Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations.

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 µM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.

2H-1,2,3-Triazole-chalcones as novel cytotoxic agents against prostate cancer.

Prostate cancer is an important cause of death in the male population and for which there is no satisfactory chemotherapy. Herein a new series of chalcone hybrids containing 2H-1,2,3-triazole core as the ring B has been synthesized and evaluated in vitro against PC-3 prostate cancer cell line. Compounds 4a, 4c and 4e significantly reduced cell viability and showed IC50 of 28.55, 15.64 and 25.56 µM, respectively. The structure-activity relationship supported by computational chemistry points that the polarity of the molecular surface area should have some relevance to the efficiency of the compounds, in particular the ratio of the partial positive charge sites and the total molecular surface area exposed to the cell environment.

Insight into and Computational Studies of the Selective Synthesis of 6H-Dibenzo[b,h]xanthenes.

Starting from 2-hydroxy-1,4-naphthoquinone (lawsone), we synthesized eight new 6H-dibenzo[b,h]xanthene derivatives selectively under solvent-free conditions. Spectroscopic investigations confirmed that only the isomer 6H-dibenzo[b,h]xanthene was obtained in all eight cases. Computational studies provide a rationalization for the selective appearance of these isomers having as an intermediate an addition product.

Modeling, kinetic, and equilibrium characterization of paraquat adsorption onto polyurethane foam using the ion-pairing technique.

We studied the adsorption of paraquat onto polyurethane foam (PUF) when it was in a medium containing sodium dodecylsulfate (SDS). The adsorption efficiency was dependent on the concentration of SDS in solution, because the formation of an ion-associate between the cationic paraquat and the dodecylsulfate anion was found to be a fundamental step in the process. A computational study was carried out to identify the possible structure of the ion-associate in aqueous medium. The obtained data demonstrated that the structure is probably formed from four units of dodecylsulfate bonded to one paraquat moiety. The results showed that 94% of the paraquat present in 45 mL of a solution containing 3.90 × 10(-5) mol L(-1) could be retained by 300 mg of PUF, resulting in the removal of 2.20 mg of paraquat. The experimental data were reasonably adjusted to the Freundlich isotherm and to the pseudo-second-order kinetic model. Also, the application of Morris-Weber and Reichenberg models indicated that both film-diffusion and intraparticle-diffusion processes were active during the control of the adsorption kinetics.

Density functional theory investigation of the contributions of π-π stacking and hydrogen bonding with water to the supramolecular aggregation interactions of model asphaltene heterocyclic compounds.

CONTEXT: A complex supramolecular process involving electrostatic and dispersion interactions and asphaltene aggregation is associated with detrimental petroleum deposition and scaling that pose challenges to petroleum recovery, transportation, and upgrading. The homodimers of seven heterocyclic model compounds, representative of moieties commonly found in asphaltene structures, were studied: pyridine, thiophene, furan, isoquinoline, pyrazine, thiazole, and 1,3-oxazole. The contributions of hydrogen bonding involving water bridges spanning between dimers and π-π stacking to the total interaction energy were calculated and analyzed. The distance between the planes of the aromatic rings is correlated with the π-π stacking interaction strength. All the dimerization reactions were exothermic, although not spontaneous. This was mostly modulated by the strength of the hydrogen bond of the water bridge and the π-π stacking interaction. Dimers bridged by two water molecules were more stable than those with additional water molecules or without any water molecule in the bridge. Energy decomposition analysis showed that the electrostatic and polarization components were the main stabilizing terms for the hydrogen bond interaction in the bridge, contributing at least 80% of the interaction energy in all dimers. The non-covalent interaction analysis confirmed the molecular sites that had the strongest (hydrogen bond) and weak (π-π stacking) attractive interactions. They were concentrated in the water bridge and in the plane between the aromatic rings, respectively. METHODS: The density functional ωB97X-D with a dispersion correction and the Def2-SVP basis set were employed to investigate supramolecular aggregates incorporating heterocycles dimers with 0, 1, 2, and 3 water molecules forming a stabilizing bridge connecting the monomers. The non-covalent interactions were analyzed using the NCIplot software and plotted as isosurface maps using Visual Molecular Dynamics.

Mechanistic insights into C(sp2)-H activation in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives: a theoretical study with palladium acetate catalyst.

CONTEXT: The activation of C-H bonds is a fundamental process in synthetic organic chemistry, which enables their replacement by highly reactive functional groups. Coordination compounds serve as effective catalysts for this purpose, as they facilitate chemical transformations by interacting with C-H bonds. A comprehensive understanding of the mechanism of activation of this type of bond lays the foundation for the development of efficient protocols for cross-coupling reactions. We explored the activation of C(sp2)-H bonds in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives with CH3, OCH3, and NO2 substituents in the para position of the phenyl ring, using palladium acetate as catalyst. The studied reaction is the first step for subsequent conjugation of the triazoles with naphthoquinones in a Heck-type reaction to create a C-C bond. The basic nitrogen atoms of the 1,2,3-triazole coordinate preferentially with the cationic palladium center to form an activated species. A concerted proton transfer from the terminal vinyl carbon to one of the acetate ligands with low activation energy is the main step for the C(sp2)-H activation. This study offers significant mechanistic insights for enhancing the effectiveness of C(sp2)-H activation protocols in organic synthesis. METHODS: All calculations were performed using the Gaussian 09 software package and density functional theory (DFT). The structures of all reaction path components were fully optimized using the CAM-B3LYP functional with the Def2-SVP basis set. The optimized geometries were analyzed by computing the second-order Hessian matrix to confirm that the corresponding minimum or transition state was located. To account for solvent effects, the Polarizable Continuum Model of the Integral Equation Formalism (IEFPCM) with water as the solvent was used.

First- and second-row transition metal oxa-aza macrocyclic complexes: a DFT study of an octahedral conformation.

A theoretical study of structures of the 1,7,1 l,17-tetraoxa-2,6,12,16-tetraaza-cycloeicosane ligand ([20]AneN(4)O(4)) coordinated to Fe(2+), Co(2+), Ni(2+), Ru(2+), Rh(2+), and Pd(2+) transition metals ions was carried out with the DFT/B3LYP method. Complexes were fully optimized in C(s) symmetry with the metal ions coordinated either to nitrogen (1a) or oxygen atoms (1b). For all the cases performed in this work, 1a was always more stable than 1b. Considering each row it is possible to see that the binding energy increases with the atomic number. The M(2+) cation binding energies increase in the following order: Fe(2+)

Structure-activity relationship studies of new acronine analogues as suggested by molecular descriptors.

This work describes the results of an investigation on the structure-activity relationships of a series of acronine (CAS 7008-42-6) analogues which possess cytotoxic and antitumor activity. The results were obtained employing a commercially available software, which correlates structure and activity through calculations with different descriptors. The best results, obtained with electrostatic descriptors, led to propose new structures which present higher calculated activity than that of acronine.