (poly(sodium acrylate), PAA) and thermosensitive side chains containing mainly N‐isopropylacrylamide (NIPA). Taking advantage of this well controlled synthesis we have selectively varied the primary structure of the copolymers concerning the grafting extent, the length of the backbone, and the hydrophilic‐lipophilic balance of the side chains by incorporating either hydrophilic or hydrophobic comonomers. The thermoassociative properties of the resulting copolymers were studied in semi‐dilute solutions by rheology. It was clearly evidenced that the association temperature of the copolymers is selectively controlled in pure water (in the 0–100°C range) by the chemical composition of the side chains. Moreover, the magnitude of the thermothickening effect is directly related to the modification extent while the absolute value of the viscosity is modulated by the length of the PAA backbone. Very sharp transitions were also evidenced by developing specific attractive interactions between the PNIPA grafts and the PAA backbone dependent on the pH of the solutions. In all the cases we demonstrate that the associative behaviour is well correlated to the thermodynamic properties of the precursors. A good knowledge of their phase diagrams in aqueous solution is therefore a very strong guideline for designing copolymers with responsive properties.     

Amphiphilic PEG‐co‐PGL‐g‐PCL Copolymer Brushes: Synthesis,Micellization and Controlled Drug Delivery

A series of amphiphilic graft copolymers of poly(ethylene glycol)‐co‐glycidol‐graft‐(ε‐caprolactone) (PEG‐co‐PGL‐g‐PCL) with PEG as the hydrophilic backbone chain and hydrophobic PCL as side chains have been synthesized by living anionic polymerization and ring‐opening polymerization. By changing the composition of the PEG‐co‐PGL backbone chains, and the molar ratio of CL monomer to PEG‐co‐PGL in the feed, copolymers with well‐defined architecture and controllable numbers and length of graft chains can be obtained. The micellization and drug release of the PEG‐co‐PGL‐g‐PCL graft copolymers have been studied in terms of dependence on graft numbers and length, and the results indicate that the micelles with shorter PCL side chains have more compact cores and a relatively small size which are favorable for drug loading and controlled release.

     

Synthesis and Characterisation of Poly[oligo(ε‐caprolactone)L‐malate‐graft‐poly(L‐lactide)]

Graft copolyesters with a PCL backbone and PLLA side chains were successfully prepared in three steps avoiding transesterification. First ε‐caprolactone was polymerised with 1,6‐hexane diol as initiator to obtain hydroxytelechelic oligo(ε‐caprolactone)s. These diols were then subjected—in the second step—to polycondensation with L ‐malic acid yielding in linear poly[oligo(ε‐caprolactone)L ‐malate] having secondary hydroxyl functions in the side chain. For both reactions scandium triflate Sc(OTf)₃ was used as a catalyst. In the third step various amounts of L ‐lactide were grafted from the polymer backbone using Zn(oct)₂ as catalyst. The successful reaction was confirmed by NMR and SEC (size exclusion chromatography) analysis. Further the thermal properties of the graft copolymers with different graft lengths were determined via differential scanning calorimetry.