Sequential Monomer Addition Research Articles

Spontaneously Healable Thermoplastic Elastomers Achieved through One-Pot Living Ring-Opening Metathesis Copolymerization of Well-Designed Bulky Monomers.

We report here a series of novel spontaneously healable thermoplastic elastomers (TPEs) with a combination of improved mechanical and good autonomic self-healing performances. Hard-soft diblock and hard-soft-hard triblock copolymers with poly[exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-benzeno-l,4-methanoanthracene] (PHBM) as the hard block and secondary amide group containing norbornene derivative polymer as the soft block were synthesized via living ring-opening metathesis copolymerization by use of Grubbs third-generation catalyst through sequential monomer addition. The microstructure, mechanical, self-healing, and surface morphologies of the block copolymers were thoroughly studied. Both excellent mechanical performance and self-healing capability were achieved for the block copolymers because of the interplayed physical cross-link of hard block and dynamic interaction formed by soft block in the self-assembled network. Under an optimized hard block (PHBM) weight ratio of 5%, a significant recovery of tensile strength (up to 100%) and strain at break (ca. 85%) was achieved at ambient temperature without any treatment even after complete rupture. Moreover, the simple reaction operations and well-designed monomers offer versatility in tuning the architectures and properties of the resulting block copolymers.

Global kinetic analysis of seeded BSA aggregation

Accelerated aggregation studies were conducted around the melting temperature (Tm) to elucidate the kinetics of seeded BSA aggregation. Aggregation was tracked by SEC-HPLC and intrinsic fluorescence spectroscopy. Time evolution of monomer, dimer and soluble aggregate concentrations were globally analysed to reliably deduce mechanistic details pertinent to the process. Results showed that BSA aggregated irreversibly through both sequential monomer addition and aggregate–aggregate interactions. Sequential monomer addition proceeded only via non-native monomers, starting to occur only by 1–2°C below the Tm. Aggregate–aggregate interactions were the dominant mechanism below the Tm due to an initial presence of small aggregates that acted as seeds. Aggregate–aggregate interactions were significant also above the Tm, particularly at later stages of aggregation when sequential monomer addition seemed to cease, leading in some cases to insoluble aggregate formation. The adherence (or non-thereof) of the mechanisms to Arrhenius kinetics were discussed alongside possible implications of seeding for biopharmaceutical shelf-life and spectroscopic data interpretation, the latter of which was found to often be overlooked in BSA aggregation studies.

Tailored Synthesis of Triblock Co- and Terpolymers Composed of Synthetically Difficult Sequence Orders by Combining Living Anionic Polymerization with Specially Designed Linking Reaction

This study demonstrates the versatility and wider applicability of the recently developed methodology combining the living anionic polymerization with a specially designed linking reaction using the α-phenylacrylate (or benzyl bromide) function, allowing the synthesis of triblock co- and terpolymers, which are otherwise difficut to be obtained by sequential addition of monomers during a sequential polymerization approach. With this methodology using styrene and four para-substituted styrene derivatives with N-cyclohexylimine, 4-N,N-dimethyl-2-oxazoline, 2,6-di(tert-butyl)-4-methylphenyl ester, and nitrile, 12 polymers among the 16 possible triblock terpolymers and 6 triblock copolymers were successfully synthesized. Furthermore, the synthesis of two tetrablock quarterpolymers was achieved by the same linking methodology. The polymers synthesized in this study are all well-controlled in chain length, composition, which are difficult to be obtained by the sequential polymerization. In addition, they possess functional groups usable for the further modification and introduction of other functionalities.

Controlled Synthesis of an Alternating Donor-Acceptor Conjugated Polymer via Kumada Catalyst-Transfer Polycondensation.

Kumada catalyst-transfer polycondensation was used to synthesize poly(5,6-difluorobenzotriazole-alt-4-hexylthiophene) (PFBTzHT), an alternating donor-acceptor conjugated polymer, in a controlled manner. Through a series of kinetic studies, a linear relationship between the monomer conversion and the molecular weight of the resulting polymer was observed while maintaining narrow polydispersities (Đs ≤ 1.4). Moreover, the Mn displayed a linear relationship with the initial monomer-to-catalyst feed ratio, and polymers with Mns up to 25 kDa were successfully synthesized. All-conjugated block copolymers containing segments of PFBTzHT and poly(3-hexylthiophene) (P3HT) were also obtained in various compositions (30-70% P3HT) via sequential monomer addition in a single vessel.

Boric acid as biocatalyst for living ring-opening polymerization of ε-caprolactone

Boric acid (1, B(OH)3) was investigated as metal-free biocatalyst for its activity towards the bulk ring-opening polymerization (ROP) of ε-caprolactone (CL) initiated by benzyl alcohol (BnOH). Moreover, other boric acid derivates such as phenylboronic acid (2), 2-thienylboronic acid (3), 2-furanylboronic acid (4) and 5-pyrimidinylboronic acid (5) were also used as acidic catalysts to synthesize poly(ε-caprolactone) (PCL), poly(δ-valerolactone) (PVL) and poly(trimethylene carbonate) (PTMC). The studies on the polymerization kinetics for all catalysts confirm that the reaction rates are first-order with respect to monomer and their catalytic activities follow the order 1 > 3 > 2 ≈ 4 > 5. Furthermore, the block copolymerization of ε-caprolactone (CL) with δ-valerolactone (VL) and trimethylene carbonate (TMC) successfully proceeded by the sequential monomer addition to give PCL-b-PVL and PTMC-b-PCL copolymers, indicating the living nature of the present polymerization system. The end group analysis by 1H NMR and MALDI-TOF MS measurements suggested that the benzyl moiety of initiator inserted into the synthesized polymeric chain. The existence of the interaction between the catalyst B(OH)3 and the monomer CL supports that B(OH)3 catalyzed ROP of CL preferred an activated monomer mechanism. A possible model for the initiation and propagation procedures of ROP of cyclic esters catalyzed by boric acid in the presence of benzyl alcohol was proposed.

Conformational Heterogeneity Determined by Folding and Oligomer Assembly Routes of the Interferon Response Inhibitor NS1 Protein, Unique to Human Respiratory Syncytial Virus.

The nonstructural NS1 protein is an essential virulence factor of the human respiratory syncytial virus, with a predominant role in the inhibition of the host antiviral innate immune response. This inhibition is mediated by multiple protein-protein interactions and involves the formation of large oligomeric complexes. There is neither a structure nor sequence or functional homologues of this protein, which points to a distinctive mechanism for blocking the interferon response among viruses. The NS1 native monomer follows a simple unfolding kinetics via a nativelike transition state ensemble, with a half-life of 45 min, in agreement with a highly stable core structure at equilibrium. Refolding is a complex process that involves several slowly interconverting species compatible with proline isomerization. However, an ultrafast folding event with a half-life of 0.2 ms is indicative of a highly folding compatible species within the unfolded state ensemble. On the other hand, the oligomeric assembly route from the native monomer, which does not involve unfolding, shows a monodisperse and irreversible end-point species triggered by a mild temperature change, with half-lives of 160 and 26 min at 37 and 47 °C, respectively, and at a low protein concentration (10 μM). A large secondary structure change into β-sheet structure and the formation of a dimeric nucleus precede polymerization by the sequential addition of monomers at the surprisingly low rate of one monomer every 34 s. The polymerization phase is followed by the binding to thioflavin-T indicative of amyloid-like, albeit soluble, repetitive β-sheet quaternary structure. The overall process is reversible only up until ~8 min, a time window in which most of the secondary structure change takes place. NS1's multiple binding activities must be accommodated in a few binding interfaces at most, something to be considered remarkable given its small size (15 kDa). Thus, conformational heterogeneity, and in particular oligomer formation, may provide a means of expand its binding repertoire. These equilibria will be determined by variables such as macromolecular crowding, protein-protein interactions, expression levels, turnover, or specific subcellular localization. The irreversible and quasi-spontaneous nature of the oligomer assembly, together with the fact that NS1 is the most abundant viral protein in infected cells, makes its accumulation highly conceivable under conditions compatible with the cellular milieu. The implications of NS1 oligomers in the viral life cycle and the inhibition of host innate immune response remain to be determined.

Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics Simulations.

Melittin is a natural peptide that aggregates in aqueous solutions with paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is known about the molecular mechanisms of melittin aggregation in solution, we simulated its self-aggregation process under various conditions. After confirming the stability of a melittin tetramer in solution, we observed—for the first time in atomistic detail—that four separated melittin monomers aggregate into a tetramer. Our simulated dependence of melittin aggregation on peptide concentration, temperature, and ionic strength is in good agreement with prior experiments. We propose that melittin mainly self-aggregates via a mechanism involving the sequential addition of monomers, which is supported by both qualitative and quantitative evidence obtained from unbiased and metadynamics simulations. Moreover, by combining computer simulations and a theory of the electrical double layer, we provide evidence to suggest why melittin aggregation in solution likely stops at the tetramer, rather than forming higher-order oligomers. Overall, our study not only explains prior experimental results at the molecular level but also provides quantitative mechanistic information that may guide the engineering of melittin for higher efficacy and safety.

Synthesis and characterization of all-conjugated hard-soft-hard ABA triblock copolythiophenes

A new thiophene monomer design was demonstrated by exploiting the flexibility and bulkiness of trisiloxane units to produce "soft" polythiophene materials. In practice, the thiophene monomer having trisiloxane units could be polymerized by Kumada Catalyst-Transfer Polymerization (KCTP) to afford well-defined poly(1,1,1,3,3,5,5-heptametyl-5-(6?-(thien-3?-yl)hexyl)trisiloxane-2?,5?-diyl) (P3SiHT) with low dispersity, which was viscous material with fluidity. To the best of our knowledge, it is first time to develop "liquid" polythiophene at room temperature. In addition, we are successful in synthesizing novel all-conjugated hard-soft-hard ABA triblock copolymer, where A and B were poly(3-hexylthiophene) (P3HT) and P3SiHT, respectively, based on KCTP method and sequential monomer addition technique. The livingness of the KCTP system was confirmed by size exclusion chromatography (SEC) UV traces. The formation of phase separated P3HT and P3SiHT domains in the triblock copolymer (P3HT-b-P3SiHT-b-P3HT) was supported by differential scanning calorimetry (DSC), although the existence of miscible domains was also implied.

Controlled homo- and copolymerization of propene and 1-undecene catalyzed by post-metallocenes

Homo- and copolymers of propene and 1-undecene were synthesized by controlled olefin polymerization (quasi-living polymerization) using two bis(phenoxyamine) zirconium complexes as catalysts. The controlled character is demonstrated by an asymptotic growth of molar mass as a function of polymerization time. For the first time, it was possible to synthesize block-like copolymers incorporating long 1-olefins like 1-undecene and propene blocks using the strategy of sequential monomer addition. The obtained copolymers have been characterized in terms of molecular and thermal properties. The copolymer composition was determined by 1H NMR spectroscopy whereas the quantification of diads by 13C NMR spectroscopy proves the blocky character of the polymers. SEC results confirm indirectly the formation of block-like copolymers showing monomodal molar mass distribution excluding the formation of two homopolymers. The DSC measurements revealed that the blocky samples show two melting and two crystallization peaks, in contrast to statistical copolymers. These results of DSC and NMR measurements give distinct indication of the blocky type of the copolymer structure.

Living Anionic Polymerization of 1,4-Diisopropenylbenzene

The anionic polymerization of diisopropenylbenzene (DIPB) derivatives was conducted in THF at −78 °C with a specially designed initiator system prepared from oligo(α-methylstyryl)lithium and an excess potassium tert-butoxide (KOBut) (2.7–5.0 equiv to the Li salt). Among the ortho-, meta-, and para-isomers of DIPB derivatives, it was found that the para-isomer (p-DIPB) successfully underwent the living polymerization in a selective manner through one of the two isopropenyl groups under the above stated conditions. With this living polymerization system, soluble polymers with controllable Mn values ranging from 7620 to 31 500 g/mol and near monodisperse distributions (Mw/Mn ≤ 1.03) were obtained for the first time. The obtained living polymers were stable at −78 °C even after 168 h and at −40 °C after 6 h, in which the intermolecular addition reaction of the chain-end anion to the pendant isopropenyl group could be completely suppressed. In contrast, the living polymerization of either the ortho- or meta-isomer was not successful under the same conditions. The block copolymerization of p-DIPB with either styrene (S), 2-vinylpyridine (2VP), or tert-butyl methacrylate (tBMA) by the sequential addition of such monomers was conducted. Four new PS-block-P(p-DIPB), P2VP-block-P(p-DIPB), P(p-DIPB)-block-P2VP, and P(p-DIPB)-block-PtBMA containing reactive P(p-DIPB) segments were synthesized. On the basis of the block copolymerization results, it is understood that p-DIPB is comparable to 2VP and located between S and tBMA in monomer reactivity. The reactivity increases as follows: S < 2VP ∼ p-DIPB < tBMA, while the nucleophilicity of the living chain-end anion decreases in the following order: PS– > P2VP– ∼ P(p-DIPB) – > P(tBMA) –.

Ring‐Expansion Living Cationic Polymerization of Vinyl Ethers: Optimized Ring Propagation

SummaryFor the “ring‐expansion” living cationic polymerization of vinyl ethers that has recently been achieved for the first time with a hemiacetal ester‐embedded cyclic initiator (1), we investigated the effects of reaction conditions (Lewis acid catalysts/activators, solvents, temperature, and reagent concentration) on the selectivity and controllability for construction of ring chains. For example, the choice of the Lewis acid catalysts turned out crucial. Specifically, tin tetrabrommide (SnBr4) was suitable, with which an undisturbed ring‐expansion propagation proceeded without irreversible side reactions, to selectively construct the ring topology, though accompanied by “ring fusion” into fused ring polymers of higher molelcular weights. The fusion event, however, could be suppressed by decreasing concentration of the initiator, namely, polymers to be formed therefrom. Under these optimized conditions, the propagation is controlled enough to allow sequential addition of monomers to give either chain‐extended homopolymers or block copolymers. Thus, the ring‐expansion cationic polymerization is potentially a powerful tool to construct ring polymer architectures with precision control similar to that for linear living polymers.

Living Vinyl Addition Polymerization of Substituted Norbornenes by a t-Bu3P-Ligated Methylpalladium Complex

The vinyl addition polymerization of substituted norbornene (NB) monomers, via (t-Bu3P)PdMeCl activated by [Li(OEt2)2.5]B(C6F5)4, is investigated. NB monomers bearing alkyl, aryl, fluoroaryl, and even hexafluoroisopropanol substituents yield polymers exhibiting monomodal and narrow molecular weight distributions, with molecular weight controlled by reaction time and monomer to initiator ratio, demonstrating the living nature of these polymerizations. These polymers are soluble in common organic solvents and possess excellent thermal stability. Block copolymers are also prepared via sequential monomer addition; these are the first examples of well-defined block copolymers of substituted NB monomers enchained by vinyl addition polymerization.

Simple Preparation of Various Nanostructures via in Situ Nanoparticlization of Polyacetylene Blocklike Copolymers by One-Shot Polymerization

Previously, we reported the one-pot synthesis of polyacetylene (PA) diblock copolymers which formed various nanostructures via the in situ nanoparticlization of conjugated polymers (INCP), using a two-step protocol based on sequential monomer addition. Herein, we report a much simpler one-shot method for nanostructure formation by the synthesis of PA blocklike copolymers. The blocklike copolymers could be prepared by the one-shot ROMP of comonomers with large differences in their reactivities because the monomers that formed the first block, namely norbornene (NB) derivatives or endo-tricyclo[4.2.2.0]deca-3,9-diene (TD) derivatives, polymerized much faster than the monomers that formed the second PA block, cyclooctatetraene (COT). Owing to their blocklike microstructures, the copolymers formed various nanostructures such as nanospheres, nanocaterpillars, and nanoaggregates depending on the chemical structures of the soluble shell polymers and feed ratio of COT, which formed the insoluble PA core. Using dynamic light scattering (DLS) and atomic force microscopy (AFM), it was observed that the nanostructures produced from the blocklike copolymers were essentially the same as those produced from the block copolymers synthesized by conventional sequential monomer addition. The blocklike microstructures of the copolymers formed by one-shot ROMP were further supported by an in situ 1H NMR kinetic experiment and UV/vis spectroscopy. From these results, we were able to confirm that the ROMP of TD and COT produced near-perfect block copolymers. Furthermore, the 1H NMR spectra of the one-shot copolymerization provided insights into the INCP process.

L-lactide homopolymerization and copolymerization with ɛ-caprolactone by tetrahydrosalen stabilized yttrium borohydride complex

L-lactide (LLA) homopolymerization and copolymerization with ɛ-caprolactone (CL) in toluene initiated by tetrahydrosalen-supported yttrium borohydride complex were systematically investigated. A possible mechanism of LLA homopolymerization was proposed according to the 1H-NMR result. In addition, PCL-b-PLLA copolymers were synthesized by sequential addition of monomers and their structure was characterized by GPC, 1H-NMR and 13C-NMR.

Phase Behavior of Poly(4-hydroxystyrene-block-styrene) Synthesized by Living Anionic Polymerization of an Acetal Protected Monomer

We have synthesized a series of poly(4-(2-tetrahydropyranyloxy)styrene) [P(OTHPSt)] homopolymers by living anionic polymerization of the protected monomer (OTHPSt) in tetrahydrofuran at −78 °C, with excellent control over molecular weight and dispersity. The high Tg of P(OTHPSt) led to facile purification and isolation of the polymer as a powder. Characterization of the POTHPSt homopolymer by nuclear Overhauser effect spectroscopy confirms the strong preference for the axial position of the relatively sterically demanding alkoxy phenyl group. By sequential monomer addition, a series of low to high molecular weight P(OTHPSt-b-styrene) BCPs with narrow dispersities were synthesized. Quantitative deprotection of the THP groups yielded poly(4-hydroxystyrene-b-styrene) with tunable molecular weights and compositions. The solid-state and melt-phase self-assembly of these diblocks was investigated using synchrotron small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Mean-field theory analysis of the temperature-dependent correlation-hole scattering for a disordered diblock was used to determine the interaction parameter as χHS/S(T) = (4.39 ± 0.83)/T + (0.109 ± 0.002), which is approximately 4 times larger than that of poly(styrene-b-methyl methacrylate) with the same disproportionately high contribution of entropy to the free energy of mixing.

Combining Enzymatic Monomer Transformation with Photoinduced Electron Transfer - Reversible Addition-Fragmentation Chain Transfer for the Synthesis of Complex Multiblock Copolymers.

A novel and facile method, involving enzymatic monomer synthesis and a photocontrolled polymerization technique, has been successfully employed for the preparation of high-order multiblock copolymers. New acrylate monomers were synthesized via enzymatic transacylation between an activated monomer, i.e., 2,2,2-trifluoroethyl acrylate (TFEA), and various functional alcohols. These synthesized monomers were successfully polymerized without further purification via photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under low energy blue LED light (4.8 W) in the presence of an iridium-based photoredox catalyst (fac-[Ir(ppy)3]). In this condition, PET-RAFT allows us to achieve high monomer conversion (∼100%) with excellent integrity of the end group (>80%). Different multiblock (co)polymers, including poly(hexyl acrylate) pentablock homopolymer, poly(methyl acylate-b-ethyl acrylate-b-n-propyl acrylate-b-n-butyl acrylate-b-n-pentyl acrylate) pentablock copolymer, and poly(3-oxobutyl acrylate-b-methyl acrylate-b-3-(trimethylsilyl)prop-2-yn-1-yl acrylate) triblock copolymer containing functional groups were rapidly prepared via sequential addition of monomers without purification steps.

Regio- and Stereospecific Cyclopolymerization of Bis(2-propenyl)diorganosilanes and the Two-State Stereoengineering of 3,5-cis,isotactic Poly(3,5-methylene-1-silacyclohexane)s.

Transition-metal-mediated coordination cyclopolymerization of bis(2-propenyl)dimethylsilane (1a) using the C1-symmetric, group 4 metal preinitiator, (η5-C5Me5)Zr(Me)2[N(Et)C(Me)N(tBu)] (I), in combination with 1 equiv of the borate coinitiator, [PhNHMe2][B(C6F5)4] (II), proceeds in a regio- and stereospecific manner to provide highly stereoregular 3,5-cis,isotactic poly(3,5-methylene-1,1-dimethyl-1-silacyclohexane) (2a). Successful stereoengineering of 2a to eliminate undesirable crystallinity while preserving a high Tg value of >120 °C was subsequently accomplished by employing a "two-state" propagation system that uniquely produces an isotactic stereoblock microstructure of decreasing stereoblock length with decreasing percent level of "activation" of I with II. The controlled character of cyclopolymerization of 1a using the less sterically encumbered preinitiator, (η5-C5Me5)Hf(Me)2[N(Et)C(Me)N(Et)] (III), and 1 equiv of II was used to prepare well-defined poly(1-hexene)-b-poly(3,5-methylene-1-silacyclohexane) block copolymers through sequential monomer additions.

Simplified TERP to achieve living free radical polymerization with crude ethyl 2-phenyltellanyl-2-methylpropionate as mediator

Organotellurium compounds-mediated living radical polymerization (TERP) is one of the most robust tools of living free radical polymerizations (LRP). However, synthesis and purification of organotellurium compounds are time-consuming and to be operated in an inert atmosphere due to their extreme sensitivity to trace oxygen. In this article, a simple process of TERP, operating in open air, has been reported. It has demonstrated that the crude organotellurium compound, ethyl 2-phenyltellanyl-2-methylpropionate, could mediate 2,2′-azobis (isobutyronitrile) initiated styrene (St) and butyl acrylate (BA) polymerization as an LRP system. For the bulk and solution polymerization of St and the solution polymerization of BA, the molecular weights of produced polymers increased linearly with the monomer conversions. During the same time, the molecular weight distributions kept under 1.3. The UV–vis spectrum showed that the PS polymer chain bearing C-TePh end group. With the sequential monomer addition technique, a clean diblock polymer of PS-b-PBA was also obtained.

Controlled synthesis of low-polydisperse regioregular poly(3-hexylthiophene) and related materials by zincate-complex metathesis polymerization

This paper reviews the development of zincate-complex metathesis polymerization (ZCMP) and its application to protection-free direct synthesis of poly(3-(6-hydroxyhexyl)thiophene) as well as block copolythiophene. The modified ZCMP system using Ni(dcpe)Cl2 as a catalyst accomplished the preparation of well-defined poly(3-hexylthiophene)s (P3HTs) (Mn up to 35 000 g mol−1) with extremely low PDI (1.03∼1.11). In addition, the first example of all-conjugated block copolythiophene, P3HT-b-poly(3-octadecylthiophene), could be synthesized on the basis of the sequential monomer addition approach based on ZCMP.

Optimization of an α‐(Amino acid)‐N‐carboxyanhydride polymerization using the high vacuum technique: Examining the effects of monomer concentration, polymerization kinetics, polymer molecular weight, and monomer purity

ABSTRACTl‐Ornithine‐based poly(peptides) have been widely utilized in the field of drug delivery, however few studies have been conducted examining the details of polymerization. In this article, the effects of monomer concentration, polymerization kinetics, polymer molecular weight and monomer purity were investigated using l‐carboxybenzyl (Cbz)‐ornithine as a model monomer. The mechanism of polymerization herein follows the normal amine mechanism to produce poly(peptides) having controlled molecular weights, known chain ends and a narrow polydispersity index (PDI). A preferred monomer concentration range was determined, which required minimal polymerization times and allowed for predictable and reproducible molecular weights with narrow PDIs. The impact of monomer purity on the polymerization was established and monomer purification conditions are reported, which produce high‐purity monomer after a single recrystallization. Additionally, the optimized polymerization conditions and monomer purification protocol were combined with a sequential monomer addition technique to produce high molecular weight poly(ornithine) with a narrow PDI and known chain ends. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1385–1391