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

Synthesis of a Structural Analogue of the Repeating Unit from <i>Streptococcus pneumoniae</i> 19F Capsular Polysaccharide Based on the Cross-Metathesis–Selenocyclization Reaction Sequence

Pseudo-oligosaccharides have attracted much interest as scaffolds for the synthesis of sugar mimics endowed with very similar biological properties but structurally and synthetically simpler than their natural counterparts. Herein, the synthesis of pseudo-oligosaccharides using the cross-metathesis reaction between distinct sugar-olefins followed by intramolecular selenocyclization of the obtained heterodimer as key steps is first investigated. This methodology has been then applied to the preparation of structural analogues of the trisaccharide repeating unit from <i>Streptococcus pneumoniae</i> 19F. The inhibition abilities of the synthetic molecules were evaluated by a competitive ELISA assay using a rabbit polyclonal anti-19F serum

Synthesis of a Structural Analogue of the Repeating Unit from <i>Streptococcus pneumoniae</i> 19F Capsular Polysaccharide Based on the Cross-Metathesis–Selenocyclization Reaction Sequence

Pseudo-oligosaccharides have attracted much interest as scaffolds for the synthesis of sugar mimics endowed with very similar biological properties but structurally and synthetically simpler than their natural counterparts. Herein, the synthesis of pseudo-oligosaccharides using the cross-metathesis reaction between distinct sugar-olefins followed by intramolecular selenocyclization of the obtained heterodimer as key steps is first investigated. This methodology has been then applied to the preparation of structural analogues of the trisaccharide repeating unit from <i>Streptococcus pneumoniae</i> 19F. The inhibition abilities of the synthetic molecules were evaluated by a competitive ELISA assay using a rabbit polyclonal anti-19F serum

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