Role of Group 12 Metals in the Reduction of H₂O₂ by Santi’s Reagent: A Computational Mechanistic Investigation

PhSeZnCl, which is also known as Santi’s reagent, can catalyze the reduction of hydrogen peroxide by thiols with a GPx-like mechanism. In this work, the first step of this catalytic cycle, i.e., the reduction of H2O2 by PhSeZnCl, is investigated in silico using state-of-the-art density functional theory calculations. Then, the role of the metal is evaluated by replacing Zn with its group 12 siblings (Cd and Hg). The thermodynamic and kinetic factors favoring Zn are elucidated. Furthermore, the role of the halogen is considered by replacing Cl with Br in all three metal compounds, and this turns out to be negligible. Finally, the overall GPx-like mechanism of PhSeZnCl and PhSeZnBr is discussed by evaluating the energetics of the mechanistic path leading to the disulfide product

Agarsenone, a Cadinane Sesquiterpenoid from <i>Commiphora erythraea</i>

Agarsenone (<b>1</b>), a new cadinane sesquiterpenoid, was isolated from the resin of <i>Commiphora erythraea.</i> The structures of <b>1</b> and its decomposition products agarsenolides (<b>2a</b> and <b>2b</b>) and myrrhone (<b>3</b>) were established by extensive NMR spectroscopic analysis. The absolute configuration of <b>3</b> and the relative and absolute configurations of <b>1</b> were assigned by comparison of experimental and calculated optical rotatory dispersion and electronic circular dichroism spectra

Catalytic Chalcogenylation under Greener Conditions: A Solvent-Free Sulfur- and Seleno-functionalization of Olefins via I₂/DMSO Oxidant System

Herein, we report a solvent- and metal-free methodology for the alkoxy-chalcogenylation of styrenes, using molecular iodine as a catalyst, DMSO as a stoichiometric oxidant, and different nucleophiles under microwave irradiation. This eco-friendly approach afforded the desired products in good to excellent yields in only 10 min. In addition, using the same protocol, we carried out the cyclization reaction of relevant molecules, such as lapachol derivatives

Design and Synthesis of DiselenoBisBenzamides (DISeBAs) as Nucleocapsid Protein 7 (NCp7) Inhibitors with anti-HIV Activity

The interest in the synthesis of Se-containing compounds is growing with the discovery of derivatives exhibiting various biological activities. In this manuscript, we have identified a series of 2,2′-diselenobisbenzamides (DISeBAs) as novel HIV retroviral nucleocapsid protein 7 (NCp7) inhibitors. Because of its pleiotropic functions in the whole viral life cycle and its mutation intolerant nature, NCp7 represents a target of great interest which is not reached by any anti-HIV agent in clinical use. Using the diselenobisbenzoic scaffold, amino acid, and benzenesulfonamide derivatives were prepared and biologically profiled against different models of HIV infection. The incorporation of amino acids such as glycine and glutamate into DISeBAs <b>7</b> and <b>8</b> resulted in selective anti-HIV activity against both acutely and chronically infected cells as well as an interesting virucidal effect. DISeBAs demonstrated broad antiretroviral activity, encompassing HIV-1 drug-resistant strains including clinical isolates, as well as simian immunodeficiency virus (SIV). Time of addition experiments, along with the observed dose dependent inhibition of the Gag precursor proper processing, confirmed that their mechanism of action is based on NCp7 inhibition

Induction of reactive oxygen species by diphenyl diselenide is preceded by changes in cell morphology and permeability in <i>Saccharomyces cerevisiae</i>

<p>Organoselenium compounds, such as diphenyl diselenide (PhSe)₂ and phenylselenium zinc chloride (PhSeZnCl), show protective activities related to their thiol peroxidase activity. However, depending on experimental conditions, organoselenium compounds can cause toxicity by oxidising thiol groups of proteins and induce the production of reactive oxygen species (ROS). Here, we analysed the toxicity of (PhSe)₂ and PhSeZnCl in yeast <i>Saccharomyces cerevisiae</i>. Cell growth of <i>S. cerevisiae</i> after 1, 2, 3, 4, 6, and 16 h of treatment with 2, 4, 6, and 10 μM of (PhSe)₂ was evaluated. For comparative purpose, PhSeZnCl was analysed only at 16 h of incubation at equivalent concentrations of selenium (i.e. 4, 8, 12, and 20 μM). ROS production (DCFH-DA), size, granularity, and cell membrane permeability (propidium iodide) were determined by flow cytometry. (PhSe)₂ inhibited cell growth at 2 h (10 μM) of incubation, followed by increase in cell size. The increase of cell membrane permeability and granularity (10 μM) was observed after 3 h of incubation, however, ROS production occurs only at 16 h of incubation (10 μM) with (PhSe)₂, indicating that ROS overproduction is a more likely consequence of (PhSe)₂ toxicity and not its determinant. All tested parameters showed that only concentration of 20 μM induced toxicity in samples incubated with PhSeZnCl. In summary, the results suggest that (PhSe)₂ toxicity in <i>S. cerevisiae</i> is time and concentration dependent, presenting more toxicity when compared with PhSeZnCl.</p