Computational Study on the Inhibition Mechanisms of the Ziegler-Natta Catalyst in the Propylene Polymerization Process: Part 1 Effects of Acetylene and Methylacetylene.

Acetylene and methylacetylene are impurities commonly found in the raw materials used for the production of polymers such as polypropylene and polyethylene. Experimental evidence indicates that both acetylene and methylacetylene can decrease the productivity of the Ziegler-Natta catalyst and alter the properties of the resulting polymer. However, there is still a lack of understanding regarding the mechanisms through which these substances affect this process. Therefore, elucidating these mechanisms is crucial to develop effective solutions to this problem. In this study, the inhibition mechanisms of the Ziegler-Natta catalyst by acetylene and methylacetylene are presented and compared with the incorporation of the first propylene monomer (chain initiation) to elucidate experimental effects. The Density Functional Theory (DFT) method was used, along with the B3LYP-D3 functional and the 6-311++G(d,p) basis set. The recorded adsorption energies were -11.10, -13.99, and -0.31 kcal mol-1, while the activation energies were 1.53, 2.83, and 28.36 kcal mol-1 for acetylene, methylacetylene, and propylene, respectively. The determined rate constants were 4.68 × 1011, 5.29 × 1011, and 2.3 × 10-8 M-1 s-1 for acetylene, methylacetylene, and propylene, respectively. Based on these values, it is concluded that inhibition reactions are more feasible than propylene insertion only if an ethylene molecule has not been previously adsorbed, as such an event reinforces propylene adsorption.

Antileishmanial Effects of Acetylene Acetogenins from Seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives.

As part of our continuous studies involving the prospection of natural products from Brazilian flora aiming at the discovery of prototypes for the development of new antiparasitic drugs, the present study describes the isolation of two natural acetylene acetogenins, (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11'-yn-19'-enyl)butanolide (1) and (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11'-ynyl)butanolide (2), from the seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound 1 showed an IC50 value of 29.9 µM against the intracellular amastigote forms of Leishmania (L.) infantum, whereas compound 2 was inactive. These results suggested that the terminal double bond plays an important role in the activity. This effect was also observed for the semisynthetic acetylated (1a and 2a) and eliminated (1b and 2b) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC50 values of 43.3 µM (1a) and 23.1 µM (1b). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds 1 + 2 was subjected to catalytic hydrogenation to afford a compound 3 containing a saturated side chain. The antiparasitic assays performed with compound 3, acetylated (3a), and eliminated (3b) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds 1, 1a, and 1b in order to investigate their physicochemical parameters, pharmacokinetics, and drug-likeness. Despite the reduced effect against amastigote forms of the parasite to the purified compounds, different mixtures of compounds 1 + 2, 1a + 2a, and 1b + 2b were prepared and exhibited IC50 values ranging from 7.9 to 38.4 µM, with no toxicity for NCTC mammalian cells (CC50 > 200 µM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of Porcelia macrocarpa are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs.

Synthesis, complete NMR assignment and structural study of a steroidal dimer of 17α-ethynyl-5α,10α-estran-17ß-ol with diethynylbenzene spacer.

A phenylene-bridged steroidal dimer derived from 17α-ethynyl-5α,10α-estran-17ß-ol with molecular rotor-like architecture was synthesized to investigate the supramolecular interactions directing the crystallization of these systems. Structures with varying importance in complementarity between H-bonding and hydrophobic interactions can be observed directing the packing of the obtained crystals, depending on the synthetic stage, though conserving the same space group for both systems. Such behavior clearly shows the versatility achievable using steroids as crystal packing directors. Alongside this structural study, the complete NMR assignment is presented for the dimer, and precursors, in which the steroids present an unconventional and noteworthy A-B ring fusion.

Mechanism of delta-aminolevulinate dehydratase inhibition by phenyl selenoacetylene involves its conversion to diphenyl diselenide.

The mechanism of delta-aminolevulinate dehydratase (delta-ALA-D) inhibition by phenyl selenoacetylene in vitro was investigated in this study. Phenyl selenoacetylene (40-400 microM) inhibition of delta-aminolevulinate dehydratase from rat liver (low speed supernatant fraction, S1 fraction) was partially prevented by incubation under argon atmosphere and completely prevented by dithiothreitol. After incubation with S1 fraction from rat liver or cysteine (40 mM), phenyl selenoacetylene was partially converted into diphenyl diselenide, which is a stronger inhibitor of delta-aminolevulinate dehydratase than phenyl selenoacetylene. Diphenyl diselenide increased the rate of oxidation of -SH groups, while phenyl selenoacetylene did not affect such oxidation. delta-Aminolevulinate dehydratase purified from bovine liver (Sigma) was less sensitive to phenyl selenoacetylene and diphenyl diselenide than the enzyme from S1 fraction. We propose that the lower sensitivity of purified enzyme to selenides could be related to the formation of selenols due to the presence of dithiothreitol (a reducing agent) in the incubation medium. In agreement, incubation of purified enzyme (Sigma) with diphenyl diselenide (2 microM) and sodium borohydride (a reducing agent) under argon atmosphere significantly increased enzyme activity. Results obtained suggest that delta-aminolevulinate dehydratase inhibition by phenyl selenoacetylene is dependent on its conversion into diphenyl diselenide that induces oxidation of essential -SH groups of delta-aminolevulinate dehydratase. We propose that oxygen could be important in the regeneration of diphenyl diselenide leading to a catalytic oxidation of the enzyme.

New evidences of antimalarial activity of Bidens pilosa roots extract correlated with polyacetylene and flavonoids.

Bidens pilosa is among the several plants used in Brazil to treat malaria. It was demonstrated that crude extracts from roots prepared with 80% ethanol by percolation are active in vitro against Plasmodium falciparum and the activity is correlated with the presence of polyacetylene and flavonoids. This extract was submitted to column chromatography with ether and ether methanol (1:1) and two fractions, enriched in polyacetylene and flavonoids, respectively, were obtained. The extract and the fractions were assessed by HPLC/DAD analysis and antimalarial tests in vivo. Ethanol extract showed by HPLC the presence of several peaks for polyacetylene and flavonoids, compounds corresponding to quercetin-3,3'-dimethoxy-7-0-rhamnoglucopyranose and the acetylene 1-phenyl-1,3-diyn-5-en-7-ol-acetate, previously identified in this extract. The peaks for flavonoids were absent in ether fraction and those ones for polyacetylene in ether:methanol. In in vivo tests, ethanol extract caused 36% of reduction of parasitaemia at fifth day, and 29% at seventh day. Ether:methanol fraction caused 38% of reduction at fifth day but was inactive at day 7. The survival of the animals treated with 80% ethanol extract was higher than in the fractions. The results showed that the in vivo activity of ethanol extract depends on the presence of polyacetylene and flavonoids.

Preparation and characterization of diacetylene polymerized liposomes for detection of autoantibodies.

Affinity diacetylene liposomes were prepared with 10,12-tricosadiynoic acid and cardiolipin as the affinity ligand for anticardiolipin antibodies at a molar ratio of 80:20. Polymerization was carried out under UV irradiation, and the color transitions were monitored by visible absorption spectroscopy. Peaks at 635 nm (blue form), 540 nm (purple form), and 480 nm (red form) were observed as a function of time. These polymerized liposomes were used in a noncompetitive immunoassay for detection of anticardiolipin antibodies. Color changes were observed when reference serum containing specific immunoglobulin G, IgG, was added to polymerized liposome dispersions. The colorimetric signal due to IgG adsorption on the liposome surface was quantified as a colorimetric response defined as the change in percentage of blue color related to the initial percentage of blue color in the solutions. The colorimetric response was 10 times higher for specific IgG compared with nonspecific ones. These results suggest the unique potentialities of affinity diacetylene polymerized liposomes in the development of biosensors for diagnosis of autoimmune diseases.

Delta-aminolevulinate dehydratase inhibition by phenyl selenoacetylene: effect of reaction with hydrogen peroxide.

The effect of phenyl selenoacetylene and its selenoxide on delta-aminolevulinate dehydratase from liver of adult rats (mammalian source) and from cucumber leaves (plant source) was investigated. In vivo, selenides can be oxidized to selenoxides by flavin-containing monooxygenases and selenoxides can regenerate selenides by thiol oxidation. The compound phenyl selenoacetylene was converted to selenoxides by reaction with hydrogen peroxide. Phenyl selenoacetylene inhibited mammalian and plant delta-aminolevulinate dehydratase with an IC50 about 250 microM and >400 microM, respectively. Its selenoxide inhibited the enzyme more strongly, with IC50 values of 45 microM and 100 microM for the mammalian and plant source, respectively. The selenoxide inhibitory action was antagonized by dithiothreitol suggesting the involvement of -SH groups. Moreover, delta-aminolevulinate dehydratase from a plant source was inhibited by the selenoxide, suggesting a possible involvement of -SH groups located at a site distinct from the region implicated in Zn2+ binding in mammalian delta-aminolevulinate dehydratase. The results of the present study suggest that (i) delta-aminolevulinate dehydratase is a potential molecular target for phenyl selenoacetylene, due to the oxidation of enzyme sulfhydryl groups, and that (ii) the monooxygenation of this selenocompound, which in vivo could be possibly mediated by flavin-containing monooxigenases, increases its inhibitory effect.

Chemical constituents from the colombian medicinal plant Niphogeton ternata.

Two coumarins and one polyacetylene, 5-0-(3-chloro-2-hydroxy-3-methylbutyl)-8-methoxypsoralen (1), 2',3'-dihydro-jatamansin (2), and 10-chloro-1-heptadecene-4,6-diyne-3,8,9-triol (3), along with 15 known compounds (4-18), were isolated from the methanol extract of Niphogeton ternata. Their structures were elucidated by spectroscopy.

Synthesis of polyacetylenic acids isolated from Heisteria acuminata.

Four linear polyacetylenic compounds were synthesized. Pentadeca-6,8,10-triynoic acid 1 and octadeca-8,10,12-triynoic acid 2 were synthesized by using acetylene coupling reactions. The syntheses of (Z)-hexadec-11-en-7,9-diynoic acid 3 and (Z)-octadec-12-en-7,9-diynoic acid 4 by using vinylic telluride coupling reactions were accomplished.

Immunosuppressive and anti-inflammatory effects of methanolic extract and the polyacetylene isolated from Bidens pilosa L.

The immunomodulatory effect of the methanolic extract obtained from dried leaves of Bidens pilosa L. (Asteraceae) and the polyacetylene 2-O-beta-D-glucosyltrideca-11 E-en-3,5,7,9-tetrayn-1,2-diol (PA-1) isolated from it was investigated. The extract inhibited the proliferative response in two in vitro models: human lymphocytes stimulated by 5 microg ml(-1) phytohemagglutinin (PHA) or to 100 nM 12-O-tetradecanoyl phorbol-13-acetate (TPA) plus 0.15 microM ionomycin and murine lymphocytes stimulated by 5 microg ml(-1) concanavalin A (Con A) or in the mixed leukocyte reaction (IC50 = 12.5 to 25 microg ml(-1)). PA-1 was 10-told more potent than the original extract in blocking both human and murine lymphocyte proliferation (IC50 = 1.25 to 2.5 microg ml(-1)). In mice, the intraperitoneal (i.p.) administration of methanolic extract of B. pilosa significantly reduced the size of the popliteal lymph node (PLN) after the inflammation induced by zymosan. One week after the injection of zymosan (150 microg) in the foot pad, PLN weighed 4.6 +/- 0.6 mg in comparison with 0.5 +/- 0.07 mg of the contralateral non-inflamed foot pad. The i.p. treatment with 10 mg extract from day 2 to day 6 after zymosan injection reduced the PLN weight to 1.8 +/- 0.3 mg. The data suggest an immunosuppressive activity of components of B. pilosa that may explain its popularly perceived anti-inflammatory effect.

New acetylenes isolated from the bark of Heisteria acuminata.

Five new linear acetylenic compounds, namely, pentadeca-6,8,10-triynoic acid (1), octadeca-8,10,12-triynoic acid (2), trans-pentadec-10-en-6,8-diynoic acid (3), cis-hexadec-11-en-7,9-diynoic acid (4), and cis-octadec-12-en-7,9-diynoic acid (5), were isolated from the bark of Heisteria acuminata by bioassay-guided fractionation, using cyclooxygenase (COX) and 5-lipoxygenase (5-LO) assays as models for antiinflammatory activity. The structures of compounds 1-5 were established by NMR, MS, IR, and Raman spectroscopy. These isolated compounds were found to be potent inhibitors of COX. Compounds 4 and 5 were the most potent inhibitors of 5-LO, whereas the other compounds only showed a weak inhibition at the same concentration.