Ternary Copper Complex of L-Glutamine and Phenanthroline as Counterions of Cyclo-Tetravanadate Anion: Experimental–Theoretical Characterization and Potential Antineoplastic Activity

Over the last decade, therapeutic metallodrugs have become substantially effective in the treatment of cancer. Thus, developing new effective anticancer drugs is a significant research area against the continuing increase in cancers worldwide. In the search for heterobimetallic prodrugs containing V/Cu, a new cyclo-tetravanadate was synthesized and characterized by UV-visible and FTIR spectroscopies and single-crystal X-ray diffraction. L-Glutamine and 1,10-phenanthroline allow the crystallization of [Cu(L-Gln)(phen)(H2O)]4[V4O12]∙8(H2O) (1), in which the cyclo-tetravanadate acts as a free anion. Density functional theory (DFT) calculations were carried out to characterize the frontier molecular orbitals and molecular electrostatic potential. Global reactivity indexes were calculated and analyzed to give insight into the cyclo-tetravanadate anion and complex counterions interactions. Also, using Bader’s theory of atoms in molecules (AIM), non-covalent interactions were analyzed. Docking analysis with the Casiopeina-like complex resulting from the hydrolysis of compound 1 provided insights into these complex potential anticancer activities by interacting with DNA/tRNA via H-bonds and hydrophobic interactions. The release of both components could act together or separately, acting as prodrugs with potential dual antineoplastic activities.

Age- and sex-related profiles for macro, macro/micro and microvascular reactivity indexes: Association between indexes and normative data from 2609 healthy subjects (3-85 years)

Vascular reactivity (VR), defined as blood vessels’ capability to actively modify the diameter and flow resistances can be non-invasively assessed analyzing vascular response to forearm occlusion. Several VR indexes can be quantified: (i) ´microvascular´, which consider variables that depend almost exclusively on changes in distal resistances, (ii)´ macrovascular´, that evaluate the changes in brachial artery (BA) diameter, adjusting for blood flow stimulus, and (iii) ´macro/micro´, whose values depend on the micro and macrovascular response without discriminating each one´s contribution. VR indexes could not be associated. Many VR indexes have been used without availability of adequate normative data (reference intervals, RIs). Aims: (1) to evaluate macro, macro/micro and micro VR indexes obtained in a cohort of healthy children, adolescents and adults, (2) to evaluate the association between VR indexes, (3) to determine the need for age and/or sex-specific RIs, and (4) to define RIs for VR indexes. Methods: Ultrasound (B-mode/Doppler) and automatic computerized analysis were used to assess BA diameter, blood flow velocity and distal resistances, at rest and in conditions of decreased and increased blood flow. Macro, macro/micro and micro VR indexes were quantified (n = 3619). RIs-subgroups were defined according to European Reference Values for Arterial Measurements Collaboration Group (n = 1688, 3–84 years) and HUNT3-Fitness Study Group (n = 2609, 3–85 years) criteria. Mean value and standard deviation equations were obtained for VR indexes. The need for age or sex-specific RIs was analyzed. Percentile curves were defined and data were compared with those obtained in other populations. Conclusion: Macro and macro/micro VR indexes showed no association (or it was very weak) with microvascular indexes. Age- and sex-related profiles and RIs for macro, macro/micro and micro VR indexes were defined in a large population of healthy subjects (3–85 y). Equations for mean, standard deviation and percentiles values (year-to-year) were included in text and spreadsheet formats.

Reactions of 4-Pyrones with Azomethine Ylides as a Chemo­selective Method for the Construction of Multisubstituted Pyrano[2,3-c]pyrrolidines

Abstract4-Pyrones bearing electron-donating and electron-withdrawing groups react with nonstabilized azomethine ylides to form pyrano[2,3-c]pyrrolidines in moderate to good yields. The reaction proceeds chemoselectively as a 1,3-dipolar cycloaddition of the azomethine ylide at the carbon–carbon double bond of the pyrone activated by the electron-withdrawing substituent. The reactivity of 4-pyrones toward azomethine ylides was rationalized by computational studies with the use of reactivity indexes. The pyrano[2,3-c]pyrrolidine moiety could be modified, for example by a ring-opening transformation under the action of hydrazine to provide pyrazolyl-substituted pyrrolidines.

Physical and Chemical Aspects of the interaction of Chitosan and Cellulose acetate with ions Ca2+ and K+ using DFT methods

Motivated by the use of chitosan (Ch), and cellulose acetate (AC) as organic matrices in several therapeutic drugs, a theoretical study has been elaborated through the density functional theory method (DFT) to investigate the interaction mechanism between two essential ions for the human body Ca2+, K+ and two organic matrices chitosan (Ch), and cellulose acetate (AC). Many physical and chemical aspects have been carried out after the achievement of structural optimization. This involves structural parameters, molecular electrostatic potential (MEPs), interaction energy, reactivity indexes, frontier molecular orbitals (FMOs), quantum theory atoms in molecules (QTAIM) analysis and non-covalent interaction (NCI) analysis. The results of FMOs, MEPs and reactivity index studies have revealed that the site of interaction can be predicted. The calculation of electron interaction energies shows that those ions interact with the matrix of AC and Ch. Concretely, the Ca2+ ion interacted efficiently with the AC matrix. The structural analysis results show that the interaction of Ch and ions appear spontaneously (ΔG < 0) while the interaction of AC and ions (ΔG > 0), requires more energy to occur. Finally, the QTAIM analysis data indicates that the interactions of AC -ions and Ch-ions are non-covalent presenting an electrostatic character.

Combustion and gasification characteristics of low-temperature pyrolytic semi-coke prepared through atmosphere rich in CH4 and H2

Thermoanalysis was used in this research to produce a comparative study on the combustion and gasification characteristics of semi-coke prepared under pyrolytic atmospheres rich in CH4 and H2 at different proportions. Distinctions of different semi-coke in terms of carbon chemical structure, functional groups, and micropore structure were examined. The results indicated that adding some reducing gases during pyrolysis could inhibit semi-coke reactivity, the inhibitory effect of the composite gas of H2 and CH4 was the most observable, and the effect of H2 was higher than that of CH4; moreover, increasing the proportion of reducing gas increased its inhibitory effect. X-ray diffractometer and Fourier-transform infrared spectrometer results indicated that adding reducing gases in the atmosphere elevated the disordering degree of carbon microcrystalline structures, boosted the removal of hydroxyl- and oxygen-containing functional groups, decreased the unsaturated side chains, and improved condensation degree of macromolecular networks. The nitrogen adsorption experiment revealed that the types of pore structure of semi-coke are mainly micropore and mesopore, and the influence of pyrolytic atmosphere on micropores was not of strong regularity but could inhibit mesopore development. Aromatic lamellar stack height of semi-coke, specific surface area of mesopore, and pore volume had a favorable linear correlation with semi-coke reactivity indexes.

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

The coagulation cascade is the process of the conversion of soluble fibrinogen to insoluble fibrin that terminates in production of a clot. Factor Xa (FXa) is a serine protease involved in the blood coagulation cascade. Moreover, FXa plays a vital role in the enzymatic sequence which ends with the thrombus production. Thrombosis is a common causal pathology for three widespread cardiovascular syndromes: acute coronary syndrome (ACS), venous thromboembolism (VTE), and strokes. In this research a series of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives as a potential factor Xa (FXa) inhibitor were designed, synthesized, and evaluated for their FXa inhibitor activity, cytotoxicity activity and coagulation parameters. Rational design for the desired novel molecules was performed through protein-ligand complexes selection and ligand clustering. The microwave-assisted synthetic strategy of selected compounds was carried out by using Ullmann-Goldberg, N-propargylation, Mannich addition, Friedel-Crafts, and 1,3-dipolar cycloaddition type reactions under microwave irradiation. The microwave methodology proved to be an efficient way to obtain all novel compounds in high yields (73–93%). Furthermore, a thermochemical analysis, optimization and reactivity indexes such as electronic chemical potential (µ), chemical hardness (η), and electrophilicity (ω) were performed to understand the relationship between the structure and the energetic behavior of all the series. Then, in vitro analysis showed that compounds 27, 29–31, and 34 exhibited inhibitory activity against FXa and the corresponding half maximal inhibitory concentration (IC50) values were calculated. Next, a cell viability assay in HEK293 and HepG2 cell lines, and coagulation parameters (anti FXa, Prothrombin time (PT), activated Partial Thromboplastin Time (aPTT)) of the most active novel molecules were performed to determine the corresponding cytotoxicity and possible action on clotting pathways. The obtained results suggest that compounds 27 and 29 inhibited FXa targeting through coagulation factors in the intrinsic and extrinsic pathways. However, compound 34 may target coagulation FXa mainly by the extrinsic and common pathway. Interestingly, the most active compounds in relation to the inhibition activity against FXa and coagulation parameters did not show toxicity at the performed coagulation assay concentrations. Finally, docking studies confirmed the preferential binding mode of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives inside the active site of FXa.

The effect of porosity on the reactivity of calcium sorbents

The current work presents the results of seven sorbent samples investigated with respect to SO2 capture. The sorbents’ reactivity and capacity indexes were determined, and the tests were carried out in accordance with the ‘classical’ procedure for limestone sorbents. The reactivity indexes (RIs) of the tested samples were in the range of 2.57 and 3.55 (mol Ca)/(mol S), while the absolute sorption coefficients as determined by the capacity index (CI) varied between 87.9 and 120.6 (g S)/(kg of sorbent). Porosimetric analysis was also carried out and the specific surface area of the samples was found to be between 0.2 and 1.7 m2/g. The number of micro-, meso- and macro-pores in individual samples was determined from the corresponding pore size distribution histograms, and the values of sorbent RIs and CIs were correlated with the samples’ total porosity and specific surface.

Synthesis and Characterization of Silicate Gel by using Sol-gel Process: Experiments and DFT calculations

The synthesis of geopolymers requires the formation of an irreversible gel. This gel is produced by the sol-gel process using sodium silicate and hydrochloric acid reagents. On the one hand, the experimental study of the gelling reaction shows that for concentrations of hydrochloric acid varying between 0.5-2.0 mol/L and concentration of sodium silicate varying between 1.0-6.0 mol/L, three reaction products are obtained. The first product is a clear solution, the second product is a reversible gel, and the last product is an irreversible gel. The products obtained are characterized by SEM, X-Ray Diffraction, FTIR spectroscopy and EDS Spectroscopy techniques. The microstructural analyzes of the two gels revealed that these obtained solids are almost similar whereas the structural and elementary analyzes show that the silica content in the irreversible gel is higher than the silica content in the reversible gel. On the other hand, the theoretical study of the reactivity of gelling, defined via the conceptual density functional theory (CDFT) combined with functional B3LYP function with a 6-31G base (d). They are allowed us to define the global and local reactivity indexes of two reagents, sodium silicate and hydrochloric acid.