Unique Ring Research Articles

Molecular Decoration and Unconventional Double Bond Migration in Irumamycin Biosynthesis

Irumamycin (Iru) is a complex polyketide with pronounced antifungal activity produced by a type I polyketide (PKS) synthase. Iru features a unique hemiketal ring and an epoxide group, making its biosynthesis and the structural diversity of related compounds particularly intriguing. In this study, we performed a detailed analysis of the iru biosynthetic gene cluster (BGC) to uncover the mechanisms underlying Iru formation. We examined the iru PKS, including the domain architecture of individual modules and the overall spatial structure of the PKS, and uncovered discrepancies in substrate specificity and iterative chain elongation. Two potential pathways for the formation of the hemiketal ring, involving either an olefin shift or electrocyclization, were proposed and assessed using 18O-labeling experiments and reaction activation energy calculations. Based on our findings, the hemiketal ring is likely formed by PKS-assisted double bond migration and TE domain-mediated cyclization. Furthermore, putative tailoring enzymes mediating epoxide formation specific to Iru were identified. The revealed Iru biosynthetic machinery provides insight into the complex enzymatic processes involved in Iru production, including macrocycle sculpting and decoration. These mechanistic details open new avenues for a targeted architecture of novel macrolide analogs through synthetic biology and biosynthetic engineering.

Is a photon ring invariably a closed structure?

In this study, we investigate the image of a rotating compact object (CO) illuminated by a geometrically thin, optically thin disk on the equatorial plane. As the radius of the CO’s surface fluctuates, the CO may partially or entirely obscure the photon region. We observe that the perceived photon ring may exhibit discontinuities, deviating from a closed structure, and may even disappear entirely. We find that the disruption and disappearance of the photon ring are dependent on the observational angle-a novel phenomenon not previously observed in black hole imaging studies. Our study reveals that while the factors influencing this unique photon ring phenomenon are diverse and the outcomes complex, we can provide a clear and comprehensive explanation of the physical essence and variation trends of this phenomenon. We do this by introducing and analyzing the properties and interrelationships of three characteristic functions, η~\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ilde{\\eta }$$\\end{document}, ηo\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\eta _o$$\\end{document}, and ηs\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\eta _s$$\\end{document} related to the photon impact parameters. Additionally, our analysis of the intensity cuts and inner shadows of the images uncovers patterns that differ significantly from the shadow curve.

Protein-RNA interactions mediated by silvestrol-insight into a unique molecular clamp.

Molecular staples or interfacial inhibitors are small molecules that exert their activity through co-association with macromolecules leading to various effects on target functions. Some molecules inhibit target activity, while others generate gain-of-function complexes. We and others have previously identified two structurally distinct classes of molecular staples, pateamine A and rocaglates. These molecules inhibit eukaryotic initiation factor (eIF) 4A, a critical RNA helicase required for translation initiation, by simultaneously interacting with both RNA and protein components. Structural insights from members of these two families indicate that they wedge themselves between RNA bases during engagement. To extend our understanding of rocaglates, we investigated the RNA-binding properties of silvestrol, a natural rocaglate distinguished by the presence of a unique dioxanyloxy ring. Our study demonstrates that silvestrol expands the RNA-binding repertoireof rocaglates due to this structural characteristic, providing a rationale for improving synthetic molecular staples targeting eIF4A.

Safety assessment of novel oxadiazole derivatives in acute and sub-acute toxicity studies.

1,3,4-Oxadiazole is a fascinating heterocyclic compound with a unique five-membered ring structure containing nitrogen and oxygen atoms. It has garnered significant attention for its interactions and activities within biological systems. This versatility has led to the production of several ligands using this compound as a pharmacophore. This study evaluates the acute toxicity of three oxadiazole derivatives (1,3,4-Bromo, Chloro, and Iodo) followed by a 28days sub-acute study involving four different doses of each derivative. The study followed the guideline, the Organization for Economic Cooperation and Development (OECD) outlined, specifically OECD Guidelines 425 for the acute toxicity study and OECD Guidelines 407 for the sub-acute study. In the acute toxicity study, a high dose of 2000 mg/kg was administered to male and female rats to establish lethal dose 50 (LD50) values, and the rats were closely monitored for 14 days. The subsequent sub-acute study involved the administration of four different doses (1.25, 2.5, 5, and 10 mg/kg) of each derivative to male and female rats for 28 days. Throughout both studies, careful monitoring for signs of toxicity and comprehensive hematological, biochemical, and histological analysis were carried out thoroughly. The results of the acute toxicity study indicated that all three derivatives had LD50 values exceeding 2000 mg/kg, and the rats did not display significant signs of toxicity. Similarly, no organ or systemic toxicity was observed in the repeated dose sub-acute study for any of the three derivatives. In conclusion, based on the findings of these studies, it was determined that the derivatives are safe for further investigation of their pharmacological activity.

Experimental investigation of material properties of GFRP pipe for numerical simulation of novel nuclear power plant cooling water intake system

The cooling systems of nuclear power plants are typically made of reinforced concrete water intake structures and special steel pipes, making them large, important structures that necessitate very expensive special productions. In the scope of this research, an innovative design for 4-meter diameter GFRP composite pipes used in nuclear power plant cooling systems was developed using the circular wrapping method. The composite GFRP pipe used in the study has a substantial embedment depth. For this reason, an innovative design was created using unique stiffening rings, and the impact of these rings on the overall behavior was investigated. The nonlinear numerical analysis model of the nuclear power station cooling system, which consists of three pipes with a diameter of 4 m, was then created with ANSYS finite element software using the determined material models, and the results were interpreted. As a result of the study, a composite GFRP pipe design that can be used as a cooling system in significant structures like nuclear power plants has been developed.

Single-Electron Qubits Based on Quantum Ring States on Solid Neon Surface.

Single electrons trapped on solid-neon surfaces have recently emerged as a promising platform for charge qubits. Experimental results have revealed their exceptionally long coherence times, yet the actual quantum states of these trapped electrons, presumably on imperfectly flat neon surfaces, remain elusive. In this Letter, we examine the electron's interactions with neon surface topography, such as bumps and valleys. By evaluating the surface charges induced by the electron, we demonstrate its strong perpendicular binding to the neon surface. The Schrödinger equation for the electron's lateral motion on the curved 2D surface is then solved for extensive topographical variations. Our results reveal that surface bumps can naturally bind an electron, forming unique quantum ring states that align with experimental observations. We also show that the electron's excitation energy can be tuned using a modest magnetic field to facilitate qubit operation. This study offers a leap in our understanding of electron-on-solid-neon qubit properties and provides strategic insights on minimizing charge noise and scaling the system to propel forward quantum computing architectures.

Discovery and biological profile of pyridachlometyl

AbstractPyridachlometyl is a novel tubulin dynamics modulator fungicide developed by Sumitomo as a new agent designed to tackle fungicide resistance. Pyridachlometyl is being developed as a first‐in‐class molecule with an anti‐tubulin mode of action, the chemical structure of which is characterized by a unique tetrasubstituted pyridazine ring. The first commercial product ‘Fuseki flowable’ received initial registration in 2023 in Japan. The concepts of the discovery project, optimization of chemical structures, and biological profiles are reviewed herein. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Stable Pentagonal Layered Palladium Diselenide Enables Rapid Electrosynthesis of Hydrogen Peroxide.

Electrosynthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction (2e- ORR) is promising for various practical applications, such as wastewater treatment. However, few electrocatalysts are active and selective for 2e- ORR yet are also resistant to catalyst leaching under realistic operating conditions. Here, a joint experimental and computational study reveals active and stable 2e- ORR catalysis in neutral media over layered PdSe2 with a unique pentagonal puckered ring structure type. Computations predict active and selective 2e- ORR on the basal plane and edge of PdSe2, but with distinct kinetic behaviors. Electrochemical measurements of hydrothermally synthesized PdSe2 nanoplates show a higher 2e- ORR activity than other Pd-Se compounds (Pd4Se and Pd17Se15). PdSe2 on a gas diffusion electrode can rapidly accumulate H2O2 in buffered neutral solution under a high current density. The electrochemical stability of PdSe2 is further confirmed by long device operational stability, elemental analysis of the catalyst and electrolyte, and synchrotron X-ray absorption spectroscopy. This work establishes a new efficient and stable 2e- ORR catalyst at practical current densities and opens catalyst designs utilizing the unique layered pentagonal structure motif.

Discovery of novel natural cardiomyocyte protectants from a toxigenic fungus Stachybotrys chartarum

Stachybatranones A–F (1a/1b and 2–6) and three known analogues, namely methylatranones A and B (7 and 8) and atranone B (9), were isolated and identified from a toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated via the extensive spectroscopic data, comparison of the experimental electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analyses. Structurally, compounds 2–6 belonged to a rare class of C-alkylated dolabellanes, featuring a unique five-membered hemiketal ring and a γ-butyrolactone moiety both fused to an 11-membered carbocyclic system, while compound 1 (1a/1b) represented the first example of a 5-11-6-fused atranone possessing a 2,3-butanediol moiety. The cardiomyocyte protective activity assay revealed that compounds 1–9 ameliorated cold ischemic injury at 24 h post cold ischemia (CI), with compounds 1 and 4 acting in a dose-dependent manner. Moreover, compound 1 prevented cold ischemia induced dephosphorylation of PI3K and AKT acting in a dose-dependent manner. In this study, a new class of natural products were found to protect cardiomyocytes against cold ischemic injury, providing a potential option for the development of novel cardioprotectants in heart transplant medicine.

Two Cytochrome P450 Enzymes Form the Tricyclic Nested Skeleton of Meroterpenoids by Sequential Oxidative Reactions.

Meroterpenoid clavilactones feature a unique benzo-fused ten-membered carbocyclic ring unit with an α,β-epoxy-γ-lactone moiety, forming an intriguing 10/5/3 tricyclic nested skeleton. These compounds are good inhibitors of the tyrosine kinase, attracting a lot of chemical synthesis studies. However, the natural enzymes involved in the formation of the 10/5/3 tricyclic nested skeleton remain unexplored. Here, we identified a gene cluster responsible for the biosynthesis of clavilactone A in the basidiomycetous fungus Clitocybe clavipes. We showed that a key cytochrome P450 monooxygenase ClaR catalyzes the diradical coupling reaction between the intramolecular hydroquinone and allyl moieties to form the benzo-fused ten-membered carbocyclic ring unit, followed by the P450 ClaT that exquisitely and stereoselectively assembles the α,β-epoxy-γ-lactone moiety in clavilactone biosynthesis. ClaR unprecedentedly acts as a macrocyclase to catalyze the oxidative cyclization of the isopentenyl to the nonterpenoid moieties to form the benzo-fused macrocycle, and a multifunctional P450 ClaT catalyzes a ten-electron oxidation to accomplish the biosynthesis of the 10/5/3 tricyclic nested skeleton in clavilactones. Our findings establish the foundation for the efficient production of clavilactones using synthetic biology approaches and provide the mechanistic insights into the macrocycle formation in the biosynthesis of fungal meroterpenoids.

Skeletal Transformations of Terpenoid Forskolin Employing an Oxidative Rearrangement Strategy.

The skeletal transformations of diterpenoid forskolin were achieved by employing an oxidative rearrangement strategy. A library of 36 forskolin analogues with structural diversity was effectively generated. Computational analysis shows that 12 CTD compounds with unique scaffolds and ring systems were produced during the course of this work.

Triazine-COF@Silicon nanowire mimicking plant leaf to enhance photoelectrocatalytic CO2 reduction to C2+ chemicals

Triazine-COF@Silicon nanowire mimicking plant leaf to enhance photoelectrocatalytic CO2 reduction to C2+ chemicals

Rxn-INSIGHT: fast chemical reaction analysis using bond-electron matrices

The challenge of devising pathways for organic synthesis remains a central issue in the field of medicinal chemistry. Over the span of six decades, computer-aided synthesis planning has given rise to a plethora of potent tools for formulating synthetic routes. Nevertheless, a significant expert task still looms: determining the appropriate solvent, catalyst, and reagents when provided with a set of reactants to achieve and optimize the desired product for a specific step in the synthesis process. Typically, chemists identify key functional groups and rings that exert crucial influences at the reaction center, classify reactions into categories, and may assign them names. This research introduces Rxn-INSIGHT, an open-source algorithm based on the bond-electron matrix approach, with the purpose of automating this endeavor. Rxn-INSIGHT not only streamlines the process but also facilitates extensive querying of reaction databases, effectively replicating the thought processes of an organic chemist. The core functions of the algorithm encompass the classification and naming of reactions, extraction of functional groups, rings, and scaffolds from the involved chemical entities. The provision of reaction condition recommendations based on the similarity and prevalence of reactions eventually arises as a side application. The performance of our rule-based model has been rigorously assessed against a carefully curated benchmark dataset, exhibiting an accuracy rate exceeding 90% in reaction classification and surpassing 95% in reaction naming. Notably, it has been discerned that a pivotal factor in selecting analogous reactions lies in the analysis of ring structures participating in the reactions. An examination of ring structures within the USPTO chemical reaction database reveals that with just 35 unique rings, a remarkable 75% of all rings found in nearly 1 million products can be encompassed. Furthermore, Rxn-INSIGHT is proficient in suggesting appropriate choices for solvents, catalysts, and reagents in entirely novel reactions, all within the span of a second, utilizing nothing more than an everyday laptop.

Cyclization Reactions of In Situ-Generated Acyl Ketene with Ynones to Form Oxacycles.

Acyl ketenes react with polar unsaturated functional groups to give unique heterocyclic rings, yet reactions with unpolarized unsaturated functional groups have not been reported. Herein, we describe two effective ring-forming reactions between acetyl ketene and electron-deficient alkynes. The first reaction involves in situ tethering between acetyl ketene and nucleophile-containing 1,3-diynones, which promotes sequential intramolecular 1,6/1,4-additions to generate 2-methylene-2H-pyrans in various yields (24-91%). The other involves a zwitterionic intermediate generated from acetyl ketene and DABCO, which undergoes a Michael addition with terminal alkynyl ketones to generate 3-acyl-4-pyrones (11-79%).

Factorization properties of quotients of polynomial and power series rings by monomial ideals

Suppose that K is a field, S = K [ x 1 , … , x n ] or S = K [ [ x 1 , … , x n ] ] and I is a monomial ideal of S. We study factorization properties of the ring R = S / I . In particular, we present conditions equivalent to R being présimplifiable, a bounded factorization ring, a finite factorization ring or a unique factorization ring.

Recent Advances in Asymmetric Synthesis of Chiral Cyclobutenes

AbstractCyclobutene scaffolds occur in natural products and bioactive compounds. Their unique structural features and intrinsic ring strain make cyclobutene a type of important building block in synthetic chemistry. In recent years, considerable efforts have been dedicated to the synthesis of chiral cyclobutenes. Enantioselective [2+2] cycloadditions and functionalization of cyclobutene derivatives have emerged as powerful and reliable protocols for achieving this goal, resulting in significant progress in this field. This review provides a comprehensive summary of the recent advancements in the asymmetric synthesis of chiral cyclobutenes, and the discussion is logically divided into four parts according to the reaction mode.

Pentazolate Anion: A Rare and Preferred Five-Membered Ligand for Constructing Pentasil-Zeolite Topology Architectures.

As the fourth full-nitrogen structure, the pentazolate anion (cyclo-N5 - ) was highly coveted for decades. In 2017, the first air-stable non-metal pentazolate salt, (N5 )6 (H3 O)3 (NH4 )4 Cl, was obtained, representing a milestone in this field. As the latest member of the azole family, cyclo-N5 - is comprised of five nitrogen atoms. Although significant attention has been paid to the potential of cyclo-N5 - as an energetic material, its poor thermostability hinders any practical application. However, the unique ring structure and multiple coordination capability of cyclo-N5 - provide a platform for the fabrication of various structures, among which pentasil-zeolite topologies are the most intriguing. In addition, the introduction of structure-directing auxiliaries enables the self-assembly of diverse topological architectures, potentially imparting cyclo-N5 - with the potential to impact wide-ranging areas of coordination chemistry and topology. In this minireview, different pentasil-zeolite topologies based on metal-pentazolate frameworks are evaluated. To date, three zeolitic and zeolite-like topologies have been reported, namely the melanophlogite (MEP), chibaite (MTN), and unj topologies. The MEP topology consists of two nanocages, Na20 N60 and Na24 N60 , whereas the MTN topology contains Na20 N60 and Na28 N80 nanocages. Furthermore, the unj topology features multiple homochiral channels consisting of two helical chains. Various possible strategies for obtaining additional pentasil-zeolite topologies are also discussed.

Pentazolate Anion: A Rare and Preferred Five‐Membered Ligand for Constructing Pentasil‐Zeolite Topology Architectures

AbstractAs the fourth full‐nitrogen structure, the pentazolate anion (cyclo‐N5−) was highly coveted for decades. In 2017, the first air‐stable non‐metal pentazolate salt, (N5)6(H3O)3(NH4)4Cl, was obtained, representing a milestone in this field. As the latest member of the azole family, cyclo‐N5− is comprised of five nitrogen atoms. Although significant attention has been paid to the potential of cyclo‐N5− as an energetic material, its poor thermostability hinders any practical application. However, the unique ring structure and multiple coordination capability of cyclo‐N5− provide a platform for the fabrication of various structures, among which pentasil‐zeolite topologies are the most intriguing. In addition, the introduction of structure‐directing auxiliaries enables the self‐assembly of diverse topological architectures, potentially imparting cyclo‐N5− with the potential to impact wide‐ranging areas of coordination chemistry and topology. In this minireview, different pentasil‐zeolite topologies based on metal‐pentazolate frameworks are evaluated. To date, three zeolitic and zeolite‐like topologies have been reported, namely the melanophlogite (MEP), chibaite (MTN), and unj topologies. The MEP topology consists of two nanocages, Na20N60 and Na24N60, whereas the MTN topology contains Na20N60 and Na28N80 nanocages. Furthermore, the unj topology features multiple homochiral channels consisting of two helical chains. Various possible strategies for obtaining additional pentasil‐zeolite topologies are also discussed.

Hysterolides A–I, dimeric or monomeric sesquiterpene lactones from Parthenium hysterophorus L.

Nine undescribed sesquiterpene lactones, including two pseudoguaianolide dimers (1 and 2), a pseudoguaiac dilactone (3), and six pseudoguaianolides (4–9), along with 13 known analogues (10–22) were isolated from Parthenium hysterophorus. Among them, hysterolide A (1) possesses an unusual carbon skeleton with a unique cyclobutane ring connecting two pseudoguaianolides. Hysterolide C (3) is a sesquiterpene dilactone incorporating a bicyclo[5.1.0]octane core. Spectroscopic analyses, 13C NMR and ECD calculations, and X-ray diffraction elucidated their structures and absolute configurations. Moreover, all the isolates were assayed for their anti-inflammatory activities by inhibiting LPS-induced nitric oxide production in BV-2 microglia cells, wherein, nine compounds displayed significant inhibitory activities with IC50 of 0.52–6.32 μM. Furthermore, the preliminary structure-activity relationship was also established.

Enantioselective Total Synthesis of (-)-Daphenylline.

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr2-catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.