Five-membered Ring Research Articles

2,3-Dihydroxynaphthalene invoked surface oxygen vacancy effect on Fe2O3 nanorods for photoanodic signal transduction tactic

The state-of-art signal transduction mechanism of anodic photoelectrochemistry is constrained to the hole oxidation reaction, which greatly hinders its application for prospective biosensing applications. Herein, we present an innovative strategy for signal transduction by exploiting the in situ formation of surface oxygen vacancies (VOs) on Fe2O3 nanorods (NRs) through the self-coordination of 2,3-dihydroxynaphthalene (2,3-DHN) on their surfaces. The 2,3-DHN was connected with Fe(Ⅲ) on the surface of Fe2O3 NRs vis the formation of the five-membered ring structures accompanied by the generation of VOs. And the generated VOs introduced a new defect energy level for trapping the photogenerated holes, which enhanced the charge separation and realized the enhancement of photocurrent signal. The developed signal transduction strategy was validated by the first photoelectrochemical (PEC) sensing platform for β-glucoside (β-Glu) and lipase (LPS), which can catalyze the hydrolysis of 3-hydroxy-2-naphthalenyl-β-D-glucoside and naphthalene-2,3-diol diacetate, respectively, to produce 2,3-DHN for signal stimuli. The β-Glu and LPS were detected with linear ranges of 0.01–10.0 U/mL and 0.001–5.0 mg/mL, respectively. Detection limits of 3.3 × 10−3 U/mL and 0.32 μg/mL (S/N = 3) were achieved, for β-Glu and LPS, respectively. The present study not only provides a new strategy for spontaneous induction of VOs in situ for n-type semiconductors, but also innovates the anodic PEC signal transduction strategy with broadened biosensing applications.

Five-Membered Heterocyclic Sulfonamides as Carbonic Anhydrase Inhibitors

The development of heterocyclic derivatives has progressed considerably over the past decades, and many new carbonic anhydrase inhibitors (CAIs) fall into this field. In particular, five-membered heterocyclic sulfonamides have been generally shown to be more effective inhibitors compared to six-membered rings ones. Despite the importance of oxygen and nitrogen five-membered heterocyclic aromatic rings in medicinal chemistry, the installation of sulfonamide moiety on such heterocycles has not received much attention. On the other hand, 1,3,4-thiadiazole/thiadiazoline ring-bearing sulfonamides are the scaffolds which have been widely used in a variety of pharmaceutically important CAIs such as acetazolamide, metazolamide and their many derivatives obtained by using the tail approach. Here, we reviewed the field focusing on the diverse biological activities of these CAIs, such as antiglaucoma, antiepileptic, antitumor and antiinfective properties. This review highlights developments involving five-membered heterocyclic sulfonamides over the last years, with a focus on their pharmacological/clinical applications.

Synthesis and Structure of P-Halogenated Benzazaphospholes and Their Reactivity toward Pt(0) Sources

Dearomatization of the five-membered ring of N-Dipp (Dipp = 2,6-diisopropylphenyl)-substituted benzazaphosphole 2 with HCl generated 1–Cl, which undergoes substitution with halide sources to provide the remaining members of the P-halogenated series (1–F, 1–Br, and 1–I). These P-heterocycles (1) were characterized by multinuclear [31P{1H}, 1H, 13C{1H}, and 19F (if applicable)] NMR spectroscopy, elemental analysis, and X-ray crystallography. 1H and 13C{1H} NMR spectroscopy revealed that derivatives 1–F, 1–Cl, and 1–Br have C1 symmetry in solution. In contrast, 1–I has effective Cs symmetry in solution due to a rapid, concentration-dependent, inversion at phosphorus, shown by density functional theory (DFT) calculations (B3LYP-D3/6-311G**++) to involve a dimeric iodine-bridged transition structure. In the solid state, 1–F through 1–I all exhibited C1 symmetry with varying degrees of elongation of their P–X bonds. Elongation of the P–X bonds is shown by DFT/natural bond orbital studies to involve NLP → σ*(P–X) negative hyperconjugation, which increases down the halogen series but is less pronounced than that for the closely related NHP–X counterparts (3–F through 3–I). Treatment of 1–Br/I with [Pt(P(t-Bu)3)2] afforded Pt(I)–Pt(I) dimers 4–Br/I, which were characterized by 31P{1H}, 1H, and 13C{1H} NMR spectroscopy, elemental analysis, and X-ray crystallography. Addition of 1–F to Pt(PPh3)4 gave Pt(1–F)(PPh3)2 (6), a coordination compound in which the P-heterocyclic ligand is bound through its lone pair without P–F bond cleavage. Recrystallization attempts resulted in ligand exchange, furnishing Pt(0) complex 7, which features 1–F and PPh3 donors in a 2:1 ratio. Reactions of 1–Cl with all tested starting materials produced unidentifiable product mixtures by 31P{1H} NMR spectroscopy, but the combination of Pt(PPh3)4 or Pt(PPh3)2(C2H4) and 1–Cl in acetone generated an unisolable Pt complex containing tentatively assigned PtP2 metallacyclopropane structural unit 8.

Study of the reaction mechanism based on the formation of the first carbocyclic ring from propargyl and diacetylene

The formation of the first carbon ring is a crucial rate-controlling step in developing polycyclic aromatic hydrocarbons (PAHs). It is vital to investigate the mechanism of the creation of the first carbon ring to inhibit the formation of PAHs. To explore the growth process of the first carbocyclic ring, this work used the average localized ionization energy (ALIE) and electrostatic potential (ESP) to predict the reaction sites. Moreover, the reaction paths and chemical kinetic parameters for the generation of the first carbocyclic ring from propargyl (C3H3) + diacetylene (C4H2) are calculated based on the density functional theory (DFT) method and transition state theory (TST). The results showed that the addition reaction of C3H3 +C4H2 can form five-, six- and seven-membered ring molecules, in which the five-membered ring formation is fastest and the six-membered ring formation is slowest. During the formation of the first carbon ring, the activation energy required for the H transfer and cyclization reactions is large, and the reaction rate is slow, which determines the formation rate of the first carbon ring. The rate of H-transfer reaction on each carbon ring depends on the number of C atoms of the carbon ring, with the five-membered ring being the fastest and the six-membered ring the slowest. This paper improves the reaction kinetics and thermodynamic data of the first carbon ring formation during the combustion of hydrocarbon fuels, which offers a powerful theoretical basis for predicting the generation of PAHs.

Reactive molecular dynamics simulations on interaction mechanisms of cold atmospheric plasmas and peptides

Plasma medicine is a rapidly growing multidisciplinary field, which mainly focuses on the application of Cold Atmospheric Plasma (CAP) in bioengineering. Several experiments have suggested that amino acids in proteins are excellent targets for plasma-derived chemical species. To gain a deep insight into the oxidative modification of proteins induced by CAP, a ReaxFF-based reactive Molecular Dynamics simulations are performed to investigate the reaction mechanism of Reactive Oxygen Species produced in CAP and the model peptides. The simulation results show that sulfur-containing amino acids with high reactivity could be oxidized to sulfuric acid moiety through sulfonation, and only H-abstraction reaction can take place for aromatic amino acids. The oxidation of five-membered ring amino acids could be observed by yielding the ring-open products in the simulations. Additionally, the dehydrogenation and hydroxylation of carbon-chain amino acids were also found from the simulations, with the formation of the hydroxyl group. The polar amino acids with the electron-rich structure were oxidized to a variety of products, such as di-hydroxylated lysine and hydroxylated asparagine. This study provides a crucial step to understand the processes of oxidative modifications and inactivation of proteins induced by CAP, showing a deep insight on the mechanism of plasma medicine.

Occurrence, Chemistry and Synthesis of Various Novel Methods of Oxadiazole

Oxadiazoles are a kind of heterocyclic molecule that can be identified by their five-membered ring structure, two azo groups, and a single oxygen atom in their make-up. These characteristics allow them to be distinguished from other heterocyclic compounds. Because of these features, it is possible to differentiate them from several other heterocyclic compounds. They have the highest importance and relevance in the area of heterocyclic chemistry, which is also where they have the most value. They are of the biggest significance. Research is being conducted on it in substantial amounts due to the fact that it has the potential to function as a starting point for the synthesis of bioactive molecules that are beneficial to the body. This article provides a brief discussion of the physicochemical features of oxadiazole, including its spectra and a few examples of how it may be synthesised. The article can be found here. The pharmacological effects of oxadiazole derivatives were investigated by our team of researchers, and the findings indicated that these compounds had a number of positive benefits, including anti-inflammatory, anti-cancer, anti-fungal, anti-osteoporotic, and anti-microbial properties. In this piece, we will have a brief discussion on both synthetic and naturally occurring medications that include the oxadiazole ring in addition to the moiety. This talk will focus on pharmaceuticals that have been manufactured. The production of these compounds may take place in a laboratory, or they may be found occurring naturally in their natural environments.

Construction of a Diverse Range of Boron Heterocycles via Ring Expansion of a Carboranyl-Substituted 9-Borafluorene.

Direct insertion of unsaturated substrates into a five-membered borole ring is a useful method to obtain valuable heterocycles containing one or more three-coordinate boron atoms. A highly Lewis acidic 9-o-carboranyl-9-borafluorene, in which the o-carboranyl substituent is connected via one of the cluster carbon atoms to the boron atom of the 9-borafluorene unit, was found to react with a vast array of unsaturated molecules, such as alkynes, aldehydes and various organic azides, to form larger boraheterocyclic products. The ring expansion reactions of the central borole ring proceed rapidly at room temperature, cementing the role of the o-carboranyl substituent in enhancing the insertion reactivity of 9-borafluorenes.

Magnetic frustration and fractionalization in oligo(indenoindenes)

Poly(indenoindenes) are {\pi}-conjugated ladder carbon polymers with alternating hexagons and pentagons hosting one unpaired electron for each five-membered ring in the open-shell limit. Here we study the main magnetic interactions that are present in finite oligo(indenoindenes) (OInIn), classifying the six possible isomers in two different classes of three isomers each. One class can be rationalized by frustrated S = 1/2 Heisenberg chains, with ferromagnetic interactions between neighbour sites and antiferromagnetic interactions between the next neighbours. The other class is characterized by the more trivial antiferromagnetic order. Employing several levels of theory we further show that the ground state of one of the isomers is a valence-bond solid (VBS) of ferromagnetic dimers (S = 1). This is topologically similar to that of the Affleck-Kennedy-Lieb-Tasaki (AKLT) model, which is known to show fractional S = 1/2 states at the edges.

Processes of 1,3-Dipolar cycloaddition in nucleoside, nucleotide and bio conjugation and its importance in medicinal chemistry

In the 1,3-dipolar cycloaddition, a 1,3-dipole and a dipolarophile interact chemically to produce a five-membered ring. The Huisgen cycloaddition occurs when an organic azide and an alkyne unite to form a 1,3-dipolar cycloaddition that results in a 1,2,3-triazole. 1,3-dipolar cycloaddition is an essential step in the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives. Some of the cycloadducts produced by these reactions were converted into enantiopure precursors known to exist in some biologically active chemicals as well as an active stereoisomer of a pine sawfly sex pheromone. The synthesis of several new enantiopure organocatalysts that were shown to be helpful in some The synthetic utility of these 1,3-dipolar cycloaddition processes with nitrones and a,b-unsaturated aldehydes was further demonstrated. There are times when these reactions have modest to moderate diastereofacial selectivity. the choose actual and nonracemic have improved. Compound collections are created in chemical biology research using the BIOS concept, which draws its inspiration from natural product scaffolds. In BIOS, the primary criterion utilized to develop hypotheses for the design and synthesis of targeted chemical libraries is biological relevance. Because they outline the chemical domains that nature has explored, the underlying scaffolds of natural product classes in particular serve as an inspiration for BIOS because they can be thought of as "trivet can often be achieved if both the azomethine ylide and the dipolarophile are chi privileged

Quantum Mechanical Assessment of Protein-Ligand Hydrogen Bond Strength Patterns: Insights from Semiempirical Tight-Binding and Local Vibrational Mode Theory.

Hydrogen bonds (HB)s are the most abundant motifs in biological systems. They play a key role in determining protein-ligand binding affinity and selectivity. We designed two pharmaceutically beneficial HB databases, database A including ca. 12,000 protein-ligand complexes with ca. 22,000 HBs and their geometries, and database B including ca. 400 protein-ligand complexes with ca. 2200 HBs, their geometries, and bond strengths determined via our local vibrational mode analysis. We identified seven major HB patterns, which can be utilized as a de novo QSAR model to predict the binding affinity for a specific protein-ligand complex. Glycine was reported as the most abundant amino acid residue in both donor and acceptor profiles, and N-H⋯O was the most frequent HB type found in database A. HBs were preferred to be in the linear range, and linear HBs were identified as the strongest. HBs with HB angles in the range of 100-110°, typically forming intramolecular five-membered ring structures, showed good hydrophobic properties and membrane permeability. Utilizing database B, we found a generalized Badger's relationship for more than 2200 protein-ligand HBs. In addition, the strength and occurrence maps between each amino acid residue and ligand functional groups open an attractive possibility for a novel drug-design approach and for determining drug selectivity and affinity, and they can also serve as an important tool for the hit-to-lead process.

Palladium-Catalyzed [3 + 2] Annulation of Aromatic Amides with Maleimides through Dual C-H Activation.

A palladium-catalyzed [3 + 2] annulation of substituted aromatic amides with maleimides providing tricyclic heterocyclic molecules in good to moderate yields through weak carbonyl chelation is reported. The reaction proceeds via a dual C-H bond activation where the first C-H activation takes place selectively at the benzylic position followed by a second C-H bond activation at the meta position to afford a five-membered cyclic ring. An external ligand Ac-Gly-OH has been used to succeed in this protocol. A plausible reaction mechanism has been proposed for the [3 + 2] annulation reaction.

Skeletal Transformation of Oxindoles into Quinolinones Enabled by Synergistic Copper/Iminium Catalysis

We describe a synergistic Cu/secondary amine catalysis for skeletal transformation of an oxindole core into a quinolinone skeleton, which generates several structurally new pyridine-fused quinolinones. The synergistic reactions allow expansion of a five-membered lactam ring by radical cation-triggered C-C bond cleavage and enable a further intramolecular cyclization with the aim to construct totally distinct core skeletons.

An Alkyne-Isocyanide Cycloaddition/Boulton-Katritzky Rearrangement/Ring Expansion Reaction: Access to 9-Deazaguanines.

An alkyne-isocyanide [3 + 2] cycloaddition followed by a Boulton-Katritzky rearrangement and a ring expansion is demonstrated. Different from the typical Boulton-Katritzky rearrangement, which forms five-membered ring products, the rearrangement-ring expansion method provides a mild, efficient, and atom-economical access to fused 9-deazaguanine structures in high yields.

Theoretical Study of Si/C Equally Mixed Dodecahedrane Analogues

To gain insight into the effect of Si/C arrangement on the molecular framework of strained polyhedral compounds, dodecahedrane analogues containing equal numbers of carbon and silicon (Si/C equally mixed dodecahedrane analogues) were investigated using the ab initio molecular orbital method. There are 1648 isomers for which the Si/C arrangement on the molecular framework is different. Based on the geometry optimization of all the isomers as well as the carbon and silicon analogues, the characteristics of the structure, relative energy, and strain energy of the Si/C equally mixed compounds are presented. Then, important factors controlling the relative energy, such as strain energy, are proposed through regression analysis. Also discussed is the correlation between the relative energy and the indices of Si/C dispersion, such as the number of skeletal C-Si single bonds and condensed five-membered rings constituting the polyhedral structure.

Indoloquinazoline alkaloids with cardiomyocyte protective activity against cold ischemic injury from Aspergillus clavatonanicus

The arthropod-associated fungi have been demonstrated to be a remarkable producer of structurally captivating and bioactive secondary metabolites for drug discovery. In this study, eleven new indoloquinazoline alkaloids, namely aspergilloids A–K (1–11), along with five known congeners (12–16), were obtained from fungus Aspergillus clavatonanicus, which was isolated from the gut of a centipede collected in our Tongji campus. All these compounds were rarely defined by a 6/5/5 indolone ring system in conjugation with a five-membered spiral ring (1–5 and 10–16) or an opening five-membered spiral ring (6–9). Their structures were elucidated by widespread spectroscopic analyses, mainly including HRESIMS and 1D and 2D NMR data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data analyses. The cardiomyocyte protective activity assay revealed that compounds 1, 2, 5, 12–14, and 16 ameliorated cold ischemic injury at 48 h post cold ischemia (CI), and compounds 1, 5, and 14 prevented cold ischemia induced Ser9 dephosphorylation of GSK3β at 12 h post CI. Our current study highlights indoloquinazoline alkaloids as the first class of natural cardiomyocyte protective agents against cold ischemic injury, which furnishes promising lead molecules for the development of new cardioprotectants in heart transplantation medicine.

Superficial and Inkjet Scalable Printed Sensors Integrated with Iron Oxide and Reduced Graphene Oxide for Sensitive Voltammetric Determination of Lurasidone.

The present work demonstrated the fabrication and the electrochemical characterization of novel printed electrochemical sensors integrated with an innovative nanosensing platform based on the synergic electrocatalytic effect of iron oxide nanoparticles (FeONPs) and reduced graphene oxide (rGO) for precise voltammetric determination of the antipsychotic drug lurasidone hydrochloride (LUH). The features of the electrode surface fabricated using the ordinary inkjet printer were characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Among different ink formulations, integration of the printing ink with the ratio 15 mg FeONPs and 20 mg rGO was found to be the most appropriate for sensitive quantification of LUH in biological fluids and pharmaceutical formulations in the presence of LUH degradation products. Under the optimized experimental and electroanalytical parameters, the recorded square-wave voltammograms were correlated to LUH within the linear concentration ranging from 50 to 2150 ng mL-1 with detection limit and limit of quantification values of 15.64 and 47.39 ng mL-1, respectively. Based on the cyclic voltammograms recorded for LUH at different scan rates, the electrode reaction was assumed to be a diffusion reaction mechanism accompanied by the transfer of two electrons/protons through the oxidation of the five-membered ring nitrogen atom as assumed by the molecular orbital calculations carried out on the LUH molecule. The C max of LUH and the efficiency of the fabricated sensors enabled their clinical application for monitoring LUH in human biological fluids and pharmaceutical formulations in the presence of degradants for diverse quality control applications and green chemistry analysis.

Reactivity of Oxygen-Bridged Geminal Al/P and Si/P Frustrated Lewis Pairs towards Heterocumulenes.

The two oxygen-bridged geminal frustrated Lewis pairs (FLP) tBu2 P-O-AlBis2 (Bis=CH(SiMe3 )2 ; 1) and tBu2 P-O-Si(C2 F5 )3 (2) were reacted with the heterocumulenes PhNCO, PhOCN, PhNCS, CS2 and PhNSO as well as SO2 . With isocyanate and cyanate, both 1 and 2, form addition products under formation of five-membered rings. With CS2 , isothiocyanate and sulfinylaniline, only 1 forms stable adducts, whereas 2 shows reactivity towards sulfinylaniline, but the product decomposed after a few minutes. The reaction of 1 with SO2 led to partial cleavage of the P-O-Al and Al-C units, as confirmed by X-ray diffraction studies of a complex aggregate. The reaction of 2 with SO2 affords the 1,2-addition product. All adducts were characterized by means of multinuclear NMR spectroscopy, X-ray crystallography and CHN analyses.

Theoretical Study on Design and Feasibility of Novel Circumtrindene Derivatives to Remove Ionic Contaminants

The structures and properties of Circumtrindene derivatives were studied at the M062X/6-31 + G(d,p) and M062X/LANL2DZ levels of theory in the gas phase and water as a solvent. Novel derivatives of Circumtrindene were designed by providing XH (X = NH, O, S) groups on the peripheral five-membered rings. Concave isomers were more stable (14.99–21.25 kcal/mol) than convex isomers. In these compounds, NH, OH, and SH groups were attached directly to the bowl and did not represent the proper size and flexibility to catch and hold ionic contaminants. Therefore, they could not be considered suitable for removing anions and cations. In the next series, the arms were extended to CH2XH (X = NH, O, S). In these flexibility derivatives, the average distances of heteroatoms were sufficient (0.99–1.26 Å) in removing anionic (Cl− and S2-) and cationic (Hg2+) contaminants. A comparison of removal equilibrium constants showed that the amine-containing derivative (X = NH) (K = 43192, 99.52% removal) was more effective than the alcoholic derivative (X = O) (K = 10, 73.49% removal) in removing Cl−. The alcohol derivative (X = OH) was more effective in removing S2− (K = 218530, 99.79% removal). On the other hand, the amine derivative (X = NH) possessed smaller energy barriers (ΔG#) of 7.44 and 8.91 kcal/mol for Cl− and S2− uptake, respectively compared to the corresponding alcohol derivative. The thiol derivative (X = S) was effective in trapping Hg2+ (K = 1.35 × 107), achieving a removal rate of 99.97%. Calculations in a PCM solvent (water) showed a decrease in Gibbs free energy barriers for ion removal, with values of 0.69 and 4.21 kcal/mol for Cl− and S2−, respectively, compared to the gas phase.

Review on Chemistry of Oxazole derivatives: Current to Future Therapeutic Prospective

ABSTRACT Oxazole and its derivatives play a very essential role in the area of medicinal chemistry. Oxazole nucleus is heterocyclic five-membered ring that seemed to be investigated in the advancement of novel compounds which shows favorable biological activities. In the modern medicinal chemistry scaffold of oxazole has been intermittently satisfied as a functional lead molecule. Prominently, enormous oxazole candidates or drugs are developed for the treatment of disease which increases its developmental values as medicinal agents. The five-membered aromatic ring of oxazole has atoms of nitrogen and oxygen. Through diverse non-covalent bonds, these rings quickly engage physiologically with many enzymes and receptors, resulting in a variety of biological actions. This review presents a logical attempt toward the researches and advancement of chemistry and oxazole derivatives’ biological action. The important information presented in this manuscript will work as impetus for new views in the pursuit for rational design of more biologically active and minimum toxic derivatives of oxazoles as medicinal agents.

Intelligent interpretation of the astronomical UIE bands: the spectra similarity

The limitations of visual inspection and interpretation of Infrared (IR) spectra from either laboratories or astronomical observations to cover a wide range of molecular types motivated us to apply a mathematical approach via a matching method called spectra similarity to identify the carriers of UIE bands in a sample of astronomical objects. The reliability of such a purely mathematical approach in targeting the correct molecular structures was tested by applying two sets of experimental IR spectra against the large pool of theoretical IR databases composed of 300,000 organic, organometallic, and, inorganic molecules. Spectra similarity calculations show that the second-row elements C, H, N, and O dominate the elemental composition of HD 44179, M 82, NGC 7023, NGC 7027, and Orion bar. In addition, the signatures of third-row elements S and Si were also identified. Our preliminary results confirm the signatures of complex organic molecules in interstellar environments. These are composed of benzene rings, five-membered rings, and side chain aliphatic groups in the cited astronomical sources. In some cases, the similarity approach suggested the fully aliphatic structures as the origin of UIE carriers.