Pyracene‐Linked Bis‐Imidazolylidene Complexes of Palladium and Some Catalytic Benefits Produced by Bimetallic Catalysts

Two new palladium complexes with a pyracene‐linked bis‐imidazolylidene (pyrabim) group have been obtained and fully characterized. The related monometallic analogues were obtained from the coordination of an acetanaphthene‐supported N‐heterocyclic carbene (NHC). The catalytic properties of all complexes were studied in the acylation of aryl halides with hydrocinnamaldehyde, and in the Suzuki–Miyaura coupling of aryl halides and aryl boronic acids. The results show that the presence of a second metal in the dimetallic complexes induces some benefits in the catalytic behavior of the complexes. This effect is more pronounced in the Suzuki–Miyaura coupling, for which the dimetallic complexes exhibit significantly higher activity than their monometallic counterparts.     

Consequences of weak Allee effect on prey in the May–Holling–Tanner predator–prey model

In this work, a modified Holling–Tanner predator–prey model is analyzed, considering important aspects describing the interaction such as the predator growth function is of a logistic type; a weak Allee effect acting in the prey growth function, and the functional response is of hyperbolic type. Making a change of variables and time rescaling, we obtain a polynomial differential equations system topologically equivalent to the original one in which the non‐hyperbolic equilibrium point (0,0) is an attractor for all parameter values. An important consequence of this property is the existence of a separatrix curve dividing the behavior of trajectories in the phase plane, and the system exhibits the bistability phenomenon, because the trajectories can have different ω ? limit sets; as example, the origin (0,0) or a stable limit cycle surrounding an unstable positive equilibrium point. We show that, under certain parameter conditions, a positive equilibrium may undergo saddle‐node, Hopf, and Bogdanov–Takens bifurcations; the existence of a homoclinic curve on the phase plane is also proved, which breaks in an unstable limit cycle. Some simulations to reinforce our results are also shown. Copyright © 2015 John Wiley & Sons, Ltd.     

Liquid–Liquid Phase Equilibrium and Ion-Exchange Exploration for Aqueous Two-Phase Systems of ([C4mim]Cl + K2CO3 or K3C6H5O7 + water) at Different Temperatures

Journal of Solution Chemistry - Liquid–liquid equilibrium (LLE) data and phase diagrams for new aqueous two-phase systems (ATPSs) containing 1-butyl-3-methylimidazolium chloride...     

Redox-Switchable Complexes Based on Nanographene-NHCs

A series of rhodium and iridium complexes with a N-heterocyclic carbene (NHC) ligand decorated with a perylene-diimide-pyrene moiety are described. Electrochemical studies reveal that the complexes can undergo two successive one-electron reduction events, associated to the reduction of the PDI moiety attached to the NHC ligand. The reduction of the ligand produces a significant increase on its electron-donating character, as observed from the infrared spectroelectrochemical studies. The rhodium complex was tested in the [3+2] cycloaddition of diphenylcyclopropenone and methylphenylacetylene, where it displayed a redox-switchable behavior. The neutral complex showed moderate activity, which was suppressed when the catalyst was reduced.     

Antiprotozoal and Antibacterial Activity of Ravenelin,a Xanthone Isolated from the Endophytic Fungus Exserohilum rostratum

The natural compound ravenelin was isolated from the biomass extracts of Exserohilum rostratum fungus, and its antimicrobial, antiplasmodial, and trypanocidal activities were evaluated. Ravenelin was isolated by column chromatography and HPLC and identified by NMR and MS. The susceptibility of Gram-positive and Gram-negative bacteria strains to ravenelin was determined by microbroth dilution assay. Cytotoxicity was evaluated in hepatocarcinoma cells (HepG2) and BALB/c peritoneal macrophages by using MTT. SYBR Green I-based assay was used in the asexual stages of Plasmodium falciparum. Trypanocidal activity was tested against the epimastigote and intracellular amastigote forms of Trypanosoma cruzi. Ravenelin was active against Gram-positive bacteria strains, with emphasis on Bacillus subtilis (MIC value of 7.5 µM). Ravenelin’s antiparasitic activities were assessed against both the epimastigote (IC₅₀ value of 5 ± 1 µM) and the intracellular amastigote forms of T. cruzi (IC₅₀ value of 9 ± 2 µM), as well as against P. falciparum (IC₅₀ value of 3.4 ± 0.4 µM). Ravenelin showed low cytotoxic effects on both HepG2 (CC₅₀ > 50 µM) and peritoneal macrophage (CC₅₀ = 185 ± 1 µM) cells with attractive selectivity for the parasites (SI values > 15). These findings indicate that ravenelin is a natural compound with both antibacterial and antiparasitic activities, and considerable selectivity indexes. Therefore, ravenelin is an attractive candidate for hit-to-lead development.     

Gelation Kinetics-Structure Analysis of pH-triggered Low Molecular Weight Hydrogelators

Properties such as shear modulus, gelation time, structure of supramolecular hydrogels are strongly dependent on self-assembly, gelation triggering mechanism and processes used to form the gel. In our work we extend reported rheology analysis methodologies to pH-triggered supramolecular gels to understand structural insight using a model system based on N−N’ Dibenzoyl-L-Cystine pH-triggered hydrogelator and Glucono-δ-Lactone as the trigger. We observed that Avrami growth model when applied to time-sweep rheological data of gels formed at lower trigger concentrations provide estimates of fractal dimension which agree well compared with visualization of the microstructure as seen via Confocal Laser Scanning Microscopy, for a range of gelator concentrations.     

Copolymeric nano/microgels of N-isopropylacrylamide and carboxyalkyl methacrylamides: Effect of methylene chains and the ionization state of the weak acids on size and sensitivity to pH and temperature

ABSTRACT

We prepared nano/microgels by precipitation copolymerization of N-isopropylacrylamide (NIPAAm), and one of three different carboxyalkyl methacrylamides [methacryloylamido hexanoic acid (M₅), 8-methacryloylamido octanoic acid (M₇), and 11-methacryloylamido undecanoic acid (M₁₀)], either in the acid forms or as carboxylates (potassium salts). The hydrodynamic diameter (Dh) of the nano/microgels prepared with the carboxylates was smaller (≈100 nm for M₁₀ copolymers), compared to the size of homopolymeric NIPAAm microgels prepared by dispersion polymerization (around 600 nm), indicating that the carboxylates act as surfactants reducing the size of the seeds during the polymerization process. These materials presented a swollen-shrunken transition temperature (T _tr) similar to the T _tr of the homopolymeric NIPAAm microgels, without pH sensitivity. On the other hand, the copolymeric microgels prepared from the acid form of the comonomers have a similar or bigger size than NIPAAm microgels. For these copolymers, the T _tr can be tuned by the type and proportion of acid comonomer used and present pH sensitivity. This is important for biomedical applications such as positive temperature control release. Polyelectrolyte titration demonstrates that the nano/microgels prepared with the carboxylates behave as hard spheres, while the microgels prepared with the weak acid behave as porous materials.     

Nutritional Value and Preventive Role of Nigella sativa L. and Its Main Component Thymoquinone in Cancer: An Evidenced-Based Review of Preclinical and Clinical Studies

In recent times, scientific attention has been paid to different foods and their bioactive components for the ability to inhibit the onset and progress of different types of cancer. Nigella sativa extract, powder and seed oil and its main components, thymoquinone and α-hederin, have showed potent anticancer and chemosensitizing effects against various types of cancer, such as liver, colon, breast, renal, cervical, lung, ovarian, pancreatic, prostate and skin tumors, through the modulation of various molecular signaling pathways. Herein, the purpose of this review was to highlight the anticancer activity of Nigella sativa and it constitutes, focusing on different in vitro, in vivo and clinical studies and projects, in order to underline their antiproliferative, proapoptotic, cytotoxic and antimetastatic effects. Particular attention has been also given to the synergistic effect of Nigella sativa and it constitutes with chemotherapeutic drugs, and to the synthesized analogs of thymoquinone that seem to enhance the chemo-sensitizing potential. This review could be a useful step towards new research on N. sativa and cancer, to include this plant in the dietary treatments in support to conventional therapies, for the best achievement of therapeutic goals.     

A Multi-Objective Approach for Drug Repurposing in Preeclampsia

Preeclampsia is a hypertensive disorder that occurs during pregnancy. It is a complex disease with unknown pathogenesis and the leading cause of fetal and maternal mortality during pregnancy. Using all drugs currently under clinical trial for preeclampsia, we extracted all their possible targets from the DrugBank and ChEMBL databases and labeled them as “targets”. The proteins labeled as “off-targets” were extracted in the same way but while taking all antihypertensive drugs which are inhibitors of ACE and/or angiotensin receptor antagonist as query molecules. Classification models were obtained for each of the 55 total proteins (45 targets and 10 off-targets) using the TPOT pipeline optimization tool. The average accuracy of the models in predicting the external dataset for targets and off-targets was 0.830 and 0.850, respectively. The combinations of models maximizing their virtual screening performance were explored by combining the desirability function and genetic algorithms. The virtual screening performance metrics for the best model were: the Boltzmann-Enhanced Discrimination of ROC (BEDROC)_α=160.9 = 0.258, the Enrichment Factor (EF)_1% = 31.55 and the Area Under the Accumulation Curve (AUAC) = 0.831. The most relevant targets for preeclampsia were: AR, VDR, SLC6A2, NOS3 and CHRM4, while ABCG2, ERBB2, CES1 and REN led to the most relevant off-targets. A virtual screening of the DrugBank database identified estradiol, estriol, vitamins E and D, lynestrenol, mifrepristone, simvastatin, ambroxol, and some antibiotics and antiparasitics as drugs with potential application in the treatment of preeclampsia.     

Lemon Oils Attenuate the Pathogenicity of Pseudomonas aeruginosa by Quorum Sensing Inhibition

The chemical composition of three Citrus limon oils: lemon essential oil (LEO), lemon terpenes (LT) and lemon essence (LE), and their influence in the virulence factors production and motility (swarming and swimming) of two Pseudomonas aeruginosa strains (ATCC 27853 and a multidrug-resistant HT5) were investigated. The main compound, limonene, was also tested in biological assays. Eighty-four compounds, accounting for a relative peak area of 99.23%, 98.58% and 99.64%, were identified by GC/MS. Limonene (59–60%), γ-terpinene (10–11%) and β-pinene (7–15%) were the main compounds. All lemon oils inhibited specific biofilm production and bacterial metabolic activities into biofilm in a dose-dependent manner (20–65%, in the range of 0.1–4 mg mL⁻¹) of both strains. Besides, all samples inhibited about 50% of the elastase activity at 0.1 mg mL⁻¹. Pyocyanin biosynthesis decreases until 64% (0.1–4 mg mL⁻¹) for both strains. Swarming motility of P. aeruginosa ATCC 27853 was completely inhibited by 2 mg mL⁻¹ of lemon oils. Furthermore, a decrease (29–55%, 0.1–4 mg mL⁻¹) in the synthesis of Quorum sensing (QS) signals was observed. The oils showed higher biological activities than limonene. Hence, their ability to control the biofilm of P. aeruginosa and reduce the production of virulence factors regulated by QS makes lemon oils good candidates to be applied as preservatives in the food processing industry.