Ring Fragmentation Research Articles

A level-set based Eulerian method for simulating problems involving high strain-rate fracture and fragmentation

In this paper, a novel method is proposed for simulating high strain-rate problems that include finite elastoplastic deformations, growth of anisotropic damage, and ultimately fragmentation. The focus of the paper is ductile fracture, although the underlying model is applicable to a broad range of materials and could be adapted to other problems. An Eulerian adaptive mesh refinement (AMR) numerical scheme is proposed that includes methods for modelling material imperfections and the nucleation, growth, and coalescence of arbitrary macro-scale crack networks. Furthermore, a method is proposed for identifying fragments on an AMR hierarchy in order to compute fragment statistics. The method is demonstrated through the simulation of high-strain rate fragmentation of metal rings. The predicted fragment characteristics are shown to be in good agreement with experimental data.

The application of artificial intelligence and machine learning to automate Gleason grading: Novel tools to develop next generation risk assessment assays.

170 Background: Postoperative risk assessment remains an important variable in the treatment of prostate cancer (PCA). Advances in genomic risk classifiers have aided clinical-decision making; however, clinical-pathologic variables such as Gleason grade and pathologic stage remain significant comparators for accurate prognostication. We aimed to standardize the descriptive pathology of PCA through automation of Gleason grading with artificial intelligence and image analysis feature selection Methods: Retrospective study using radical prostatectomy (RP) tissue microarrays from Henry Ford Hospital and Roswell Park Cancer Center with 8-year median follow-up. Samples were stained with a multiplex immunofluorescent assay: Androgen Receptor (AR), Ki67, Cytokeratin 18, Cytokeratin 5/6 and Alpha-methylacyl-CoA racemase); imaged with a CRI Nuance FX camera and then analyzed with proprietary software to generate a suite of morphometric - attributes that quantitatively characterize the Gleason spectrum. Derived features were univariately correlated with disease progression using the concordance index (CI) along with the hazards ratio and p-value. Results: Starting with a training cohort of 306 patients and a 15% event rate, MIF PCA images were subjected to a machine learning analysis program which incorporates a graph theory-based approach for characterization of gland / ring fusion and fragmentation of tumor architecture (TA) with biomarker quantitation (BQ) (i.e. AR and Ki67). 19 unique image features with 7 TA and 12 TA+BQ were identified, by univariate CI, all TA features were strongly associated with Gleason grading with CI’s reflecting degree of tumor differentiation (CI 0.29-.33, p-value = 0.005). Four TA+BQ features were selected in a training risk model and effectively replaced the clinical Gleason features. By comparison, dominant RP Gleason had a CI of 0.31. Conclusions: Image-based feature selection guided by principles of machine learning has the potential to automate and replace traditional Gleason grading. Such approaches provide the necessary foundation for next generation risk assessment assays.

Structural and Spectral Features of 4'-Substituted 2'-Hydroxychalcones in Solutions and Crystals: Spectroscopic and Theoretical Investigations.

The article describes investigations of 2'-hydroxychalcone and its three derivatives bearing differently sized alkyloxy groups at position 4'. The compounds are investigated from the point of view of crystal structure, electronic absorption, fluorescence features in solutions and crystals using X-ray diffraction and electronic spectroscopy methods, and quantum chemistry calculations. In general, both in solutions and in the crystal phase, the influence of substituents on absorption spectra of chalcones was found to be insignificant. Exclusively in the case of 4'-(4-methoxybenzyloxy)-2'-hydroxychalcone, molecular packing influences the absorption features, which is because of the intermolecular interactions of substituent's phenyl ring and chromophore fragment of the neighboring molecules. The lack of fluorescence of the excited enol form of chalcones in solutions and crystals is mainly due to intersystem crossing and excited-state intramolecular proton transfer. Fluorescent properties of the phototautomer keto species formed by the proton transfer depend on molecular conformation. In solutions, the excited keto form is twisted and effectively deactivates nonradiatively due to conical intersection. In the crystal phase, the fixed planar geometry disables the conical intersection and the fluorescence of the keto form becomes detectable.

Radical-induced expeditious stereoselective synthesis of 2-alkyl 3-allyl trans-2,3-dihydrobenzofurans (TADHBs)

ABSTRACTA thorough study on radical-induced cyclopropyl ring fragmentation with encompassed olefinic and cyclopropane environment has been performed. Interestingly, the fragmentation has occasioned onto a stereoselective synthesis of 3-allyl trans-2,3-dihydrobenzofurans with impressive yields. The trans-dihydrobenzofurans are present as central core in many molecules of medicinal interest and the present protocol deliver a straight forward access to the embedded molecular architecture.

Recent examples of α-ketoglutarate-dependent mononuclear non-haem iron enzymes in natural product biosyntheses.

Covering: up to 2018 α-Ketoglutarate (αKG, also known as 2-oxoglutarate)-dependent mononuclear non-haem iron (αKG-NHFe) enzymes catalyze a wide range of biochemical reactions, including hydroxylation, ring fragmentation, C-C bond cleavage, epimerization, desaturation, endoperoxidation and heterocycle formation. These enzymes utilize iron(ii) as the metallo-cofactor and αKG as the co-substrate. Herein, we summarize several novel αKG-NHFe enzymes involved in natural product biosyntheses discovered in recent years, including halogenation reactions, amino acid modifications and tailoring reactions in the biosynthesis of terpenes, lipids, fatty acids and phosphonates. We also conducted a survey of the currently available structures of αKG-NHFe enzymes, in which αKG binds to the metallo-centre bidentately through either a proximal- or distal-type binding mode. Future structure-function and structure-reactivity relationship investigations will provide crucial information regarding how activities in this large class of enzymes have been fine-tuned in nature.

Synthetic Studies of Yessotoxin: Stereoselective Annulation of the CD and JK Ring Fragments by Using Pd(II)-Catalyzed Cyclization

Synthetic Studies of Yessotoxin: Stereoselective Annulation of the CD and JK Ring Fragments by Using Pd(II)-Catalyzed Cyclization

Cyclopropanation of Benzene Rings by Oxidatively Generated α-Oxo Gold Carbene: One-Pot Access to Tetrahydropyranone-Fused Cycloheptatrienes from Propargyl Benzyl Ethers.

Cyclopropanations of benzene rings by oxidatively generated α-oxo gold carbenes are for the first time demonstrated in a Buchner reaction, in which readily available propargyl benzyl ethers are converted in one-pot to tetrahydropyranone-fused cycloheptatrienes via sequential oxidative gold catalysis and base-promoted isomerization. Additional examples of arene cyclopropanations without fragmentation of the cyclopropane ring are also realized.

One-Pot Synthesis of 2H-Indazolo[1,2-b]phthalazine-1,6,11(13H)-trione Derivatives Using Nano Hybrid MoO3/α-Al2O3

The development of new synthetic methods for the efficient preparation of heterocycles containing the phthalazine ring fragment is an interesting challenge because they are known to possess multipl...

Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms.

Metronidazole, a nitroimidazole, remains a front-line choice for treatment of infections related to inflammatory disorders of the gastrointestinal tract including colitis linked to Clostridium difficile. Despite >60 years of research, the metabolism of metronidazole and associated cytotoxicity is not definitively characterized. Nitroimidazoles are prodrugs that are reductively activated (the nitro group is reduced) under low oxygen tension, leading to imidazole fragmentation and cytotoxicity. It remains unclear if nitroimidazole reduction (activation) contributes to the cytotoxicity profile, or whether subsequent fragmentation of the imidazole ring and formed metabolites alone mediate cytotoxicity. A molecular mechanism underpinning high level (>256 mg/L) bacterial resistance to metronidazole also remains elusive. Considering the widespread use of metronidazole and other nitroimidazoles, this review was undertaken to emphasize the structure-cytotoxicity profile of the numerous metabolites of metronidazole in human and murine models and to examine conflicting reports regarding metabolite-DNA interactions. An alternative hypothesis, that DNA synthesis and repair of existing DNA is indirectly inhibited by metronidazole is proposed. Prokaryotic metabolism of metronidazole is detailed to discuss new resistance mechanisms. Additionally, the review contextualizes the history and current use of metronidazole, rates of metronidazole resistance including metronidazole MDR as well as the biosynthesis of azomycin, the natural precursor of metronidazole. Changes in the gastrointestinal microbiome and the host after metronidazole administration are also reviewed. Finally, novel nitroimidazoles and new antibiotic strategies are discussed.

Benefits and weaknesses of radiocarbon dating of plant material as reflected by Neolithic archaeological sites from Poland, Slovakia and Hungary

Radiocarbon dating of the plant material is important for chronology of archaeological sites. Therefore, a selection of suitable plant samples is an important task. The contribution emphasizes the necessity of taxonomical identification prior to radiocarbon dating as a crucial element of such selection. The benefits and weaknesses of dating of taxonomically undetermined and identified samples will be analysed based on several case studies referring to Neolithic sites from Hungary, Slovakia and Poland. These examples better illustrate the significance of the taxonomical identification since plant materials of the Neolithic age include only a limited number of cultivated species (e.g. hulled wheats) and typically do not contain remains of late arrived plants (e.g. <i>Carpinus betulus</i> and <i>Fagus sylvatica</i>). For more accurate dating results cereal grains, fruits and seeds, which reflect a single vegetative season, are preferred. Among charred wood, fragments of twigs, branches and external rings should mainly be taken into account, while those of trunks belonging to long-lived trees should be avoided. Besides the absolute chronology of archaeological features and artefacts, radiocarbon dating of identified plant remains might significantly contribute to the history of local vegetation and food production systems.

Photocatalytic Properties of Tetraphenylporphyrins Immobilized on Calcium Alginate Aerogels

We have prepared photocatalytic systems based on tetraphenylporphyrins (TPP) immobilized on calcium alginate solid gels in the conditions of thermal drying on air (xerogel), freeze drying in vacuum (cryogel) and supercritical drying in the supercritical carbon dioxide (scCO2) medium (aerogel). As a test reaction to measure the prepared systems’ efficiency, we studied tryptophan photooxidation in the aqueous medium. We have demonstrated that the systems with aerogel as a carrier exhibited the highest photocatalytic efficiency. In that case, the rate constant for the test substrate (tryptophan) oxidation exceeds the corresponding rate constants of similar systems based on xerogel and cryogel by more than 5 times. Moreover, the aerogel-based photocatalytic systems demonstrated enhanced functional stability and a possibility of multiple use of such a catalyst in tryptophan oxidation. Based on the data of small-angle X-ray scattering and thermooxidative destruction, we have made a conclusion about the relationship between the high photocatalytic activity of aerogel-immobilized TPP and formation of a developed porous aerogel structure in the conditions of drying in the scCO2 medium, which is stabilized due to formation of additional complex bonds of calcium ions with fragments of glycoside rings.

Finite Size Effects in Anisotropic u = ∞ Hubbard Ladder Rings

We apply perturbation theory and cyclic spin permutation formalism to study the lowest energy states of the infinite-repulsion Hubbard model on finite fragments of n-leg ladder rings and show jump-wise behavior of the ground state spin S 0 as a function of fragment parameters.

Emission properties of diazines chromophores: Structure-properties relationship

Abstract This article presents the photophysical properties of a series of diazine chromophores. The influence of five parameters has been studied: the presence of a diazine/benzodiazine fragment, the nature of the diazine fragment (1,3-diazine/1,4-diazine), the presence or not of an vinyl linker between diazine ring and phenylene fragments of the π-conjugated bridge, the presence of a phenylene/biphenylene linker and the nature of electron donating group (dimethylamino/diphenylamino). Taguchi's design of experiment combined with analysis of variance methodologies have been employed to highlight the main structural parameters influencing the position of absorption and emission maxima of dichloromethane solution and the extend of emission solvatochromic range exhibited by this family of chromophores.

Anthracene and phenanthrene tropospheric oxidation promoted by the nitrate radical in the gas-phase. Theoretical modelistic study

Polycyclic aromatic hydrocarbons and their oxidized derivatives are ubiquitous environmental pollutants that are toxic to different degrees. The NO3 radical is known to be an important actor in fostering nighttime atmospheric chemistry; hence it could elicit some nocturnal PAH-loss processes. In this study the gas phase pathways open to the initial anthracene and phenanthrene NO3 π−radical adducts in the presence of O2, NO and NO2 are examined by Density Functional Theory to ascertain the mechanistic features of their NO3-initiated oxidative degradation. Unimolecular steps involving the initial adducts (ring closures or fragmentation) present rather high free energy barriers and seem unlikely. Regarding bimolecular reactions, any radical present in the tropospheric environment can give an intrinsically fast radical coupling with the initial adducts, thus producing bifunctional closed shell species. The addition of ground state dioxygen is a relatively fast step that is reversible in some cases, less so in others. It entails subsequent reaction steps, which involve the peroxyl radical intermediate and addition and loss of small species as NO, NO3, NO2 and O2. These steps can either trigger a β−fragmentation with formation of a closed shell dialdehyde or formation of a closed shell nitroxy ketone, bifunctional species that appear to be the most likely products when typical tropospheric concentrations are taken into account.

Solid-phase peptide synthesis of analogues of the N-terminus A-ring fragment of the lantibiotic nisin: Replacements for the dehydroalanine (Dha) residue at position 5 and the first incorporation of a thioamide residue

A number of A-ring analogues of the lantibiotic nisin, containing replacements for the Dha residue at position 5, have been successfully prepared by solid-phase peptide synthesis. The Dha replacements include glycine, alanine, phenylalanine, serine and 1-aminocyclopropyl carboxylic acid (ACCa). The incorporation of a thioamide-isoleucine residue at position 4 is also described and represents the first reported preparation of a lantibiotic ring fragment containing a thioamide link.

Structure and hydrophilicity of azo‐dye‐derived rotaxane: density functional theory approach

We investigated the most probable molecular structure, energy, and corresponding properties, including the solvation energy and binding free energy in solution, for non‐encapsulated azo dyes using quantum mechanical density functional theory (DFT). The structures of non‐encapsulated azo dyes with six conformations were optimised to find the most stable conformation with the lowest energy, but the energy differences among the conformations were within ~2.2 kcal mol−1. The LUMO–HOMO gaps were also similar, meaning that their interaction with light would be similar. The energies of alpha‐cyclodextrin (α‐CD) encircling the phenyl ring fragments were significantly higher than other conformations, because α‐CD tends preferably to encircle azo fragments to create a thermodynamically stable form. From solvation free energy calculations, the hydrophobic non‐encapsulated azo dye and hydrophilic α‐CD showed reasonable values for solvation free energy with respect to dimethyl sulphoxide (DMSO) and water: the former has more solvation in DMSO, while the latter has more solvation in water. Rotaxane formation is thermodynamically feasible in water (−3.06 kcal mol−1) but not in DMSO (25.56 kcal mol−1) according to calculation of binding free energy in solution state.

A Computational Study on the Stability of Oxaphosphirane Rings towards Closed‐Shell Valence Isomerization

The stability of both unligated oxaphosphiranes 1 and their P‐M(CO)5 complexes 2 (M = Cr, W) has been explored with respect to their closed‐shell isomers, formed from either heterolytic C–O or P–C ring bond cleavage. C–O bond cleavage of 1 leads to valence isomers 3 featuring trigonal‐planar hybridization at P, whereas pyramidalized isomers 3′ are obtained for push–pull systems featuring electron‐donating substituents at C and electron‐withdrawing groups at P. Complexes 2 undergo C–O ring cleavage, affording side‐on complexes 4, except for the unstable C,C‐diamino‐substituted complex 2d, which yielded the end‐on complex 4′d. Most of the C–O bond‐cleavage processes are exergonic, but have moderately high energy barriers; C,C‐difluoro‐substituted oxaphosphiranes were identified as thermodynamically stable. C–P bond‐cleavage pathways afford zwitterionic species 6 or 7 as a result of pericyclic 4π‐electron conrotatory processes and are always disfavoured, compared with C–O bond cleavages. The cases of 1n,u,v and 2e are noteworthy, as attempted C–P bond cleavage led to ring fragmentation to give carbonic acid difluoride and phosphinidene derivatives.

A Short Covalent Synthesis of an All-Carbon-Ring [2]Rotaxane.

While the current supramolecular syntheses of [2]rotaxanes are generally efficient, the final product always retains the functional groups required for non-covalent preorganization. A short and high-yielding covalent-template-assisted approach is reported for the synthesis of a [2]rotaxane. A terephthalic acid template core preorganizes the covalently connected ring precursor fragments to induce a clipping-type cyclization over the thread moiety. Cleavage of the temporary ester bonds that connect the ring and thread fragments liberates the [2]rotaxane.

Study on the Photoinduced Nitric‐Oxide‐Releasing Ability of 4‐Alkoxy Furoxans

AbstractNitric oxide (NO) has a range of biological activities in living systems. Because NO is a gaseous and short‐lived molecule, the development of methods to enable a temporally and spatially resolved NO supply has been a challenging task. Herein, 3‐aryl‐4‐alkoxy furoxan is revealed as a potent photoinduced NO donor. Whilst negligible levels of NO release were observed under ambient fluorescent light, a significant amount of NO was released under UV irradiation (λ=300–400 nm). A thiol mediator that contains a pendant amino group was found to be indispensable for NO release from aryl alkoxy furoxans. Analysis of the NO‐releasing mechanism of aryl alkoxy furoxan revealed that the main co‐product was the corresponding aryl nitrile, which was derived from fragmentation of the furoxan ring. Based on these results, we have proposed a plausible mechanism for photoinduced NO release, in which the key steps are nucleophilic attack of the thiol at the 3‐position of the furoxan, thereby leading to fragmentation of the furoxan ring, and the formation of a tetrahydrothiazole that contains a C‐nitroso group. A comparison of fluorofuroxan and alkoxy furoxan is also discussed.

Convergent synthesis of stereoisomers of THF ring moiety of acetogenin thiophene analogue and their antiproliferative activities against human cancer cell lines

The convergent synthesis of thiophene-3-carboxamide analogues of annonaceous acetogenins was accomplished through the asymmetric alkynylation of a 2-formyl THF ring fragment with an alkyne having a thiophene ring as the key step. Eight stereoisomers of the THF ring moiety were synthesized by this convergent route and their antiproliferative activities against 39 human cancer cell lines were evaluated. It was revealed that derivatives having the threo configuration between C17–C18 positions showed more potent activities than the corresponding erythro ones.