A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O2: a Study from a System Far-From-Equilibrium to Biological Assays in Mitochondria.

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolil quinone thiocyanate (PQ 5) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 5 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 5 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 5 reduced ROS production and catalase activity in yeast. The results suggest that PQ 5 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

A One-Pot Six-Component Reaction for the Synthesis of 1,5-Disubstituted Tetrazol-1,2,3-Triazole Hybrids and Their Cytotoxic Activity against the MCF-7 Cell Line.

A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (SN2), and copper-catalyzed alkyne-azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity. Finally, to evaluate the antitumoral potential of the synthetized molecules, a proliferation study was performed in the breast cancer (BC) derived cell line MCF-7. The hybrid compounds showed several degrees of cell proliferation inhibition with a remarkable effect in those compounds with cyclohexane and halogens in their structures. These compounds represent potential drug candidates for breast cancer treatment. However, additionally assays are needed to elucidate their complete effect over the cellular hallmarks of cancer.

Cooperative Recognition of Ni2+ Triggered by Fluoride Ions in Naturally Occurring α-Hydroxyquinone Derivatives.

Perezone is a naturally occurring hydroxyquinone that has been deeply studied from different chemical aspects, such as therapeutics, electrochemistry, physical-chemical properties, or synthetic approaches that turn it an attractive template for new semisynthetic derivatives with a wide range of purposes. Herein, we describe a facile synthetic pathway to obtain new perezone derivatives by the addition of a pyrrole moiety that can be used for ion recognition. Compounds 2-4 showed the capability to interact with several anions and M2+ cations as separate events that result in colorimetric changes. Moreover, the compounds can behave as heteroditopic receptors. Besides, a previous interaction between fluoride ions and perezone derivatives triggered a successful recognition of M2+ ions, remarking Ni2+ as the most interesting phenomenon. These results project the compounds as potential colorimetric receptors for nickel ions in complex solutions.

Deep Eutectic Solvent Choline Chloride/p-toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition.

Deep eutectic solvents (DESs) have been considered "the organic reaction medium of the century" because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample. This article shows a systematic study of the impact of DES choline chloride/p-toluenesulfonic acid and DES choline chloride/p-toluenesulfonic acid-water in the aza-Michael addition of arylamines to maleimide to obtain aminopyrrolidine-2,5-dione derivatives. The derivatives are obtained under very mild reaction conditions with good yield. The global reaction is exothermic, spontaneous, permitted by enthalpy, and prohibited for entropy. The calculated potential energy surface shows a reaction mechanism of six steps controlled by enthalpy (except the last step that is controlled by entropy). The water incorporated in the supramolecular DES complex stabilizes the transition states and favors the enthalpy-driven binding. A set of H/D exchange NMR experiments validates the transition state existing in the fourth stage of the mechanism.

Oxidative amidation of benzaldehyde using a quinone/DMSO system as the oxidizing agent.

An efficient transition-metal-based heterogeneous catalyst free procedure for obtaining the oxidative amidation of benzaldehyde using quinones as oxidizing agents in low molar proportions is described here. Pyrrolylquinones (PQ) proved to be more suitable than DDQ and 2,5-dimethylbenzoquinone to conduct the oxidation process. Although the solvent itself acted as the oxidant with low to moderate yields, PQ/DMSO provided an efficient system for carrying out the reaction under operational simplicity, mild reaction conditions, short reaction times and high yields of the desired product. The scope of the method was evaluated with substituted benzaldehydes and secondary amines. Theoretical foundations are given to explain the participation of quinones as an oxidizing agent in the reaction.

A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki-Miyaura cross-coupling reactions of aryl halides.

A simple and efficient catalytic system based on a Pd complex of 4-aminoantipyrine, 4-AAP-Pd(II), was found to be highly active for Suzuki-Miyaura cross-coupling of aryl iodides and bromides with phenylboronic acids under mild reaction conditions. Good to excellent product yields from the cross-coupling reaction can be achieved when the reaction is carried out in ethanol, in the open air, using low loading of 4-AAP-Pd(II) as a precatalyst, and in the presence of aqueous K2CO3 as the base. A variety of functional groups are tolerated.

A Novel Semisynthetic Anion Receptor: Synthesis and Ion Recognition of (1-H-pyrrol-2-yl)-4-oxo-perezone.

We describe the synthesis of the novel 2-(1,5-dimethyl-4-oxo-hexyl)-3-hydroxy-5-methyl-6-pyrrolyl-1,4-benzoquinone 2 from the natural product perezone 1. The anion-guest properties of the new compound were evaluated in the presence of fluoride, chloride, bromide and iodide tetrabutylammonium salts using 1H NMR titration techniques in deuterated dichloromethane or dimethylformamide. The title compound showed interesting colorimetric behavior in the presence of inorganic salts.