Novel 4-azaandrostenes as prostate cancer cell growth inhibitors: Synthesis,antiproliferative effects,and molecular docking studies

In this study, synthesis, structural characterization, molecular docking studies, and antiproliferative effects in four different cell lines of several novel 16-arylidene-4-azaandrost-5-ene compounds are reported. These compounds were prepared by oxidative cleavage of the enone system of androstenedione followed by an azacyclization reaction and an aldol condensation with various aldehydes at C16. In the androgen-dependent LNCaP cells, the most relevant antiproliferative effects were observed with the 16-phenyl, 16-p-tolyl, and 16-p-nitrophenyl derivatives. Compound 16E-[(4-methylphenyl)methylidene]-4-azaandrost-5-ene-3,17-dione was the most potent in these cells (IC₅₀ = 28.28 μM), having lower antiproliferative effects in the androgen-independent PC-3 cells (IC₅₀ = 45.31 μM). In addition, an interesting selectivity toward cancer cell lines was found for all compounds because a generally low cytotoxicity was detected in healthy human fibroblasts. Furthermore, the 16-p-tolylazaandrostene steroid induced a reduction of viability in LNCaP cells similar to that observed with finasteride, a clinically used 5α-reductase inhibitor. Moreover, molecular docking studies predicted that these 4-azaandrostene derivatives can interact with 5β-reductase, which has a high level of similarity to 5α-reductase enzyme, and with other common targets of steroidal drugs, particularly the enzyme 17α-hydroxylase/17,20-lyase.     

New multifunctional heterobinuclear palladium (II) complexes based on organometallic dithiocarbazate ligands

In the research of new compounds with multifunctional applications, heterobinuclear palladium (II) complexes based on organometallic dithiocarbazates (DTCZs) have been isolated. The organometallic DTCZ ligands of the general formula [{(η⁵-C₅H₄)-CH=NNHC(S)SCH₃}]MLn [MLn = Re (CO)₃ ( 2a ); Mn (CO)₃ ( 2b ); FeCp ( 2c )] were prepared by the reaction between formyl organometallic precursors ( 1a−c ) with S-methyldithiocarbazate. Subsequently, a two-step reaction of 2a−c with: (i) K₂[PdCl₄] and (ii) PPh₃ yielded heterobinuclear complexes [Pd{MLn(η⁵-C₅H₄)-CH=NNHC(S)SCH₃}–(Cl)(PPh₃)] [MLn = Re (CO)₃ ( 3a ); Mn (CO)₃ ( 3b ); FeCp ( 3c )]. All compounds were characterized by conventional spectroscopic techniques (infrared spectroscopy, nuclear magnetic resonance spectroscopy, mass spectrometry and elemental analysis). In addition, the molecular structures of 2a , 2c and 3c were determined by single-crystal X-ray diffraction. The new palladium (II) complexes ( 3a−c ) were evaluated as antiproliferative agents against non-small cell lung cancer cells (H1299 cells). Complexes 3a and 3b containing cyrhetrenyl- and cymantrenyl-DTCZ ligands, respectively, were more active than their ferrocenyl analogue 3c . The activity was associated with the electron-withdrawing properties of the (η⁵-C₅H₄)M (CO)₃ moieties and their better lipophilicity than that of the ferrocenyl analogue. In addition, we studied the capacity of metalloligands ( 2a−c ) and palladium (II) complexes ( 3a−c ) to remove methylene blue in water under UV–visible light irradiation. The results established that the complexes showed moderate efficiency and were less active than their corresponding free ligands.     

Synthesis of Na<Subscript>2</Subscript>Ti<Subscript>3</Subscript>O<Subscript>7</Subscript> nanoparticles by sonochemical method for solid state electrolyte applications

Na₂Ti₃O₇ ceramic materials have been widely used in sodium-ion battery applications with relative good results; however, there are still several studies that might be carried out in the improvement of the Na₂Ti₃O₇ properties and the overall batteries’ performance. In this direction, we used sonochemical method following a thermal treatment in order to synthetized pure phase Na₂Ti₃O₇ nanopowders. X-ray diffraction characterization revealed that Na₂Ti₃O₇ is the primary phase in nanopowders and ceramic sample; although, a high level of amorphization was observed in the sonicated nanopowder without heat treatment process. Nanopowder-prepared ceramic sample showed a crystallite size of 50 nm after sintering at 900 °C for 1 h. The specific surface area, pore volume, and pore size were obtained from the B.E.T. measurements, being 51 m² g^?1, 0.07 cm³ g^?1, and 55 Å, respectively. The capacitance values of the nanopowder-prepared ceramic sample were in the order of microfarad. The total energy of the system was used to determine relaxation time of the sample (τ ₀ = 31 ms).     

Thermoanalytical characterization of molybdenum-based catalytic materials

Thermoanalytical techniques, especially temperature-programmed reduction (TPR), were employed for the characterization of oxidic precursors of molybdenum-based catalysts, sulfides derived from them, and three thiomolybdate compounds, employed as models or precursors of hydrodesulfurization atalysts. Correlations were found between TPR data and the presence of single and mixed oxides of Mo and Ni, Co or Fe, as demonstrated by XRD. The same phases and the thiomolybdates were shown to be present in supported catalytic precursors. Differences between the reducibilities of the mixed oxides of Ni-Mo, Co-Mo and Fe-Mo are easily appreciated from TPR, including those of the - and - polymorphic modifications of NiMoO₄.Support from Venezuela's Consejo Nacional de Investigations Científicas y Tecnológicas (CONICIT) and the International Activities Program of the American Chemical Society is gratefully acknowledged. The use of the TPR/TPD 2900 instrument was made possible by a generous loan of Micromeritics. Special thanks to my students and coworkers, who co-authored the publications cited in the list of references.     

Self-diffusion in simple models: Systems with long-range jumps

We review some exact results for the motion of a tagged particle in simple models. Then, we study the density dependence of the self-diffusion coefficientD _N() in lattice systems with simple symmetric exclusion in which the particles can jump, with equal rates, to a set ofN neighboring sites. We obtain positive upper and lower bounds onF _N()=N{(1–)–[D_N()/D_N(0)]}/[(1–)]x for [0, 1]. Computer simulations for the square, triangular, and one-dimensional lattices suggest thatF _N becomes effectively independent ofN forN20.     

Electrocatalysis of oxygen reduction by lanthanum-strontium manganate

The electrocatalysis of the oxygen reduction reaction by lanthanum-strontium manganate La_0.5Sr_0.5MnO₃ (LSM) has been studied by cyclic voltammetry using the rotating ring-disc electrode technique (RRDE) in alkaline medium. From the ring-disc data and other kinetic parameters it was concluded that the oxygen reduction occurs by dissociative chemisorption at low overpotentials. At higher overpotentials, the formation of hydrogen peroxide (HO₂⁻ in this case) on the electrocatalyst has been observed. The apparent exchange current density for oxygen reduction on LSM has been found to be 2 × 10⁻⁷ A cm⁻², while the corresponding Tafel slope is 0.100 V per decade. The possible reaction mechanism for electroreduction of oxygen on this oxide catalyst has been discussed. Published in Russian in Elektrokhimiya, 2008, Vol. 44, No. 7, pp. 919–923. The text was submitted by the authors in English.     

Quantum monte carlo study of the energetics of small hydrogenated and fluoride lithium clusters

An investigation of the energetics of small lithium clusters doped either with a hydrogen or with a fluorine atom as a function of the number of lithium atoms using fixed‐node diffusion quantum Monte Carlo (DMC) simulation is reported. It is found that the binding energy (BE) for the doped clusters increases in absolute values leading to a more stable system than for the pure ones in excellent agreement with available experimental measurements. The BE increases for pure, remains almost constant for hydrogenated, and decreases rapidly toward the bulk lithium for the fluoride as a function of the number of lithium atoms in the clusters. The BE, dissociation energy as well as the second difference in energy display a pronounced odd–even oscillation with the number of lithium atoms. The electron correlation inverts the odd–even oscillation pattern for the doped in comparison with the pure clusters and has an impact of 29%–83% to the BE being higher in the pure cluster followed by the hydrogenated and then by the fluoride. The dissociation energy and the second difference in energy indicate that the doped cluster Li₃H is the most stable whereas among the pure ones the more stable are Li₂, Li₄, and Li₆. The electron correlation energy is crucial for the stabilization of Li₃H. © 2016 Wiley Periodicals, Inc.     

Nonsymmetric and symmetric fractional calculi on arbitrary nonempty closed sets

We introduce a nabla, a delta, and a symmetric fractional calculus on arbitrary nonempty closed subsets of the real numbers. These fractional calculi provide a study of differentiation and integration of non‐integer order on discrete, continuous, and hybrid settings. Main properties of the new fractional operators are investigated and some fundamental results presented, illustrating the interplay between discrete and continuous behaviors. Copyright © 2015 John Wiley & Sons, Ltd.     

Dissociative photoionization of adenine following valence excitation

We present results on the valence level excitation, ionization and dissociation of adenine, using time-of-flight mass spectrometry and synchrotron radiation, in the vacuum ultraviolet (VUV) range of 12-21 eV. The measurements were performed using a gas-phase (Ne) harmonics filter in order to eliminate contributions from higher-order harmonics. Mass spectra were obtained using the photoelectron-photoion coincidence technique (PEPICO). The relative abundances for each ionic fragment and their mean kinetic energy release have been determined from the analysis of the corresponding peak shapes in the mass spectra. Comparison with the available photoelectron spectra and previous measurements allowed the assignment of the main features in the spectra. A discussion on the dissociative photoionization channels of this molecule has also been included. Due to our harmonics-free incident photon beam we were able to propose new appearance energy (AE) for the most important ionic channels in this energy range. The precursor ion, C(5)H(5)N(5)+, is the most abundant species (40% at 15 eV and 20% at 20 eV), which confirms the high stability of adenine upon absorption of VUV photons. We have observed other intense fragment ions such as: C(4)H(4)N(4)+, C(3)H(3)N(3) (+), C(2)H(2)N(2)+ and HCNH+. The production of the neutral HCN fragment represents up to 40% of the dissociative channels for this molecule as induced by VUV photons.     

Gas phase activation energy for unimolecular dissociation of biomolecular ions determined by focused RAdiation for gaseous multiphoton ENergy transfer (FRAGMENT)

We present a novel approach for the determination of activation energy for the unimolecular dissociation of a large (>50 atoms) ion, based on measurement of the unimolecular dissociation rate constant as a function of continuous-wave CO(2) laser intensity. Following a short ( approximately 1 s) induction period, CO(2) laser irradiation produces an essentially blackbody internal energy distribution, whose 'temperature' varies inversely with laser intensity. The only currently available method for measuring such activation energies is blackbody infrared radiative dissociation (BIRD). Compared with BIRD, FRAGMENT: (a) eliminates the need to heat the surrounding ion trap and vacuum chamber to each of several temperatures (each requiring hours for temperature equilibration); (b) offers a three-fold wider range of effective blackbody temperature; and (c) extends the range of applications to include initially cold ions (e.g., gas-phase H/D exchange). Our FRAGMENT-determined activation energy for dissociation of protonated bradykinin, 1.2 +/- 0.1 eV, agrees within experimental error to the value, 1.3 +/- 0.1 eV, previously reported by Williams et al. from BIRD experiments. Copyright 1999 John Wiley & Sons, Ltd.