Statistical Copolymers Research Articles

Ultrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers.

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, invivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

Electron beam irradiation as a straightforward way to produce tailorable non-biofouling poly(2-methyl-2-oxazoline) hydrogel layers on different substrates

Uncontrolled accumulation of proteins and cells on implantable materials often leads to failure of their performance in vivo. The idea presented in this paper is the use of electron beam irradiation as a widely applicable, cost-effective, and defined method to produce non-biofouling hydrogel coatings to improve the biocompatibility and in vivo performance of implantable materials. Statistical copolymers poly[2-methyl-2-oxazoline-co-2-(3-butenyl)-2-oxazoline]s were deposited on different substrates and irradiated with beta radiation of different radiation doses (2–100 kGy). In the bulk state experiments, we found that the higher content of crosslinkable 3-butenyl units and a higher radiation dose resulted in more efficient crosslinking. Similarly, the irradiation of coatings demonstrated the high impact of the concentration of 3-butenyl units on crosslinking efficiency. Accordingly, the concentration of crosslinkable double bonds in the copolymer is crucial for the stability and homogeneity of the formed hydrogel layer. Stable and uniform hydrogel layers with thicknesses in the micrometer range were prepared from a 5 wt% copolymer solution. Depending on the preparation conditions, the hydrogel layers showed excellent non-biofouling properties with a low number of adherent cells. In addition, stiffness was dependent on the degree of crosslinking, and can thus be tailored for specific application in living tissue.

Doxorubicin-loaded polymeric nanoparticles containing ketoester-based block and cholesterol moiety as specific vehicles to fight estrogen-dependent breast cancer

The presented research concerns the preparation of polymer nanoparticles (PNPs) for the delivery of doxorubicin. Several block and statistical copolymers, composed of ketoester derivative, N-isopropylacrylamide, and cholesterol, were synthesized. In the nanoprecipitation process, doxorubicin (DOX) molecules were kept in spatial polymeric systems. DOX-loaded PNPs show high efficacy against estrogen-dependent MCF-7 breast cancer cell lines despite low doses of DOX applied and good compatibility with normal cells. Research confirms the effect of PNPs on the degradation of the biological membrane, and the accumulation of reactive oxygen species (ROS), and the ability to cell cycle arrest are strictly linked to cell death.Graphical

Chain-Extendable Crosslinked Hydrogels Using Branching RAFT Modification.

Functional crosslinked hydrogels were prepared from 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA). The acid monomer was incorporated both via copolymerization and chain extension of a branching, reversible addition-fragmentation chain-transfer agent incorporated into the crosslinked polymer gel. The hydrogels were intolerant to high levels of acidic copolymerization as the acrylic acid weakened the ethylene glycol dimethacrylate (EGDMA) crosslinked network. Hydrogels made from HEMA, EGDMA and a branching RAFT agent provide the network with loose-chain end functionality that can be retained for subsequent chain extension. Traditional methods of surface functionalization have the downside of potentially creating a high volume of homopolymerization in the solution. Branching RAFT comonomers act as versatile anchor sites by which additional polymerization chain extension reactions can be carried out. Acrylic acid grafted onto HEMA-EGDMA hydrogels showed higher mechanical strength than the equivalent statistical copolymer networks and was shown to have functionality as an electrostatic binder of cationic flocculants.

Framework for Optimizing Polymeric Supports for Immobilized Biocatalysts by Computational Analysis of Enzyme Surface Hydrophobicity

Immobilization is a powerful strategy for improving enzyme usability and stability in various technologies that employ biocatalysis. However, the interactions leading to stabilization or destabilization remain poorly understood, and a support that may stabilize one enzyme may destabilize another. Employing chemically heterogeneous and complex random copolymer brushes as supports, we demonstrate a rational approach toward estimating the chemical composition of an optimally stabilizing enzyme immobilization support by computational analysis of enzyme surface hydrophobicity. This approach was tested by immobilizing a range of enzymes with diverse functions and hydrophobicity on tunable statistical random copolymer brush supports composed of poly(ethylene glycol) methacrylate (PEGMA) and sulfobetaine methacrylate (SBMA). Remarkably, we observed greatly improved enzyme performance as a function of brush composition with enhancements in the retention of catalytic activity at temperatures as high as 90 °C. Additionally, we observed an increase in activity at the optimal temperature by as much as 20-fold relative to the activity at the optimal temperature of the unimmobilized form of the enzyme. Most significantly, our results showed that the optimal composition of the brush support correlated with the overall hydrophobicity of the enzyme surface (ΔGsolv,total/area), which was determined from computational analysis. This correlation provides a framework for the choice of polymer brush supports based on enzyme structure and stabilizing enzymes using complex synthetic materials.

Heterocene-catalyzed ethylene/oct-1-ene copolymerization under MAO-free and low-MAO conditions: The synthesis of highly statistical copolymers and their use in blending with HDPE

Sandwich SiMe2-bridged ansa-complexes of zirconium, containing heterocycle-fused η5-cyclopentadienyls, derivatives of 2,5-dimethyl-7H-cyclopenta[1,2-b:4,3-b']dithiophene (2), 5,10-dihydroindeno[1,2-b]indole (3) and 5,6-dihydroindeno[2,1-b]indole (4) – 'heterocenes' – catalyzed ethylene homopolymerization and ethylene/oct-1-ene (E/O) copolymerization in the presence of triisobutylaluminum (TIBA) without MAO and perfluoroaryl borate activators, the benchmark bis(η5-fluorenyl) complex 1 was virtually inactive under these conditions. In the absence of MAO, E/O copolymerization resulted in a formation of copolymers not containing EOOE fragments even at E/O ratio of 2.4. Addition of 10 eq. of MMAO-12 resulted in increase of both catalytic activities of 2–4 and oct-1-ene incorporation. E/O copolymers POE-05 (obtained on TIBA activated precatalyst 2) and POE-17 (obtained on TIBA/MMAO-12 activated precatalyst 4) were not inferior to the best commercial E/O copolymers in physico-mechanical characteristics at −45 °C. Extrusion blends of POE-05 and POE-17 with high density polyethylene (HDPE) demonstrated high impact strength and frost resistance.

A Transformable and Bulky Methacrylate Monomer That Enables the Synthesis of an MMA-nBA Alternating Copolymer: Sequence-Dependent Self-Healing Properties.

In this study, we designed a methacrylate molecule with an alkyl-substituted trichloro salicylic acid pendant as a transformable bulky monomer to enable the synthesis of an alternating copolymer of methyl methacrylate (MMA) and n-butyl acrylate (nBA). The adamantyl-substituted methacrylate monomer (1-Ad) showed very low homopolymerization propensity in radical polymerizations, but afforded the alternating copolymer with nBA via copolymerization. The 1-Ad units in the resultant copolymer were quantitatively and selectively transformed into MMA via transesterification with methanol to yield the alternating copolymer of MMA and nBA. Its alternating sequence was clearly demonstrated by a structural analysis via 13 C NMR spectroscopy as well as the low reactivity ratios for the 1-Ad and nBA pair. Finally, we verified the superior self-healing ability of the alternating copolymer compared to that of the corresponding 1 : 1 statistical copolymer.

A Transformable and Bulky Methacrylate Monomer That Enables the Synthesis of an MMA‐nBA Alternating Copolymer: Sequence‐Dependent Self‐Healing Properties

AbstractIn this study, we designed a methacrylate molecule with an alkyl‐substituted trichloro salicylic acid pendant as a transformable bulky monomer to enable the synthesis of an alternating copolymer of methyl methacrylate (MMA) and n‐butyl acrylate (nBA). The adamantyl‐substituted methacrylate monomer (1‐Ad) showed very low homopolymerization propensity in radical polymerizations, but afforded the alternating copolymer with nBA via copolymerization. The 1‐Ad units in the resultant copolymer were quantitatively and selectively transformed into MMA via transesterification with methanol to yield the alternating copolymer of MMA and nBA. Its alternating sequence was clearly demonstrated by a structural analysis via 13C NMR spectroscopy as well as the low reactivity ratios for the 1‐Ad and nBA pair. Finally, we verified the superior self‐healing ability of the alternating copolymer compared to that of the corresponding 1 : 1 statistical copolymer.

One-Pot Synthesis of CO2-Based Polylactide-b-Poly(ether carbonate)-b-Polylactide Triblock Copolymers and Their Mechanical Properties

The synthesis of CO2-based triblock copolymers made of a central poly(ether carbonate) blocks flanked by two external polylactide blocks is described. Such triblock copolymers are obtained in one-pot by first CO2/epoxides copolymerization using a difunctional onium salt initiator in the presence of triethylborane, followed by ring-opening polymerization (ROP) of lactide (LA) assisted by diphenylurea (UPh), a hydrogen-bonding activator. Upon varying the pressure of CO2 during its copolymerization with propylene oxide (PO), the Tg of the central block could be fine-tuned allowing the synthesis of poly(propylene oxide-co-propylene carbonate) (PPPC) with various carbonate versus ether contents. These PPPC samples are then mechanically characterized; as their content in ether linkages progressively increased, a transition from brittle-to-ductile-to-elastomeric behavior could be seen. Upon appending two external enantiomeric poly(d-lactide) (PDLA) blocks to the central PPPC block, the generated PDLA-b-PPPC-b-PDLA triblock copolymers exhibit an impressive increase of their ductility compared to that of the parent statistical PPPC copolymers. When benchmarked against commercial polyolefins the latter CO2-based triblock copolymers outperform the mechanical performances of high density polyethylene (HDPE) and low density polyethylene (LDPE) by all accounts, their elasticity modulus, tensile strength, toughness and elongation at break being indeed superior to those of the polyolefins tested.

Pathway Complexity in Supramolecular Copolymerization and Blocky Star Copolymers by a Hetero-Seeding Effect.

This study unravels the intricate kinetic and thermodynamic pathways involved in the supramolecular copolymerization of the two chiral dipolar naphthalene monoimide (NMI) building blocks (O-NMI and S-NMI), differing merely by a single heteroatom (oxygen vs sulfur). O-NMI exhibits distinct supramolecular polymerization features as compared to S-NMI in terms of its pathway complexity, hierarchical organization, and chiroptical properties. Two distinct self-assembly pathways in O-NMI occur due to the interplay between the competing dipolar interactions among the NMI chromophores and amide-amide hydrogen (H)-bonding that engenders distinct nanotapes and helical fibers, from its antiparallel and parallel stacking modes, respectively. In contrast, the propensity of S-NMI to form only a stable spherical assembly is ascribed to its much stronger amide-amide H-bonding, which outperforms other competing interactions. Under the thermodynamic route, an equimolar mixture of the two monomers generates a temporally controlled chiral statistical supramolecular copolymer that autocatalytically evolves from an initially formed metastable spherical heterostructure. In contrast, the sequence-controlled addition of the two monomers leads to the kinetically driven hetero-seeded block copolymerization. The ability to trap O-NMI in a metastable state allows its secondary nucleation from the surface of the thermodynamically stable S-NMI spherical "seed", which leads to the core-multiarmed "star" copolymer with reversibly and temporally controllable length of the growing O-NMI "arms" from the S-NMI "core". Unlike the one-dimensional self-assembly of O-NMI and its random co-assembly with S-NMI, which are both chiral, unprecedentedly, the preferred helical bias of the nucleating O-NMI fibers is completely inhibited by the absence of stereoregularity of the S-NMI "seed" in the "star" topology.

Enhanced Solvent and Thermal Stability in Cross-Linkable Conjugated Statistical Copolymers for Organic Field-Effect Transistors.

The ability to enhance both the solvent and thermal stability of semiconducting π-conjugated polymers is highly desired for various device-related applications. Herein, a series of poly(3-hexylthiophene)-stat-poly[3-(6-hydroxy)hexylthiophene] (P3HT-stat-P3HHT) statistical copolymers with thermally cross-linkable hydroxyl groups is synthesized and their crystalline structures in three different states, solvent and thermal stability for use in organic field-effect transistors (OFETs) are elucidated. Importantly, these initial P3HT-stat-P3HHT thin films in their as-cast state crystallize well in an edge-on orientation. During annealing at 150 °C, these P3HT-stat-P3HHT occur cross-linked and retain edge-on orientation with increased crystallinity and ordering. In contrast, after high-temperature annealing at 300 °C, their edge-on orientation is significantly destroyed due to the cross-linking of hydroxyl groups at melted state. The correlation between different P3HT-stat-P3HHT and their charge mobilities is scrutinized. These cross-linked P3HT-stat-P3HHT exhibit good solvent resistance property and improved thermal stability in OFETs. Conceptually, such side-chain functionalization approach to improve the stability of P3HT-stat-P3HHT can be conveniently extended to other conjugated polymers for diverse optoelectronic applications.

Boosting the photoreduction uranium activity for donor–acceptor–acceptor type conjugated microporous polymers by statistical copolymerization

Conjugated microporous polymers (CMPs) have attracted much attention due to their environmental friendliness, high conjugation and design ability, but the development of efficient CMPs photocatalysts for the photoreduction of uranium remains a challenge due to the monolithic nature of polymer synthesis and the mismatch of band gaps. Here, the two acceptors dibenzothiophene-S,S-dioxide (SO) and benzothiadiazole (TH) with different electron-absorbing capacities were chosen, with the acceptor II TH having the greater electron-absorbing capacity, and then a series of donor-acceptor-acceptor (D-A-A) CMPs photocatalysts were innovatively designed by adjusting the ratio between the electron donor benzene (B) and the electron acceptor TH by means of statistical copolymerization. As well as photocatalytic characterization, the effect of different ratios of CMPs on its performance was explored. The results show that the band gap of D-A-A polymers can be regularly regulated by statistical copolymerization, and the PBSOTH-2 polymer with a feed ratio of 1.0: 3.0: 1.5 achieves 99.2% uranium removal when methanol is the sacrificial agent. This work has established a database for the photocatalytic reduction of uranium by D-A-A terpolymer by statistical copolymerization, which provides some ideas for the design of catalysts for the efficient reduction of uranium.

Anionic Polymerization of 4-Allyldimethylsilylstyrene: Versatile Polymer Scaffolds for Post-Polymerization Modification

A facile synthesis using a Grignard reaction was employed to prepare the silicon containing functional monomer 4-allyldimethylsilylstyrene (4ADSS). Detailed studies regarding the living nature of anionic polymerization of 4ADSS and its polymerization via the styrene vinyl bond in cyclohexane at room temperature were conducted, and P4ADSS samples with Mn up to 80 kg mol–1 were accessible. This evidences that the 4ADSS structure disables undesired proton transfer side reactions, as known for the carbon-based analogue functional monomer 4-but-3-enyl-styrene. Real-time 1H NMR kinetics of the statistical copolymerization of 4ADSS with styrene (r4ADSS = 3.55; rS = 0.047) revealed a remarkable gradient microstructure in the resulting copolymers. Based on this observation, a library of well-defined gradient copolymers P(4ADSS-co-S) with Mn in the range of 5–50 kg mol–1 was synthesized, varying 4ADSS content. A comprehensive discussion regarding the glass transition temperatures (Tg) of the synthesized homo- and copolymers is presented. Furthermore, thiol–ene click reactions at the pendant allyl moiety of P(4ADSS-co-S) were explored to introduce functional groups. Likewise, P(4ADSS-co-S) copolymers were subjected to hydrosilylation reactions, and the impact of the introduced siloxane moieties on the glass transition of the resulting copolymers is presented. Both thiol–ene reactions as well as hydrosilylation of the P(4ADSS-co-S) copolymers proceeded quantitatively. Consequently, copolymerization of 4ADSS provides access to a wide range of polystyrene-based functional materials with specific applications using versatile post-polymerization chemistry.

Toward high-performance dibenzo[g,p]chrysene-based conjugated polymer photocatalysts for photocatalytic hydrogen production through donor-acceptor-acceptor structure design

The exploration on boosting the photocatalytic performance of donor-acceptor (D-A) type polymer photocatalysts is hindered by their fixed chemical compositions. Herein, a series of donor-acceptor-acceptor (D-A-A) type conjugated polymer photocatalysts with tunable components was synthesized through ternary statistical copolymerization by adopting dibenzo[g,p]chrysene and dibenzothiophene-S,S-dioxide as the donor and acceptor, respectively. It reveals that the hydrogen evolution rate (HER) of the resulting copolymers strongly depends on the molar ratio of donor to acceptor. The optimized photocatalyst DBC-BTDO-2 with a molar ratio of 1:3 for donor to acceptor shows an attractive HER of 214.43 mmol h−1 g−1 under UV–vis light without cocatalysts, which is twice as that of its counterpart DBC-BTDO with a D-A structure. Remarkably, DBC-BTDO-2 also realizes an ultra-high HER of 301.92 mmol h−1 g−1 under solar light. These findings highlight the great potential of D-A-A structural design with finely tuned component for boosting the photocatalytic activity of polymer photocatalysts.

A combination of surface-initiated controlled radical polymerization (SET-LRP) and click-chemistry for the chemical modification and fluorescent labeling of cellulose nanofibrils: STED super-resolution imaging of a single fibril and a single fibril embedded in a composite

A strategy is developed to modify cellulose nanofibril (CNF) surfaces with a combination of Cu0-mediated radical polymerization (SET-LRP) and CuI-catalyzed azide-alkyne click-chemistry (CuAAC). CNFs were grafted with statistical copolymers of di(ethylene glycol) ethyl ether acrylate (DEGEEA) and acrylic acid 3-trimethylsilyl-prop-2-ynyl ester (TMSPgA) that allows labeling of multiple fluorescent dyes, e.g. AF488 and ATTO633, special dyes for confocal laser scanning microscopy and stimulated emission depletion (STED) microscopy. Through our strategy and these microscopic techniques, we visualized isolated fibrils and fibrils embedded in a PVA composite in a high resolution. This work also provides new insight into the effect of the clickable entity/precursor on the compatibility of modified fibrils with the composite matrix.Graphical abstract

Critical conditions for liquid chromatography of statistical polyolefins: Evaluation of diene distribution in EPDM terpolymers

Liquid chromatography at critical conditions is of interest as it may unravel molecular information on macromolecular structures not accessible by any other analytical techniques. Yet so far, such conditions have never been experimentally established for copolymers, where a particular need for such information exists. Toward this goal, critical conditions for statistical ethylene propylene copolymers were identified. In the first approach the composition of the binary mobile phase was varied at a constant temperature, and secondly by modulating the adsorption-desorption temperature at constant mobile phase composition. Solvents for both methods were identified by using a novel approach that combines structure retention relationships with Hansen Solubility Parameters. As a result, for the first time, the heterogeneity of an ethylene propylene diene terpolymer sample with regard to the pendant double bond of the diene could be determined. The novel chromatographic approach was validated by measuring the composition of fractions taken over the chromatographic run offline by nuclear magnetic resonance. In summary, this work gave the first experimental evidence for the existence of critical conditions for polyolefin random copolymers, as postulated by Brun. This novel chromatographic approach holds immense potential to engineer complex polymers towards future applications by making use of the now-accessible molecular information.

Tailoring Glass Transition Temperature in a Series of Poly(methylene-1,3-cyclopentane-stat-cyclohexane) Statistical Copolymers

A systematic investigation of the synthesis and characterization of a new class of amorphous atactic cis, trans poly(methylene-1,3-cyclopentane-stat-cyclohexane) statistical copolymers (I) is reported. Production of different grades of I that vary with respect to the ratio of 5- and 6-membered cycloalkane repeat units was achieved through the living coordinative chain transfer cyclopolymerization of different initial feed ratios of 1,5-hexadiene and 1,6-heptadiene comonomers. It was determined that the glass transition temperature, Tg, of I can be systematically increased from -16 to 100 °C as a function of increasing 6-membered ring content, although not in a strictly linear fashion. It was further determined that a small level of 6-membered ring content is sufficient to disrupt the crystallinity of the limiting atactic cis, trans poly(methylene-1,3-cyclopentane) (PMCP) homopolymer that possesses a melting temperature, Tm, of 98 °C. These results establish a foundation for future potential technological applications of this unique class of polyolefin copolymers.

Anionic Polymerization of the Terpene-Based Diene β-Ocimene: Complex Mechanism Due to Stereoisomer Reactivities

Motivated by the need for sustainable, bio-based materials, the living anionic polymerization of the under-explored terpene monomer β-ocimene (Oc) was investigated for the first time. Homopolymers with Mn up to 50 kg mol–1 of the Oc isomeric mixture (E:Z = trans:cis = 70:30) were synthesized in cyclohexane and analyzed with respect to molecular weight control, dispersity, microstructure, and glass transition temperature, Tg. Employing styrene as a comonomer, diblock copolymers, and a series of statistical copolymers with Mn up to 20 kg mol–1 with varying comonomer compositions offered the opportunity to tailor the glass transition of the copolymers. Real-time 1H nuclear magnetic resonance (NMR) kinetics indicated a remarkably divergent reactivity of the trans and cis isomers. This unveiled the unique observation that the homopolymerization of Oc is in fact a copolymerization of the cis and trans isomers, which one might name as “stereo-copolymerization” (rtrans = 3.16; rcis = 0.32). Kinetic studies of the statistical copolymerization of the Oc isomeric mixture with styrene revealed an astonishingly contradictory reactivity of the two isomers (rtrans < rcis). The reactivity differences of the cis and trans isomers in the polymerization were utilized to isolate the individual isomers for the first time. Subsequently, they were independently homo- and copolymerized with styrene. The complex mechanism of these polymerizations and the rather high polymer dispersities (Đ ≈ 1.6–2) are discussed using various kinetic models supported by density functional theory modeling. The surprisingly different behavior of the two isomers with styrene was validated experimentally via a 1H NMR-monitored chemical titration.

Polypentenamer thermoplastic elastomers via copolymerization of cyclopentene and dicyclopentadiene

Dicyclopentadiene monomer was incorporated into statistical copolymerizations with cyclopentene to determine its influence on the resulting copolymers. These dicyclopentadiene nanodomains acted as crosslinks providing strength to the uncured network.

Alternating styrene-propylene and styrene-ethylene copolymers prepared by photocatalytic decarboxylation.

Synthesis of olefin-styrene copolymers with defined architecture is challenging due to the limitations associated with the inherent reactivity ratios for these monomers in radical or metal-catalyzed polymerizations. Herein, we developed a straightforward approach to alternating styrene-propylene and styrene-ethylene copolymers by combining radical polymerizations and powerful post-polymerization modification reactions. We employed reversible addition-fragmentation chain transfer (RAFT) copolymerization between styrene derivatives and saccharin (meth)acrylamide to generate alternating copolymers. Once polymerized, the amide bond of the saccharin monomers was highly reactive toward hydrolysis, an observation exploited to obtain alternating styrene-acrylic acid/methacrylic acid copolymers. Subsequent mild decarboxylation of the (meth)acrylic acid groups in the presence of a photocatalyst and a hydrogen source under visible light resulted in the styrene-alt-ethylene/propylene copolymers. Alternating copolymers comprised of either propylene or ethylene units alternating with functional styrene derivatives were also prepared, illustrating the compatibility of this approach for functional polymer synthesis. Finally, the thermal properties of the alternating copolymers were compared to those from statistical copolymer analogs to elucidate the effect of microarchitecture and styrene substituents on the glass transition temperature.