Elucidation of the Nucleophilic Potential of Diazocyclopentadiene

Diazocyclopentadiene reacts with benzhydrylium ions (Ar2CH+) to give 2,5-dibenzhydryl-substituted diazocyclopentadienes. The kinetics have been determined photometrically in dichloromethane under pseudo-first-order conditions using diazocyclopentadiene in excess. Plots of the second-order rate constants (log k 2) versus the electrophilicity parameters E of the benzhydrylium ions gave the nucleo­philicity parameter N = 4.84 and susceptibility s N = 1.06 for diazo­cyclopentadiene according to the correlation log k(20 °C) = s N(E + N). Diazocyclopentadiene thus has a similar nucleophilic reactivity as pyrrole. Previously reported electrophilic substitutions of diazocyclopentadiene are rationalized by these parameters and new reaction possibilities are predicted.

4,6-Dichloro-5-Nitrobenzofuroxan: Different Polymorphisms and DFT Investigation of Its Reactivity with Nucleophiles

This research focuses on the X-ray structure of 4,6-dichloro-5-nitrobenzofuroxan 1 and of some of its amino derivatives (4a, 4e, 4g, and 4l) and on DFT calculations concerning the nucleophilic reactivity of 1. We have found that by changing the solvent used for crystallization, it is possible to obtain 4,6-dichloro-5-nitrobenzofuroxan (1) in different polymorphic structures. Moreover, the different torsional angles observed for the nitro group in 1 and in its amino derivatives (4a, 4e, 4g, and 4l) are strictly dependent on the steric hindrance of the substituent at C-4. DFT calculations on the course of the nucleophilic substitution confirm the role of the condensed furoxan ring in altering the aromaticity of the carbocyclic frame, while chlorine atoms strongly influence the dihedral angle and the rotational barrier of the nitro group. These results corroborate previous observations based on experimental kinetic data and give a deep picture of the reaction with amines, which proceeds via a “non-aromatic” nucleophilic substitution.

A side-on Mn(iii)–peroxo supported by a non-heme pentadentate N3Py2 ligand: synthesis, characterization and reactivity studies

A new non-heme Mn(iii)–peroxo (1a) has been generated, characterized and reactivity is in aldehyde deformylation reaction. A nucleophilic reactivity of 1a in aldehyde oxidation is proposed.

Nucleophilic reactivity of the gold atom in a diarylborylgold(i) complex toward polar multiple bonds

A di(o-tolyl)borylgold complex added to CO/N double bond to form Au–C and B–O/N bonds. DFT calculations revealed a two-step mechanism consisting of the coordination of O/N atom to B atom followed by nucleophilic migration of Au atom.

Acidity and nucleophilic reactivity of glutathione persulfide

Persulfides (RSSH/RSS−) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (H2S). Despite their growing relevance, their chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/GSS−), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS− presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called α effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the α effect correlated with the Brønsted nucleophilic factor, βnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the α effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.

Leloir glycosyltransferases of natural product C-glycosylation: structure, mechanism and specificity

A prominent attribute of chemical structure in microbial and plant natural products is aromatic C-glycosylation. In plants, various flavonoid natural products have a β-C-d-glucosyl moiety attached to their core structure. Natural product C-glycosides have attracted significant attention for their own unique bioactivity as well as for representing non-hydrolysable analogs of the canonical O-glycosides. The biosynthesis of natural product C-glycosides is accomplished by sugar nucleotide-dependent (Leloir) glycosyltransferases. Here, we provide an overview on the C-glycosyltransferases of microbial, plant and insect origin that have been biochemically characterized. Despite sharing basic evolutionary relationships, as evidenced by their common membership to glycosyltransferase family GT-1 and conserved GT-B structural fold, the known C-glycosyltransferases are diverse in the structural features that govern their reactivity, selectivity and specificity. Bifunctional glycosyltransferases can form C- and O-glycosides dependent on the structure of the aglycon acceptor. Recent crystal structures of plant C-glycosyltransferases and di-C-glycosyltransferases complement earlier structural studies of bacterial enzymes and provide important molecular insight into the enzymatic discrimination between C- and O-glycosylation. Studies of enzyme structure and mechanism converge on the view of a single displacement (SN2)-like mechanism of enzymatic C-glycosyl transfer, largely analogous to O-glycosyl transfer. The distinction between reactions at the O- or C-acceptor atom is achieved through the precise positioning of the acceptor relative to the donor substrate in the binding pocket. Nonetheless, C-glycosyltransferases may differ in the catalytic strategy applied to induce nucleophilic reactivity at the acceptor carbon. Evidence from the mutagenesis of C-glycosyltransferases may become useful in engineering these enzymes for tailored reactivity.