Microstructure Of Copolymer Chains Research Articles

The impacts of feed fraction on copolymer microstructure in ATRcP: a kinetic Monte Carlo simulation

A research has been carried out to simulate an atom transfer radical copolymerization (ATRcP) system of styrene and n-butyl acrylate using the stochastic Monte Carlo method and to investigate the variation of reactant concentration, average molecular weight and molecular weight distribution, average sequence length and sequence length distribution, different dyad fractions and copolymer composition as a function of styrene feed fraction. To this end, a finely tuned program was written in C++ language to implement the simulation algorithm. It was observed that although styrene feed fraction alteration affected all the factors under review, weight-average molecular weight showed the least variation in its trend for styrene fractions higher than 5%. Finally, the outputs of the current work can be effectively used in tuning and controlling the topology and microstructure of copolymer chains.

Biodegradable polycarbonates containing side carboxyl groups—synthesis, properties, and degradation study

ABSTRACTThe main objective of the presented research was to synthesise biodegradable aliphatic polycarbonates containing reactive carboxyl pendant groups and to examine the influence of the copolymer chain microstructure and composition on the process of their hydrolytic degradation and cytocompatibility. The work describes copolymerization of cyclic trimethylene carbonate derivative containing benzyl‐ester pendant group (benzyl 5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐carboxylate) with trimethylene carbonate. The copolymerization was conducted with the use of zinc (II) and lanthanum (III) acetylacetonates as ring‐opening polymerization coordination initiators. Detailed NMR analysis allowed to define the microstructure of the obtained copolymers, which depended on the composition and type of used initiator. The final tapered chain microstructure of the obtained copolymers was related to huge differences in comonomers reactivity and evidenced low level of transesterification of the main copolymer backbone. Chosen copolymers, with unprotected carbonyl groups, were subjected to in vitro degradation test and cytocompatibility studies. It was found that high concentration of carboxyl groups resulted in copolymers which formed hydrogels and were very prone to hydrolytic degradation; they were also cytotoxic toward osteoblast‐like MG 63 cells. Copolymers with lower content of carboxyl groups were found less susceptible to degradation and cytocompatible with studied cells. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2756–2769

Characterization of Aliphatic Polyesters Synthesized via Enzymatic Ring-Opening Polymerization in Ionic Liquids.

To evaluate the effects of ionic liquids (ILs) on the microstructural features of aliphatic polyesters for biomedical applications, a series of copolymers were synthesized by lipase ring opening polymerization of rac-lactide (rac-LA) and ε-caprolactone (CL). The chemical structures of resulting polymers were characterized by 1H- and 13C-NMR and the average molecular weight (Mn) and dispersity index were characterized by gel permeation chromatography. The structure of the copolymers confirms the presence of linear polymer chains with end-functional hydroxyl groups allowing covalent coupling of the therapeutic agents. Chain microstructure of copolymers indicates the presence of both random and block copolymers depending on the synthesis conditions. Moreover, it was found that CL is the most active co-monomer during copolymerization which enhances the polymerizability of rac-LA and allows to obtain higher Mn of the copolymers. The results demonstrate that ILs could be promising solvents in synthesis of aliphatic esters for biomedical applications.

Synthesis of trimethylene carbonate/ϵ -caprolactone copolymers initiated with zinc alkoxide: influence of copolymer chain microstructure on thermal and mechanical properties

Synthesis of trimethylene carbonate/<i>ϵ</i> -caprolactone copolymers initiated with zinc alkoxide: influence of copolymer chain microstructure on thermal and mechanical properties

Surface topography and crystal and domain structures of films of ferroelectric copolymer of vinylidene difluoride and trifluoroethylene

The crystallization of a copolymer from a solution at room temperature is found to lead to the formation of a metastable structure, characterized by the coexistence of ferroelectric and paraelectric phases. The fraction of the latter decreases after annealing above the Curie point. Atomic force microscopy (AFM) has revealed a difference in the surface topographies between the films contacting with air and the films contacting with a glass substrate. The microstructure of copolymer chains has been investigated by 19F NMR spectroscopy. The chain fragments with “defect” attached monomeric units are ejected to the surface. The character of the ferroelectric domains formed during crystallization and their size distribution are analyzed.

Evolution of Chain Microstructure and Kinetics of Reaching Equilibrium in Living Reversible Copolymerization

Theoretical considerations and Monte Carlo simulations have proved that the microstructure of copolymer chains in living reversible copolymerization can be effectively described by the first‐order Markov chain process only when the system space of this process reaches chain lengths above the number‐average degree of polymerization (DPn). The time scale of equilibration depends mostly on DPn of the product, rate constants of depropagation, as well as on the equilibrium microstructure of copolymer. During the process, evolution encompasses, besides the chain‐length distribution like in homopolymerization, also the chain microstructure. The kinetically determined microstructure (gradient, alternate, etc.) observed in the first stage of copolymerization is related to reactivity ratios. It evolves into the equilibrium microstructure, determined exclusively by the equilibrium constants and initial conditions. Discussion of this evolution together with the statistical description of the reversible binary copolymerization systems at various stages of equilibration is given. image

A Monte Carlo-based feeding policy for tailoring microstructure of copolymer chains: Reconsidering the conventional metallocene catalyzed polymerization of α-olefins

A standard Monte Carlo-based program with innovative data storage structure was developed and put into practice to tailor ethylene/1-hexene copolymers through semibatch single site metallocene catalyzed copolymerization. The distribution of copolymer composition, ethylene sequence length, longest ethylene sequence length, as well as the number-average degree of polymerization, and sequential placement of 1-hexene comonomer segments along copolymer chains were monitored and evaluated applying a computerized feeding to metallocene catalyzed ethylene/1-hexene copolymerization. In particular, bivariate copolymer composition–chain length (CC–CL) distribution was compared for two feeding recipes with uncontrolled and well-controlled comonomer insertion. The advantages of controlled feeding in comparison to uncontrolled feeding were discussed in view of aforementioned architectural features. To obtain macromolecules with tailored comonomer distributions, special feeding strategies were developed by training and examining the developed model to capture crystallization analysis fractionation (CRYSTAF) of ethylene/1-hexene chains, as a unique signature of tailored copolymers with rather narrow bivariate CC–CL distribution. The simulation results appropriately highlight the critical importance of computerized feeding with respect to uncontrolled feeding.

Polyesters and polyestercarbonates for controlled drug delivery. Part I. Tailoring of the drug release

A crucial factor in the design of safe and effective drug delivery systems is the development of biocompatible carriers, which offer the possibility to tailor the drug release kinetics for specific drugs. The determination of the factors controlling drug release, as well as the methods to adjust the properties of the polymer, is necessary. The influence of the copolymer chain microstructure on degradation, and thus the drug release profile, has been demonstrated; therefore, this factor cannot be neglected during the development of controlled drug delivery systems.

Novel Poly(L-lactide-co-ε-caprolactone) Matrices Obtained with the Use of Zr[Acac]4as Nontoxic Initiator for Long-Term Release of Immunosuppressive Drugs

Slowly degradable copolymers of L-lactide and ε-caprolactone can provide long-term delivery and may be interesting as alternative release systems of cyclosporine A (CyA) and rapamycin (sirolimus), in which available dosage forms cause a lot of side effects. The aim of this study was to obtain slowly degradable matrices containing immunosuppressive drug from PLACL initiated by nontoxic Zr[Acac]4. Three kinds of poly(L-lactide-co-ε-caprolactone) (PLACL) matrices with different copolymer chain microstructure were used to compare the release process of cyclosporine A and rapamycine. The influence of copolymer chain microstructure on drug release rate and profile was also analyzed. The determined parameters could be used to tailor drug release by synthesis of demanded polymeric drug carrier. The studied copolymers were characterized at the beginning and during the degradation process of the polymeric matrices by NMR spectroscopy, GPC (gel permeation chromatography), and DSC (differential scanning calorimetry). Different drug release profiles have been observed from each kind of copolymer. The correlation between drug release process and changes of copolymer microstructure during degradation process was noticed. It was determined that different copolymer composition (e.g., lower amount of caprolactone units) does not have to influence the drug release, but even small changes in copolymer randomness affect this process.

Synthesis, structure and properties of poly(L-lactide-co-[formula omitted]-caprolactone) statistical copolymers

Four poly(L-lactide-co-ε-caprolactone) (PLCL) copolymers were synthesized at 120, 130, 140 and 150 °C by ring opening polymerization using stannous octoate catalyst at a 2000:1 comonomer:catalyst ratio. Gel permeation chromatography (GPC) and 1H NMR measurements were performed to determine the molecular weight, composition and chain microstructure of copolymers of L-lactide(LA):ε-caprolactone(CL) synthesized using 90:10, 80:20, 75:25 and 70:30 feed ratios. The overall conversion of these PLCL copolymers was in the range of 80%–90% leading to weight average molecular weights (Mw) between 98,500 and 226,000 g mol−1 depending on feed composition and polymerization temperature. At temperatures lower than 140 °C, the incorporation of CL units into polymer chains was incomplete because of the low reactivity of CL, thus at 120 °C the copolymer composition was difficult to control obtaining more LA in the copolymer than the desired, hence the blocky character of PLCL copolymers also increased. At 150 °C the catalyst was less effective and the molecular weights of the copolymers took lower values. A temperature of 140 °C was established as optimal to obtain highest yields and molecular weight. The number average crystallizable lactide sequence lengths (lLA) shifted from 6.5 to 16.7 LA repeat units for PLCL polymerized at 140 °C while the randomness character (R) value shifted from 0.4 for polymerization at 130 °C to 0.6, at 150 °C. Increasing the LA content in the copolymers the glass transition temperature and the crystallizability and melting temperature of PLCLs approached to that of PLLA homopolymer. The aging sensitivity of PLCLs increased with CL content. A double Tg behavior due to phase separation associated to crystallizing LA blocks was observed during aging. The mechanical properties, however, evolved toward the PLLA character when the molar content of LA in PLCL was increased from 66% to 90%, observing a shift from an elastomeric thermoplastic behavior to that of a glassy plastic, reflected by an increase in tensile modulus (from 12.0 to 1343.1 MPa) and a decrease in strain recovery after break (from 93.5% to 25.0%). Small amounts of CL content in the copolymers produced large improvements in their deformability with regard to PLLA. In addition, thermogravimetric analysis demonstrated that PLCLs are more stable to thermal degradation than PLLA and they undergo a more complex degradation mechanism than those of the corresponding homopolymers.

Controlled poly( l-lactide-co-trimethylene carbonate) delivery system of cyclosporine A and rapamycine – the effect of copolymer chain microstructure on drug release rate

The effect of poly( l-lactide-co-TMC) chain microstructure (and its changes during degradation) on immunosuppressive drugs’ release process was analyzed. Three kinds of poly( l-lactide-co-TMC) (PLATMC) – two semiblock and one random were used to prepare matrices containing cyclosporine A or rapamycine and drug free matrices. All of them degraded slowly enough to provide long term delivery of immunosuppressive agents. Moreover, copolymer chain microstructure determined the effect of drug loading on the degradation process. It was observed that matrices without drug obtained from semiblock copolymer degraded differently than matrices containing cyclosporine A or rapamycine, whereas all kinds of matrices obtained from random PLATMC degraded in similar way. This is the evidence that the only in case of semiblock copolymer factors concerning the presence of drug and the kind of drug influenced degradation process. Based on the obtained results, correlations between copolymer degradation and drug release process are proposed. According to our outcomes, regular drug release process may be obtained from highly randomized copolymers ( R ≈ 1) that remain amorphous during degradation process. Determination of this factor may help in development of biodegradable systems, in which drug release rate and profile can be tailored by synthesis of polymer with appropriate chain microstructure.

Controlled poly(l-lactide-co-trimethylene carbonate) delivery system of cyclosporine A and rapamycine - the effect of copolymer chain microstructure on drug release rate

Controlled poly(l-lactide-co-trimethylene carbonate) delivery system of cyclosporine A and rapamycine - the effect of copolymer chain microstructure on drug release rate

Designing bioresorbable polyester matrices for controlled doxorubicin release in glioma therapy

The influence of the chain microstructure on release process of doxorubicin from polymeric matrices was analyzed. Aliphatic polyester copolymers with optimal chain microstructure, i.e. poly(glycolide-co- l-lactide, 15/85) (PGLA) and poly(glycolide-co-ɛ-caprolactone, 10/90) (PGCA) were synthesized for long-term doxorubicin delivery systems. Various release profiles from PGLA and PGCA matrices were obtained. The investigations revealed the most steadily doxorubicin release from PGCA matrices with 5% (w/w) of drug content. Degradation of matrices with and without drug was monitored by means of NMR spectroscopy and confirmed stability of degradation process. From PGCA matrices the increase of released doxorubicin amount was observed during first 60 days. On the contrary in case of matrices obtained from PGLA the delay of doxorubicin release was observed during first 50 days, what was caused by interaction of drug molecules with polylactide chain of polymer matrix. The interaction between doxorubicin molecules and polylactide chains was confirmed by IR spectroscopy. This fact can be used for designing of delivery systems consisting of combination of matrices with different microstructure of copolymer chains in order to adjust concentration of released doxorubicin and stabilization of drug release process.

The influence of copolymer chain microstructure on cyclosporine a (CyA) and Sirolimus prolonged and sustained release from PLA/TMC and PLA/PCL matrices

The influence of copolymer chain microstructure on cyclosporine a (CyA) and Sirolimus prolonged and sustained release from PLA/TMC and PLA/PCL matrices

Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior.

Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).

Chemical composition distribution of multicomponent copolymer chains

AbstractProbability theory was used to model the microstructure of copolymer chains. Specifically, we derived analytical expressions to describe the chemical composition distribution of multicomponent random copolymers and the longest monomer sequence length distribution of binary copolymers. The results agree with Stockmayer's distribution for binary copolymers and with Monte Carlo simulations for multicomponent copolymers.

Characterization of a Polymeric Chain by Pyrolysis Gas Chromatography and Computer Simulation

A method has been developed which utilizes the experimental results from pyrolysis−gas chromatography (Py−GC) integrated with that from a Monte Carlo simulation to characterize the microstructure of a copolymer chain. The bridge between Py−GC and the Monte Carlo simulation is the relative triad peak intensities as well as the “number-average sequence length” values. By appropriate adjustment of the copolymerization parameters such as relative reactivity ratio, the triad intensity profile from a Monte Carlo simulation can be successfully fit to the Py−GC experimental values of relative trimer intensities. If the triad intensity profile and the value of “number-average sequence length” are a unique parameter set for every copolymer chain microstructure, all copolymer microstructure information on the real polymer can be explored based on the chain created by the Monte Carlo simulation. The development of this method makes it possible to extend microstructure determination beyond the current instrumentation limit.

THE MECHANISM OF COPOLYMER RETENTION IN INTERACTIVE POLYMER CHROMATOGRAPHY. I. CRITICAL POINT OF ADSORPTION FOR STATISTICAL COPOLYMERS

A comprehensive analysis of interactive polymer chromatography is presented. Isocratic liquid chromatography of polymers at the critical eluent composition (the transition point where size-exclusion and adsorption interactions completely compensate each other) is currently used to separate functional oligomers and block copolymers. We have extended the concept of this critical elution chromatography to the cases of statistical copolymers as well as porous stationary phases with heterogeneous surfaces (viz., surfaces with both inert and active groups). The theory provides the quantitative condition for statistical copolymer chains to have a single adsorption-desorption transition point. The random copolymers with narrow chemical composition distribution (CCD) always posses such a point. For non-random copolymers this condition includes the comparison between the mean length of chain segments connecting the attractive walls of the pore and the chemical correlation segment characterizing the randomness of the copolymer microstructure or the surface of this pore. If the critical transition point exists, then the copolymer chains behave as hypothetical homopolymer chains with a single energy of interaction between the effective monomer units and the active groups at the surface. The relationship between this energy and the microstructure of copolymer chains has been also analyzed. If copolymer has a broad CCD, each compositionally homogeneous fraction has its own adsorption-desorption threshold. The partial transition points have been established for the copolymers with blocky or alternating microstructure. Only a portion of the copolymer chain effectively behaves as a homopolymer chain at these points. This property was used in the past for the separation of block copolymers according to the length of blocks comprised of the monomer units of a specific type.

A new approach in copolymerization: Monte Carlo method for the reactivity ratios calculation in copolymerization of furfuryl acrylate with 2-hydroxyethyl methacrylate

Copolymers of furfuryl acrylate (A) with 2-hydroxyethyl methacrylate (H) were prepared by free radical copolymerization in DMF solution at 50°C, using 2,2'-azobisisobutyronitrile (AIBN) as initiator. The reactivity ratios of both monomers were calculated according to the general copolymerization equation using the Fineman-Röss and Kelen-Tüdos 1inearization methods, as well as the Tidwell-Mortimer non linear least-squares treatment and the Monte Carlo random method. The reactivity ratios obtained were rA = 0.93 and rH = 1.42. Similar results were obtained by both, the Monte Carlo and the non-linear least squares methods. The microstructure of copolymer chains based on the first order Markov statistics is described.

Copolymers of N-vinylcarbazole and N,N-dimethylaminoethyl methacrylate

Copolymers of N-vinylcarbazole (NVC) and N,N-dimethylaminoethyl methacrylate (DMAEMA) were prepared by free-radical polymerization in a toluene solution at 60°C using 2,2′-azobisisobutyronitrile (AIBN) as an initiator. The reactivity ratios of both monomers were calculated using the extended Kelen-Tudős method and found to be r1 = 0.441 ± 0.052 and r2 = 1.632 ± 0.102. The microstructure of copolymer chains is described on the basis of first-order Markov statistics. The microstructure of copolymers was also studied by UV and 1H-NMR spectroscopy. Copolymers were characterized by viscocity and number-average molecular weight (M¯n) measurements. The glass transition temperatures (Tg) of the copolymers were determined calorimetrically and the variation of Tg with the copolymer composition is discussed. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 1815–1824, 1997