Monomeric Structure Research Articles

Synthesis and characterisation of Vanadium(III) fluorides α-BaVF5 and BaV(F,OH)5 with an S = 1 spin chain structure

Two new vanadium(III) fluorides, α-BaVF5 and BaV(F,OH)5, were hydrothermally synthesised. The crystal structures of both α-BaVF5 and BaV(F,OH)5 contain chain structures consisting of corner-sharing VIIIF6 or VIII(F,OH)6 octahedra. A monomeric cis-chain structure is found in α-BaVF5, in contrast to the helical-chain structure in BaV(F,OH)5. Although predominantly antiferromagnetic interactions are present in these tilted compounds at high temperatures, the strength of the exchange interaction is greater in α-BaVF5 due to the high Curie−Weiss temperature of θCW = −66.0(1)K. Furthermore, magnetic measurements revealed that α-BaVF5 exhibits a canted antiferromagnetic ground state, while BaV(F,OH)5 displays antiferromagnetic behaviour at low temperatures.

Interfacial Pickering Emulsion Polycondensation for Degradable Nanocomposites.

Pickering emulsion polymerization is a practical method to fabricate functional composite materials. However, most reported systems proceed homogeneously within the stabilized monomer phase and create nondegradable chemical bonds. Here, interfacial Pickering emulsion polycondensation between aromatic aldehydes and polymercaptans is developed using sustainable cellulose nanoparticles as the stabilizer. When sulfonated cellulose nanocrystals (S-CNCs) were utilized, they also catalyzed the polycondensation to produce the oxidatively degradable S,S-acetal groups on the polymer chains. The influence of monomer and cellulose structures on the polymerization behavior and composite properties were compared.

Cryo-EM structures of the membrane repair protein dysferlin

Plasma membrane repair in response to damage is essential for cell viability. The ferlin family protein dysferlin plays a key role in Ca2+-dependent membrane repair in striated muscles. Mutations in dysferlin lead to a spectrum of diseases known as dysferlinopathies. The lack of a structure of dysferlin and other ferlin family members has impeded a mechanistic understanding of membrane repair mechanisms and the development of therapies. Here, we present the cryo-EM structures of the full-length human dysferlin monomer and homodimer at 2.96 Å and 4.65 Å resolution. These structures define the architecture of dysferlin, ferlin family-specific domains, and homodimerization mechanisms essential to function. Furthermore, biophysical and cell biology studies revealed how missense mutations in dysferlin contribute to disease mechanisms. In summary, our study provides a framework for the molecular mechanisms of dysferlin and the broader ferlin family, offering a foundation for the development of therapeutic strategies aimed at treating dysferlinopathies.

α-Synuclein plastic antibody applied to monitor monomeric structures and discriminate aggregated forms in human CSF

Aggregation of alpha-synuclein (aSyn) occurs in presynaptic neurons and constitutes a key factor for the progression of Parkinson's disease, emphasising the urgency of early detection to support effective treatment. Unfortunately, a reliable, sensitive and cost-effective diagnostic tool has so far been lacking.Thus, this work presents a novel biosensor for detecting aSyn using plastic antibodies coupled to electrochemical detection. This biosensor was designed for portability and compatibility with point-of-care devices and exploits the electropolymerization of methylene blue (MB) together with aSyn on the carbon working electrode of screen-printed electrodes (SPEs). By electrochemical impedance spectroscopy (EIS) measurements, the sensor showed exceptional analytical performance in detecting aSyn monomers in human CSF samples. It showed a linear trend of response from 1 fM to 10 pM with an impressively low limit of detection of 69 aM. Selectivity tests confirmed the predominant response to aSyn monomers, a less intense response to oligomers and insensitivity to fibrils.Overall, this plastic antibody-based electrochemical sensor represents a significant breakthrough as it is the first of its kind to accurately, sensitively and selectively detect aSyn monomers with a partial response to oligomers. Its simplicity and reproducibility promise to contribute to the early and effective diagnosis of Parkinson's disease.

When annealing is detrimental: The case of HMGB1-targeting G-quadruplex aptamers

In this work, we present the case of the G-quadruplex(G4)-forming aptamers we recently identified for the recognition of HMGB1, protein involved in inflammation, autoimmune diseases and cancer. These aptamers were previously analyzed, without annealing them, after proper dilution of the stock solution in a pseudo-physiological buffer mimicking the extracellular environment where the protein exerts its pathological activity, and showed high thermal stability and nuclease resistance, good protein affinity and remarkable in vitro activity. These features were more marked for the aptamers forming dimeric, parallel G4 structures in solution.Herein, we fully characterized the same anti-HMGB1 aptamers after a standard annealing procedure performed on diluted samples. Notably, upon a thermal unfolding/folding cycle, these aptamers, and particularly the best ones in the not-annealed form, showed significant conformational switches compared to the same systems analyzed without annealing, forming exclusively monomeric G4 structures, featured by poor thermal and enzymatic stabilities, along with lower protein affinities.These results prove that, for these aptamers, analyzed in the chosen conditions, annealing at low concentration does not produce a beneficial effect in terms of favouring the most bioactive species.

A Rare Example of a Gallium-Based Lewis Superacid: Synthesis and Reactivity of Ga(OTeF5)3.

The Lewis superacid Ga(OTeF5)3 has been synthesized and characterized, revealing a monomeric structure in solution and a dimeric structure in the solid state. Isolated adducts of Ga(OTeF5)3 with strong and weak Lewis bases have been characterized spectroscopically as well as by single-crystal X-ray diffractometry. The Lewis acidity of this new species has been evaluated by means of different experimental and theoretical methods, which has allowed to classify it as one of only a few examples of a gallium-based Lewis superacid. The high Lewis acidity of Ga(OTeF5)3 was used to amplify the strength of the Brønsted acid HOTeF5, leading to the protonation of diethyl ether. Furthermore, Ga(OTeF5)3 was utilized to access the strong oxidizing system Ga(OTeF5)3/Xe(OTeF5)2 in SO2ClF, which was successfully employed in the synthesis of the dimethyl chloronium salt [Cl(CH3)2][Ga(OTeF5)4], a strong electrophilic methylation reagent.

MassiveFold: unveiling AlphaFold’s hidden potential with optimized and parallelized massive sampling

Massive sampling in AlphaFold enables access to increased structural diversity. In combination with its efficient confidence ranking, this unlocks elevated modeling capabilities for monomeric structures and foremost for protein assemblies. However, the approach struggles with GPU cost and data storage. Here we introduce MassiveFold, an optimized and customizable version of AlphaFold that runs predictions in parallel, reducing the computing time from several months to hours. MassiveFold is scalable and able to run on anything from a single computer to a large GPU infrastructure, where it can fully benefit from all the computing nodes.

Design and Development of Infiltration Resins: From Base Monomer Structure to Resin Properties.

The resin infiltration concept is one of the most widely used minimally invasive restorative techniques in restorative dentistry with the most outstanding therapeutic effect, and it is also one of the key research directions in restorative dentistry. "Infiltration resin" is the specialty restorative material for the technology, which is the key factor to success. The specialized restorative material is commonly known as "infiltrant/infiltration resins" "resins infiltrant" "infiltrant" or "resins," which will be consistently referred to as "infiltration resins" throughout the article. The paper aims to provide a comprehensive overview of infiltration resins by introducing the development of their therapeutic mechanisms, basic components, current challenges, and future trends, Based on existing literature, we analyze and compare how changes in the base monomer's structure and ratio affect the effectiveness of infiltration resins, from the material's structure-effective relationship. After compiling the information, the existing solution strategies have been listed to offer substantial support and guidance for future research endeavors.

A new discrete-geometry approach for integrative docking of proteins using chemical crosslinks.

The structures of protein complexes allow us to understand and modulate the biological functions of the proteins. Integrative docking is a computational method to obtain the structures of a protein complex, given the atomic structures of the constituent proteins along with other experimental data on the complex, such as chemical crosslinks or SAXS profiles. Here, we develop a new discrete geometry-based method, wall-EASAL, for integrative rigid docking of protein pairs given the structures of the constituent proteins and chemical crosslinks. The method is an adaptation of EASAL (Efficient Atlasing and Search of Assembly Landscapes), a state-of-the-art discrete geometry method for efficient and exhaustive sampling of macromolecular configurations under pairwise inter-molecular distance constraints. We provide a mathematical proof that the method finds a structure satisfying the crosslink constraints under a natural condition satisfied by energy landscapes. We compare wall-EASAL with IMP (Integrative Modeling Platform), a commonly used integrative modeling method, on a benchmark, varying the numbers, types, and sources of input crosslinks, and sources of monomer structures. The wall-EASAL method performs better than IMP in terms of the average satisfaction of the configurations to the input crosslinks and the average similarity of the configurations to their corresponding native structures. The ensembles from IMP exhibit greater variability in these two measures. Further, wall-EASAL is more efficient than IMP. Although the current study uses crosslinks, the method is general and any source of distance constraints can be used for integrative docking with wall-EASAL. However, the current implementation only supports binary rigid protein docking, i.e., assumes that the monomer structures are known and remain rigid. Additionally, the current implementation is deterministic, i.e., it does not account for uncertainties in the crosslinking data beyond using distance bounds. Neither of these appears to be a theoretical or algorithmic limitation of the EASAL methodology. Structures from wall-EASAL can be incorporated in methods for modeling large macromolecular assemblies, for example by suggesting rigid bodies or restraints for use in these methods. This will facilitate the characterization of assemblies and cellular neighborhoods at increased efficiency, accuracy, and precision. The wall-EASAL method is available at https://bitbucket.org/geoplexity/easal-dev/src/Crosslink and the benchmark is available at https://github.com/isblab/Integrative_docking_benchmark.

Synthesis, curing kinetics and processability of a low melting point aliphatic silicon-containing bismaleimide

An aliphatic silicon-containing maleimide monomer 1,1′-((1,1,3,3-tetramethyldisiloxane-1,3-diyl)bis(propane-3,1-diyl))bis(1H-pyrrole-2,5-dione) (TBB) with low melting point (56 °C) was successfully synthesized based on maleic anhydride (MA) and 3,3′-(1,1,3,3-tetramethyldisiloxane-1,3-diyl)bis(propan-1-amine) (BAT). The structure of TBB monomer was determined by FTIR, 1H NMR and 13C NMR. Meanwhile, the 3,3′-(1,1,3,3-tetramethyldisiloxane-1,3-diyl)bis(propan-1-amine) (BAT) and 4,4’-Bismaleimidodiphenylmethane (BDM) monomers were respectively prepared from diallyl bisphenol A (DBA), following a 1:0.87 molar ratio, and named TD resins and BD resins. The curing kinetics, thermal stability and processability of TD resins and BD resins were discussed and compared. The activation energy (E) value of TD resins was 26.2 % higher than BD resins, resulting in exothermic peak temperature (TP) of TD resins was higher than BD resins at different heating rates. Compared with BD resins, the crosslinking density (ve) of TD resins was reduced by 93.5 %, which effectively destroyed the thermal stability of TD resins. However, TD resins exhibited outstanding processing window of 195.6 °C. The processing window of TD resins was 110.1 % wider than that of the BD resins, indicating that the former had excellent processability. Overall, this study has enriched the discussion on the curing kinetics of aliphatic bismaleimide resins and has a positive influence on the design of resins monomer with low melting point.

Graph masked self-distillation learning for prediction of mutation impact on protein–protein interactions

Assessing mutation impact on the binding affinity change (ΔΔG) of protein–protein interactions (PPIs) plays a crucial role in unraveling structural-functional intricacies of proteins and developing innovative protein designs. In this study, we present a deep learning framework, PIANO, for improved prediction of ΔΔG in PPIs. The PIANO framework leverages a graph masked self-distillation scheme for protein structural geometric representation pre-training, which effectively captures the structural context representations surrounding mutation sites, and makes predictions using a multi-branch network consisting of multiple encoders for amino acids, atoms, and protein sequences. Extensive experiments demonstrated its superior prediction performance and the capability of pre-trained encoder in capturing meaningful representations. Compared to previous methods, PIANO can be widely applied on both holo complex structures and apo monomer structures. Moreover, we illustrated the practical applicability of PIANO in highlighting pathogenic mutations and crucial proteins, and distinguishing de novo mutations in disease cases and controls in PPI systems. Overall, PIANO offers a powerful deep learning tool, which may provide valuable insights into the study of drug design, therapeutic intervention, and protein engineering.

Bio-Based Epoxy-Phthalonitrile Resin: Preparation, Characterization, and Properties.

Preparation of high-performance thermosetting resins via bio-based resources is important for the development of a sustainable world. In this work, we proposed the introduction of cyanide structure groups into the molecular structure of epoxy resins to give them excellent heat resistance. A eugenol-based epoxy-phthalonitrile (EEPN) resin was synthesized by a two-step process using the bio-based renewable resource of eugenol, and a series of EEPN/Epoxide resin (E51) blend resins with different EEPN contents were prepared. The structure of the EEPN monomer was characterized and confirmed by Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and elemental analysis. The thermal stability and dynamic mechanical properties of the cured resins were investigated by thermogravimetric analysis and dynamic mechanical thermal analysis. The experimental results showed that EEPN had excellent heat resistance; the char yield at 800 °C was 67.9 wt%, which was much higher than that of E51 at 26.3 wt%; and the heat resistance of the blended resins was significantly improved with the increase in the EEPN content.

One-pot aqueous-phase synthesis of polyimides from typical monomers

One-pot aqueous-phase synthesis of polyimides (PIs) offers great economic and environmental benefits and improves the hydrolytic stability of the precursor (polyamic acid) obviously. However, this method is only suitable for the polymerization of very limited dianhydride and diamine monomers up to now. In this study, the most commonly used dianhydrides and diamines for the preparation of commercially available PI products were selected for one-pot aqueous-phase synthesis of various polyamic acid salts (PAAS). The effects of the structure of monomers, the reaction temperature and the adding process of the organic base on the polymerization reaction were explored by rotational rheology, nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The polymerization products obtained via the aqueous-phase route show high molecular weight when the reaction conditions have been optimized. Various PI films prepared by the thermal imidization of corresponding PAAS demonstrate good optical transparency, excellent thermal stability, and outstanding mechanical and electrical properties. This work proposes the reaction mechanism of PAAS via one-pot aqueous-phase route and utilizes this novel polymerization strategy to synthesize high-molecular-weight PIs from typical aromatic dianhydride and diamine monomers.

Characterization of Luciferase from Photorhabdus kayaii and its Application for In vivo Imaging Studies in Mice.

Bioluminescence, or the production of light by luciferases, is the basis of a well-known reporter technology. A quick way to study the efficacy of antimicrobial drugs and vaccines is in vivo bioluminescence imaging (BLI). Photorhabdus spp. represent the only terrestrial group of bioluminescent bacteria. The luciferase obtained from Photorhabdus luminescence has been widely used in BLI studies. However, little information is available about the functions of luciferases obtained from other members of this genera. This study aimed to evaluate the applicability of the luciferase obtained from Photorhabdus kayaii for BLI studies. P. kayaii starE, an Iranian isolate of P. kayaii, was cultivated on NBTA agar plates. The resulting colonies were cultured on McConkey agar to determine the bacterial phase. Bioluminescence emission was measured using a multimode reader. The luciferase genes of this bacterium were sequenced following the PCR amplification, and the corresponding amino acid sequences were determined. The luciferase tertiary structure was then obtained from the TACOS web server and compared to that of P. luminescence in CE software. The lux operon encoding the luciferase (luxA and luxB genes) and substrate synthesis complex was cloned and expressed in Escherichia coli BL21 (DE3) using the pBBR1MCS2_START vector. The luminescence emission during the growth was examined. Moreover, the effects of pH and sodium deoxycholate (bile salt) on bioluminescence emission were investigated. Appropriate conditions for the use of bioluminescent E. coli for BLI studies in mice were demonstrated in terms of cell numbers and injection routes. The bacterium was luminescent and in phase I. Its luciferase monomers (α and β) shared 100% amino acid homology with P. kayaii M-HU2 and more than 92% with P. luminescence. Tertiary structures of the luciferase monomers were 93%- 95% identical to those of P. luminescence. The lux operon was expressed in E. coli, and the maximum bioluminescence signal was observed during the decelerating phase of growth. The bioluminescence at different pH values correlated with the cell survival. The luminescence was emitted by cells exposed to the bile salt. A strong bioluminescent signal was emitted from mice after subcutaneous injection of bioluminescent E. coli at 107 CFU. However, no signals were emitted from mice that were administered the same cell number via intraperitoneal injection. A 2.5-fold increase in the cell number resulted in bioluminescence detection in the abdomen of mice after intraperitoneal injection and a 3.22-fold increase in signal intensity after subcutaneous injection. These results demonstrated the usefulness of P. kayaii luciferase for BLI studies.

Sustainable recovery of monomers from PET and PC waste via Thermocatalytic depolymerization for synthesis of polycarbonates and co-polycarbonates

The increasing global demand for sustainable plastics recycling methods has propelled the research and development of innovative depolymerization processes. The Thermocatalytic depolymerization (TCDP) of polyethylene terephthalate (PET) and polycarbonate (PC) has been performed at 200 ℃. Ethylene glycol (EG) is used as a reactant and as well a polymer bond-cleaving agent and Yttrium Oxide (Y2O3) is used as an effective catalyst. Y2O3 acted as a dual role during depolymerization reaction, which converts EG into cyclic ethylene oxide (CEO) and as well as to break the ester and carbonate bonds in the polymer structure of PET and PC respectively. The TCDP reaction conditions were optimized and the maximum quantity of Bis(2-hydroxyethyl) terephthalate (BHET) (80%) and (Bisphenol A (BPA)) (83%) has been recovered by TCDP reaction of PET and PC respectively. The polycarbonate and co-polycarbonate (Co-PC) were synthesized using recovered BPA and BHET with triphosgene via polycondensation reaction. The structure of monomers and polymers was confirmed by existing analytical (FTIR, NMR, XRD and GPC) techniques. The thermal properties of PC and Co-PC were performed by TG analysis. The TGA results reveal that the degradation temperature (Td) of PC and Co-PC are observed at 420.5 and 442.8 °C respectively, which shows that the Td of Co-PC has been increased by 22 ℃ than PC. The TCDP process is an effective method to recover specific value-added products from waste plastics, which could be made into a new versatile material for different applications. This research finding will provide a new direction to convert plastic waste into useful chemicals, which could reduce waste plastic and their carbon footprint and contribute to a more sustainable future by reusing plastic materials and achieving a circular economy.

A N-heterocyclics induced π-π interaction strategy to synthesis hyper-crosslinked polymers with enhanced porosity for xenon adsorption

Hyper-crosslinked polymers (HCPs) with large specific surface areas play an important role in gas adsorption and separation. However, the method to enhance the specific surface area of HCPs and gas adsorption performance without changing the polyaromatic hydrocarbons (PAHs) monomer structure and reaction condition is still missing. Here, we present a general and facile N-heterocyclics induced π-π interaction strategy to increase the specific surface area of HCPs by simply adding N-heterocyclics during the Friedel-Crafts alkylation reaction. The specific surface areas of HCP (tetraphenylmethane based HCPs, TPMBPy-TCM) increased up to 7.78 times compared to the one without adding N-heterocyclics. The crosslinking and stacking of PAHs was influenced by the π-π stacking between the N-heterocyclic complexes and PAHs. More importantly, N-heterocyclics coordinated with Lewis acids have lower electron density and do not react with PAHs in the Friedel-Crafts alkylation reaction, which can be removed easily from HCPs. The HCPs obtained shown good xenon adsorption performance with Xe uptake of 3.63 mmol/g, which is the highest value for organic adsorbents reported in literature. This work provides new insight into the preparation of high-performance HCPs.

Programmable In‐Situ Co‐Assembly of Organic Multi‐Block Nanowires for Cascade Optical Waveguides

AbstractOrganic heterostructures (OHs) with multi‐segments exhibit special optoelectronic properties compared with monomeric structures. Nevertheless, the synthesis of multi‐block heterostructures remains challenging due to compatibility issues between segment parts, which restricts their application in optical waveguides and integrated optics. Herein, we demonstrate programmable in‐situ co‐assembly engineering, combining multi‐step spontaneous self‐assembly processes to promote the synthesis of multi‐block heterostructures with a rational arrangement of three or more segments. The rational design of segments enables exciton manipulation and ensures optical waveguides and proper output among the multi‐segment OHs. This work enables the controllable growth of segments within multi‐block OHs, providing a pathway to construct complex OHs for the rational development of future optical applications.

Programmable In-Situ Co-Assembly of Organic Multi-Block Nanowires for Cascade Optical Waveguides.

Organic heterostructures (OHs) with multi-segments exhibit special optoelectronic properties compared with monomeric structures. Nevertheless, the synthesis of multi-block heterostructures remains challenging due to compatibility issues between segment parts, which restricts their application in optical waveguides and integrated optics. Herein, we demonstrate programmable in-situ co-assembly engineering, combining multi-step spontaneous self-assembly processes to promote the synthesis of multi-block heterostructures with a rational arrangement of three or more segments. The rational design of segments enables exciton manipulation and ensures optical waveguides and proper output among the multi-segment OHs. This work enables the controllable growth of segments within multi-block OHs, providing a pathway to construct complex OHs for the rational development of future optical applications.

Easy and accurate protein structure prediction using ColabFold.

Since its public release in 2021, AlphaFold2 (AF2) has made investigating biological questions, by using predicted protein structures of single monomers or full complexes, a common practice. ColabFold-AF2 is an open-source Jupyter Notebook inside Google Colaboratory and a command-line tool that makes it easy to use AF2 while exposing its advanced options. ColabFold-AF2 shortens turnaround times of experiments because of its optimized usage of AF2's models. In this protocol, we guide the reader through ColabFold best practices by using three scenarios: (i) monomer prediction, (ii) complex prediction and (iii) conformation sampling. The first two scenarios cover classic static structure prediction and are demonstrated on the human glycosylphosphatidylinositol transamidase protein. The third scenario demonstrates an alternative use case of the AF2 models by predicting two conformations of the human alanine serine transporter 2. Users can run the protocol without computational expertise via Google Colaboratory or in a command-line environment for advanced users. Using Google Colaboratory, it takes <2 h to run each procedure. The data and code for this protocol are available at https://protocol.colabfold.com .

Exploring the wear resistance of EPDM‐PAE/SWCNTs composites with a novel perspective of micro‐network structure

AbstractThe effect of single‐walled carbon nanotubes (SWCNTs) on the crosslinking network structure of Ethylene Propylene Diene Monomers (EPDM)—Polyamide elastomers (PAE) is investigated in detail using Hansen Solubility Parameter (HSP) theory. Rheological method and scanning electron microscopy (SEM) are used to investigate the effect of SWCNTs on the molecular chain movement and their interaction with the filler network of EPDM‐PAE. The DIN abrasion test is conducted to obtain the effect of SWCNTs on the wear characteristics of EPDM‐PAE/SWCNTs composites. The linear synergistic relationship between crosslinking density and wear volume indicates that the change in wear properties is contributed by the micro‐network structure. The addition of SWCNTs increases the chemical crosslinking density and improves the wear properties of EPDM‐PAE. However, the decrease in the physical crosslinking density leads to an increase in the degree of internal friction within the network structure, resulting in a decrease in the wear performance. Changes in wear resistance can be related to the micro‐network structure, which provides a novel approach to studying the wear characteristics of high‐performance elastomers. It is also an innovative work based on the network structure to guide the preparation of new wear‐resistant elastomeric materials.