Monomer Sequence Research Articles

An Arbitrarily Regulated Monomer Sequence in Multi-Block Copolymer Synthesis by Frustrated Lewis Pairs.

Rapid access to sequence-controlled multi-block copolymers (multi-BCPs) remains as a challenging task in the polymer synthesis. Here we employ a Lewis pair (LP) composed of organophosphorus superbase and bulky organoaluminum to effectively copolymerize the mixture of methacrylate, cyclic acrylate, and two acrylates, into well-defined di-, tri-, tetra- and even a hepta-BCP in one-pot one-step manner. The combined livingness, dual-initiation and CSC feature of Lewis pair polymerization enable us to achieve not only a trihexaconta-BCP with the highest record in 8 steps by using four-component monomer mixture as building blocks, but also the arbitrarily-regulated monomer sequence in multi-BCP, simply by changing the composition and adding order of the monomer mixtures, thus demonstrating the powerful capability of our strategy in improving the efficiency and enriching the composition of multi-BCP synthesis.

Protecting-Group-Free Iterative Divergent/Convergent Method for Preparing Sequence-Defined Polymers

A new iterative growth method is reported to prepare monodisperse sequence-defined polymers by combining the chain growth mechanisms of the traditional iterative sequential growth (ISG) and iterative exponential growth (IEG) strategies. Using three orthogonal click reactions to couple three groups of monomers, each containing two orthogonal clickable groups. This method grows monodisperse sequence-defined polymers in a protecting-group-free divergent/convergent way. Each iterative cycle of this method involves two divergent sequential growth steps and one convergent exponential growth step, which endows the new method with the chain growth advantages of both traditional ISG and IEG. The two divergent sequential growth reactions introduce new monomer structures into main chains and provide the resultant sequence-defined polymers with varied monomer sequences, while the convergent exponential growth reaction guarantees the method a fast chain growth speed. The repetition of the abovementioned iterative cycle allows this method to grow monodisperse sequence-defined polymers with a fast chain growth manner of 3 × 2n–2.

PH response of sequence-controlled polyampholyte brushes.

We use molecular simulation to investigate the pH response of sequence-controlled polyampholyte brushes (PABs) with polymer chains consisting of alternating blocks of weakly acidic and basic monomers. Changes in the ionization state, height, lateral structure, and chain conformations of PABs with pH are found to differ qualitatively from those observed for polyelectrolyte brushes. Grafting density has a relatively modest effect on PAB properties. By contrast, monomer sequence strongly affects the pH response, with the extent of the response increasing with the block size. This trend is attributed to strong electrostatic attractions between oppositely charged blocks, which lead to an increase in chain backfolding as block size increases. This behavior is consistent with that observed for polyampholytes with similar monomer sequences in solution in previous studies. Our study shows that monomer sequence can be used to tune the pH response of weak PABs to generate stimuli-responsive surfaces.

Influence of polymerisation conditions on the kinetics of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) triblock synthesis and the occurrence of transesterification side reactions

Investigating how different reaction conditions influence the reaction kinetics, monomer sequence and side reactions for the synthesis of a PLGA-PEG-PLGA triblock copolymer.

Molecular dynamics simulations of copolymer compatibilizers for polylactide/poly(butylene succinate) blends.

The effects of the molecular architecture of polylactide (PLA)-poly(butylene succinate) (PBS) copolymers on their compatibilization efficiency in immiscible PLA/PBS blends were studied using atomistic molecular-dynamics simulations. The results showed that the diblock copolymer is the most efficient at mixing with PLA and PBS homopolymers and reducing the interfacial tension of the blend. Tensile properties of the compatibilized blends were examined using uniaxial deformation simulations. Deformation behaviours of the blends at the molecular level were revealed. Both the structure (i.e. linear and branch) and the monomer sequence of the copolymers were found to affect the tensile performance. The system with a diblock copolymer showed a much greater tensile strength and elastic modulus than the other compatibilized blends. Comparing between triblock and graft copolymers, the former yielded the blends with better tensile performance than the latter. Our results suggest that copolymers with a linear structure, especially the diblock one, could be good candidates for the compatibilizer of PLA/PBS blends.

A single monomer difference can impact the nanostructure output of precision oligo(phosphodiesters)

In this paper, we describe the precise synthesis of poly(phosphodiesters) with up to four monomers. These self-assemble into various nanostructures where a single monomer difference drastically impacts the structure's size and morphology.

Synthesis of Stereoregular Uniform Oligomers Possessing a Dense 1,2,3-Triazole Backbone

Recent remarkable progress of precision polymerization techniques has allowed researchers to synthesize polymers of controlled molecular weight, tacticity, and monomer sequence with narrow distributions. However, it is still a challenging subject to synthesize uniform polymers and oligomers, which possess specific molecular weight, tacticity, and monomer sequence. Utilizing the advantages of t-butyl 4-azido-5-hexynoate (tBuAH), which we designed recently, for the synthesis of uniform polymers and oligomers, uniform oligomers of different stereoregularities possessing a dense 1,2,3-triazole backbone were synthesized using optically active tBuAH precursors by iterative procedures containing azidation, deprotection of the protecting group, and copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The stereoregular uniform oligomers were characterized in the solid state by powder X-ray diffraction (PXRD) and in the solution state by pulse-field-gradient spin-echo (PGSE) NMR, ultraviolet (UV) absorption, and circular dichroism (CD) spectroscopic techniques. While the solubility of stereoregular uniform oligomers was investigated using common organic solvents, gelation was observed for solutions of two octamers of different stereoregularities in some solvents, e.g., toluene, tetrahydrofuran (THF), acetone, and methanol. It is noteworthy that the intermolecular attractive interaction depended on the stereoregularity in aprotic polar solvents, i.e., THF and acetone, presumably because of the different polarities of octamers.

Mannuronan C-5 Epimerases: Review of Activity Assays, Enzyme Characteristics, Structure, and Mechanism

Mannuronan C-5 epimerases (ManC5-Es) are produced by brown algae and some bacteria, such as Azotobacter and some Pseudomonas species. It can convert the transformation of β-D-mannuronic acid (M) to α-L-guluronic acid (G) in alginate with different patterns of epimerization. Alginate with different compositions and monomer sequences possess different properties and functions, which have been utilized in industries for various purposes. Therefore, ManC5-Es are key enzymes that are involved in the modifications of alginate for fuel, chemical, and industrial applications. Focusing on ManC5-Es, this review introduces and summarizes the methods of ManC5-Es activity assay especially the most widely used nuclear magnetic resonance spectroscopy method, characterization of the ManC5-Es from different origins especially the research progress of its enzymatic properties and product block distributions, and the catalytic mechanism of ManC5-E based on the resolved enzyme structures. Additionally, some potential future research directions are also outlooked.

Self-Assembly of Repetitive Segment and Random Segment Polymer Architectures.

Recent advances in chemical synthesis have created new methodologies for synthesizing sequence-controlled synthetic polymers, but rational design of monomer sequence for desired properties remains challenging. In this work, we synthesize periodic polymers with repetitive segments using a sequence-controlled ring-opening metathesis polymerization (ROMP) method, which draws inspiration from proteins containing repetitive sequence motifs. The repetitive segment architecture is shown to dramatically affect the self-assembly behavior of these materials. Our results show that polymers with identical repetitive sequences assemble into uniform spherical nanoparticles after thermal annealing, whereas copolymers with random placement of segments with different sequences exhibit disordered assemblies without a well-defined morphology. Overall, these results bring a new understanding to the role of periodic repetitive sequences in polymer assembly.

One-pot approach for multi-step, iterative synthesis of sequence-defined oligocarbamates

High-yielding and scalable methods for iterative synthesis of sequence-defined macromolecules are a great challenge in modern polymer chemistry. Sequence-defined macromolecules are fabricated by multi-step iterative processes that involve high reagent and solvent consumption. Moreover, every consecutive step causes yield losses that result in low overall yield. Despite the envisioned valuable functions and applications of sequence-defined polymers, the synthetic limitations constitute a barrier for the exploitation of their practical potential. Here, we investigated the one-pot synthesis of oligocarbamates without the purification of intermediates. To control the monomer sequence without isolation of intermediate product at every step, we introduced a monitoring feedback loop to fuel the exact amount of reagents to the reaction mixture, assuring full conversion of each reaction. Based on a one-pot strategy, we have developed a facile approach for the preparation of uniform oligocarbamates with full control of monomer order and defined stereochemistry. The great advantage of the presented methodology is the scalability of the process (demonstrated for synthesis of 50 g) and high yield (up to 95%). Oligomers obtained on a large scale can be further used as precursors for the synthesis of polymers with high molar mass. One-pot methods combined with chemoselective reactions bear the potential to overcome existing synthesis limitations and unlock the practical use of sequence-defined macromolecules. The presented concept might be further extended to different multi-step processes.

Improving the accuracy of copolymer sequence length determination by pyrolysis gas chromatography: A comprehensive study

Many industrial polymers which find application in contemporary materials are copolymers. Copolymers feature multiple distributions, that govern their physical properties, including the sequence distribution. Styrene-acrylate copolymers are an important class of polymers, their monomer sequence is typically determined by 13C NMR which suffers from low sensitivity and spectral resolution. A series of studies have shown that Py-GC can be applied to determine the sequence length of copolymers. The accuracy of the trimer assignments and the appropriate calibration approaches yielding reliable data have however not yet been validated. In the present study we propose a comprehensive workflow to ensure the accuracy of the sequence determination by Py-GC, next to NMR. In-depth analysis of the trimers observed in the Py-GC pyrograms of model styrene-acrylate copolymers was performed and specific MS fragments relating to the trimer sequence were assigned. A comparison of a series of copolymers yielded reliable assignments for the trimer signals. The obtained sequence lengths were in agreement with those calibrated with the benchmark method, 13C NMR. Py-GC was found to consistently underestimate the acrylate sequence length. Py-GC calibration with 13C NMR was thus found to be indispensable for the accurate absolute quantification of the sequence length by Py-GC. The calculated randomness did not vary significantly after NMR calibration, indicating that NMR calibration might not be required in all cases to obtain (relative) information on the sequence of a copolymer.

Degradable terpolyesters synthesized from a monomer mixture mediated by a heterometallic complex: Defined monomer- and stereo-sequences

Copolymers provide a feasible platform to extend the structures of polymeric material, and the control of architecture (such as monomer sequence and stereo sequence) plays a critical role in tailoring specific properties. Herein, a heterometallic (Salph Zn)2-Ho complex was screened out for the synthesis of architecture-defined block terpolymers from a monomer mixture of epoxide, cyclic anhydride and l-lactide (LLA). The polymerization in one-pot firstly underwent ring-opening copolymerization reaction producing completely alternating ester linkage, and then transformed to LLA polymerization with trace stereoerrors, forming block polyesters with a semicrystalline segment and an amorphous segment. The polymerization was “immortal” with the ability to synthesize sequence-defined multiblock polyesters by sequential monomer addition. Furthermore, DSC traces revealed that the obtained block polyesters exhibited distinct thermal properties stemming from each segment. The melting temperature of block terpolymer was increased to 207.6 °C facilitated by the stereocomplexes of PLA segment.

Homo- and copolymerization of 2-benzothiazoylacrylamide with α-methyl styrene and methyl acrylate: synthesis, characterization and reactivity

2-benzothiazolyl acrylamide (BTA) monomer was synthesized by reacting of 2-aminobenzothiazole with acryloyl chloride. Homo- and copolymerization of this monomer with α-methylstyrene (MSt) and methyl acrylate (MA) was carried out in dimethylsulfoxide (DMSO) solution. The prepared homo-and copolymers were characterized by Fourier Transform Infrared (FTIR) and their thermal stability was studied by thermogravimetric analysis (TGA). The composition of copolymers and the reactivity coefficients (r1, r2) were determined on the basis of sulfur analysis using linearization methods proposed by Fineman-Ross and Kelen-Tudos and the Mayo-Lewis intersection method. The derived (r1, r2) for BTA-co-MSt and BTA-co-MA are: (0.197, 0.230) and (0.294, 4.314), respectively. The microstructure of the copolymers and the distribution of the monomer sequences in the copolymers were calculated statistically, the results obtained are consistent with the values (r1, r2). BTA with MSt form alternative copolymer whilst BTA-co-MA tends to be block with MA.

Isotope Ratio Encoding of Sequence-Defined Oligomers.

Information storage at the molecular level commonly entails encoding in the form of ordered sequences of different monomers and subsequent fragmentation and tandem mass spectrometry analysis to read this information. Recent approaches also include the use of mixtures of distinct molecules noncovalently bonded to one another. Here, we present an alternate isotope ratio encoding approach utilizing deuterium-labeled monomers to produce hundreds of oligomers endowed with unique isotope distribution patterns. Mass spectrometric recognition of these patterns then allowed us to directly readout encoded information with high fidelity. Specifically, we show that all 256 tetramers composed of four different monomers of identical constitution can be distinguished by their mass fingerprint using mono-, di-, tri-, and tetradeuterated building blocks. The method is robust to experimental errors and does not require the most sophisticated mass spectrometry instrumentation. Such isotope ratio-encoded oligomers may serve as tags that carry information, but the method mainly opens up the capability to write information, for example, about molecular identity, directly into a pure compound via its isotopologue distribution obviating the need for additional tagging and avoiding the use of mixtures of different molecules.

Microstructural Analysis of Poly(ethylene-co-propylene-co-1-butene) terpolymers by Multidimensional NMR Spectroscopy

Physical, rheological and optical properties of polymer depend on its molecular microstructure. Specifically, the monomer content and sequence distribution of polymer significantly affect the mechanical performance of the final product. To this base, Nuclear Magnetic Resonance Spectroscopy (NMR) has been introduced as a very powerful technique to study the microstructure of polymer. The purpose of this study was to develop a methodology to investigate the microstructure of poly(ethylene-co-propylene-co-butene) terpolymer by using multidimensional NMR spectroscopy, including pulsed-field-gradient (PFG) 1H-13C heteronuclear single quantum coherence (GHSQC), heteronuclear multiple bond coherence (gHMBC), and heteronuclear single quantum coherence-total correlation spectroscopy (GHSQC-TOCSY). The combination of 1D and 2D NMR experiments, permit the characterization of the complex structure of poly(ethylene-co-propylene-co-butene) terpolymer. The completed 13C NMR assignments provided in this work allow more accurate quantitative determination of the microstructure in these polymers.

Binding of Proteins to Copolymers of Varying Charges and Hydrophobicity: A Molecular Mechanism and Computational Strategies.

Because of their ability to selectively bind to a target protein, copolymer nanoparticles (NPs) containing a selected combination of hydrophobic and charged groups have been frequently reported as potent antibody-like analogues. However, due to the intrinsic disorder of the copolymer NP in terms of its random monomer sequence and the cross-linked copolymer matrix, the copolymer NP is indeed strikingly different from a well-folded protein antibody and the complexation between the copolymer NP and a target protein is likely not due to a lock-key type of interaction but possibly due to a novel and unexplored molecular mechanism. Here, we study a key biomarker protein, vimentin, interacting with a set of random copolymer chains using implicit-water explicit-ion coarse-grained (CG) molecular dynamics (MD) simulations along with biolayer interferometry (BLI) analysis. Due to the charge and hydrophobicity anisotropy on the vimentin dimer (VD) surface, a set of bound copolymers are found inhomogenously adsorbed on the VD, with energetic heterogeneity for different binding sites and cooperative effect in the adsorption. Increasing the charge or hydrophobicity of the copolymer may have different consequences on the adsorption. In this study, we found that with more copolymer charges, the protein coverage increases for copolymers of low hydrophobicity and decreases of high hydrophobicity, which is explained by the distribution and size of various functional patches on the VD in loading those copolymers. Employing a coverage-dependent Langmuir model, we propose a simulation protocol to address the full profile of the copolymer binding free energy through the fit to the simulated binding isotherm. The obtained results correlate well with those from the BLI experiment, indicating the significance of this method for the rational design of the copolymer NP with engineered protein binding affinity.

Random copolymer adsorption onto a periodic heterogeneous surface: A partially directed walk model.

The adsorption of a single AB random copolymer (RC) chain onto an inhomogeneous ab surface with a regular periodic pattern is studied theoretically. The problem is considered within the simplest model of a partially directed random walk in two dimensions by using the method of generating functions and the annealed approximation for the averaging over disorder in the RC sequence. The existence of the "optimal" RC composition and the degree of correlation in the monomer sequence, at which the inverse transition temperature has a local minimum, is shown. This is characteristic for symmetric and weakly asymmetric surfaces, whereas for surfaces with pronounced asymmetry there is no such local minimum. The best adsorbate for a strongly asymmetric surface is the homopolymer composed of monomer units that are complimentary to the majority sites on the surface. The results for the adsorption transition point obtained in the annealed approximation are compared with the numerical results for random-periodic AB-copolymers with a long period being a quenched random sequence of A and B units. The comparison shows that the annealed approximation provides a very good quantitative estimate of the adsorption transition point.

Microstructure, thermal and rheological properties of poly(L‐lactide‐co‐ε‐caprolactone) tapered block copolymer for potential use in biomedical applications

AbstractThis work investigates the thermal and rheological properties of the poly(L‐lactide‐co‐ε‐caprolactone), PLC, tapered block copolymer synthesized by ring‐opening polymerization (ROP) using stannous octoate (Sn[Oct]2) as an initiator. The PLC copolymer (LL: CL = 48.9:51.1 mol% from 1H‐NMR) was obtained as a transparent, elastomeric material with a tapered monomer sequencing (R = 0.38 from 13C‐NMR data) due to randomizing effect of transesterification. The Mn, Mw, and ĐM of the PLC copolymer from GPC are 8.04 × 104, 1.36 × 105, and 1.69 respectively. The obtained moduli of the copolymer at 100% and 300% strain are rather low at 0.91 and 1.16 MPa. The rheological properties of the PLC melt are studied in terms of steady and oscillatory shear flow. The master curves at a reference temperature of 150°C with 5% and 100% strain suggest that the copolymer melt may contain some regular microstructures, such as small crystalline domains of poly(L‐lactide), which remained intact at high strain deformation. The flow curve of the PLC melt at 150°C constructed from a cross model shows a Newtonian viscosity () of 6754 Pa‐s, a consistency index (k) of 0.59, and a Power Law index of 0.35 where the onset of Power Law behavior is observed at around 10 s−1. For the fabrication of the PLC nerve tubes, the best result is observed from the extruded PLC tubes with a combination of PEG porosifying agent leaching and phase immersion precipitation at 2°C using DMF/1,4‐dioxane (1:1) as a mixed solvent and ethanol/chloroform (9:1) as a non‐solvent. The porous tube obtained under this condition has a pore diameter and pore depth of approximately 2.3–2.5 and 30 μm respectively.

Design and development of a self-assembling protein nanoparticle displaying PfHAP2 antigenic determinants recognized by natural acquired antibodies.

BackgroundsIn order to move towards the elimination and eradication of malaria in the world, the development of vaccines is inevitable. Many modern vaccines are based on recombinant technology; however, they may not provide a fully protective, long-lasting immune response. One of the strategies to improve recombinant vaccines is designing the nanovaccines such as self-assembling protein nanoparticles (SAPNs). Hence, the presentation of epitopes in a repeat array and correct conformation should be considered. P. falciparum generative cell-specific 1 (PfGCS1) is a main transmission-blocking vaccine candidate with two highly conserved fragments, HAP2-GCS1 and cd loop, inducing partial malaria transmission inhibitory antibodies. Therefore, to design an effective malaria vaccine, we used cd loop and HAP2-GCS1 fragments at the amino and carboxy terminuses of the SAPN-forming amino acid sequence, respectively.Methodology/Principal findingsThe SAPN monomer (PfGCS1-SAPN) sequence was designed, and the three-dimensional (3D) structure was predicted. The result of this prediction ensured the presence of antigens on the SAPN surface. Then the accuracy of the predicted 3D structure and its stability were confirmed by 100 ns molecular dynamics (MD) simulation. The designed SAPN substructure sequence was synthesized, cloned, and expressed in Escherichia coli. With a gradual decrease in urea concentration in dialysis solutions, the purified proteins progressed to the final desired structure of the SAPN, which then was confirmed by Dynamic Light Scattering (DLS) and Field Emission Scanning Electron Microscopy (FESEM) tests. According to the Enzyme-Linked Immunosorbent Assay (ELISA), antigenic determinants were presented on the SAPN surface and interacted with antibodies in the serum of malaria patients.Conclusions/SignificanceOur results show that the SAPN formed by PfGCS1-SAPN has produced the correct shape and size, and the antigenic determinants are presented on the surface of the SAPN, which indicates that the designed SAPN has great potential to be used in the future as a malaria vaccine.

Determination of Chemical Composition and Monomer Sequence Distributions of Methacrylate Copolymers by Multivariate Analysis of NMR Spectra

Determination of Chemical Composition and Monomer Sequence Distributions of Methacrylate Copolymers by Multivariate Analysis of NMR Spectra