Understanding Conformational Properties and Role of Hydrogen Bonds in Glycosaminoglycans-Interleukin8 Complexes in Aqueous Medium by Molecular Dynamics Simulation

Atomistic molecular dynamics simulations were performed under ambient conditions to explore the conformational features and binding affinities of hexameric glycosaminoglycans (GAGs) with chemokine Interleukin8 (IL8) in an aqueous medium. We tried to understand the role of hydrogen bonds (HBs) involving conserved water in mediating the interactions. The Luzar-Chandler model was adopted to study the kinetics of HB breaking and formation concerning different water-mediated HBs. The conformational flexibilities of bound GAGs are due to the flexible glycosidic linkages than the occasional/rare ring pucker conformation. The free energy landscape constructed with ϕ, and ψ, depicted that different conformational minima associated with the glycosidic linkage flexibility of the GAGs in bound states are separated by energy barriers. The binding affinities of IL8 towards GAGs are favored through the electrostatic and non-polar solvation interactions. 4-different types of conserved water were explored in the solvent-mediated binding of GAGs with IL8. The average lifetime of the IL8-GAG direct HB pairs was ∼ten times less than the IL8-GAG-shared water HBs. This is due to the rapid establishment of HB breaking and reformation kinetics involving water of a shared layer. We find that despite the highly negatively charged surface of GAGs, the IL8 surface populated by non-cationic amino acids could serve as a promising binding site in addition to the cationic surface of the protein.     

Hyperacmosin R,a New Decarbonyl Prenylphloroglucinol with Unusual Spiroketal Subunit from Hypericum acmosepalum

Two previously undescribed polycyclic polyprenylated acylphloroglucinols, hyperacmosins R-S (1–2), were obtained from the aerial parts of Hypericum acmosepalum. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism calculation (ECD). Compound 1 featured an unprecedented 5,8-spiroketal subunit as well as the loss of C-2′ carbonyl in the phloroglucinol ring. In addition, compounds 1 and 4 showed weak hepatoprotective activity against paracetamol-induced HepG2 cell damage at 10 μm. The plausible biosynthetic pathway of 1 was proposed via a retro-Clasisen reaction and decarboxylation.     

Iridoids Isolation from a Phytochemical Study of the Medicinal Plant Teucrium parviflorum Collected in Iraqi Kurdistan

Herbal medicines are still widely practiced in Kurdistan Region-Iraq, especially by people living in villages on mountainous regions. Among plants belonging to the genus Teucrium (family Lamiaceae), which are commonly employed in the Kurdish traditional medicine, we have analyzed, for the first time, the methanol and aqueous methanol extracts of T. parviflorum aerial parts. The plant is mainly used by Kurds to treat jaundice, liver disorders and stomachache. We aimed to determine the phytochemical profile of the extracts and the structures of the main components, so to provide a scientific rationale for the ancient use of the plant in the ethno-pharmacological field. TLC analysis of the two extracts on silica gel and reversed phase TLC plates, using different visualization systems, indicated similar contents and the presence of phenolics, flavonoids, terpenoids and sugars. The chlorophyll-free extracts exhibited weak/no antimicrobial activities against a panel of bacteria (MICs = 800–1600 µg/mL) and fungal strains (MICs ≥ 5 mg/mL). At the concentration of 600 µg/mL, the methanol extract showed moderate antiproliferative effects against A549 and MCF-7 cancer cell lines in the MTS assay. Moreover, both extracts exhibited a significant dose-dependent free radical scavenging action against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (EC₅₀ = 62.11 and 44.25 μg/mL, respectively). In a phytochemical study, a high phenolic content (77.08 and 81.47 mg GAE/g dry extract, respectively) was found in both extracts by the Folin–Ciocalteu assay. Medium pressure liquid chromatographic (MPLC) separation of the methanol extract on a reversed phase cartridge eluted with a gradient of MeOH in H₂O, afforded two bioactive iridoid glucosides, harpagide (1) and 8-O-acetylharpagide (2). The structures of 1 and 2 were established by spectral data, chemical reactions, and comparison with the literature. Interestingly, significant amounts of hepatotoxic furano neo-clerodane diterpenoids, commonly occurring in Teucrium species, were not detected in the extract. The wide range of biological activities reported in the literature for compounds 1 and 2 and the significant antiradical effects of the extracts give scientific support to the traditional use in Iraqi Kurdistan of T. parviflorum aerial parts for the preparation of herbal remedies.     

Synthesis and Properties of Double Calix[4]arene Derivatives Linked by Schiff-base in the Lower Rim

Calixarenesareregardedasthethirdgenerationofh0stmoleculesbecauseoftheirinclusionabilitytocati0ns,anionsandneutralmoleculesI'2.Duringthepastdecademosteff0rtshavebeentakenonthefunctionalizati0n0fcalixareness0thattheycanbeappliedn0tonlyastheionoph0resintheextractionprocess','andassensitivematerialsforionelectrodes"',butalsoastheenZymemimicscatalyzingthecleavageofphosphatediesters"'.Inordertoenablethemtoincludeandrecognizelargerchemicalspecies,manyappr0acheshavebeenusedtoc0nstructoIigo-calixarene…     

Ionic solid-state dimers and polymers derived from imidazolium dicarboxylic acids

A series of imidazolium dicarboxylic acids have been prepared from the reaction of the 1,3‐bis(carboxymethyl)imidazolium zwitterion with the Brønsted acids HX (X=F, Br, Cl, ClO₄). The structures of these acids have been established in the solid state by single‐crystal X‐ray diffraction, which revealed that the cations and anions form strong hydrogen bonds through O? H???X interactions, leading to the formation of dimeric and polymeric networks. These acids react with elemental zinc and cobalt to form stable polymeric coordination complexes, some of which have also been characterised by X‐ray diffraction.     

Formation of 8-nitroguanine and 8-oxoguanine due to reactions of peroxynitrite with guanine

Reactions of peroxynitrite with guanine were investigated using density functional theory (B3LYP) employing 6-31G** and AUG-cc-pVDZ basis sets. Single point energy calculations were performed at the MP2/AUG-cc-pVDZ level. Genuineness of the calculated transition states (TS) was tested by visually examining the vibrational modes corresponding to the imaginary vibrational frequencies and applying the criterion that the TS properly connected the reactant and product complexes (PC). Genuineness of all the calculated TS was further ensured by intrinsic reaction coordinate (IRC) calculations. Effects of aqueous media were investigated by solvating all the species involved in the reactions using the polarizable continuum model (PCM). The calculations reveal that the most stable nitro-product complex involving the anion of 8-nitroguanine and a water molecule i.e. 8NO(2)G(-) + H(2)O can be formed according to one reaction mechanism while there are two possible reaction mechanisms for the formation of the oxo-product complex involving 8-oxoguanine and anion of the NO(2) group i.e. 8OG + NO(2)(-). The calculated relative stabilities of the PC, barrier energies of the reactions and the corresponding enthalpy changes suggest that formation of the complex 8OG + NO(2)(-) would be somewhat preferred over that of the complex 8NO(2)G(-) + H(2)O. The possible biological implications of this result are discussed.     

Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts

A Ru‐catalyzed direct C? H activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future C? H activation development that would allow the remote functionalization of aromatic systems.     

On the Role of the Electronic Structure of the Heteronuclear Oxide Cluster [Ga2Mg2O5].+ in the Thermal Activation of Methane and Ethane: An Unusual Doping Effect

The reactivity of the heteronuclear oxide cluster [Ga₂Mg₂O₅]^.+, bearing an unpaired electron at a bridging oxygen atom (O_b^.?), towards methane and ethane has been studied using Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR‐MS). Hydrogen‐atom transfer (HAT) from both methane and ethane to the cluster ion is identified experimentally. The reaction mechanisms of these reactions are elucidated by state‐of‐the‐art quantum chemical calculations. The roles of spin density and charge distributions in HAT processes, as revealed by theory, not only deepen our mechanistic understanding of C? H bond activation but also provide important guidance for the rational design of catalysts by pointing to the particular role of doping effects.     

Regioselective synthesis of functionalized 4-nitro- and 4-amino-phenols based on formal [3+3] cyclocondensations of 3-ethoxy-2-nitro-2-en-1-ones with 1,3-bis(silyloxy)-1,3-butadienes

Functionalized 4-nitro- and 4-aminophenols were regioselectively prepared based on [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-ethoxy-2-nitro-2-en-1-ones.