Structural Core Research Articles

Phosphoric Acid‐Catalyzed Enantioselective Synthesis of Axially Chiral Anthrone‐based Compounds

AbstractAnthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2‐rich nature imposes inherent obstruction to introduce stereogenic element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone‐derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long‐range chirality control. The enantioenriched anthrones could be elaborated into dibenzo‐fused seven‐membered N‐heterocycles containing well‐defined stereogenic center via Beckmann rearrangement with axial‐to‐point chirality conversion.

Compression properties of carbon fiber reinforced polymer grid sandwich structure

Carbon fiber reinforced polymer (CFRP) grid sandwich structure with four different grid configurations was prepared using the interlocking assembly process in the present work. All test specimens were subjected to quasi-static out-of-plane uniform compression. The equivalent density, height, geometric configuration, and other factors of the structural core layer were analyzed, and their effects on the failure mode, damage mechanism, and energy absorption characteristics of CFRP grid sandwich structure were discussed. The results showed that there are four distinct stages in the load versus displacement curve of CFRP grid sandwich structure specimens subjected to uniform compression, namely, preloading stage, elastic stage, load drop stage, and platform stage. The main failure modes of CFRP grid sandwich structure are the local buckling and compression fracture of the core rib. The failure load, compression strength, breaking absorbed energy, and specific absorbed energy of CFRP grid sandwich structure are positively correlated with the equivalent density of the structure core layer, and negatively correlated with the height of the structure core layer. When the equivalent density of the core layer of the Mixed CFRP grid sandwich structure was increased by 10 kg/m3, the compressive strength and specific energy absorption of the structure increased by about 5.08 MPa and 186.79 mJ, respectively, and when the core layer height was increased by 10 mm, the compressive strength and specific energy absorption decreased by about 12.04 MPa and 67.39 mJ, respectively; The strength and stability of the Mixed CFRP grid sandwich structure are significantly higher than those of the Triangular, Diamond, and Square CFRP grid sandwich structures.

‘We’re not a separate entity, we're staff now’ The involvement of transition age youth peer supporters in trauma-informed community partnerships

BackgroundTransition age youth (TAY) experiencing mental illness, homelessness, and trauma face challenges in navigating the transition to adulthood. Age appropriate, trauma-informed support from peer specialists (PS) can assist TAY who have experienced trauma in navigating their transition to adulthood. Whether and how TAY PS are involved in trauma-informed community-based partnerships is unclear. This study explores TAY PS experiences with and social network positions in trauma-informed ‘TAY-support networks.’ MethodsSocial network data were collected from four TAY-support networks. Structural analyses (network size and density) and core periphery analyses were conducted to elucidate TAY PS network positions, while focus groups were conducted with TAY PS to understand their experiences delivering services. Focus group data were analyzed using thematic analysis. Data were triangulated to understand whether and how focus group results expanded on our social network analysis. ResultsTAY support networks included 194 persons (range: 32–55) and 26 TAY PS. In two networks, TAY PS were located at the network’s core and periphery, and reported ongoing contributions to initiative activities. In two other networks, TAY PS were located at the network periphery and reported challenges with team communication. ConclusionsTo maximize TAY PS contributions to multidisciplinary partnerships, organizations should 1) include TAY PS throughout program planning and implementation and 2) provide age-appropriate professional supports to TAY PS.

Metal-Free Multicomponent Strategy for Amidine Synthesis.

Amidines are a ubiquitous class of bioactive compounds found in a wide variety of natural products; thus, efficient strategies for their preparation are in great demand. Specifically, their common structural core decorated with three substituents sets amidines as perfect candidates for multicomponent synthesis. Herein, we present a highly modular metal-free multicomponent strategy for the synthesis of sulfonyl amidines. This work was focused on selecting readily accessible reagents to facilitate the in situ formation of enamines by the addition of amines to ketones. These components were coupled with azides to provide a broad reaction scope with respect to all three coupling partners. Aromatic and aliphatic amines and ketones were tolerated under our reaction conditions. Likewise, the presence of a methyl group on the ketone was critical to reactivity, which was leveraged for the design of a highly regioselective reaction with aliphatic ketones. A biologically active compound was successfully synthesized in one step, demonstrating the practical utility of our methodology. Finally, the postulated mechanism was investigated and supported both experimentally and by means of a multivariate statistical model.

Mirror-image T7 transcription of chirally inverted ribosomal and functional RNAs.

To synthesize a chirally inverted ribosome with the goal of building mirror-image biology systems requires the preparation of kilobase-long mirror-image ribosomal RNAs that make up the structural and catalytic core and about two-thirds of the molecular mass of the mirror-image ribosome. Here, we chemically synthesized a 100-kilodalton mirror-image T7 RNA polymerase, which enabled efficient and faithful transcription of the full-length mirror-image 5S, 16S, and 23S ribosomal RNAs from enzymatically assembled long mirror-image genes. We further exploited the versatile mirror-image T7 transcription system for practical applications such as biostable mirror-image riboswitch sensor, long-term storage of unprotected kilobase-long l-RNA in water, and l-ribozyme-catalyzed l-RNA polymerization to serve as a model system for basic RNA research.

Impact of the acoustic transmission path on the vibro-acoustic performance of sandwich panels with structural cores with bandgap behavior

In the search for lightweight and compact structures with favorable vibro-acoustic performance, periodic structures such as phononic crystals and locally resonant metamaterials have shown potential.Recently, these periodic structures are included between two panels in a sandwich configuration to combine the interesting vibro-acoustic performance of the core with the potential load-carrying capacity of the sandwich configuration.During the design and numerical analysis of the vibro-acoustic performance of these structures, commonly only the structural connection between the plates is considered.However, next to the structural connection, also an acoustic transmission path is present between the plates of the sandwich configuration in reality.Because of this, the promising performance due to the structural decoupling of the double panel configuration by the bandgap behavior of the periodic core predicted with the analyses only considering the structural connection, are often not attained in experimental measurements.In this work, the impact of the ignored acoustic transmission path on the sound transmission loss of sandwich panels with structural periodic cores which exhibit bandgap behavior, is investigated.It is shown that the sound transmission follows the path of least resistance.Therefore, it is crucial to consider both the structural as the acoustic path in the partitions during the design phase to correctly predict the vibro-acoustic performance of these novel sandwich panel configurations.

Chirality Transfer from an Innately Chiral Nanocrystal Core to a Nematic Liquid Crystal 2: Lyotropic Chromonic Liquid Crystals.

The importance of and the difference between molecular versus structural core chirality of substances that form nanomaterials, and their ability to transmit and amplify their chirality to and within a surrounding condensed medium is yet to be exactly understood. Here we demonstrate that neat as well as disodium cromoglycate (DSCG) surface-modified cellulose nanocrystals (CNCs) with both molecular and morphological core chirality can induce homochirality in racemic nematic lyotropic chromonic liquid crystal (rac-N-LCLC) tactoids. In comparison to the parent chiral organic building blocks, D-glucose, endowed only with molecular chirality, both CNCs showed a superior chirality transfer ability. Here, particularly the structurally compatible DSCG-modified CNCs prove to be highly effective since the surface DSCG moieties can insert into the DSCG stacks that constitute the racemic tactoids. Overall, this presents a highly efficient pathway for chiral induction in an aqueous medium and thus for understanding the origins of biological homochirality in a suitable experimental system.

Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction.

An enantiomerically enriched 3-hydroxymethyl pentenal unit is one of the key structural cores in plenty of natural products and drug candidates with significant biological activities. However, very few synthetic methodologies for the facile construction of the related skeletons have been reported to date. Herein, an elegant iridium-catalyzed asymmetric cascade allylation/retro-Claisen reaction of readily available β-diketones with VEC was successfully developed, and a wide range of functionalized chiral 3-hydroxymethyl pentenal derivatives could be prepared in good yields with excellent enantioselectivities. Various 1,3-diketones and functionalized ketones containing different electron-withdrawing groups on the β-position were well tolerated as outstanding partners with high reactivity and excellent regio-/chemo-/enantioselectivity. The synthetic utility of product chiral 3-hydroxymethyl pentenal derivatives was well shown through gram-scale transformation, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. Moreover, this elegant protocol demonstrated synthetic applications in the concise synthesis of synthetically useful chiral building block (S)-Taniguchi lactone and the formal synthesis of natural product cytisine. A rational reaction pathway was proposed based on the experimental results and control experiments.

Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes

Genome duplication is safeguarded by constantly adjusting the activity of the replicative CMG (CDC45-MCM2-7-GINS) helicase. However, minichromosome maintenance proteins (MCMs)—the structural core of the CMG helicase—have never been visualized at sites of DNA synthesis inside a cell (the so-called MCM paradox). Here, we solve this conundrum by showing that anti-MCM antibodies primarily detect inactive MCMs. Upon conversion of inactive MCMs to CMGs, factors that are required for replisome activity bind to the MCM scaffold and block MCM antibody binding sites. Tagging of endogenous MCMs by CRISPR-Cas9 bypasses this steric hindrance and enables MCM visualization at active replisomes. Thus, by defining conditions for detecting the structural core of the replicative CMG helicase, our results explain the MCM paradox, provide visual proof that MCMs are an integral part of active replisomes in vivo, and enable the investigation of replication dynamics in living cells exposed to a constantly changing environment.

In situ gelation strategy based on ferrocene-hyaluronic acid organic copolymer biomaterial for exudate management and multi-modal wound healing

Exudate management remains a major concern in slow or non-healing wound management. Therefore, there is a need to devise a massive exudate-absorbing, exudate-locking, and stable extracellular matrix structure-maintaining functional wound dressing. Inspired by metal-organic frameworks, we chemically introduced sandwich ferrocene (Fc) into hyaluronic acid (HA) to fabricate an innovative metal Fc-HA organic copolymer (FHoC) as the skeleton material for in situ gelation, which was then gently compressed into a pre-hydrogel patch (FHoCP). Fc promoted the rearrangement of polymer chains to form additional microcrystalline and hydrophobic regions, which improved hydrogel transition and the exudate-locking ability. Thus, the simple composition FHoCP(5) absorbed 150 times its weight of water and maintained a firm three-dimensional network, which contributed to reducing inflammation and acted as a physical barrier against hemostasis and anti-bacterial invasion. Meanwhile, multi-modal processes, including fibroblast migration, angiogenesis, and antibacterial effects, were integrated into the gelled FHoCP(5) guided by Fe to promote wound healing. This study suggested that FHoC biomaterial could accelerate the closure of chronic wounds. We believe that this unique FHoCP(5)-based in situ gelation strategy could provide a solid drug-loaded scaffold for cell or adjunctive drug therapies, which holds great potential for the development of multifunctional biomaterials. Statement of significanceHydrogels that absorb excessive exudates while maintaining stable ECM-like network as well as exert multimodal wound healing activities are ideal dressings for accelerating chronic wound contraction. Herein, we reported an innovative metal ferrocene-hyaluronic acid organic copolymer patch (FHoCP) and FHoCP-mediated in situ gelation strategy. Ferrocene (Fc) induced in situ gelation by promoting polymer chain rearrangement, acting as a physical barrier for hemostasis and anti-bacterial invasion, and absorbing massive exudates, resulting in reducing delayed inflammation. As the structural core, rigid Fc enhanced the stability of the hydrogel backbone, and hydrophobic Fc improved fibroblast migration. In addition, Fe2+ chemically inhibited bacteria and increased angiogenesis. These results indicated the potential of FHoCP-based hydrogel for application in clinical skin reconstruction.

Evolutionarily Conserved Proline Residues Impede the Misfolding of the Mouse Prion Protein by Destabilizing an Aggregation-competent Partially Unfolded Form

The misfolding of the prion protein has been linked to several neurodegenerative diseases. Despite extensive studies, the mechanism of the misfolding process remains poorly understood. The present study structurally delineates the role of the conserved proline residues present in the structured C-terminal domain of the mouse prion protein (moPrP) in the misfolding process. It is shown that mutation of these Pro residues to Ala leads to destabilization of the native (N) state, and also to rapid misfolding. Using hydrogen–deuterium exchange (HDX) studies coupled with mass spectrometry (MS), it has been shown that the N state of moPrP is in rapid equilibrium with a partially unfolded form (PUF2*) at pH 4. It has been shown that the Pro to Ala mutations make PUF2* energetically more accessible from the N state by stabilizing it relative to the unfolded (U) state. The apparent rate constant of misfolding is found to be linearly proportional to the extent to which PUF2* is populated in equilibrium with the N state, strongly indicating that misfolding commences from PUF2*. It has also been shown that the Pro residues restrict the boundary of the structural core of the misfolded oligomers. Overall, this study highlights how the conserved proline residues control misfolding of the prion protein by modulating the stability of the partially unfolded form from which misfolding commences.

Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies.

RNA-dependent RNA polymerases (RdRPs) represent a distinctive yet versatile class of nucleic acid polymerases encoded by RNA viruses for the replication and transcription of their genome. The structure of the RdRP is comparable to that of a cupped right hand consisting of fingers, palm, and thumb subdomains. Despite the presence of a common structural core, the RdRPs differ significantly in the mechanistic details of RNA binding and polymerization. The present review aims at exploring these incongruities in light of recent structural studies of RdRP complexes with diverse cofactors, RNA moieties, analogs, and inhibitors.

ZnII-DyIII single-molecule magnets constructed by salen-type ligand, acetate and β-diketonate

A series of ZnII-DyIII complexes with molecular formula [LZn(CH3COO)Dy(hfac)2] (1), [LZn(CH3COO)2Dy(dbm)]·CH2Cl2 (2), [LZn(CH3COO)Dy(btfa)2]·CH2Cl2 (3), (H2L = N,N'-bis(3-methoxysalicylidene)-1,2-phenylenediamine, hfac = hexafluoroacetylacetone, dbm = dibenzoylmethane, btfa = benzoyltrifluoride acetone) were structurally and magnetically characterized. They have similar ZnII-DyIII structural cores bridged by N and O atoms of the hexadentate salen type ligand (L). The main difference between them is the peripheral β-diketonate co-ligands surrounding DyIII ion. Dynamic magnetic properties measurements revealed that complexes 1-3 exhibit the field-induced SMM behavior with relaxation energy barriers Ueff/kB of 45.49 K, 69.28 K and 101.34 K, respectively. The ac magnetic susceptibility of diluted sample 3Dy0.05Y0.95 confirmed the single molecule original relaxation, in which the quantum tunneling of magnetization (QTM) was suppressed efficiently and a butterfly-shaped hysteresis loop at 1.8 K was observed.

High-velocity impact resistance of stepwise gradient sandwich beams with metal foam cores

This paper aims to reveal the impact resistance of the graded sandwich beams subjected to high-velocity impacts experimentally. By using the one-stage gas gun system, the dynamic response and failure of the sandwich beams are analyzed by considering the effects of core gradient, impulsive loading, and boundary condition. The results show that the dynamic structural response of beams is noticeably influenced by the different initial failure mode under the fully clamped condition. The core gradient configuration is confirmed to have no significant effect on the impact resistance performance in terms of the dynamic central deflection, permanent deformation, and failure modes. Under the simply clamped condition, however, the core gradient effect is confirmed to be the predominant factor for the noticeably changed impact resistance performances of the sandwich beams. Due to the advantages on structural response and core compression, the graded sandwich beams have significantly better impact resistance than the uniform sandwich beam under the low-velocity impact. The negative correlation between this advantage and impulsive intensity indicates that impact resistance of the uniform sandwich beam is superior to that of the graded sandwich beams under the intensive impact. This study provides guidance of the gradient designation of the energy absorption sandwich structure and its subsequent engineering applications.

Lead and copper metal ion uptake by a novel nanoscale hydroxy-terminated dendritic macromolecules

A rapidly growing global population has prompted a pressing concern about how to maintain a safe environment for future generations as a result of massive growth in agricultural, industrial, and economic activities. Environment harmful metals are found in industrial wastewater, which can harm living organisms. Because of heavy metals' strong recalcitrance and long-term existence in the environment, it's crucial to create novel materials for their adsorption. A dendrimer is a good way to adsorb heavy metals. The current work's purpose is to design dendritic macromolecules up to generation three using 1,3-bis(4,6-Dichloro-1,3,5-triazine-2-yl)thiourea as a structural core. Dendrimer structure was characterized by FT-IR and 1H NMR measurements. The adsorption properties of synthesized dendrimer were investigated using different pH, contact duration and generation number for the removal of Pb+2 and Cu+2 metal ions from aqueous systems. Dendrimer-metal complexes were analysed using FT-IR methods to confirm their metal content. In this Research study, divergent growth of dendrimers was successfully used to synthesize different generations of hydrophilic triazine-based dendritic macromolecules. We aimed to investigate the capability of synthesized dendrimer as an adsorbent to remove Pb+2 and Cu+2 metal ion in aqueous systems. According to the study data, products synthesized with higher generations of dendrimers have greater adsorption capability than products synthesized with lower generations of dendrimers.

Synthesis and biological evaluation of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates

This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10–30 μM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa), & 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery.

Development of a new method for manufacturing hollow fibre-reinforced plastic structures for aeronautical applications using structural CFRP cores

ABSTRACT Currently applied manufacturing technologies for hollow composite structures impose design restrictions, such as limited integration potential, whereas differential designs are limited regarding lightweight design and load transfer due to the need of joints. This paper introduces the patented concept of structural carbon fibre-reinforced polymer (CFRP) cores, intending to overcome limitations allowing for integral, yet complex designs. The hollow cores are initially manufactured and partially cured via resin transfer moulding (RTM) with inflatable rubber core. These cores are then integrated in a dry textile-based preform which is impregnated in another RTM process. Here, the cores stabilize the preform during injection and afterwards remain in the component as load-carrying elements. Thereby the partial degree of cure of the cores before the second RTM process is optmised to balance dimensional stability and bonding strength. The process route using structural CFRP cores was successfully applied to a generic structure and proven by structural testing.

3-Methoxy-5-methyl-12-phenylbenzacridinium Iodide

N-alkylacridinium derivatives are some of the most popular azo dye templates. Herein, we report the synthesis of 3-methoxy-5-methyl-12-phenylbenzacridinium iodide (MMPBAI) via N-alkylation. The structure of MMPBAI was elucidated using 1H Nuclear magnetic resonance (NMR), 13C NMR, Electronspray ionization mass spectrometry (ESI-MS), and Fourier-transform infrared spectroscopy (FT-IR). MMPBAI could not visualize double-stranded DNA in agarose gel, although the structural core would still be interesting as a template for new azo dyes.

Orchestrating copper binding: structure and variations on the cupredoxin fold.

A large number of copper binding proteins coordinate metal ions using a shared three-dimensional fold called the cupredoxin domain. This domain was originally identified in Type 1 "blue copper" centers but has since proven to be a common domain architecture within an increasingly large and diverse group of copper binding domains. The cupredoxin fold has a number of qualities that make it ideal for coordinating Cu ions for purposes including electron transfer, enzyme catalysis, assembly of other copper sites, and copper sequestration. The structural core does not undergo major conformational changes upon metal binding, but variations within the coordination environment of the metal site confer a range of Cu-binding affinities, reduction potentials, and spectroscopic properties. Here, we discuss these proteins from a structural perspective, examining how variations within the overall cupredoxin fold and metal binding sites are linked to distinct spectroscopic properties and biological functions. Expanding far beyond the blue copper proteins, cupredoxin domains are used by a growing number of proteins and enzymes as a means of binding copper ions, with many more likely remaining to be identified.

Structural efficiency of a stitched integrated thermal protection system with thermal protection/insulation and load-bearing capacity

A stitched integrated thermal protection system (SITPS) has thermal protection/insulation and load-bearing capacity. According to the thermal protection/insulation, loading-bearing, and lightweight requirements, the SITPS has multiple characterizations and optimization parameters. So, it is essential to calculate its thermal and mechanical performance indexes in specific working environments to evaluate its structural efficiency. SITPS contains different components and spans multiple dimensions; therefore, multiscale models and hierarchical statistical methods are tailored to calculate the thermal and mechanical properties of the SITPS. This approach investigates the influences of the two critical structural parameters, stitching density and thermal insulation core thickness, on four key performance indicators of the SITPS. A structural efficiency indicator for the SITPS is proposed, which quantitatively characterizes the thermal insulation, load-bearing, and lightweight performance of the SITPS. It provides new insights into the structural design and optimization of the SITPS in its engineering applications.