Urease inhibitors are considered promising compounds for the treatment of ureolytic bacterial infections, particularly infections resulting from Helicobacter pylori in the gastric tract. Herein, we present the synthesis and the inhibitory activity of novel and highly effective organoselenium compounds as inhibitors of Sporosarcina pasteurii and Helicobacter pylori ureases. These studied compounds represent a class of competitive reversible urease inhibitors. The most active compound, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen), displayed Ki values equal to 2.11 and 226 nM against S. pasteurii and H. pylori enzymes, respectively, indicating ebselen as one of the most potent low-molecular-weight inhibitors of bacterial ureases reported to date. Most of these molecules penetrated through the cell membrane of the Gram-negative bacteria Escherichia coli (pGEM::ureOP) in vitro. Furthermore, whole-cell studies on the H. pylori J99 reference strain confirmed the high efficiency of the examined organoselenium compounds as urease inhibitors against pathogenic bacteria.

Oxidation reactions are fundamental processes widely applied in organic synthesis. Elemental selenium and more often its compounds have been successfully used as stoichiometric reagents and catalysts for oxidation of different organic substrates. Selenium(IV) oxide, areneseleninic acids and their anhydrides are widely used as stoichiometric oxidants or as oxygen‐transfer agents for oxygen donors, particularly hydrogen peroxide and tert‐butyl hydroperoxide. Organic diselenides (the precursors of seleninic acids) have been used as oxidation catalysts while dimethyl and diphenyl selenoxides are stoichiometric oxidants. Selenenamides, such as 2‐phenyl‐1,2‐benzisoselenazol‐3(2H)‐one (ebselen) and its analogues, known as glutathione peroxidase mimics acting via active hydroperoxide intermediates, are efficient and selective oxidation catalysts. Selenium(IV) oxide and some organoselenium compounds have been successfully applied for various oxidations useful in practical organic syntheses such as epoxidation, 1,2‐dihydroxylation, and α‐oxyfunctionalization of alkenes as well as for ring contraction of cycloalkanones, conversion of halomethyl, hydroxymethyl, or active methylene groups into formyl groups, oxidation of aldehydes into carboxylic acids, sulfides into sulfoxides, and secondary amines into nitrones, regeneration of parent carbonyl compounds from their azomethine derivatives and for other reactions. The oxidation mechanisms depend on the substrate and oxidant or catalyst used. The electrophilic center localized on the selenium atom or the nucleophilic center localized on the oxygen atom of the selenahydroperoxide group are involved in the reaction mechanism. In both cases the selenium‐containing moiety is a good leaving group. Exceptionally oxidation can proceed via free radical selenium species. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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The mixed ligand complex [Ni(CMA)2(im)2(MeOH)2] (where CMA = 9,10-dihydro-9-oxo-10-acridineacetate ion, im = imidazole) was prepared, and its crystal and molecular structure were determined. The nickel ions are hexa-coordinated by four oxygen atoms of the carboxylate and hydroxyl groups and by two imidazole nitrogen atoms, to form a distorted octahedral arrangement. The structure consists of a one-dimensional network of the complex molecules connected by strong intermolecular hydrogen bonds. The weak intermolecular C-H...X hydrogen bonds and stacking interactions make up the 2-D structure. Very strong intramolecular hydrogen bonds significantly affect the geometry and vibrational characteristics of the carboxylate group. The UV-vis-NIR electronic spectrum was deconvoluted into Gaussian components. Electronic bands of the Ni(II) ion were assigned to suitable spin-allowed transitions in the D4h symmetry environment. The single ion zero-field splitting (ZFS) parameters for the S = 1 state of Ni(II), as well as the g components, have been determined by high-field and high-frequency EPR (HF-HFEPR) spectroscopy over the frequency range of 52-432 GHz and with the magnetic fields up to 14.5 T: D = 5.77(1) cm-1, E = 1.636(2) cm-1, gx = 2.29(1), gy = 2.18(1), and gz = 2.13(1). These values allowed us to simulate the powder magnetic susceptibility and field-dependent magnetization of the complex.