Cytochrome P450 Can Epoxidize an Oxepin to a Reactive 2,3-Epoxyoxepin Intermediate: Potential Insights into Metabolic Ring-Opening of Benzene

Dimethyldioxirane epoxidizes 4,5-benzoxepin to form the reactive 2,3-epoxyoxepin intermediate followed by very rapid ring-opening to an o-xylylene that immediately isomerizes to the stable product 1H-2-benzopyran-1-carboxaldehyde. The present study demonstrates that separate incubations of 4,5-benzoxepin with three cytochrome P450 isoforms (2E1, 1A2, and 3A4) as well as pooled human liver microsomes (pHLM) also produce 1H-2-benzopyran-1-carboxaldehyde as the major product, likely via the 2,3-epoxyoxepin. The reaction of 4,5-benzoxepin with cerium (IV) ammonium nitrate (CAN) yields a dimeric oxidized molecule that is also a lesser product of the P450 oxidation of 4,5-benzoxepin. The observation that P450 enzymes epoxidize 4,5-benzoxepin suggests that the 2,3-epoxidation of oxepin is a major pathway for the ring-opening metabolism of benzene to muconaldehyde.

Efficient Synthesis of O-tert-Propargylic Oximes via Nicholas Reaction

A synthetic protocol to access O-tert-propargylic oximes derived from tertiary propargylic alcohols was established via Nicholas reaction. Thus, BF3·OEt2-mediated reaction between the dicobalt hexacarbonyl complex of tert-propargylic alcohols and p-nitrobenzaldoxime followed by decomplexation with cerium(IV) ammonium nitrate afforded the corresponding O-tert-propargylic oximes in good to high yields. The obtained O-tert-propargylic oximes were effectively converted into heterocycles, such as four-membered cyclic nitrones, oxazepines, and isoxazolines, by using π-Lewis acidic catalysts.

Green and Facile Synthesis of Pyrimidine Derivatives Using Choline Chloride-urea Mixture as a Deep Eutectic Solvent or Cerium (IV) Ammonium Nitrate

An efficient and facile synthesis of substituted pyrimidine derivatives through Biginelli type reaction was achieved in high yields via one-pot reaction of aromatic aldehydes, active methylene compounds and urea or thiourea in the presence of choline chloride- urea mixture as a deep eutectic solvent or cerium (IV) ammonium nitrate (CAN) as a catalyst at different conditions. The reaction was carried out using different ratio of CAN in different solvents to determine the optimum conditions. In addition, 2-mercapto-6-oxo- 4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile was employed in the synthesis of pyrimidinylhydrazide and its corresponding hydrazone. The structural formula of all derivatives was confirmed and characterized by their elemental analyses and spectral data (IR, MS, 1H NMR, 13C NMR).

Characteristics of the response of the microalga (Dunaliella viridis) to cerium compounds in culture

Recently, nanobiotechnology has been developing intensively; therefore, various properties of nanoparticles, which depend on their origin, concentration, and size, are of interest. It is known that CeO2 nanoparticles cause a positive biological effect. These particles are able to penetrate through biomembranes. At the same time, there are assumptions about a high degree of biological risks when using nanomaterials, and it is obvious that the biosafety of nanomaterials is decisive in the development of new products, including for medicine. The cytotoxicity of samples of cerium salts and cerium dioxide nanoparticles of different sizes was assessed at different concentrations using D. viridis. The cytotoxicity level by morphological and functional disorders of D. viridis was investigated, as determined by the change in cell shape, accumulation of inclusions, loss of flagellum, change in nature and movement, the formation of micro- and macroaggregates by D. viridis cells and exometabolite release. The cytotoxicity coefficient was calculated as a quotient of total detected changes divided by their number. It was shown that cerium salts (cerium (IV) ammonium nitrate and cerium (III) chloride) had pronounced cytotoxicity, which exceeded cytotoxicity values of the control by 7 and 6 times, respectively. Cerium dioxide nanoparticles with a size of 6 nm at a concentration of 0.01 M showed intermediate cytotoxicity, which exceeded control values by 3.5 times, and after the effect of nanoparticles with a size of 2 nm at a concentration of 0.1 M, the cytotoxicity coefficient corresponded to control values. The addition of inactivated blood serum to the incubation mixture resulted in a decreased cytotoxic effect of cerium dioxide. The use of D. viridis as a test system will supplement the arsenal of biotesting tools for nanomaterials and the study of the mechanisms of their effect.