Complex Macromolecular Structures Research Articles

Complex macromolecular structures from stable radical containing block copolymers

ABSTRACTA novel synthetic strategy for the synthesis of graft copolymers is reported. Block copolymers containing segments with stable nitroxyl radicals side groups were first prepared by anionic polymerization, which were then used as a precursor for the subsequent nitroxide‐mediated radical polymerization (NMRP) of styrene. This way, block–graft copolymers with polystyrene side chains grafted from one of the blocks were successfully synthesized in a controlled manner. In addition, block–graft copolymers with grafted polystyrene chains and a poly(tert‐butyl methacrylate) block were subjected to hydrolysis to yield the corresponding amphiphilic polymers. The structures and the molecular weight characteristics of the polymers were characterized by spectral and chromatographic analyses. The surface morphology of thus obtained polymers was also investigated by microscopic techniques. © 2019 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 62–69

Near‐Infrared Photoinduced Copper‐Catalyzed Azide‐Alkyne Click Chemistry with a Cyanine Comprising a Barbiturate Group

AbstractA new near‐infrared (NIR) photosensitization system for the activation of a copper‐catalyzed azide‐alkyne cycloaddition click reaction (CuAAC) is reported. Selected cyanines comprising either a cationic or zwitterionic structural pattern were tested for their photosensitization activity to generate Cu(I) by photoreduction of Cu(II) to trigger CuAAC under NIR light at ambient temperature. The photosensitization system described also facilitates chemical modification of UV‐sensitive materials by CuAAC. Upon exposure to light of wavelength 790 nm under anaerobic conditions, the cyanine with a zwitterionic structure comprising a barbiturate group; that is 5‐(6‐(2‐(3‐ethyl‐1,1‐dimethyl‐1H‐benzo[e]indol‐2(3H)‐ylidene)ethylidene)‐2‐(2‐(3‐ethyl‐1,1‐dimethyl‐1H‐benzo[e]‐indol‐3‐ium‐2‐yl)vinyl)cyclohex‐1‐en‐1‐yl)‐1,3‐dimethyl‐2,6‐dioxo‐1,2,3,6‐tetrahydropyrimidin‐4‐olate in combination with Cu(II)‐N,N,N′,N′′,N′′‐pentamethyldiethylene‐triamine complex, exhibited excellent activity with high yields. The possibility to synthesise different macromolecular structures such as telechelic polymers and block copolymers by NIR‐sensitized CuAAC is demonstrated. The structural and molecular characteristics of the intermediates and final products were evaluated by spectral and chromatographic analyses. This new photochemical reaction opens up new pathways for the macromolecular synthesis of complex macromolecular structures and applications requiring light as an activation tool.

Full-color emissive carbon-dots targeting cell walls of onion for in situ imaging of heavy metal pollution.

Plant cell walls (CWs) with complex macromolecular structures can surround and protect cells from a variety of harsh environmental conditions such as pathogens, herbivores, and trace metals. Here, a novel strategy for in situ imaging of plant cell walls was developed to evaluate heavy metal pollution via thiolated full-color emissive carbon-dots (F-CDs) targeting Pb(ii)-adsorbed onion cell walls. The thiolated F-CDs with excellent optical properties from red light to blue light were synthesized through a facile electrochemical approach using new precursors of luminol and l-tryptophan and further modified with l-cysteine. Based on a strong covalent interaction of Pb(ii) and thiolated F-CDs, we achieved in situ fluorescence imaging for the Pb(ii) adsorbed on CWs, which showed enhanced red, blue and green multi-color fluorescence (FL) on CWs with increased Pb(ii)-ion content. In contrast, multi-color fluorescence on cytoplasm diminished, attributed to F-CDs targeting and accumulating on the cytoskeleton which thus limited F-CD diffusion into protoplasm. Therefore, in situ fluorescent images for CWs can demonstrate heavy metal contamination degrees in plant cells. This facile and undamaging protocol will be beneficial for investigating heavy metal migration into the protoplast and fast evaluation of food quality and safety.

Visible light induced one-pot synthesis of amphiphilic hyperbranched copolymers

Dimanganese decacarbonyl (Mn2(CO)10) and alkyl halide combination has unique visible light radical generating property which is useful in the fabrication of many complex macromolecular structures. Herein, we present a generic simple and rapid synthetic approach for the preparation amphiphilic hyperbranched macromolecular structures with controlled branching density and hydrophilicity. The method is based on the visible light induced self-condensing vinyl copolymerization of methyl methacrylate (MMA), 2-(2-bromoisobutryloxy)ethyl methacrylate (BIBEM) and poly(ethylene glycol) methyl ether methacrylate as monomer, inimer and hydrophilic comonomer, respectively, in the presence of Mn2(CO)10. The resulting polymers possess both hydrophobic and hydrophilic sequences offering many potential bio applications such as controlled drug delivery and release. Moreover, the resulting polymers contain also unreacted bromide groups in the final structure which allow postfunctionalization through copper(I)-catalyzed alkyne-azide cycloaddition “click” reactions.

Click and Multicomponent Reactions Work Together for Polymer Chemistry

AbstractThis article investigates the current combinations of click and multicomponent reactions (MCRs) to produce complex macromolecular structures through polymer–polymer conjugation or hetero‐functionalization of polymers. The click and MCRs display similar features covering the equimolarity, fast time scale, high yields, stable compounds, modular, orthogonal and single reaction trajectory. Of classical click reactions, CuAAC, Diels–Alder, thiol‐ene (‐yne), and nucleophilic substitution on perfluoroaryl groups reactions are combined with MCRs, namely, Passerini, Ugi, or Biginelli reactions. It should be noted that these combinations can afford the target polymer structures, which are not attainable by employing one of these reactions alone.

Curvatures of smectic liquid crystals and their applications

ABSTRACTCurvature is an important concept for understanding layering structures in soft matters, ranging from complex macromolecular self-assembled structures to simple lipid bilayers. Among the various kinds of soft matters, smectic liquid crystal (LC) phases have been widely studied because of their periodic featured curvatures under various external forces. Generally, their curvatures are on the micron-scale due to the bulk elasticity of smectic LC materials. In this review, a combination of sublimation and recondensation of smectic LC materials generates a variety of curvatures at the nanometer scale, which cannot be achieved by self-assembly under thermal equilibrium conditions. In particular, we have focused on the change of curvatures in focal conic domains under non-equilibrium conditions, in which negative and zero Gaussian curvatures in the micron-scale transform to positive Gaussian curvatures in the micron- and nanometer scales. Finally, the review closes with applications using such non-equilibrium self-assembly of smectics.

Characterization of Ultrahigh-Molecular-Weight Oilfield Polyacrylamides Under Different pH Environments by Use of Asymmetrical-Flow Field-Flow Fractionation and Multiangle-Light-Scattering Detector

Summary Various types of ultrahigh-molar-mass polyacrylamides (HPAMs) and their copolymers and terpolymers used not only in enhanced oil recovery (EOR) but also in drilling, fracturing, water treatment, and tailing applications require an accurate description of polymer molar mass (Mw) and hydrodynamic size for their optimal design. The range of Mw for various types of available HPAMs is between 4 and 30 million g/mol and is typically determined by use of intrinsic-viscosity measurement. Molecular-weight distribution (MWD) cannot be determined because neither standard with low polydispersity index (PDI) nor gel-permeation-chromatography (GPC) or size-exclusion-chromatography (SEC) techniques exist today for such ultrahigh-molar-mass polymers. Moreover, the solution environment in underground reservoirs, characterized by high temperatures, pH values, and the presence of monovalent and divalent ions, may often lead to changes in polymer-macromolecular conformation. Current techniques, SEC, ultraviolet-visible measurements, and liquid chromatography, are not capable of accurately investigating these complex macromolecular structures for various reasons. In this paper, the asymmetrical-flow field-flow fractionation (AF4) system was used to fractionate four different ultrahigh-molecular-weight HPAM samples, varying in molar mass and commercially used for oilfield applications, in various carrier pH values ranging from 12 to 3 (pH values of 12, 7.4, and 3). The system uses field-flow fractionation (FFF), a family of analytical techniques developed specifically for separating and characterizing macromolecules, colloids, and particles. The theoretical separation range for AF4 is between 103 to 1012 g/mol. Other advantages over conventional GPC/SEC include minimum shear degradation, mild operating conditions, and no sample loss caused by adsorption. The flow system was equipped with a multiangle-light-scattering (MALS) and refractive-index (RI) detectors to measure molar mass and radius of gyration (Rg). The results show that the observed molecular weight of the polymer aggregate increased substantially as the pH value of the carrier solution decreased from 12 to 3, especially for higher-molar-mass polymers. The sample Rg showed the opposite trend, decreasing as the pH of the carrier solution changed from basic to acidic. For ultrahigh molecular HPAM at high pH, a narrower molar mass and radius distribution was observed with disaggregated molar mass and increased branching or swelling (therefore larger hydrodynamic radius). Use of this direct separation and measurement technique can improve understanding of polymer-macromolecular structure and corresponding changes in the reservoir brines.

Dynamic Macromolecular Material Design-The Versatility of Cyclodextrin-Based Host-Guest Chemistry.

Dynamic and adaptive materials are powerful constructs in macromolecular and polymer chemistry with a wide array of applications in drug delivery, bioactive systems, and self-healing materials. Very often, dynamic materials are based on carefully tailored cyclodextrin host-guest interactions. The precise incorporation of these host and guest moieties into macromolecular building blocks allows the formation of complex macromolecular structures with predefined functions. Thus, dynamic materials with extraordinary adaptive property profiles-responsive to thermal, chemical, and photonic fields-become accessible. This Review explores the hierarchical formation of dynamic materials and complex macromolecular structures from the molecular via the macromolecular to the colloidal and macroscopic level, with a specific emphasis on the functionality and responsiveness of the assemblies, specifically in biological contexts.

Copolymerization of Norbornene and Norbornadiene Using a cis-Selective Bimetallic W-Based Catalytic System.

The bimetallic cluster Na[W2(μ-Cl)3Cl4(THF)2]·(THF)3 ({W2}, {W 3 W}6+, a′2e′4), which features a triple metal-metal bond, is a highly efficient room-temperature initiator for ring opening metathesis polymerization (ROMP) of norbornene (NBE) and norbornadiene (NBD), providing high-cis polymers. In this work, {W2} was used for the copolymerization of the aforementioned monomers, yielding statistical poly(norbornene)/poly(norbornadiene) PNBE/PNBD copolymers of high molecular weight and high-cis content. The composition of the polymer chain was estimated by 13C CPMAS NMR data and it was found that the ratio of PNBE/PNBD segments in the polymer chain was relative to the monomer molar ratio in the reaction mixture. The thermal properties of all copolymers were similar, resembled the properties of PNBD homopolymer and indicated a high degree of cross-linking. The morphology of all materials in this study was smooth and non-porous; copolymers with higher PNBE content featured a corrugated morphology. Glass transition temperatures were lower for the copolymers than for the homopolymers, providing a strong indication that those materials featured a branched-shaped structure. This conclusion was further supported by viscosity measurements of copolymers solutions in THF. The molecular structure of those materials can be controlled, potentially leading to well-defined star polymers via the “core-first” synthesis method. Therefore, {W2} is not only a cost-efficient, practical, highly active, and cis-stereoselective ROMP-initiator, but it can also be used for the synthesis of more complex macromolecular structures.

Biodegradable functional biomaterials exploiting substituted trimethylene carbonates and organocatalytic transesterification

Biodegradable aliphatic carbonyl polymers, such as polylactides, polylactones and polycarbonates, have been studied for application in a broad range of resorbable medical devices. With progress in diagnostic and therapeutic technologies for an aging society, the demand for diverse and highly developed biodegradable biomaterials has increased. A combination of heterocyclic monomers with functional substituents and complex macromolecular architecture has been proposed as a means to produce multifunctional biodegradable polymers. This review mainly highlights the synthesis and application of poly(trimethylene carbonate) (PTMC) analogs with various substituents derived from 2,2-bis(methylol)propionic acid. In addition, organocatalytic transesterification is discussed as an indispensable tool for further functionalization and sophistication of the PTMC analogs. Metal-free controlled polymerization allows for both the safer production of biomedical devices and the precise formation of complex macromolecular structures. The organocatalytic depolymerization of engineering polyesters has also been exploited to efficiently produce valuable aromatic terephthalamides that, in turn, can be used to extend the functionality of PTMC analogs such as mesogen-like motifs. Finally, the use of supramolecular chemistry for further multi-functionalization and hydration-based improvement of biocompatibility is briefly discussed. Biodegradable aliphatic carbonyl polymers, such as polylactides, polylactones and polycarbonates, have been studied for applications in a broad range of resorbable medical devices. This review mainly highlights the synthesis and application of poly(trimethylene carbonate) (PTMC) analogs with various substituents derived from 2,2-bis(methylol)propionic acid. In addition, organocatalytic transesterification is discussed as an indispensable tool for further functionalization and sophistication of the PTMC analogs.

Macromolecular design and application using Mn2(CO)10‐based visible light photoinitiating systems

AbstractThe environmentally friendly Mn2(CO)10‐based visible light photoinitiating system is a powerful method for the preparation of linear and crosslinked polymeric structures. From a practical point of view, the most important feature of this initiating system is its optical characteristics in the visible range with high quantum yield and good solubility properties. This photoinitiating system is applicable for a variety of monomers that can be polymerized via either radical or cationic mechanisms. Various complex macromolecular structures such as telechelic polymers, block and graft copolymers, polymer networks and surface modifications can be simply prepared by using halogenated precursors. This photoinitiating system is also combined with controlled radical polymerization techniques providing a mild and efficient method for polymer synthesis. © 2016 Society of Chemical Industry

Tandem Photoinduced Cationic Polymerization and CuAAC for Macromolecular Synthesis

A novel synthetic strategy involving sequential photoinduced cationic and copper-catalyzed azide–alkyne cycloaddition (CuAAC) click processes for the synthesis of complex macromolecular structures such as side-chain functional polymers, graft copolymers, and organogels is described. In the approach, first a set of copolymers possessing side-chain alkyne or halide functionalities, namely, poly(cyclohexene oxide-co-glycidyl propargyl ether) (P(CHO-co-GPE)), poly(cyclohexene oxide-co-epichlorohydrin) (P(CHO-co-ECH)), and poly(tetrahydrofuran-co-epichlorohydrin) (P(THF-co-ECH)), were synthesized by photoinitiated free-radical-promoted cationic copolymerization of the corresponding monomers using phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) and diphenyl iodonium hexafluorophosphate (Ph2I+PF6–) as free radical photoinitiator and oxidant, respectively. While P(CHO-co-GPE) readily contained clickable alkyne side-chains, the halide groups of P(THF-co-ECH) were converted to azide groups by conventional a...

Computational close up on protein–protein interactions: how to unravel the invisible using molecular dynamics simulations?

As an essential part of many biological processes, protein–protein interactions (PPIs) offer exciting and promising opportunities for drug discovery by extension of the druggable target space. Over the last decade, studies on protein networks have significantly increased the number of identified PPIs. However, despite steadily growing data on PPIs, detailed understanding of the interaction surfaces and their dynamics remains limited. Furthermore, the development of small‐molecule inhibitors of PPIs faces technological challenges, leaving the question about the ‘druggability’ of PPIs open. Molecular dynamics (MD) simulations may facilitate the prediction of druggable binding sites on protein–protein interfaces by detecting binding hot spots and transient pockets. MD allows for a detailed analysis of structural and functional aspects of PPIs and thus provides valuable insights into PPI mechanisms and supports the design of PPI modulators. We provide an overview on the main areas of MD applications to PPIs including structural investigations and the design of PPI disruptors. Emphasizing the beneficial synergies between computational and experimental techniques, MD techniques are also frequently applied to low‐resolution structural data and have been used to elucidate structure and movements of complex macromolecular structures relevant for biological processes. WIREs Comput Mol Sci 2015, 5:345–359. doi: 10.1002/wcms.1222This article is categorized under: Structure and Mechanism > Molecular Structures Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods Molecular and Statistical Mechanics > Molecular Interactions

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma.

Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients.

Computationally Projecting the Influence of Nucleic Acid on Pathways of Nucleation-Limited Virus Capsid Assembly

Elucidating assembly pathways of complex macromolecular structures, such as virus capsids, is an important problem for understanding the many cellular processes dependent on self-assembly but also challenging given limited experimental technologies for observing such systems. We have previously addressed this problem through simulation-based data fitting, learning rate parameters of coarse-grained stochastic simulation models to match light scattering data from bulk assembly of purified coat protein in vitro providing an unprecedented view of the fine-scale reaction pathways that might have produced those data. A key question raised by such models, though, is how well they might reflect assembly under more natural cellular conditions where factors such as local concentration changes, non-specific crowding, and often the influence of nucleic acid during assembly become relevant. In the present study, we examine the latter issue, how using analytical models of various contributions of RNA folding to assembly would influence overall pathways and kinetics, primarily with reference to cowpea chlorotic mottle virus (CCMV). We find a surprising complexity and synergy of interaction effects. Energetic effects that gain or lower free energy tend to disrupt successful assembly relative to the in vitro model individually, while the full combination of positive and negative effects collectively promotes greatly accelerated assembly without loss of yield. Furthermore, it accomplishes this change in kinetics while substantially altering the ensemble of assembly pathways open to the system. These simulation results help us understand how RNA viral coat and genome may interact in assembly to promote rapid growth while avoiding kinetic traps expected from much prior theory, bringing us a step closer to the goal of understanding how viral assembly in the cell may differ from our current conception based largely on in vitro models.

Macromolecular structure evolution toward giant molecules of complex structure: tandem synthesis of asymmetric giant gemini surfactants

Precise control of primary chemical structures, especially those of complex structures, is a prerequisite to understand the structure–property relationships of functional macromolecules. In this article, we report the rational design and tandem synthesis of three asymmetric giant gemini surfactants (AGGSs) of complex macromolecular structures based on polyhedral oligomeric silsesquioxane (POSS). In two cascading processes (typically within 5 hours), AGGSs can be synthesized where the length of the two polymer tails and the identity of the two POSS heads can be independently controlled and systematically varied. It represents a convenient, efficient, and modular way to prepare giant molecules with rigorous structural precision in only a few steps. This study expands the scope of synthetically available giant surfactants and facilitates further structural evolution toward even more complex macromolecules.

Curli biogenesis: Order out of disorder

Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures must be highly coordinated to avoid the accumulation of potentially toxic intracellular protein aggregates. Extracellular amyloid fiber assembly poses an even greater threat to cellular health due to the highly aggregative nature of amyloids and the inherent toxicity of amyloid assembly intermediates. Therefore, temporal and spatial control of amyloid protein secretion is paramount. The biogenesis and assembly of the extracellular bacterial amyloid curli is an ideal system for studying how bacteria cope with the many challenges of controlled and ordered amyloid assembly. Here, we review the recent progress in the curli field that has made curli biogenesis one of the best-understood functional amyloid assembly pathways. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.

Synthesis of H-shaped complex macromolecular structures by combination of atom transfer radical polymerization, photoinduced radical coupling, ring-opening polymerization, and iniferter processes

Three controlled/living polymerization processes, namely atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and iniferter polymerization, and photoinduced radical coupling reaction were combined for the preparation of ABCBD-type H-shaped complex copolymer. First, a-benzophenone functional polystyrene (BP-PS) and poly( methyl methacrylate) (BP-PMMA) were prepared independently by ATRP. The resulting polymers were irradiated to form ketyl radicals by hydrogen abstraction of the excited benzophenone moieties present at each chain end. Coupling of these radicals resulted in the formation of polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) with benzpinacole structure at the junction point possessing both hydroxyl and iniferter functionalities. ROP of e-caprolactone (CL) by using PS-b-PMMA as bifunctional initiator, in the presence of stannous octoate yielded the corresponding tetrablock copolymer, PCL-PSPMMA- PCL. Finally, the polymerization of tert-butyl acrylate (tBA) via iniferter process gave the targeted H-shaped block copolymer

Searching for Recursively Defined Generic Chemical Patterns in Nonenumerated Fragment Spaces

Retrieving molecules with specific structural features is a fundamental requirement of today's molecular database technologies. Estimates claim the chemical space relevant for drug discovery to be around 10⁶⁰ molecules. This figure is many orders of magnitude larger than the amount of molecules conventional databases retain today and will store in the future. An elegant description of such a large chemical space is provided by the concept of fragment spaces. A fragment space comprises fragments that are molecules with open valences and describes rules how to connect these fragments to products. Due to the combinatorial nature of fragment spaces, a complete enumeration of its products is intractable. We present an algorithm to search fragment spaces for generic chemical patterns as present in the SMARTS chemical pattern language. Our method allows specification of the chemical surrounding of an atom in a query and, therefore, enables a chemically intuitive search. During the search, the costly enumeration of products is avoided. The result is a fragment space that exactly describes all possible molecules that contain the user-defined pattern. We evaluated the algorithm in three different drug development use-cases and performed a large scale statistical analysis with 738 SMARTS patterns on three public available fragment spaces. Our results show the ability of the algorithm to explore the chemical space around known active molecules, to analyze fragment spaces for the presence of likely toxic molecules, and to identify complex macromolecular structures under additional structural constraints. By searching the fragment space in its nonenumerated form, spaces covering up to 10¹⁹ molecules can be examined in times ranging between 47 s and 19 min depending on the complexity of the query pattern.

Calibration and quality assurance procedures at the far UV linear and circular dichroism experimental station DISCO

Circular and Linear dichroism spectroscopy used in biophysics, are both differential absorption techniques, which explore the chirality of complex macromolecular structures such as proteins and nucleic acids in solution. In the past two decades synchrotron radiation facilities throughout the world, have accommodated circular dichroism (SRCD) experiments. These intense VUV light sources have greatly expanded the wavelength range exploitable (down to 120nm) at high constant photon flux improving signal to noise ratio and data acquisition speed. Here we present the calibration procedure for the circular and linear dichroism experiments explored on the SRCD beam line DISCO at the synchrotron SOLEIL as well as the specially designed automated sample rotation chamber.