Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine

Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.     

Microwave-assisted, solid-phase synthesis of a chiral 1,2,3,4-tetrahydro-quinoline library

The synergy of a solution-phase preparation of scaffolds with a solid-phase combinatorial synthesis let to develop an efficient route to a small library of chiral, highly functionalized tetrahydroisoquinolines. Both loading on the Merrifield resin and the key acid-catalyzed Pictet-Spengler condensation were efficiently promoted by microwave irradiation. The library was designed such that up to five points of diversity would be potentially introduced, making the strategy in principle suitable for generation of a large number of compounds.     

Environmentally induced quantum dynamical phase transition in the spin swapping operation

Quantum information processing relies on coherent quantum dynamics for a precise control of its basic operations. A swapping gate in a two-spin system exchanges the degenerate states |(up arrow, down arrow)> and |(down arrow, up arrow)>. In NMR, this is achieved turning on and off the spin-spin interaction b=DeltaE that splits the energy levels and induces an oscillation with a natural frequency DeltaE/Planck's. Interaction of strength Planck's/tau(SE), with an environment of neighboring spins, degrades this oscillation within a decoherence time scale tau(phi). While the experimental frequency omega and decoherence time tau(phi) were expected to be roughly proportional to b/Planck's and tau(SE), respectively, we present here experiments that show drastic deviations in both omega and tau(phi). By solving the many spin dynamics, we prove that the swapping regime is restricted to DeltaEtau(SE) similar or greater than Planck's. Beyond a critical interaction with the environment the swapping freezes and the decoherence rate drops as 1/tau(phi) proportional to (b/Planck's)2tau(SE). The transition between quantum dynamical phases occurs when omega proportional to sqrt (b/Planck's)2-(k/tau(SE)2 becomes imaginary, resembling an overdamped classical oscillator. Here, 0< or =k2< or =1 depends only on the anisotropy of the system-environment interaction, being 0 for isotropic and 1 for XY interactions. This critical onset of a phase dominated by the quantum Zeno effect opens up new opportunities for controlling quantum dynamics.     

Evaluation of zirconocene-based silica phases in organochloride pesticides preconcentration

Silica was chemically modified with zirconocenes, namely Cp(2)ZrCl(2), (MeCp)(2)ZrCl(2), (iBuCp)(2)ZrCl(2) and (nBuCp)(2)ZrCl(2) by grafting. Hybrid silica bearing surface indene groups was synthesized by the sol-gel method, followed by metallation with ZrCl(4)2THF. According to RBS measurements, metal content was 0.2-0.3 wt% Zr/SiO(2) for the grafted systems and 4.5 wt% Zr/SiO(2) for the phase prepared by the sol-gel method. The solid phases were evaluated in the adsorption/preconcentration of organochloride (hexachlorobenzene, lindane, heptachlor, heptachlor epoxide, dieldrin and endrin) pesticides from aqueous solution. For comparative reasons, commercial LC-18 phase was also evaluated. Analyte concentration was monitored by GC-ECD. For the grafted phases, the coordination sphere around the metal center seems not to influence the adsorption/desorption properties of these phases vis-à-vis the studied analytes. Recoveries results for both analytes were comparable to those observed in the case of LC-18 in the case of the phases prepared by the sol-gel method. Experiments using ZrO(2) and ZrO(2)/SiO(2) phases led to lower recovery results.     

Use of statistical design of experiments to evaluate the sorption capacity of 7-amine-4-azaheptylsilica and 10-amine- 4-azadecylsilica for Cu(II), Pb(II), and Fe(III) adsorption

7-Amine-4-azaheptylsilica (AAH Si) and 10-amine-4-azadecylsilica (AAD Si) were prepared and used for removal of Cu(II), Pb(II), and Fe(III) from aqueous solutions. Full 2(3) factorial designs with two pseudo-central points were carried out in order to achieve the best conditions of the batch adsorption procedure for metallic ion uptake by the adsorbents. To continue the optimizations, central composite surface design was also employed. These two independent statistical designs of experiments lead to the following conditions: m=30.0 mg of adsorbent; pH 6.0 for Cu(II) and Pb(II), pH 4.0 for Fe(III); t of contact 180 min to guarantee equilibration at higher adsorbate concentration. After optimization of the conditions, isotherms of the metallic ions adsorbed on the AAH Si and AAD Si adsorbents were obtained, which were fitted to nonlinear Langmuir and Freundlich isotherm models.     

Determination of Na, K, Ca and Mg in biodiesel samples by flame atomic absorption spectrometry (F AAS) using microemulsion as sample preparation

This study proposes a procedure for determining sodium, potassium, calcium and magnesium in biodiesel samples by flame atomic absorption spectrometry (F AAS). The sample was prepared as a microemulsion without surfactant. The optimized composition of the microemulsion was 10% (w/v) biodiesel, 75% (v/v) n-propanol, 1% (v/v) concentrated nitric acid and 14% (v/v) of aqueous solution formed by 0.2% (v/v) of nitric acid and 0.5% (v/v) of ionization suppressor. Analyte signals in the samples as microemulsion were found to be stable for a period of 15 days. Analytical curves were obtained using organometallic standard solutions. The limits of detection (LOD) found for the proposed procedure were 0.1 µg g^− 1, 0.01 µg g^− 1, 0.04 µg g^− 1, and 0.004 µg g^− 1 for Na, K, Ca and Mg, respectively. The reference method established by ABNT (Brazilian Association of Technical Norms) NBR 15556:2008 was used to verify the accuracy of the proposed procedure. No significant statistical difference was found between the results obtained with the proposed and the chosen reference procedure. The proposed procedure showed no matrix influence when recovery tests were performed (89%-103%). The results found in this study show that the proposed procedure is a good alternative for determining Na, K, Ca, and Mg by F AAS in biodiesel samples.     

On sizes of complete caps in projective spaces PG(n, q) and arcs in planes PG(2, q)

More than thirty new upper bounds on the smallest size t ₂(2, q) of a complete arc in the plane PG(2, q) are obtained for (169 ≤ q ≤ 839. New upper bounds on the smallest size t ₂(n, q) of the complete cap in the space PG(n, q) are given for n = 3 and 25 ≤ q ≤ 97, q odd; n = 4 and q = 7, 8, 11, 13, 17; n = 5 and q = 5, 7, 8, 9; n = 6 and q = 4, 8. The bounds are obtained by computer search for new small complete arcs and caps. New upper bounds on the largest size m ₂(n, q) of a complete cap in PG(n, q) are given for q = 4, n = 5, 6, and q = 3, n = 7, 8, 9. The new lower bound 534 ≤ m ₂(8, 3) is obtained by finding a complete 534-cap in PG(8, 3). Many new sizes of complete arcs and caps are obtained. The updated tables of upper bounds for t ₂(n, q), n ≥ 2, and of the spectrum of known sizes for complete caps are given. Interesting complete caps in PG(3, q) of large size are described. A proof of the construction of complete caps in PG(3, 2 ^h ) announced in previous papers is given; this is modified from a construction of Segre. In PG(2, q), for q = 17, δ = 4, and q = 19, 27, δ = 3, we give complete ${(\frac{1}{2}(q + 3) + \delta)}$ -arcs other than conics that share ${\frac{1}{2}(q + 3)}$ points with an irreducible conic. It is shown that they are unique up to collineation. In PG(2, q), ${{q \equiv 2}}$ (mod 3) odd, we propose new constructions of ${\frac{1}{2} (q + 7)}$ -arcs and show that they are complete for q ≤ 3701.     

Selective Cytotoxicity of Portuguese Propolis Ethyl Acetate Fraction towards Renal Cancer Cells

Renal cell carcinoma is the most lethal cancer of the urological system due to late diagnosis and treatment resistance. Propolis, a beehive product, is a valuable natural source of compounds with bioactivities and may be a beneficial addition to current anticancer treatments. A Portuguese propolis sample, its fractions (n-hexane, ethyl acetate, n-butanol and water) and three subfractions (P1–P3), were tested for their toxicity on A498, 786-O and Caki-2 renal cell carcinoma cell lines and the non-neoplastic HK2 kidney cells. The ethyl acetate fraction showed the strongest toxicity against A498 (IC₅₀ = 0.162 µg mL⁻¹) and 786-O (IC₅₀ = 0.271 µg mL⁻¹) cells. With similar toxicity against 786-O, P1 (IC₅₀ = 3.8 µg mL⁻¹) and P3 (IC₅₀ = 3.1 µg mL⁻¹) exhibited greater effect when combined (IC₅₀ = 2.5 µg mL⁻¹). Results support the potential of propolis and its constituents as promising coadjuvants in renal cell carcinoma treatment.     

Fertility and Iron Bioaccumulation in Drosophila melanogaster Fed with Magnetite Nanoparticles Using a Validated Method

Research on nanomaterial exposure-related health risks is still quite limited; this includes standardizing methods for measuring metals in living organisms. Thus, this study validated an atomic absorption spectrophotometry method to determine fertility and bioaccumulated iron content in Drosophila melanogaster flies after feeding them magnetite nanoparticles (Fe₃O₄NPs) dosed in a culture medium (100, 250, 500, and 1000 mg kg⁻¹). Some NPs were also coated with chitosan to compare iron assimilation. Considering both accuracy and precision, results showed the method was optimal for concentrations greater than 20 mg L⁻¹. Recovery values were considered optimum within the 95–105% range. Regarding fertility, offspring for each coated and non-coated NPs concentration decreased in relation to the control group. Flies exposed to 100 mg L⁻¹ of coated NPs presented the lowest fertility level and highest bioaccumulation factor. Despite an association between iron bioaccumulation and NPs concentration, the 500 mg L⁻¹ dose of coated and non-coated NPs showed similar iron concentrations to those of the control group. Thus, Drosophila flies’ fertility decreased after NPs exposure, while iron bioaccumulation was related to NPs concentration and coating. We determined this method can overcome sample limitations and biological matrix-associated heterogeneity, thus allowing for bioaccumulated iron detection regardless of exposure to coated or non-coated magnetite NPs, meaning this protocol could be applicable with any type of iron NPs.     

Needle Trap Device-GC-MS for Characterization of Lung Diseases Based on Breath VOC Profiles

Volatile organic compounds (VOCs) have been assessed in breath samples as possible indicators of diseases. The present study aimed to quantify 29 VOCs (previously reported as potential biomarkers of lung diseases) in breath samples collected from controls and individuals with lung cancer, chronic obstructive pulmonary disease and asthma. Besides that, global VOC profiles were investigated. A needle trap device (NTD) was used as pre-concentration technique, associated to gas chromatography-mass spectrometry (GC-MS) analysis. Univariate and multivariate approaches were applied to assess VOC distributions according to the studied diseases. Limits of quantitation ranged from 0.003 to 6.21 ppbv and calculated relative standard deviations did not exceed 10%. At least 15 of the quantified targets presented themselves as discriminating features. A random forest (RF) method was performed in order to classify enrolled conditions according to VOCs’ latent patterns, considering VOCs responses in global profiles. The developed model was based on 12 discriminating features and provided overall balanced accuracy of 85.7%. Ultimately, multinomial logistic regression (MLR) analysis was conducted using the concentration of the nine most discriminative targets (2-propanol, 3-methylpentane, (E)-ocimene, limonene, m-cymene, benzonitrile, undecane, terpineol, phenol) as input and provided an average overall accuracy of 95.5% for multiclass prediction.