1-Substituted Perylene Derivatives by Anionic Cyclodehydrogenation: Analysis of the Reaction Mechanism.

Perylene derivatives constitute a promising class of compounds with technological applications mainly due to their optoelectronic properties. One mechanism proposed to synthesize them, starting from binaphthyl derivatives, is anionic cyclodehydrogenation (under reductive conditions). However, the scope of this reaction is limited.

Visible light mediated synthesis of 6-benzo[]chromenes: transition-metal-free intramolecular direct C-H arylation.

A synthetic approach towards the 6-benzo[]chromene ring under visible light and transition-metal-free conditions has been developed. Benzochromenes are synthesized from the corresponding (2-halobenzyl) phenyl ethers or (2-halophenyl) benzyl ethers using KOBu in dimethyl sulfoxide (DMSO) at room temperature (rt) and blue light-emitting diodes (LEDs) as the light source. This methodology replaces the use of ligands or additives, high temperatures and toxic solvents.

Artificial stabilization of the fusion pore by intra-organelle styrene-maleic acid copolymers.

Styrene-maleic acid copolymers have become an advantageous detergent-free alternative for membrane protein isolation. Since their discovery, experimental membrane protein extraction and purification by keeping intact their lipid environment has become significantly easier. With the aim of identifying new applications of these interesting copolymers, their molecular binding and functioning mechanisms have recently become intense objects of study.

Design, synthesis and evaluation of cholinesterase hybrid inhibitors using a natural steroidal alkaloid as precursor.

To date, Alzheimer's disease is the most alarming neurodegenerative disorder worldwide. This illness is multifactorial in nature and cholinesterase inhibitors have been the ones used in clinical treatments. In this context, many of these drugs selectively inhibit the acetylcholinesterase enzyme interacting in both the active site and the peripheric anionic site.

An activity prediction model for steroidal and triterpenoidal inhibitors of Acetylcholinesterase enzyme.

Nowadays, the importance of computational methods in the design of therapeutic agents in a more efficient way is indisputable. Particularly, these methods have been important in the design of novel acetylcholinesterase enzyme inhibitors related to Alzheimer's disease. In this sense, in this report a computational model of linear prediction of acetylcholinesterase inhibitory activity of steroids and triterpenes is presented.

Nitro-oleic acid, a ligand of CD36, reduces cholesterol accumulation by modulating oxidized-LDL uptake and cholesterol efflux in RAW264.7 macrophages.

Macrophages play a pivotal role in the early stages of atherosclerosis development; they excessively accumulate cholesterol in the cytosol in response to modified Low Density Lipoprotein (mLDL). The mLDL are incorporated through scavenger receptors. CD36 is a high-affinity cell surface scavenger receptor that facilitates the binding and uptake of long-chain fatty acids and mLDL into the cell.

Arenium cation or radical cation? An insight into the cyclodehydrogenation reaction of 2-substituted binaphthyls mediated by Lewis acids.

Perylene and its derivatives are some of the most interesting chromophores in the field of molecular design. One of the most employed methodologies for their synthesis is the cyclodehydrogenation of binaphthyls mediated by Lewis acids. In this article, we investigated the cyclodehydrogenation reaction of 2-substituted binaphthyls to afford the -substituted perylene.

Melanogenic inhibitory effects of Triangularin in B16F0 melanoma cells, in vitro and molecular docking studies.

The lack of secure therapies for hyperpigmentation disorders, without serious adverse effects, and the latest reports relating melanogenic disorders with development of neurodegenerative diseases, encourage the continuing search for new drugs for the treatment of such disorders. In this sense, the plant kingdom is an important source of bioactive natural products with great potential for the research and development of new therapeutics. The present study evaluated the anti-melanogenic activity of the natural methoxylated chalcone, 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (Triangularin, T), on diphenolase activity from mushroom tyrosinase and on murine B16F0 melanoma cell model.

Clinanthus microstephium, an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure-Activity Analysis of Haemanthamine Skeleton Derivatives.

Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR.

Room-Temperature and Transition-Metal-Free Intramolecular α-Arylation of Ketones: A Mild Access to Tetracyclic Indoles and 7-Azaindoles.

A novel approach for the synthesis of tetracyclic indoles and 7-azaindoles is reported. The strategy involves four steps, with a fast rt intramolecular α-arylation of ketones as key step. The reaction was inspected synthetically to achieve the synthesis of 11 novel tetracyclic structures with moderate to very good yields (39-85%).

Photoinduced nucleophilic substitution of iodocubanes with arylthiolate and diphenylphosphanide ions. Experimental and computational approaches.

A new synthetic route to modify the cubane nucleus is reported here. Methyl-4-iodocubane-1-carboxylate (1) and 1,4-diiodocubane (2) were employed as reagents to react with arylthiolate and diphenylphosphanide ions under irradiation in liquid ammonia and dimethylsulphoxide. The reactions proceed to afford thioaryl- and diphenylphosphoryl- cubane derivatives in moderate to good yields.

Initiation in Photoredox C-H Functionalization Reactions. Is Dimsyl Anion a Key Ingredient?

Previous studies have reported the arylation of unactivated arenes with ArX, base (KOBu or NaOBu), and an organic additive at high temperatures. Recently, we showed that this reaction proceeds in the absence of additives at rt but employs UV-vis light. However, details of mechanisms that can use a photoinduced base-promoted homolytic aromatic substitution reaction (photo-BHAS) have remained elusive until now.

In search of the best DFT functional for dealing with organic anionic species.

Quantum chemical computational methods are thought to have problems in dealing with unstable organic anions. This work assesses the ability of different Density Functional Theory (DFT) functionals to reproduce the electron affinity and reduction potential of organic compounds. The performance of 23 DFT functionals was evaluated by computing the negative electron affinities (from 0 eV to -3.

Molecular view of the interaction of S-methyl methanethiosulfonate with DPPC bilayer.

We present molecular dynamics (MD) simulation studies of the interaction of a chemo preventive and protective agent, S-methyl methanethiosulfonate (MMTS), with a model bilayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We analyzed and compared its diffusion mechanisms with the related molecule dimethyl sulfoxide (DMSO). We obtained spatially resolved free energy profiles of MMTS partition into a DPPC bilayer in the liquid-crystalline phase through potential of mean force (PMF) calculations using an umbrella sampling technique.

Study of the interaction of Huperzia saururus Lycopodium alkaloids with the acetylcholinesterase enzyme.

In the present study, we describe and compare the binding modes of three Lycopodium alkaloids (sauroine, 6-hydroxylycopodine and sauroxine; isolated from Huperzia saururus) and huperzine A with the enzyme acetylcholinesterase. Refinement and rescoring of the docking poses (obtained with different programs) with an all atom force field helped to improve the quality of the protein-ligand complexes. Molecular dynamics simulations were performed to investigate the complexes and the alkaloid's binding modes.

Interaction of S-methyl methanethiosulfonate with DPPC bilayer.

The present study is a first step towards the investigation of S-methyl methanethiosulfonate (MMTS) interaction with membrane model systems like liposomes. In this paper, the interaction of MMTS with dipalmitoylphosphatidylcholine (DPPC) bilayers was studied by FTIR and SERS spectroscopy. Lysolipid effect on vesicle stability was studied.

In search for an optimal methodology to calculate the valence electron affinities of temporary anions.

Recently, we have proposed an approach for finding the valence anion ground state, based on the stabilization exerted by a polar solvent; the methodology used standard DFT methods and relatively inexpensive basis sets and yielded correct electron affinity (EA) values by gradually decreasing the dielectric constant of the medium. In order to address the overall performance of the new methodology, to find the best conditions for stabilizing the valence state and to evaluate its scope and limitations, we gathered a pool of 60 molecules, 25 of them bearing the conventional valence state as the ground anion and 35 for which the lowest anion state found holds the extra electron in a diffuse orbital around the molecule (non valence state). The results obtained by testing this representative set suggest a very good performance for most species having an experimental EA less negative than -3.

Species with negative electron affinity and standard DFT methods. Finding the valence anions.

Recently, we have shown that traditional bound-electron DFT models are reliable enough to reproduce negative electron affinities (EA) within a few meV, as long as the valence anion state is found, but they seem to fail in predicting the lowest EA when the ground anion state obtained is non-valence, which holds the extra electron in a diffuse orbital around the molecule; here we propose an alternative approach for finding the valence anion state, based on the stabilization exerted by a polar solvent; the methodology yields correct EA values (i.e. beyond the Koopman's theorem approximation) by gradually decreasing the dielectric constant of the medium.