Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Nitrenium Salts in Lewis Acid Catalysis

Molecular compounds featuring nitrogen atoms are typically regarded as Lewis bases and are extensively employed as donor ligands in coordination chemistry or as nucleophiles in organic chemistry. By contrast, electrophilic nitrogen‐containing compounds are much rarer. Nitrenium cations are a new family of nitrogen‐based Lewis acids, the reactivity of which remains largely unexplored. In this work, nitrenium ions are explored as catalysts in five organic transformations. These reactions are the first examples of Lewis acid catalysis employing nitrogen as the site of substrate activation. Moreover, these compounds are readily accessed from commercially available reagents and exhibit remarkable stability toward moisture, allowing for benchtop transformations without the need to pretreat solvents.     

Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability

All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders and malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as therapeutics for a variety of cancers and neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we investigated the effects of these retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10⁻⁶–10⁻⁵ M concentration range. All compounds induced DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex biological functions.     

Thermal Etching on Calcite Cleavages

Thermal etch pits are observed on calcite cleavages at very small range of temperatures in atmosphere. Different characteristics such as nonmovement of cleavage lines and dislocations, thermal percussion by gas molecules, are observed in thermal etching. It is found that chemical and thermal etching are not the same process for calcite cleavage etching. The origin of thermal etch pits is not at dislocations intersecting the cleavage surfaces.     

Chemical Etching of Calcite Cleavages by Diluted Solutions

Very low concentration of mineral acids and monocarboxylic acid (less then 0.001%) produces triangular etch pits on calcite cleavages at dislocations intersecting the surface. The orienation of triangular etch pits is opposite with respect to percussion mark on calcite cleavages. This may be due to opposite process of percussion and reaction at very low concentrations. When percentage of water is slightly decreased in both above acids, rhombic etch pits were formed. The non-coincidence of depth points and geometerical centres of rhombic etch pits are explained. The similarity of shape cycle will not hold at higher concentrations.     

Dehydration of Selenite Cleavage Faces

Initial dehydration of selenite cleavage surfaces start at temperature 86 °C. The dislocations are revealed by distilled water. Dislocations are mobile at dehydration temperature. Impurity centres may act as obstacles for dislocation movement. Dehydration figures are in probability formed at impurity centres.     

Eccentricity of symmetrical and asymmetrical etch pits on calcite cleavages

There are two types of chemical eccentric etch pits.

• (1) Deepest points are always lying on the shorter diagonal. – Symmetrical etch pits the deepest points of which lying on the diagonals show dislocation lines in the plane (110). Eccentricity of symmetrical etch pits along the [110] direction is depending on the concentration of the etchant and on the inclination of the dislocation line in the plane (110).
• (2) Depth points do not lie on any diagonals. Eccentricity of asymmetrical etch pits along the [110] direction is depending on the concentration of the etchant and on the inclination of the dislocation line in the plane (110).

     

Dose distribution in electron-irradiated PMMA: effect of dose and geometry

Depth-dose distributions for an electron beam are generally determined with either a stack irradiation geometry or a wedge (generally with an angle of about 50°–60°) made from an electrically-conducting material (such as, aluminium) or a non-conducting material (such as, PMMA). If the non-conducting wedge is thicker than the electron range, the stored charge in the material could influence the measured depth-dose distribution. This effect was investigated for 7-MeV electrons for PMMA with the wedge angle varying from 0° to 60°. The maximum-to-surface dose ratio was used as a characteristic parameter of the shape of the distribution. The depth-dose distribution measured by a dosimetry film placed inside the wedge-pair was similar to the standard shape when the wedge angle was larger than about 55° (dose ratio 1.5). However, as the angle was decreased, this ratio sharply increased almost linearly up to about 15°, and then leveled off at about 3. We also studied the effect of the surface dose on this dose ratio for the wedge angle of 0°, where we found that the ratio increased with the dose. Both of these effects can be explained by the presence of the electrostatic field around the dosimetry film due to stored charge in the non-conducting PMMA.     

Para Substituted Benzaldehydes as Expedient Reagents for the Oxidative Aromatization of Hydroquinoline

A Cannizzaro‐type reaction of tetrahydro‐5(1H)‐quinolinones with para substituted benzaldehydes in the presence of a base formed the corresponding quinoline and aryl methanol rather than arylidene derivatives because of the oxidation of tetrahydroquinoline and reduction of benzaldehydes as a result of unprecedented hydride transfer from tetrahydroquinoline to arylaldehydes. The reaction proceeds best with the participation of substituents with +M effect in substrate molecule.