Acyclic Chain Research Articles

Bond topology of chain, ribbon and tube silicates. Part II. Geometrical analysis of infinite 1D arrangements of (TO4)n- tetrahedra.

In Part I of this series, all topologically possible 1-periodic infinite graphs (chain graphs) representing chains of tetrahedra with up to 6-8 vertices (tetrahedra) per repeat unit were generated. This paper examines possible restraints on embedding these chain graphs into Euclidean space such that they are compatible with the metrics of chains of tetrahedra in observed crystal structures. Chain-silicate minerals with T = Si4+ (plus P5+, V5+, As5+, Al3+, Fe3+, B3+, Be2+, Zn2+ and Mg2+) have a grand nearest-neighbour ⟨T-T⟩ distance of 3.06±0.15 Å and a minimum T...T separation of 3.71 Å between non-nearest-neighbour tetrahedra, and in order for embedded chain graphs (called unit-distance graphs) to be possible atomic arrangements in crystals, they must conform to these metrics, a process termed equalization. It is shown that equalization of all acyclic chain graphs is possible in 2D and 3D, and that equalization of most cyclic chain graphs is possible in 3D but not necessarily in 2D. All unique ways in which non-isomorphic vertices may be moved are designated modes of geometric modification. If a mode (m) is applied to an equalized unit-distance graph such that a new geometrically distinct unit-distance graph is produced without changing the lengths of any edges, the mode is designated as valid (mv); if a new geometrically distinct unit-distance graph cannot be produced, the mode is invalid (mi). The parameters mv and mi are used to define ranges of rigidity of the unit-distance graphs, and are related to the edge-to-vertex ratio, e/n, of the parent chain graph. The program GraphT-T was developed to embed any chain graph into Euclidean space subject to the metric restraints on T-T and T...T. Embedding a selection of chain graphs with differing e/n ratios shows that the principal reason why many topologically possible chains cannot occur in crystal structures is due to violation of the requirement that T...T > 3.71 Å. Such a restraint becomes increasingly restrictive as e/n increases and indicates why chains with stoichiometry TO<2.5 do not occur in crystal structures.

Toward a Template for Synthetic Actin-Targeting Macrolide Analogues That Inhibit Cancer Cell Invasiveness.

Actin barbed end-binding macrolides have been shown to inhibit cancer cell motility and invasion of extracellular matrix (ECM), evoking their potential utility as therapies for metastatic cancers. Unfortunately, the direct use of these compounds in clinical settings is impeded by their limited natural abundance, challenging total synthesis, and detrimental effects on normal tissues. To develop potent analogues of these compounds that are simpler to synthesize and compatible with cell-specific targeting systems, such as antibodies, we designed over 20 analogues of the acyclic side chain (tail) of the macrolide Mycalolide B. These analogues probed the contributions of four distinct regions of the tail towards the inhibition of actin polymerization and ECM invasion by human lung cancer A549 cells. We observed that two of these regions tolerate considerable substituent variability, and we identified a specific combination of substituents that leads to the optimal inhibition of the ECM invasion activity of A549 cells.

Synthesis of graphene oxide from post-consumer PET bottles by a one-step thermal treatment in air atmosphere for removal of methylene blue

Post-consumer polyethylene terephthalate (PET) bottles are promising raw materials to produce value-added materials. This work uses a simple thermal treatment (TT) in an air atmosphere to transform post-consumer PET (PET-W) into graphene-oxide-like material (GOL). A careful analysis of the thermogravimetric (TGA) curves allowed us to determine the optimal temperature for controlling the oxidative decomposition reactions of PET-W at 412 °C while maximizing the bidimensional character of the products. The products of thermal transformation were characterized by Raman spectroscopy, DRX, FTIR, SEM, EDS, XPS, and BET. The results of the characterization indicate the obtaining of a material (identified here as GOLPET) which is characterized by an ID/IG ratio of 0.61, the presence of oxygenated groups such as CO, C-O-C and phenyls at the interphase, and an elemental composition of ∼83.7 (wt.%) and ∼16.27% of carbon and oxygen (wt.%), respectively. XPS allowed us to determine the formation of assembled aromatic chains (Csp2 = 61.53%) and acyclic chains (Csp3=38.47%). Finally, GOLPET absorption capacity was explored for a commercial application such as removing methylene blue (MB dye); complete elimination of MB (99.6%) in an aqueous solution was demonstrated. Considering the annual generation of plastic waste ∼300 million t, the methodology developed in this research can be envisage as an affordable and innovative alternative to produce GO-like materials.

Improving Gene Delivery: Synergy between Alkyl Chain Length and Lipoic Acid for PDMAEMA Hydrophobic Copolymers.

In the field of gene delivery, hydrophobic cationic copolymers hold great promise. They exhibit improved performance by effectively protecting genetic material from serum interactions while facilitating interactions with cellular membranes. However, managing cytotoxicity remains a significant challenge, prompting an investigation into suitable hydrophobic components. A particularly encouraging approach involves integrating nutrient components, like lipoic acid, which is known for its antioxidant properties and diverse cellular benefits such as cellular metabolism and growth. In this study, a copolymer library comprising 2-(dimethylamino)ethyl methacrylate (DMAEMA) and lipoic acid methacrylate (LAMA), combined with either n-butyl methacrylate (nBMA), ethyl methacrylate (EMA), or methyl methacrylate (MMA), is synthesized. This enables to probe the impact of lipoic acid incorporation while simultaneously exploring the influence of pendant acyclic alkyl chain length. The inclusion of lipoic acid results in a notable boost in transfection efficiency while maintaining low cytotoxicity. Interestingly, higher levels of transfection efficiency are achieved in the presence of nBMA, EMA, or MMA. However, a positive correlation between pendant acyclic alkyl chain length and cytotoxicity is observed. Consequently, P(DMAEMA-co-LAMA-co-MMA), emerges as a promising candidate. This is attributed to the optimal combination of low cytotoxic MMA and transfection-boosting LAMA, highlighting the crucial synergy between LAMA and MMA.

Relationship chains of subhealth physical examination indicators: a cross-sectional study using the PLS-SEM approach

Subhealth is a transitional state between health and disease, and it can be detected through routine physical check-ups. However, the complexity and diversity of physical examination items and the difficulty of quantifying subhealth manifestations are the main problems that hinder its treatment. The aim of this study was to systematically investigate the physical examination performance of the subhealthy population and further explore the deeper relationships between indicators. Indicators were obtained for 878 subjects, including basic information, Western medicine indicators, inquiries of traditional Chinese medicine and sublingual vein (SV) characteristics. Statistical differences were analysed using R software. To explore the distribution of symptoms and symptom clusters in subhealth, partial least squares-structural equation modelling (PLS-SEM) was applied to the subhealth physical examination index, and a structural model was developed to verify whether the relationship chain between the latent variables was reasonable. Finally, the reliability and validity of the PLS-SE model were assessed. The most common subclinical clinical symptoms were limb soreness (37.6%), fatigue (31.6%), shoulder and neck pain (30.5%) and dry eyes (29.2%). The redness of the SV in the subhealthy group was paler than that in the healthy group (p < 0.001). This study validates the establishment of the directed acyclic relationship chain in the subhealthy group: the path from routine blood tests to lipid metabolism (t = 7.878, p < 0.001), the path from lipid metabolism to obesity (t = 8.410, p < 0.001), the path from obesity to SV characteristics (t = 2.237, p = 0.025), and the path from liver function to SV characteristics (t = 2.215, p = 0.027). The innovative application of PLS-SEM to the study of subhealth has revealed the existence of a chain of relationships between physical examination indicators, which will provide a basis for further exploration of subhealth mechanisms and causal inference. This study has identified the typical symptoms of subhealth, and their early management will help to advance the treatment of diseases.

Synthesis and structure-activity optimization of 7-azaindoles containing aza-β-amino acids targeting the influenza PB2 subunit

The PB2 subunit of influenza virus polymerase has been demonstrated as a promising drug target for anti-influenza therapy. In this work, 7-azaindoles containing aza-β3- or β2,3 -amino acids were synthesized possessing a good binding affinity of PB2. The aza-β-amino acid moieties with diverse size, shape, steric hindrance and configuration were investigated. Then a lead HAA-09 was validated, and the attached aza-β3-amino acid moiety with acyclic tertiary carbon side chain well occupied in the key hydrophobic cavity of PB2_cap binding domain. Importantly, HAA-09 displays potent polymerase inhibition capacity, low cytotoxicity (selectivity index up to 2915) as well as robust anti-viral activity against A/WSN/33 (H1N1) virus and oseltamivir-resistant H275Y variant. Moreover, HAA-09 exhibited druggability with high plasma stability (t1/2 ≥ 12 h) and no obvious hERG inhibition (IC50 > 10 μM). Also, HAA-09 demonstrated a favorable safety profile when orally administrated in healthy mice at a high dose of 40 mg/kg QD for consecutive 3 days. Besides, in vivo therapeutic efficacy (85.7% survival observed at the day 15 post infection) was demonstrated when HAA-09 was administrated orally at 12.5 mg/kg BID starting 48 h post infection for 9 days. These data support that exploring the interactions between side chains on aza-β3- or β2,3 -amino acid moieties and hydrophobic pocket of PB2_cap binding domain is a potential medicinal chemistry strategy for developing potent PB2 inhibitors.

The homotopy category of acyclic complexes of pure-projective modules

Abstract Let R be any ring with identity. We show that the homotopy category of all acyclic chain complexes of pure-projective R-modules is a compactly generated triangulated category. We do this by constructing abelian model structures that put this homotopy category into a recollement with two other compactly generated triangulated categories: The usual derived category of R and the pure derived category of R.

A stochastic reconstruction strategy based on a stratified library of structural descriptors and its application in the molecular reconstruction of naphtha

Molecular reconstruction is a rapid and reliable way to provide molecular detail of petroleum fractions, which is required in the kinetic modeling of petroleum conversation processes at the molecular level. In the typical stochastic reconstruction method, the estimation of properties of pseudo molecules that are generated by Monte Carlo sampling depends on the building of predefined molecular libraries, which is expensive and inaccessible for certain petroleum fractions. In this paper, a novel stochastic reconstruction strategy is proposed, which is based on a stratified library of structural descriptors. Properties of pseudo molecules generated in the novel strategy can be directly estimated by group contribution method in the condition of lacking predefined molecular libraries. In this strategy, the molecular building diagram comprises two steps. First, the ring structure is configured by determining the number of rings. Different from the length of chain adopted in the traditional stochastic reconstruction method, in the second step, number of structural descriptors (SDs) for binding site and chain were determined sequentially for the configuration of binding site and saturated acyclic hydrocarbon chain. These structural descriptors for binding site and chain were selected from group contribution methods. To count the number of partial overlapping sections between structural descriptors for chain, two supplementary structural descriptors were created. All possible saturated structures of hydrocarbon chains can be represented by structural descriptors at the scale of property estimation. This strategy separates the building of a predefined molecule library from the stochastic reconstruction process. The exact structures of pseudo molecules represented by structural descriptors in this work can be determined with sufficient chemical knowledge. Fifty naphtha samples are tested independently to demonstrate the performance of the proposed strategy and the results show that the estimated properties were close enough to the experimental values. This strategy will benefit the molecular management of petrochemical industries and therefore improve economic and environmental efficiencies.

Noncanonical Strigolactone Analogues Highlight Selectivity for Stimulating Germination in Two Phelipanche ramosa Populations.

Strigolactones (SLs) are plant hormones exuded in the rhizosphere with a signaling role for the development of arbuscular mycorrhizal (AM) fungi and as stimulants of seed germination of the parasitic weeds Orobanche, Phelipanche, and Striga, the most threatening weeds of major crops worldwide. Phelipanche ramosa is present mainly on rape, hemp, and tobacco in France. P. ramosa 2a preferentially attacks hemp, while P. ramosa 1 attacks rapeseed. The recently isolated cannalactone (14) from hemp root exudates has been characterized as a noncanonical SL that selectively stimulates the germination of P. ramosa 2a seeds in comparison with P. ramosa 1. In the present work, (-)-solanacol (5), a canonical orobanchol-type SL exuded by tobacco and tomato, was established to possess a remarkable selective germination stimulant activity for P. ramosa 2a seeds. Two cannalactone analogues, named (±)-SdL19 and (±)-SdL118, have been synthesized. They have an unsaturated acyclic carbon chain with a tertiary hydroxy group and a methyl or a cyclopropyl group instead of a cyclohexane A-ring, respectively. (±)-SdL analogues are able to selectively stimulate P. ramosa 2a, revealing that these minimal structural elements are key for this selective bioactivity. In addition, (±)-SdL19 is able to inhibit shoot branching in Pisum sativum and Arabidopsis thaliana and induces hyphal branching in the AM fungus Rhizophagus irregularis, like SLs.

Reshaping an Acyclic Nucleoside Phosphonate into a Selective Anti-hepatitis B Virus Compound.

Minor structural modifications of acyclic nucleoside phosphonates can dramatically affect their antiviral properties. This work discloses a shift in the selectivity spectrum of 3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) nucleotides from herpesviruses toward hepatitis B virus (HBV) induced by their acyclic chain 2-substitution with a nonpolar group. Two series of racemic (R,S)-2-methyl-3-hydroxy-2-(phosphonomethoxy)propyl (MHPMP) and (R,S)-2-ethynyl-3-hydroxy-2-(phosphonomethoxy)propyl (EHPMP) nucleotides were initially synthesized. Among these, guanine-containing derivatives exhibited significant anti-HBV activities in the submicromolar range. Enantioenriched MHPMPG and EHPMPG analogues were subsequently obtained by Sharpless asymmetric epoxidation. The (S)-enantiomers possessed an 8- to 26-fold higher potency than the relative (R)-forms. A further comparison of the EC90 values indicated that (S)-EHPMPG inhibited HBV replication more effectively than its 2-methyl analogue. A phosphonodiamidate prodrug of (S)-EHPMPG was thus prepared and found to exert a remarkably high anti-HBV activity (EC50 = 9.27 nM) with excellent selectivity (SI50 > 10,787), proving to be a promising candidate for anti-HBV drug development.

Atom typing using graph representation learning: How do models learn chemistry?

Atom typing is the first step for simulating molecules using a force field. Automatic atom typing for an arbitrary molecule is often realized by rule-based algorithms, which have to manually encode rules for all types defined in this force field. These are time-consuming and force field-specific. In this study, a method that is independent of a specific force field based on graph representation learning is established for automatic atom typing. The topology adaptive graph convolution network (TAGCN) is found to be an optimal model. The model does not need manual enumeration of rules but can learn the rules just through training using typed molecules prepared during the development of a force field. The test on the CHARMM general force field gives a typing correctness of 91%. A systematic error of typing by TAGCN is its inability of distinguishing types in rings or acyclic chains. It originates from the fundamental structure of graph neural networks and can be fixed in a trivial way. More importantly, analysis of the rationalization processes of these models using layer-wise relation propagation reveals how TAGCN encodes rules learned during training. Our model is found to be able to type using the local chemical environments, in a way highly in accordance with chemists' intuition.

Lycopene - A Review: Chemistry, Source, Health Role, Extraction, Applications

Lycopene is an unsaturated carotenoid pigment which is acyclic and open chain, of great dietary prominence obtained mainly from colored plant sources. It is a phytochemical which is found mainly in red amaranth, tomatoes, water melon and other plants and fruits mostly red colored which covered various antioxidant which attracted attentions due to its biological properties. Lycopene has critical role in the prevention of tumor and cancer. Various ways can be utilized to identify, extract and purify lycopene from various sources by efficient analytical support. Several analyses have been attended for the extraction and quantification of lycopene in various natural sources such as various red leaf plants and fruits. This review study highlights lycopene as a carotenoid pigment including auspicious nutraceutical implications, and counts the important plant and also microbial sources for its production, and methods to calculate its bioavailability and utilization.

Evolution mechanism of cyclized structure of PAN-based pre-oxidized fiber during low temperature carbonization process

The low temperature carbonization process is an important stage to realize the structural transition from the organic cyclized structure of PAN based pre-oxidized fiber to the inorganic pseudo-graphite structure of the ultimate carbon fiber. In the present paper, the evolution mechanism of cyclized structure and aggregation structure of PAN stabilized fiber during low temperature carbonization was studied by means of TGA, 13C-NMR, XRD, XPS and Raman. The results indicated that when the heat-treated temperature was lower than 450 °C, the mainly chemical reactions were the dehydrogenation and pyrolysis reactions in acyclic linear molecular chain or partial cyclized structure. At this stage, the growth of cyclized structure was not obvious. While the original ordered structure was destroyed gradually and the internal stress increased significantly. It induced the cyclized structure to be further oriented. When the temperature was higher than 450 °C, the polycondensation and reconstruction in aromatic heterocyclic structure was more important. The early aromatic heterocycles had many different structural scales, poor homogeneity and many defects in the heterocycles. At this stage, a new pseudo-graphite crystalline structure gradually formed and the d-spacing of graphite layer decreased slightly and crystallites size increased slowly with the increase of heat-treated temperature. When the temperature was higher than 550 °C, the pseudo-graphite base structure gradually formed. The d-spacing were further reduced slightly, and the crystallites size increased slowly. A new ordered basis structure was gradually developed into carbon fiber.

Witnessing Subsystems for Probabilistic Systems with Low Tree Width

A standard way of justifying that a certain probabilistic property holds in a system is to provide a witnessing subsystem (also called critical subsystem) for the property. Computing minimal witnessing subsystems is NP-hard already for acyclic Markov chains, but can be done in polynomial time for Markov chains whose underlying graph is a tree. This paper considers the problem for probabilistic systems that are similar to trees or paths. It introduces the parameters directed tree-partition width (dtpw) and directed path-partition width (dppw) and shows that computing minimal witnesses remains NP-hard for Markov chains with bounded dppw (and hence also for Markov chains with bounded dtpw). By observing that graphs of bounded dtpw have bounded width with respect to all known tree similarity measures for directed graphs, the hardness result carries over to these other tree similarity measures. Technically, the reduction proceeds via the conceptually simpler matrix-pair chain problem, which is introduced and shown to be NP-complete for nonnegative matrices of fixed dimension. Furthermore, an algorithm which aims to utilise a given directed tree partition of the system to compute a minimal witnessing subsystem is described. It enumerates partial subsystems for the blocks of the partition along the tree order, and keeps only necessary ones. A preliminary experimental analysis shows that it outperforms other approaches on certain benchmarks which have directed tree partitions of small width.

Spliceostatins and Derivatives: Chemical Syntheses and Biological Properties of Potent Splicing Inhibitors.

Spliceostatins and thailanstatins are intriguing natural products due to their structural features as well as their biological significance. This family of natural products has been the subject of immense synthetic interest because they exhibit very potent cytotoxicity in representative human cancer cell lines. The cytotoxic properties of these natural products are related to their ability to inhibit spliceosomes. FR901564 and spliceostatins have been shown to inhibit spliceosomes by binding to their SF3B component. Structurally, these natural products contain two highly functionalized tetrahydropyran rings with multiple stereogenic centers joined by a diene moiety and an acyclic side chain linked with an amide bond. Total syntheses of this family of natural products led to the development of useful synthetic strategies, which enabled the synthesis of potent derivatives. The spliceosome modulating properties of spliceostatins and synthetic derivatives opened the door for understanding the underlying spliceosome mechanism as well as the development of new therapies based upon small-molecule splicing modulators. This review outlines the total synthesis of spliceostatins, synthetic studies of structural derivatives, and their bioactivity.

Finite inventory budgets in production capacity and safety stock placement under the guaranteed service approach

Following the guaranteed service approach (GSA), several studies have investigated the interaction between production and inventory decisions in multistage supply systems and developed efficient algorithms to solve the large-scale optimization problems that emerge. These works have largely ignored limited inventory budgets and their effect on production and inventory decisions. In reality, however, firms tend to limit the amount of capital tied-up in inventories, and there is usually a limited amount of storage space at a warehouse or a retailer. This study investigates the problem of production capacity and safety stock placement with both limited capacity and inventory budgets in general acyclic supply chains. This problem allocates capacity to production stages and sets inventory targets at logistics stages, with the objective to minimize the expected total supply chain cost while meeting a target customer service level.The present paper contributes to the GSA literature in several ways. First, we compare guaranteed and chance-constraint approaches to model limited inventory budgets and analyze their effect on safety stock placement. Second, we present two new equivalent formulations of the production capacity and safety stock placement problem. Solving these new models using a successive piecewise linear approximation algorithm outperforms existing solution procedures in terms of solution quality and time, in both cases of infinite and finite inventory budgets. Third, taking advantage of the structure of these formulations, we develop a two-phase heuristic, which finds optimal or near-optimal solutions and greatly improves CPU times. Finally, our numerical experiments show that inventory budgets affect production capacity and safety stock placement decisions, increasing both work in process (WIP) and safety stock levels.

Femtosecond solvation dynamics study of hydrophobic and hydrophilic probes in various room temperature ionic liquids (RTILs) containing microemulsions

The locations of hydrophobic and hydrophilic probes in room temperature ionic liquids (RTILs) containing microemulsions have been investigated using femtosecond solvation dynamics study, as the time correlated single photon counting (TCSPC) measurement has limitation in terms of detecting the ultrafast component of relaxation time less than 100 ps. Here, choice of two different RTILs unveils the information about the effect of acyclic and cyclic hydrocarbon chain on solvation dynamics. The exclusive information from dynamic light scattering (DLS) measurement, anisotropy study and the fluorescence correlation spectroscopy (FCS) judiciously help to perform detailed analysis of these systems.

A Polyol-Polyol Super-Carbon-Chain Compound Containing Thirty-Six Carbon Stereocenters from the Dinoflagellate Amphidinium gibbosum: Absolute Configuration and Multi-Segment Modification

A super-carbon-chain compound, named gibbosol C, featuring a polyoxygenated C70-linear-carbon-chain backbone encompassing two acyclic polyol chains, was obtained from the South China Sea dinoflagellate Amphidinium gibbosum. Its planar structure was elucidated by extensive NMR investigations, whereas its absolute configurations, featuring the presence of 36 carbon stereocenters and 30 hydroxy groups, were successfully established by comparison of NMR data of the ozonolyzed products with those of gibbosol A, combined with J-based configuration analysis, Kishi’s universal NMR database, and the modified Mosher’s MTPA ester method. Multi-segment modification was revealed as the smart biosynthetic strategy for the dinoflagellate to create remarkable super-carbon-chain compounds with structural diversity.

Determination of the Absolute Configuration of Super-Carbon-Chain Compounds by a Combined Chemical, Spectroscopic, and Computational Approach: Gibbosols A and B.

Marine dinoflagellates produce remarkable organic molecules, particularly those with polyoxygenated long-carbon-chain backbones, namely super-carbon-chain compounds (SCCCs), characterized by the presence of numerous stereogenic carbon centers on acyclic polyol carbon chains. Even today, it is a challenge to determine the absolute configurations of these compounds. In this work, the planar structures and absolute configurations of two highly flexible SCCCs, featuring either a C69 - or C71 -linear carbon backbone, gibbosols A and B, respectively, each containing thirty-seven stereogenic carbon centers, were unambiguously established by a combined chemical, spectroscopic, and computational approach. The discovery of gibbosols A and B with two hydrophilic acyclic polyol chains represents an unprecedented class of SCCCs. A reasonable convergent strategy for the biosynthesis of these SCCCs was proposed.

Determination of the Absolute Configuration of Super‐Carbon‐Chain Compounds by a Combined Chemical, Spectroscopic, and Computational Approach: Gibbosols A and B

AbstractMarine dinoflagellates produce remarkable organic molecules, particularly those with polyoxygenated long‐carbon‐chain backbones, namely super‐carbon‐chain compounds (SCCCs), characterized by the presence of numerous stereogenic carbon centers on acyclic polyol carbon chains. Even today, it is a challenge to determine the absolute configurations of these compounds. In this work, the planar structures and absolute configurations of two highly flexible SCCCs, featuring either a C69‐ or C71‐linear carbon backbone, gibbosols A and B, respectively, each containing thirty‐seven stereogenic carbon centers, were unambiguously established by a combined chemical, spectroscopic, and computational approach. The discovery of gibbosols A and B with two hydrophilic acyclic polyol chains represents an unprecedented class of SCCCs. A reasonable convergent strategy for the biosynthesis of these SCCCs was proposed.