Linear Block Copolymer Synthesis.

Block copolymers form the basis of the most ubiquitous materials such as thermoplastic elastomers, bridge interphases in polymer blends, and are fundamental for the development of high-performance materials. The driving force to further advance these materials is the accessibility of block copolymers, which have a wide variety in composition, functional group content, and precision of their structure. To advance and broaden the application of block copolymers will depend on the nature of combined segmented blocks, guided through the combination of polymerization techniques to reach a high versatility in block copolymer architecture and function. This review provides the most comprehensive overview of techniques to prepare linear block copolymers and is intended to serve as a guideline on how polymerization techniques can work together to result in desired block combinations. As the review will give an account of the relevant procedures and access areas, the sections will include orthogonal approaches or sequentially combined polymerization techniques, which increases the synthetic options for these materials.

Block Copolymers of Polyolefins with Polyacrylates: Analyzing and Improving the Blocking Efficiencies Using MILRad/ATRP Approach.

Despite their industrial ubiquity, polyolefin-polyacrylate block copolymers are challenging to synthesize due to the distinct polymerization pathways necessary for respective blocks. This study utilizes MILRad, metal-organic insertion light-initiated radical polymerization, to synthesize polyolefin-b-poly(methyl acrylate) copolymer by combining palladium-catalyzed insertion-coordination polymerization and atom transfer radical polymerization (ATRP). Brookhart-type Pd complexes used for the living polymerization of olefins are homolytically cleaved by blue-light irradiation, generating polyolefin-based macroradicals, which are trapped with functional nitroxide derivatives forming ATRP macroinitiators. ATRP in the presence of Cu(0), that is, supplemental activators and reducing agents , is used to polymerize methyl acrylate. An increase in the functionalization efficiency of up to 71% is demonstrated in this study by modifying the light source and optimizing the radical trapping condition. Regardless of the radical trapping efficiency, essentially quantitative chain extension of polyolefin-Br macroinitiator with acrylates is consistently demonstrated, indicating successful second block formation.

Deciphering the Olefin Isomerization-Polymerization Paradox of Palladium(II) Diimine Catalysts: Discovery of Simultaneous and Independent Pathways of Olefin Isomerization and Living Polymerization.

This work elucidates a long-standing unexplained paradox commonly observed within the polymerization of α-olefin using palladium (Pd)(II)-diimine catalysts, in which isomerization and living polymerization of α-olefins are both observed. With a classical mechanistic understanding of these complexes, this behavior is often dismissed and interpreted as experimental error. Herein, we present a comprehensive mechanistic investigation into this phenomenon that supports the existence of a novel mechanistic pathway for Pd(II)-diimine complexes. Part one of the mechanistic study lays the foundation of the proposed mechanism, in which neutral Pd(II)-diimine complexes were found to exhibit a moderate to good catalytic activity for olefin isomerization of α-olefins despite the established notion that catalyst activation is required. Extensive experimental and computational studies reveal the possibility of a partial dissociation of the diimine ligand, which frees up one coordination site and enables coordination-insertion. This finding is significant as the coexistence of two reactive coordination sites at the palladium center becomes a valid proposal for the activated cationic Pd(II)-diimine complexes. In part two, we examined and validated the simultaneously observed α-olefin isomerization and living polymerization using the cationic Pd(II)-diimine catalyst, which supports the presence of two independent reaction pathways of isomerization and polymerization, respectively. Moreover, the addition of a strong Lewis acid, such as AlCl3, accelerates the ligand dissociation and the consequential isomerization as it weakens the palladium-nitrogen bond through competitive binding. In part three, Lewis acid-triggered olefin isomerization-polymerization is employed to prepare living olefinic block copolymers and further synthesize novel polyolefin-polar block copolymers with unique architectures, distinct levels of branching, crystallinity, and polar functionality in a one-pot manner.

One-For-All Polyolefin Functionalization: Active Ester as Gateway to Combine Insertion Polymerization with ROP, NMP, and RAFT.

This work develops the Polyolefin Active-Ester Exchange (PACE) process to afford well-defined polyolefin-polyvinyl block copolymers. α-Diimine PdII -catalyzed olefin polymerizations were investigated through in-depth kinetic studies in comparison to an analog to establish the critical design that facilitates catalyst activation. Simple transformations lead to a diversity of functional groups forming polyolefin macroinitiators or macro-mediators for various subsequent controlled polymerization techniques. Preparation of block copolymers with different architectures, molecular weights, and compositions was demonstrated with ring-opening polymerization (ROP), nitroxide-mediated polymerization (NMP), and photoiniferter reversible addition-fragmentation chain transfer (PI-RAFT). The significant difference in the properties of polyolefin-polyacrylamide block copolymers was harnessed to carry out polymerization-induced self-assembly (PISA) and study the nanostructure behaviors.

Tandem Living Insertion and Controlled Radical Polymerization for Polyolefin-Polyvinyl Block Copolymers.

Practical synthesis of polyolefin-polyvinyl block copolymers remains a challenge for transition-metal catalyzed polymerizations. Common approaches functionalize polyolefins for post-radical polymerization via insertion methods, yet sacrifice the livingness of the olefin polymerization. This work identifies an orthogonal radical/spin coupling technique which affords tandem living insertion and controlled radical polymerization. The broad tolerance of this coupling technique has been demonstrated for diverse radical/spin traps such as 2,2,5-trimethyl-4-phenyl-3-azahexane-3-nitroxide (TIPNO), 1-oxyl-(2,2,6,6-tetramethylpiperidine) -4-yl-α-bromoisobutyrate (TEMPO-Br), and N-tert-butyl-α-phenylnitrone (PBN). Subsequent controlled radical polymerization is demonstrated with nitroxide-mediated polymerization (NMP) and atom transfer radical polymerization (ATRP), yielding polyolefin-polyvinyl di- and triblock copolymers (D<1.3) with acrylic, vinylic and styrenic segments. These findings highlight radical trapping as an approach to expand the scope of polyolefin-functionalization techniques to access polyolefin macroinitiators.

Distorted Sandwich α-Diimine PdII Catalyst: Linear Polyethylene and Synthesis of Ethylene/Acrylate Elastomers.

The introduction of m-xylyl substituents to α-diimine PdII catalyst promotes living ethylene polymerization at room temperature and low pressure to yield high molecular weight polyethylene (PE) with low branching (<17/1000 C). m-Xylyl groups provide a highly effective blockage to the axial sites of the catalytic center and form a distorted sandwich geometry. The shielding prevents chain-transfer and easy accessibility of polar monomers, leading to a living polymerization. Conducting a light irradiation as part of the one-step metal-organic insertion light initiated radical (MILRad) process leads to diblock copolymers of ethylene and acrylates. Incorporation of different acrylate block sequences can significantly modify the mechanical and chemical properties of block copolymers which can be modulated to be a hard plastic, elastomer, or semi-amorphous polymer.

Switching the Reactivity of Palladium Diimines with "Ancillary" Ligand to Select between Olefin Polymerization, Branching Regulation, or Olefin Isomerization.

Coordinating solvents are commonly employed as ancillary ligands to stabilize late transition metal complexes and are conventionally considered to have little effect on the reaction products. Our work identifies that the presence of ancillary ligand in Pd-diimine catalyzed polymerizations of α-olefins can drastically alter reactivity. The addition of different amounts of acetonitrile allows for switching between distinct reaction modes: isomerization-polymerization with high branching (0 equiv.), regular chain-walking polymerization (1 equiv.), and alkene isomerization with no polymerization (>20 equiv.). Optimization of the isomerization reaction mode led to a general set of conditions to switch a wide variety of diimine complexes into efficient alkene isomerization catalysts, with catalyst loading as low as 0.005 mol %.

Dual Polymerization Pathway for Polyolefin-Polar Block Copolymer Synthesis via MILRad: Mechanism and Scope.

This work explores the mechanism whereby a cationic diimine Pd(II) complex combines coordination insertion and radical polymerization to form polyolefin-polar block copolymers. The initial requirement involves the insertion of a single acrylate monomer into the Pd(II)-polyolefin intermediates, which generate a stable polymeric chelate through a chain-walking mechanism. This thermodynamically stable chelate was also found to be photochemically inactive, and a unique mechanism was discovered which allows for radical polymerization. Rate-determining opening of the chelate by an ancillary ligand followed by additional chain walking allows the metal to migrate to the α-carbon of the acrylate moiety. Ultimately, the molecular parameters necessary for blue-light-triggered Pd-C bond homolysis from this α-carbon to form a carbon-centered macroradical species were established. This intermediate is understood to initiate free radical polymerization of acrylic monomers, thereby facilitating block copolymer synthesis from a single Pd(II) complex. Key intermediates were isolated and comprehensively characterized through exhaustive analytical methods which detail the mechanism while confirming the structural integrity of the polyolefin-polar blocks. Chain walking combined with blue-light irradiation functions as the mechanistic switch from coordination insertion to radical polymerization. On the basis of these discoveries, robust di- and triblock copolymer syntheses have been demonstrated with olefins (ethylene and 1-hexene) which produce amorphous or crystalline blocks and acrylics (methyl acrylate, ethyl acrylate, n-butyl acrylate, and methyl methacrylate) in broad molecular weight ranges and compositions, yielding AB diblocks and BAB triblocks.

Polyolefin Analyses with a 10 mm Multinuclear NMR Cryoprobe.

Polyolefins are important and broadly used materials. Their molecular microstructures have direct impact on macroscopic properties and dictate end-use applications. 13C NMR is a powerful analytical technique used to characterize polyolefin microstructures, such as long-chain branching (LCB), but it suffers from low sensitivity. Although the 13C sensitivity of polyolefin samples can be increased by about 5.5 times with a cryoprobe, when compared with a conventional broadband observe (BBO) probe, further sensitivity enhancement is in high demand for studying increasingly complex polyolefin microstructures. Toward this goal, distortionless enhancement by polarization transfer (DEPT) and refocused insensitive nuclei enhanced by polarization transfer (RINEPT) are explored. The use of hard, regular, and new short adiabatic 180° 13C pulses in DEPT and RINEPT is investigated. It is found that RINEPTs perform better than DEPTs and a sensitivity enhancement of 3.1 can be achieved with RINEPTs. The results of RINEPTs are further analyzed with statistics software JMP and recommendations for optimal usage of RINEPTs are suggested. An example of analyzing saturated chain ends in an ethylene-octene copolymer sample with a hard 180° 13C RINEPT pulse is demonstrated. It is shown that the experimental time can be further reduced in half because of faster proton relaxation, where the total experimental time is about 580 times shorter when compared to using a conventional method and a 10 mm BBO probe. A naturally abundant nitrogen-containing polyolefin is analyzed using 1H-15N HMBC and, to our knowledge, is the first 1H-15N HMBC presented in the field of polyolefin characterization. The relative amount of similar nitrogen-containing structures is quantified by two-dimensional integration of 1H-15N HMBC. Two pragmatic technical challenges related to using high-sensitivity NMR cryoprobes are also addressed: (1) A new 1H decoupling sequence Bi_Waltz_65_256pl is proposed to address decoupling artifacts in 13C{1H} NMR spectra which contain a strong 13C signal with a high signal-to-noise ratio (S/N). (2) A simple pulse sequence that affords zero-slope spectral baselines and quantitative results is presented to address acoustic ringing that is often associated with high-sensitivity cryoprobe use.

Branching Regulation in Olefin Polymerization via Lewis Acid Triggered Isomerization of Monomers.

We present a new strategy to regulate branching in chain-walking olefin polymerization by triggering a rapid isomerization of 1-alkene monomers into internal olefins by adding a Lewis acid. Polymerization of internal alkenes proceeds via chain-walking to give polymers with much higher branching than 1-alkene analogues. The utility of this approach is exemplified by synthesis of well-defined block copolymers with distinct branching characteristics per block by addition of Lewis acid midway through a reaction. We propose a novel mechanism whereby Lewis acid undergoes a counterion swap with the complex which favors isomerization as well as forming adducts with ancillary ligands, freeing coordination sites for internal alkene coordination polymerization.

Olefins and Vinyl Polar Monomers: Bridging the Gap for Next Generation Materials.

The inherent differences in reactivity between activated and non-activated alkenes prevents copolymerization using established polymer synthesis techniques. Research over the past 20 years has greatly advanced the copolymerization of polar vinyl monomers and olefins. This Review highlights the challenges associated with conventional polymerization systems and evaluates the most relevant methods which have been developed to "bridge the gap" between polar vinyl monomers and olefins. We discuss advancements in heteroatom tolerant coordination-insertion polymerizations, methods of controlling radical polymerizations to incorporate olefinic monomers, as well as combined approaches employing sequential polymerizations. Finally, we discuss state-of-the-art stimuli-responsive systems capable of facile switching between catalytic pathways and provide an outlook towards applications in which tailored copolymers are ideally suited.

Trans-meningeal drug delivery to optic nerve ganglion cell axons using a nanoparticle drug delivery system.

The purpose of this study was to investigate if neuroprotective drugs can cross the optic nerve sheath in vitro. Four optic nerves were used for this study. Two porcine nerves were harvested at the time of euthanasia and two human nerves were obtained at the time of therapeutic globe enucleation. The optic nerve sheaths were dissected and placed as a membrane in a two chamber diffusion cell to test meningeal penetration by both brimonidine alone and brimonidine encapsulated in nanoparticle (NP-brimonidine). Brimonidine concentration was assayed by UV-vis spectrometer measurement of absorbance at 389 nm. Increasing concentration of brimonidine on the receiver side of the chamber was measured in both the brimonidine alone and the brimonidine encapsulated experiments. The human data were fitted with a two parameter exponential regression analysis (brimonidine alone donor r(2) = 0.87 and receiver r(2) = 0.80, NP-brimonidine donor r(2) = 0.79 and receiver r(2) = 0.84). Time constant (τ) was 10.2 h (donor) and 13.1 h (receiver) in the brimonidine study, and 24.0 h (donor) and 15.9 h (receiver) in the NP-brimonidine study. Encapsulated brimonidine had a longer time to reach equilibrium. Passage of brimonidine through the optic nerve sheath was demonstrated in the experiments. Increase in time constants when comparing the NP-brimonidine with the brimonidine curves in the human studiesindicates that diffusion is delayed by the initial parameter of drug being loaded in NP. Direct treatment of injured optic nerve axons may be possible by trans-meningeal drug diffusion.

Sequential targeted delivery of paclitaxel and camptothecin using a cross-linked "nanosponge" network for lung cancer chemotherapy.

The applicability of a HVGGSSV peptide targeted "nanosponge" drug delivery system for sequential administration of a microtubule inhibitor (paclitaxel) and topoisomerase I inhibitor (camptothecin) was investigated in a lung cancer model. Schedule-dependent combination treatment with nanoparticle paclitaxel (NP PTX) and camptothecin (NP CPT) was studied in vitro using flow cytometry and confocal imaging to analyze changes in cell cycle, microtubule morphology, apoptosis, and cell proliferation. Results showed significant G2/M phase cell cycle arrest, changes in microtubule dynamics that produced increased apoptotic cell death and decreased proliferation with initial exposure to NP PTX, followed by NP CPT in lung cancer cells. In vivo molecular imaging and TEM studies validated HVGGSSV-NP tumor binding at 24 h and confirmed the presence of Nanogold labeled HVGGSSV-NPs in tumor microvascular endothelial cells. Therapeutic efficacy studies conducted with sequential HVGGSSV targeted NP PTX and NP CPT showed 2-fold greater tumor growth delay in combination versus monotherapy treated groups, and 4-fold greater delay compared to untargeted and systemic drug controls. Analytical HPLC/MS methods were used to quantify drug content in tumor tissues at various time points, with significant paclitaxel and camptothecin levels in tumors 2 days postinjection and continued presence of both drugs up to 23 days postinjection. The efficacy of the NP delivery system in sequential treatments was corroborated in both in vitro and in vivo lung cancer models showing increased G2/M phase arrest and microtubule disruption, resulting in enhanced apoptotic cell death, decreased cell proliferation and vascular density.

Stretchable gas barrier achieved with partially hydrogen-bonded multilayer nanocoating.

Super gas barrier nanocoatings are recently demonstrated by combining polyelectrolytes and clay nanoplatelets with layer-by-layer deposition. These nanobrick wall thin films match or exceed the gas barrier of SiOx and metallized films, but they are relatively stiff and lose barrier with significant stretching (≥ 10% strain). In an effort to impart stretchability, hydrogen-bonding polyglycidol (PGD) layers are added to an electrostatically bonded thin film assembly of polyethylenimine (PEI) and montmorillonite (MMT) clay. The oxygen transmission rate of a 125-nm thick PEI-MMT film increases more than 40x after being stretched 10%, while PGD-PEI-MMT trilayers of the same thickness maintain its gas barrier. This stretchable trilayer system has an OTR three times lower than the PEI-MMT bilayer system after stretching. This report marks the first stretchable high gas barrier thin film, which is potentially useful for applications that require pressurized elastomers.

Enzyme assisted peptide self-assemblies trigger cell adhesion in high density oxime based host gels.

Peptide supramolecular self-assemblies are recognized as important components in responsive hydrogel based materials with applications in tissue engineering and regenerative medicine. Studying the influence of hydrogel matrices on the self-assembly behavior of peptides and interaction with cells is essential to guide the future development of engineered biomaterials. In this contribution, we present a PEG based host hydrogel material generated by oxime click chemistry that shows cellular adhesion behavior in response to enzyme assisted peptide self-assembly (EASA) within the host gel. This hydrogel prepared from poly(dimethylacrylamide-co-diacetoneacrylamide), poly(DMA-DAAM) with high molar fractions (49%) of DAAM and dialkoxyamine PEG cross-linker, was studied in the presence of embedded enzyme alkaline phosphatase (AP) and a non-adhesive cell behavior towards NIH 3T3 fibroblasts was observed. When brought into contact with a Fmoc-FFpY peptide solution (pY: phosphorylated tyrosine), the gel forms intercalated Fmoc-FFY peptide self-assemblies upon diffusion of Fmoc-FFpY into the cross-linked hydrogel network as was confirmed by circular dichroism, fluorescence emission spectroscopy and confocal microscopy. Nevertheless, the mechanical properties do not change significantly after the peptide self-assembly in the host gel. This enzyme assisted peptide self-assembly promotes fibroblast cell adhesion that can be enhanced if Fmoc-F-RGD peptides are added to the pre-gelator Fmoc-FFpY peptide solution. Cell adhesion results mainly from interactions of cells with the non-covalent peptide self-assemblies present in the gel despite the fact that the mechanical properties are very close to those of the native host gel. This result is in contrast to numerous studies which showed that the mechanical properties of a substrate are key parameters of cell adhesion. It opens up the possibility to develop a diverse set of hybrid materials to control cell fate in culture due to tailored self-assemblies of peptides responding to the environment provided by the host guest gel.

Enzyme-assisted self-assembly within a hydrogel induced by peptide diffusion.

The diffusion of adequate peptide through an enzyme-embedded host hydrogel leads to the in situ start-up and growth of an interpenetrated fibrous network. Based on the enzyme-assisted self-assembly concept, both chemistry and mechanical features of the hybrid hydrogel can be tuned.

Approach to formation of multifunctional polyester particles in controlled nanoscopic dimensions.

We present the synthesis of discrete functionalized polyester nanoparticles in selected nanoscale size dimensions via a controlled intermolecular chain cross-linking process. The novel technique involves the controlled coupling of epoxide functionalized polyesters with 2,2'-(ethylenedioxy)bis(ethylamine) to give well-defined nanoparticles with narrow size distribution and selected nanoscopic size dimensions. Diverse functionalized polyesters, synthesized with pendant functionalities via ring-opening copolymerization of delta-valerolactone with alpha-allyl-delta-valerolactone, alpha-propargyl-delta-valerolactone and 2-oxepane-1,5-dione, were prepared as linear precursors which facilitated 3-D nanoparticles with functionalities such as amines, keto groups, and alkynes for post modification reactions. We found that the nanoparticle formation and the control over the nanoscopic dimension is primarily influenced by the degree of the epoxide entity implemented in the precursor polymers and the amount of 2,2'-(ethylenedioxy)bis(ethylamine) as cross-linking reagent. The other functionalities in the linear polyester do not participate in the nanoparticle formation and particles with defined functionalities can be prepared from batches of identical linear polymers containing various functionalities or by mixing different polyester materials to achieve controlled amounts of specific functional groups. The utilization of integrated functionalities was demonstrated in one post-modification reaction with N-Boc-ethylenediamine via reductive amination. This work describes the development of a novel methodology to prepare functionalized well-defined 3-D nanoparticle polyester materials in targeted nanoscopic ranges with amorphous morphologies or tailored crystallinities that offer a multitude of utilizations as a result of their unique properties and control in preparation.

Controlled electrophoretic deposition of uniquely nanostructured star polymer films.

The controlled electrophoretic deposition of polystyrene/divinylbenzene (PS/DVB) star polymer films from a colloidal suspension is reported. Liquid suspensions, containing the PS/DVB star polymer, were prepared by injecting a dichloromethane (DCM) solution of the star polymer into a stratified liquid combination of hexane and DCM. A variety of hexane/DCM volume ratios were examined to identify the optimal solution conditions for electrophoretic deposition; thin films were produced from both unmixed and well-mixed hexane/DCM suspensions. Unmixed suspensions yielded spatially separated thin films, deposited in a controlled fashion, that were dependent on the polarity of the corresponding electrode. Films on the positive electrode differed in thickness, microstructure, and appearance from those formed on the negative electrode. In contrast, films produced from well-mixed hexane/DCM suspensions deposited uniformly across only the negative electrode. Atomic force microscopy studies revealed nanostructured surface morphologies that were unique to each of these films. Additionally, these microscopy studies shed light on the possible conformations of star polymers adsorbed on a surface. By controlling the composition and the mixing state of the solution and by controlling the bias of electrodes, we achieved controlled deposition of star polymer films with a specific nanostructure. These nanostructured films may have broad use in optical and biological device applications.

Photocontrolled Growth of Cross-Linked Nanonetworks.

We report the preparation of photoresponsive nanomaterials and the increase of their nanoscopic size through a "photogrowth" mechanism. The photogrowable nanonetworks (PGNNs) were synthesized by cross-linking two components, a thiolated acrylate copolymer and a symmetrical bismaleimide trithiocarbonate (TTC), utilizing thiol-maleimide click chemistry. With this strategy, nanonetwork growth was achieved through a photoinduced polymerization from the integrated trithiocarbonate by either direct photolysis or photoredox catalysis. Via direct photolysis, we generated a series of expanded particles by polymerizing methyl acrylate (MA) under irradiation with violet light (400 nm) over a period of 1, 3, and 6 h, starting from a 58 nm parent particle, resulting in particles of increased sizes of 77, 156, and 358 nm, respectively. Nanoparticle expansion reactions catalyzed by 10-phenylphenothiazine (PTH) were experienced to progress faster in 20 and 30 min to reach particle sizes of 195 and 300 nm. The addition of the photoredox catalyst to the expansion polymerizations with MA resulted in an increased control over the dispersity of the particles as well as of the promoted disassembly products. In this work, we demonstrated that nanoparticle structures designed as cross-linked networks with integrated trithiocarbonates can be expanded by photocontrolled radical polymerizations (photo-CRPs) in the presence or absence of a photoredox catalyst. These proof-of-concept experiments showcase the dynamic growth and integration of functional units into existing scaffolds and open up the possibility to prepare highly tailorable nanomaterials.

Poly(glycidol) Coating on Ultrahigh Molecular Weight Polyethylene for Reduced Biofilm Growth.

Semibranched poly(glycidol) (PG-OH) and poly(glycidol allylglycidyl ether) (PG-Allyl) coatings were formed on ultrahigh molecular weight polyethylene (UMWPE) in a unique two-step process which included radiation of UHMWPE followed by grafting of PG-OH or PG-Allyl to the surface via free radical cross-linking. Resulting surfaces were extensively characterized by FTIR-ATR, XPS, fluorescent microscopy, and contact goniometry. The performance was evaluated using the most prominent biofilm-forming bacteria Staphylococcus aureus for 24 and 48 h. The PG-Allyl coating demonstrated a 3 log reduction in biofilm growth compared to noncoated control, demonstrating a promising potential to inhibit adherence and colonization of biofilm-forming bacteria that often develop into persistent infections.