Revisiting the Oxidation of Flavonoids: Loss, Conservation or Enhancement of Their Antioxidant Properties

Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode of the antioxidant action of flavonoids relies on the high susceptibility of their phenolic moieties to undergo oxidation. As a consequence, upon reaction with ROS, the antioxidant capacity of flavonoids is severely compromised. Other phenol-compromising reactions, such as those involved in the biotransformation of flavonoids, can also markedly affect their antioxidant properties. In recent years, however, increasing evidence has indicated that, at least for some flavonoids, the oxidation of such residues can in fact markedly enhance their original antioxidant properties. In such apparent paradoxical cases, the antioxidant activity arises from the pro-oxidant and/or electrophilic character of some of their oxidation-derived metabolites and is exerted by activating the Nrf2–Keap1 pathway, which upregulates the cell’s endogenous antioxidant capacity, and/or, by preventing the activation of the pro-oxidant and pro-inflammatory NF-κB pathway. This review focuses on the effects that the oxidative and/or non-oxidative modification of the phenolic groups of flavonoids may have on the ability of the resulting metabolites to promote direct and/or indirect antioxidant actions. Considering the case of a metabolite resulting from the oxidation of quercetin, we offer a comprehensive description of the evidence that increasingly supports the concept that, in the case of certain flavonoids, the oxidation of phenolics emerges as a mechanism that markedly amplifies their original antioxidant properties. An overlooked topic of great phytomedicine potential is thus unraveled.

N-Heterocyclic Carbene Mediated Organocatalysis Reactions

Arduengo et al., isolated the first ‘bottleable’ carbene, the first N-heterocyclic carbene (NHC) 1,3-di(adamantyl)imidazol-2-ylidene resulted to an explosion of experimental and theoretical studies of novel NHCs being synthesized and analyzed have huge practical significance. These compounds emerged as successful ligands for coordinating transition metals, the complexes with NHC show diverse applications in the field of catalysis and organic transformation, NHC as ligand to main group elements and their properties and applications. Here this chapter provides the concise overview of N-heterocycle carbene as an organocatalyst that provides different organic transformation on to a carbonyl group. The majority of the NHC catalyzed reactions are employed in the phenomenon of reversing the electrophilic character of carbonyl carbon to nucleophilic carbon (umpolung activity) on coordination suggests benzoin, Stetter and hydroacylation reactions. Also, non-umpolung activity of bis-electrophile α,β-unsaturated acylazoliums reaction with suitable bis-nucleophiles in the organic synthesis have been studied.

NH3 Sensor Based on rGO-PANI Composite with Improved Sensitivity

This work reports on a reduced graphene oxide and poly(aniline) composite (rGO-PANI), with rGO clusters inserted between PANI chains. These clusters were formed due the plasticizing effect of N-methyl-2-pyrrolidone (NMP) solvent, which was added during the synthesis. Further, this composite was processed as thin film onto an interdigitated electrode array and used as the sensitive layer for ammonia gas, presenting sensitivity of 250% at 100 ppm, a response time of 97 s, and a lowest detection limit of 5 ppm. The PANI deprotonation process, upon exposure to NH3, rGO, also contributed by improving the sensitivity due its higher surface area and the presence of carboxylic acids. This allowed for the interaction between the hydrogen of NH3 (nucleophilic character) and the -COOH groups (electrophilic character) from the rGO surface, thereby introducing a promising sensing composite for amine-based gases.

Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD), with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity, have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G (d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol−1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study establishes the depopulation of the N–N–C core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD) with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol-1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study allows establishing that the depopulation of the NNC core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

Hydrogen Sulfide and Persulfides Oxidation by Biologically Relevant Oxidizing Species

Hydrogen sulfide (H2S/HS–) can be formed in mammalian tissues and exert physiological effects. It can react with metal centers and oxidized thiol products such as disulfides (RSSR) and sulfenic acids (RSOH). Reactions with oxidized thiol products form persulfides (RSSH/RSS–). Persulfides have been proposed to transduce the signaling effects of H2S through the modification of critical cysteines. They are more nucleophilic and acidic than thiols and, contrary to thiols, also possess electrophilic character. In this review, we summarize the biochemistry of hydrogen sulfide and persulfides, focusing on redox aspects. We describe biologically relevant one- and two-electron oxidants and their reactions with H2S and persulfides, as well as the fates of the oxidation products. The biological implications are discussed.

Enantioselective Catalytic Transformations of Barbituric Acid Derivatives

Since the beginning of the 20th century, numerous research efforts made elegant use of barbituric acid derivatives as building blocks for the elaboration of more complex and useful molecules in the field of pharmaceutical chemistry and material sciences. However, the construction of chiral scaffolds by the catalytic enantioselective transformation of barbituric acid and derivatives has only emerged recently. The specific properties of these rather planar scaffolds, which also encompass either a high Brønsted acidity concerning the native barbituric acid or the marked electrophilic character of alkylidene barbituric acids, required specific developments to achieve efficient asymmetric processes. This review covers the enantioselective catalytic reactions developed for barbituric acid platforms using an organocatalytic and metal-based enantioselective sequences. These achievements currently allow several unique addition and annulation reactions towards the construction of high valued chiral heterocycles from barbituric acid derivatives along with innovative enantioselective developments.

A Molecular Electron Density Theory Study of the Competitiveness of Polar Diels–Alder and Polar Alder-ene Reactions

The competitiveness of the BF3 Lewis acid (LA) catalyzed polar Diels–Alder (P-DA) and polar Alder-ene (P-AE) reactions of 2-methyl-1,3-butadiene, a diene possessing an allylic hydrogen, with formaldehyde has been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Coordination of BF3 LA to the oxygen of formaldehyde drastically accelerates both reactions given the high electrophilic character of the BF3:formaldehyde complex. As a consequence, these reactions present a very low activation enthalpy—less than 2.2 kcal·mol−1—thus becoming competitive. In dioxane, the P-AE reaction is slightly favored because of the larger polar character of the corresponding transition state structure (TS). In addition, the Prins reaction between hexahydrophenanthrene and the BF3:formaldehyde complex has also been studied as a computational model of an experimental P-AE reaction. For this LA-catalyzed reaction, the P-DA reaction presents very high activation energy because of the aromatic character of the dienic framework. The present MEDT study allows establishing the similarity of the TSs associated with the formation of the C–C single bond in both reactions, as well as the competitiveness between P-AE and P-DA reactions when the diene substrate possesses at least one allylic hydrogen, thus making it necessary to be considered by experimentalists in highly polar processes. In this work, the term “pseudocyclic selectivity” is suggested to connote the selective formation of structural isomers through stereoisomeric pseudocyclic TSs.

Cooperative bimetallic reactivity of a heterodinuclear molybdenum–copper model of Mo–Cu CODH

Modeling the reactivity of Mo–Cu CODH: Cu(i) brings the substrate close to Mo–oxo and develops electrophilic character in CO carbon.

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

4-Aza-6-nitrobenzofuroxan (ANBF) reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts – 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic β-diketones, which exist mainly in the enol form in polar solvents, the reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems.