Regiospecific synthesis of 1-acetamide-5-methoxy-2-oxindoles in two steps: (Ugi-SN2)/xanthate mediated free radical cyclization

A series of twelve novel 1-acetamide-5-methoxy-2-oxindoles were prepared in moderate to good yields (30–88%) by an Ugi-S_N2 one pot process with a xanthate mediated free radical cyclization. Additionally, Density Functional Theory (DFT) based calculations were performed at UB3LYP/6-311G(d) level in order to rationalize the energy profile of the xanthate mediated free radical cyclization because the benzo-fused γ-lactams (ortho products) were obtained as sole regioisomers over the spiro β-lactams (ipso products).     

An updated version of the computational package SIMPRE that uses the standard conventions for Stevens crystal field parameters

The crystal field approach used by SIMPRE is analyzed, verifying the exactness of the results concerning energy levels and magnetic properties calculated by the package. To coincide with the prevailing conventions, we reformulate the presentation of the crystal field parameters, so that the results are now, also from a formal point of view, strictly correct. New calculations are presented to test the influence of neglecting the excited J states, a common but critical approximation employed by SIMPRE. For that, we examine the case of Er(trensal) complex (H₃trensal = 2,2′,2″‐tris(salicylideneimino)triethylamine) where the influence of this approximation is found to be minimal. A patched version of the code, SIMPRE 1.1, and an updated version of the user manual are now available. Finally, we comment on “Software package SIMPRE – revisited,” which apparently revisits a software package without inspecting or using the code. © 2014 Wiley Periodicals, Inc.     

A new rotating-disk sorptive extraction mode,with a copolymer of divinylbenzene and N-vinylpyrrolidone trapped in the cavity of the disk,used for determination of florfenicol residues in porcine plasma

A novel extraction approach was developed based on rotating-disk sorptive extraction (RDSE). In this approach the rotating-disk extraction device consists of a Teflon disk, with a cavity that is loaded with a commercial sorbent phase selected according to the polarity of the analyte. To avoid leakage of the sorbent, the cavity is covered with a fiberglass filter and sealed with a Teflon ring. The proposed novel analytical RDSE technique was used in this study to determine florfenicol levels in plasma as a model analyte, or sample system, to describe the pharmacokinetics of a veterinary formulation. The sorbent used for this application was the copolymer of divinylbenzene and N-vinylpyrrolidone (Oasis HLB), which was selected because the florfenicol molecule contains both hydrophilic and lipophilic moieties. After the extraction, final determination of the analyte was performed by HPLC–DAD. Calibration plots and other analytical features were obtained after 90 min of extraction. The calibration plot was linear over the interval 0.4–16 μg mL^?1 (n?=?6), with R ²?=?0.9999. Recovery and repeatability were determined using a blank plasma sample spiked with 4.8 μg mL^?1 florfenicol. A recovery of 91.5 %, with a relative standard deviation (RSD) of 8.8 %, was obtained when the extraction was evaluated using six different rotating-disk devices. Precision was also assessed, using the same disk (containing the same sorbent phase) for eight aliquots of the same sample. The RSD under these conditions was 10.2 %, clearly indicating that the sorptive phase could possibly be re-used. Accordingly, RDSE is a suitable sample preparation alternative to liquid–liquid extraction (LLE), solid-phase extraction (SPE), and stir-bar sorptive extraction (SBSE).     

Synthesis and Antifungal Activity of New Valine-Azole Hybrids

Russian Journal of General Chemistry - Herein, the synthesis of six new derivatives via molecular hybridization of imidazole or triazole and valine methyl ester as a rational design for accessing...     

Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α₁-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α₁-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α₁-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α₁-adrenoceptor density in whole hypothalamus and the expression levels of α_1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α₁-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α_1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular–coerulear excitatory interactions in prenatally undernourished young-adult rats.     

Li8Si8, Li10Si9, and Li12Si10: Assemblies of Lithium-Silicon Aromatic Units

We report the global minima structures of Li₈Si₈, Li₁₀Si₉, and Li₁₂Si₁₀ systems, in which silicon moieties maintain structural and chemical bonding characteristics similar to those of their building blocks: the aromatic clusters T_d−Li₄Si₄ and C_2v−Li₆Si₅. Electron counting rules, chemical bonding analysis, and magnetic response properties verify the silicon unit‘s aromaticity persistence. This study demonstrates the feasibility of assembling silicon-based nanostructures from aromatics clusters as building blocks.     

Alkaloids Analysis of Habranthus cardenasianus (Amaryllidaceae), Anti-Cholinesterase Activity and Biomass Production by Propagation Strategies

Plants in the Amaryllidaceae family synthesize a diversity of bioactive alkaloids. Some of these plant species are not abundant and have a low natural multiplication rate. The aims of this work were the alkaloids analysis of a Habranthus cardenasianus bulbs extract, the evaluation of its inhibitory activity against cholinesterases, and to test several propagation strategies for biomass production. Eleven compounds were characterized by GC-MS in the alkaloid extract, which showed a relatively high proportion of tazettine. The known alkaloids tazettine, haemanthamine, and the epimer mixture haemanthidine/6-epi-haemanthidine were isolated and identified by spectroscopic methods. Inhibitory cholinesterases activity was not detected. Three forms of propagation were performed: bulb propagation from seed, cut-induced bulb division, and micropropagated bulbs. Finally, different imbibition and post-collection times were evaluated in seed germination assays. The best propagation method was cut-induced bulb division with longitudinal cuts into quarters (T1) while the best conditions for seed germination were 0-day of post-collection and two days of imbibition. The alkaloids analyses of the H. cardenasianus bulbs showed that they are a source of anti-tumoral alkaloids, especially pretazettine (tazettine) and T1 is a sustainable strategy for its propagation and domestication to produce bioactive alkaloids.     

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.     

Black hole entropy quantization

Ever since the pioneering works of Bekenstein and Hawking, black hole entropy has been known to have a quantum origin. Furthermore, it has long been argued by Bekenstein that entropy should be quantized in discrete (equidistant) steps given its identification with horizon area in (semi-)classical general relativity and the properties of area as an adiabatic invariant. This lead to the suggestion that the black hole area should also be quantized in equidistant steps to account for the discrete black hole entropy. Here we shall show that loop quantum gravity, in which area is not quantized in equidistant steps, can nevertheless be consistent with Bekenstein's equidistant entropy proposal in a subtle way. For that we perform a detailed analysis of the number of microstates compatible with a given area and show consistency with the Bekenstein framework when an oscillatory behavior in the entropy-area relation is properly interpreted.     

Development of a Simple and Fast Electrochemical Method for Screening and Stoichiometric Determination of Dimenhydrinate

Dimenhydrinate (DIM) is a salt composed by the combination of two active pharmaceutical ingredients: diphenhydramine (DIP) and 8‐chlorotheophylline (CTP). In this work, the use of batch injection analysis with multiple pulse amperometric detection (BIA‐MPA) was proposed for the first time for fast stoichiometric determination of DIM. DIP (cation) and CTP (anion) were determined simultaneously in pharmaceutical samples with a simple and fast injection procedure (70 injections h^?1). Additional strategies were also proposed for rapid screening of samples containing the DIM salt. By a simple injection of a sample into the BIA system (without using of calibration curve), reliable information about stoichiometry of the DIM salt (1 : 1; DIP:CTP) and presence or absence of interfering species (electroactive) can be achieved.