Metabolites profiling of Chrysanthemum pacificum Nakai parts using UPLC-PDA-MS coupled to chemometrics

Methanol-soluble constituents from the flowers, non-flowering aerial parts and roots of Chrysanthemum pacificum Nakai were analysed via high resolution UPLC-PDA-qTOF-MS followed by chemometrics. Forty-seven chromatographic peaks belonging to various metabolite classes were detected. Most metabolite classes showed qualitative and quantitative differences across parts, with luteolin conjugates being mostly enriched in flowers whereas non-flowering aerial parts contained mostly quercetin and methoxylated flavone conjugates. Root sample ranked the lowest for all flavones and dicaffeoylquinic acids. In contrast, 1,5-di-caffeoylquinic acid levels were found at high levels in flowers and aerial parts reaching 3145 and 1390 μg/g, respectively, suggesting that C. pacificum could serve as a natural resource of this well-recognised anti-hepatotoxic phenolic. Principal component analysis was further used for organs classification in an untargeted manner. This study provides the first map of secondary metabolites distribution in C. pacificum Nakai organs.     

Dioxygen activation at a single copper site: structure, bonding, and mechanism of formation of 1:1 Cu-O2 adducts

To evaluate the fundamental process of O(2) activation at a single copper site that occurs in biological and catalytic systems, a detailed study of O(2) binding to Cu(I) complexes of beta-diketiminate ligands L (L(1) = backbone Me; L(2) = backbone tBu) by X-ray crystallography, X-ray absorption spectroscopy (XAS), cryogenic stopped-flow kinetics, and theoretical calculations was performed. Using synchrotron radiation, an X-ray diffraction data set for L(2)CuO(2) was acquired, which led to structural parameters in close agreement to theoretical predictions. Significant Cu(III)-peroxo character for the complex was corroborated by XAS. On the basis of stopped-flow kinetics data and theoretical calculations for the oxygenation of L(1)Cu(RCN) (R = alkyl, aryl) in THF and THF/RCN mixtures between 193 and 233 K, a dual pathway mechanism is proposed involving (a) rate-determining solvolysis of RCN by THF followed by rapid oxygenation of L(1)Cu(THF) and (b) direct, bimolecular oxygenation of L(1)Cu(RCN) via an associative process.     

Reactivity of a 1:1 copper-oxygen complex: isolation of a Cu(II)-o-iminosemiquinonato species

While a 1:1 Cu-O2 adduct is generally unreactive with organic substrates, phosphines displace O2 via an associative process and added Cu(I) leads to a novel internal ligand oxidation to yield a Cu(II)-o-iminosemiquinone complex.     

Synthesis of functionalized thiazoles via attack of heterocyclic nucleophiles on allenyl isothiocyanates

New examples of substituted thiazole derivatives carrying different heterocyclic ring systems at C-2 position were prepared via the reaction of several allenyl isothiocyanates with nucleophiles such as imidazoles, pyrazoles, benzimidazoles, indazole, 1,2,3-triazole, 1,2,4-triazole, and 1H-benzotriazole. Although these allenyl isothiocyanates are very reactive electrophiles and tend to polymerize, the yield of the thiazole products ranked between modest and very good. The regiochemistry of the reactions was proved by NMR and X-ray studies indicating that the attack of ambident nucleophiles proceeded very selectively. In some cases, however, the products were formed as mixtures of aromatic heterocycles and non-aromatic isomers. The latter could be rearranged to yield the uniform aromatic thiazoles.     

Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways

Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the Bcl-2 gene and upregulated the Bax gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines’ levels, and suppression of the MAPK (ERK1/2, JNK, p38)–NF-κB intracellular signaling pathway.     

Design,Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by ¹H-NMR, ¹³C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC₅₀ = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.     

Water‐based inorganic/polymer hybrid particles prepared via a multiple miniemulsion process

A universal method for the synthesis of water‐based inorganic–polymer hybrid particles was developed in which no organic solvent is required. To demonstrate the versatility of this process, zinc phosphate, calcium carbonate, and barium sulfate were chosen as different pigment examples which additionally can be utilized for functional coating applications. Furthermore, a complex polymeric composition based on epoxy–acrylic–styrene was chosen to illustrate the versatility from a soft matter point of view. The overall synthesis process was carried out by coemulsification of two inverse miniemulsions, containing two precursors, surrounded with a polymerizable continuous phase. This was then transferred to a direct miniemulsion by addition to a surfactant solution and subsequent homogenization followed by radical polymerization of the vinylic monomers. To our knowledge, this is the first work where a polymerizable continuous phase has been used in an inverse miniemulsion formation followed by transfer to a direct miniemulsion, followed by polymerization, so that the result is a water‐based dispersion. The resultant dispersion was characterized by dynamic light scattering; the particles were investigated via transmission electron microscopy with in situ determination of crystallinity using electron diffraction. Elemental analysis was also performed for the particles and the polymerized miniemulsions using X‐ray fluorescence and inductively coupled plasma‐optical emission spectroscopy, respectively. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

beta-diketiminate ligand backbone structural effects on Cu(I)/O(2) reactivity: unique copper-superoxo and bis(mu-oxo) complexes

Copper(I) and -(II) complexes of beta-diketiminate ligands with identical flanking 2,6-diisopropylphenyl groups but divergent backbone substitution patterns were prepared and structurally characterized, and reactions of the Cu(I) species with O(2) at low temperature were explored. Despite being far removed from the coordinated metal ion, the different backbone patterns significantly influence the steric encumbrance exerted by the ligands, as revealed by differences in (a) the structural features of the Cu(I) and Cu(II) complexes and (b) the course of the oxygenation reactions of the Cu(I) compounds. With the less hindered ligand, a rare example of a neutral bis(mu-oxo)dicopper complex was identified on the basis of its diagnostic spectral features (UV-vis, resonance Raman, EPR) and the stoichiometry of O(2) uptake (Cu:O(2) = 2:1). In contrast, oxygenation of the Cu(I) complexes supported by the more hindered ligands yielded novel (superoxo)copper complexes, identified by a Cu:O(2) ratio of 1:1, a lack of an EPR signal, and O-isotope sensitive resonance Raman spectral features (nu(O)(-)(O) = 968 cm(-1), Delta(18)O(2) = 51 cm(-1)). Symmetric coordination of the superoxo ligand is proposed on the basis of Raman data acquired using (16)O(18)O (single peak at 943 cm(-1)).     

Steroidal glycoalkaloids from the berries of Solanum distichum

Two steroidal glycoalkaloids, Solanidine 3-O-[alpha-L-rhamnopyranosyl-(1' --> 4)-[alpha-L-rhamnopyranosyl-(1' --> 2)]-beta-D-glucopyranoside] (1) and Solanidine 3-O-[alpha-L-rhamnopyranosyl-(1' --> 4)-beta-D-glucopyranoside] (2) commonly known as alpha-chanonine and beta 2-chanonine, were isolated from the berries of Solanum distichum. The structures of the isolated compounds were studied by 1D and 2D NMR techniques and FAB MS analysis. The 13C NMR signal assignments and direct elucidation of the glycoside linkages were established. Glycoalkaloids level in the dried berries, determined by a simple colorimetric method, was found to be 5.08 +/- 0.18 g%.     

X-ray absorption edge spectroscopy and computational studies on LCuO2 species: Superoxide-Cu(II) versus peroxide-Cu(III) bonding

The geometric and electronic structures of two mononuclear CuO2 complexes, [Cu(O2){HB(3-Ad-5-(i)Prpz)3}] (1) and [Cu(O2)(beta-diketiminate)] (2), have been evaluated using Cu K- and L-edge X-ray absorption spectroscopy (XAS) studies in combination with valence bond configuration interaction (VBCI) simulations and spin-unrestricted broken symmetry density functional theory (DFT) calculations. Cu K- and L-edge XAS data indicate the Cu(II) and Cu(III) nature of 1 and 2, respectively. The total integrated intensity under the L-edges shows that the 's in 1 and 2 contain 20% and 28% Cu character, respectively, indicative of very covalent ground states in both complexes, although more so in 1. Two-state VBCI simulations also indicate that the ground state in 2 has more Cu (/3d8) character. DFT calculations show that the in both complexes is dominated by O2(n-) character, although the O2(n-) character is higher in 1. It is shown that the ligand L plays an important role in modulating Cu-O2 bonding in these LCuO2 systems and tunes the ground states of 1 and 2 to have dominant Cu(II)-superoxide-like and Cu(III)-peroxide-like character, respectively. The contributions of ligand field (LF) and the charge on the absorbing atom in the molecule (Q(mol)M) to L- and K-edge energy shifts are evaluated using DFT and time-dependent DFT calculations. It is found that LF makes a dominant contribution to the edge energy shift, while the effect of Q(mol)M is minor. The charge on the Cu in the Cu(III) complex is found to be similar to that in Cu(II) complexes, which indicates a much stronger interaction with the ligand, leading to extensive charge transfer.