Phenoxy- and Phenylamino-Heterocyclic Quinones: Synthesis and Preliminary Anti-Pancreatic Cancer Activity.

The successful application of fragment-based drug discovery strategy for the efficient synthesis of phenoxy- or phenylamino-2-phenyl-benzofuran, -benzoxazole and -benzothiazole quinones is described. Interestingly, in the final step of the synthesis of the target compounds, unusual results were observed on the regiochemistry of the reaction of bromoquinones with phenol and aniline. A theoretical study was carried out for better understanding the factors that control the regiochemistry of these reactions.

Gutmann's Donor and Acceptor Numbers for Ionic Liquids and Deep Eutectic Solvents.

An experimental and computational methodology for the analysis of the Lewis acid/base responses of ionic liquids (ILs) and deep eutectic solvents (DES) is proposed. It is based on the donor and acceptor of the electronic charge ability of Lewis acid and bases concepts (donicity and acceptor numbers, DN and AN, respectively) proposed by Viktor Gutmann. The binding enthalpy between the IL/DES with the probe antimony pentachloride (SbCl) in dichloroethane displays good correlations with experimental data.

On the role of water in the hydrogen bond network in DESs: an molecular dynamics and quantum mechanical study on the urea-betaine system.

We herein report an ab initio molecular dynamics study on a natural DES composed of urea and betaine in a 3 : 2 ratio, as a test case for evaluating the water effect. The article deals with a theoretical study using both ab initio molecular dynamics and quantum chemistry computations in order to unravel the role of water in the nanostructure of a urea-betaine mixture. Preliminary molecular dynamics outcomes (both radial and spatial distribution functions) suggest that water promotes the association between urea and betaine by increasing the hydrogen bond network and precluding the aggregation of urea molecules.

Methodological Issues in First-Principle Calculations of CHNHPbI Perovskite Surfaces: Quantum Confinement and Thermal Motion.

Characterization and control of surfaces and interfaces are critical for photovoltaic and photocatalytic applications. In this work, we propose CHNHPbI (MAPI) perovskite slab models whose energy levels, free of quantum confinement, explicitly consider the spin-orbit coupling and thermal motion. We detail methodological tools based on the density functional theory that allow achieving these models at an affordable computational cost, and analytical corrections are proposed to correct these effects in other systems.

Theoretical insights into the E1cB/E2 mechanistic dichotomy of elimination reactions.

E1cB and E2 eliminations have been described as competing mechanisms that can even share a common pathway when the E1cB/E2 borderline mechanism operates. A suitable case study evincing such a mechanistic dichotomy corresponds to the elimination reaction of β-phenylmercaptoethyl phenolate, since its mechanism has been thought to be an E2 elimination. Nonetheless, according to the computational assessment of the substituents on the leaving group, we demonstrate that the reaction proceeds via a borderline E1cB mechanism.

Activation of Electrophile/Nucleophile Pair by a Nucleophilic and Electrophilic Solvation in a SAr Reaction.

Nucleophilic aromatic substitution reactions of 4-chloroquinazoline toward aniline and hydrazine were used as a model system to experimentally show that a substrate bearing heteroatoms on the aromatic ring as substituent is able to establish intramolecular hydrogen bond which may be activated by the reaction media and/or the nature of the nucleophile.

How Meaningful Is the Halogen Bonding in 1-Ethyl-3-methyl Imidazolium-Based Ionic Liquids for CO Capture?

We report on several parameters that can be used to describe the 1-ethyl-3-methyl-4,5-(X)imidazolium cations (where X = H, Br, and I) within the Canongia-Lopez and Padua Force Field (CL&P) framework. Geometrical parameters like intramolecular distances and radial distribution functions are close to the experimental structure. Density values obtained with our force field are within the expected ones from CL&P calculations in related systems.

Gutmann's Donor Numbers Correctly Assess the Effect of the Solvent on the Kinetics of SN Ar Reactions in Ionic Liquids.

We report an experimental study on the effect of solvents on the model SN Ar reaction between 1-chloro-2,4-dinitrobenzene and morpholine in a series of pure ionic liquids (IL). A significant catalytic effect is observed with reference to the same reaction run in water, acetonitrile, and other conventional solvents. The series of IL considered include the anions, NTf2 (-) , DCN(-) , SCN(-) , CF3 SO3 (-) , PF6 (-) , and FAP(-) with the series of cations 1-butyl-3-methyl-imidazolium ([BMIM](+) ), 1-ethyl-3-methyl-imidazolium ([EMIM](+) ), 1-butyl-2,3-dimethyl-imidazolium ([BM2 IM](+) ), and 1-butyl-1-methyl-pyrrolidinium ([BMPyr](+) ).

Lewis Acidity/Basicity Changes in Imidazolium Based Ionic Liquids Brought About by Impurities.

We herein report on the effect that water molecules, present as impurities, in the vicinity of an ionic liquid model structure, may induce on the Lewis acidity/basicity patterns normally observed in these materials. Depending on the position and orientation of water, the Lewis acidity/basicity pattern changes from "normal distribution" (i.e.

Mechanistic insights into the ANRORC-like rearrangement between methylhydrazine and 1,2,4-oxadiazole derivatives.

We herein present the first in-depth theoretical study devoted to elucidate the mechanism of the reaction between 1,2,4-oxadiazole derivatives and methylhydrazine. For this purpose, the reaction between methylhydrazine and some polyfluoroaryl-1,2,4-oxadiazoles has been employed as a model reaction. The analysis of the potential energy surface (PES) indicates that the most favorable path involves an initial amine attack at the C(2') site of the aryl moiety to yield an aryl-hydrazine intermediate whose thermodynamic stability appears as the main determinant of the favored reaction path.

Regional electrophilic and nucleophilic Fukui functions efficiently highlight the Lewis acidic/basic regions in ionic liquids.

The origin of catalysis and selectivity induced by room temperature ionic liquids in several organic reactions has putatively been associated with the concept of cation effect (hydrogen bond donor ability of the ionic liquids) or anion effect (hydrogen bond accepting ability of the ionic liquids). We show that there may be cases where this a priori classification may not be correctly assigned. Cations may concentrate both Lewis acidity and basicity functions in one fragment of the ionic liquid: an effect we tentatively call bifunctional distribution of the molecular Lewis acidity/basicity.

Hydrogen bond contribution to preferential solvation in S(N)Ar reactions.

Preferential solvation in aromatic nucleophilic substitution reactions is discussed using a kinetic study complemented with quantum chemical calculations. The model system is the reaction of a series of secondary alicyclic amines toward phenyl 2,4,6-trinitrophenyl ether in aqueous ethanol mixtures of different compositions. From solvent effect studies, it is found that only piperidine is sensitive to solvation effects, a result that may be traced to the polarity of the solvent composition in the ethanol/water mixture, which points to a specific electrophilic solvation in the aqueous phase.

Specific nucleophile-electrophile interactions in nucleophilic aromatic substitutions.

We herein report results obtained from an integrated experimental and theoretical study on aromatic nucleophilic substitution (S(N)Ar) reactions of a series of amines towards 1-fluoro-2,4-dinitrobenzene in water. Specific nucleophile-electrophile interactions in the title reactions have been kinetically evaluated. The whole series undergoes S(N)Ar reactions where the formation of the Meisenheimer complex is rate determining.

Lewis molecular acidity of ionic liquids from empirical energy-density models.

Two complementary models of Lewis molecular acidity are introduced and tested in a wide series of 45 room temperature ionic liquids (RTIL). They are defined in the context of the conceptual density functional theory. The first one, which we tentatively call the excess electronic chemical potential, assesses the electron accepting power of the RTIL by relating the H-bond donor acidity with the charge transfer associated to the acidic H-atom migration at the cation of the RTIL considered as a HB-donor species.

Reactivity indices profile: a companion tool of the potential energy surface for the analysis of reaction mechanisms. Nucleophilic aromatic substitution reactions as test case.

We herein report on the usefulness of the reactivity indices profiles along a reaction coordinate. The model is tested to fully describe the reaction mechanism of the title reactions. Group nucleophilicity and electrophilicity profiles help describe the bond-breaking/bond-formation processes and the intramolecular electron density reorganization.

On the catalytic effect of water in the intramolecular Diels–Alder reaction of quinone systems: a theoretical study.

The mechanism of the intramolecular Diels–Alder (IMDA) reaction of benzoquinone 1, in the absence and in the presence of three water molecules, 1w, has been studied by means of density functional theory (DFT) methods, using the M05-2X and B3LYP functionals for exploration of the potential energy surface (PES). The energy and geometrical results obtained are complemented with a population analysis using the NBO method, and an analysis based on the global, local and group electrophilicity and nucleophilicity indices. Both implicit and explicit solvation emphasize the increase of the polarity of the reaction and the reduction of activation free energies associated with the transition states (TSs) of this IMDA process.

Quantum mechanical continuum solvation models for ionic liquids.

The quantum mechanical SMD continuum universal solvation model can be applied to predict the free energy of solvation of any solute in any solvent following specification of various macroscopic solvent parameters. For three ionic liquids where these descriptors are readily available, the SMD solvation model exhibits a mean unsigned error of 0.48 kcal/mol for 93 solvation free energies of neutral solutes and a mean unsigned error of 1.

Microbial transformation of marine halogenated sesquiterpenes.

The sesquiterpene pacifenol is one of the main constituents of the red alga Laurencia claviformis. Earlier work on the semisynthetic derivatives of pacifenol afforded a series of halogenated sesquiterpenes. The aim of the present work was to obtain new hydroxylated derivatives of halogenated sesquiterpenes by means of microbial transformation using Aspergillus niger, Gibberella fujikuroi and Mucor plumbeus.

Are electrophilicity and electrofugality related concepts? A density functional theory study.

It is proposed that the electrofugality of a fragment within a molecule is determined by its group nucleophilicity. The variation of electrofugality should be tightly related to the electron releasing ability of the substituent attached to the electrofuge moiety. This contribution closes the set of relationships between philicity and fugality quantities: while nucleofugality appears related to the group electrophilicity of the leaving group, electrofugality is related to the group nucleophilicity of the permanent group.

Quantitative characterization of group electrophilicity and nucleophilicity for intramolecular Diels-Alder reactions.

In a previous work (L. R. Domingo, M.

Experimental and theoretical studies on the nucleofugality patterns in the aminolysis and phenolysis of S-aryl O-aryl thiocarbonates.

The reactions of S-phenyl, S-(4-chlorophenyl), and S-(2,3,4,5,6-pentafluorophenyl) 4-nitrophenyl thiocarbonates (9, 11, and 16, respectively) with a series of secondary alicyclic (SA) amines and those of S-(4-methylphenyl) 4-nitrophenyl thiocarbonate (8) and compounds 9 and 11 with a series of phenols are subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 degrees C and an ionic strength of 0.2 M.

On the Gas-Phase Electronic Chemical Potential of Anions.

In the process of evaluating intrinsic electronic chemical potentials and related properties of anions in the gas phase, positive values for this quantity often arise. We herein examine in detail this result in terms of computational grounds. At a low level of theory, this result is often obtained, but its origin is mainly traced to the fact that the LUMO energy level is not really converged.

Endohedral cluster of Li(10)O with T(d) symmetry.

A detailed numerical study of several isomers of the Li(10) cluster has been done. The analysis of the electronic localization function and the analysis of energy diagrams revealed the existence of one cluster with an inner space capable to suit a heteroatom. The perfect candidate is the Li(10)O cluster due to the experimental evidence of the [Li(6)O](4+) core, the same core present in Li(10)O.

An unusual halogenated meroditerpenoid from Stypopodium flabelliforme: studies by NMR spectroscopic and computational methods.

Meroditerpenoids, 2-[2'(E)-3',7',11',15'-tetramethylhexadec-2-en-1'-yl]-6-methyl-1,4-benzohydroquinone diacetate and 4'-chlorostypotriol triacetate, along with eight known compounds isolated from the dichloromethane extract of the brown alga Stypopodium flabelliforme after peracetylation are reported. One of them, 2-(1-oxo-hexadecyl)-1,3,5-trihydroxybenzene, is described for the first time within this genus. Structural elucidation was carried out on the basis of spectroscopic data and theoretical studies using GIAO/DFT analysis at B3LYP/6-31G(d) and mPW1PW91/6-31G(d) levels of theory for 4'-chlorostypotriol.

On the role of short and strong hydrogen bonds on the mechanism of action of a model chymotrypsine active site.

The electronic properties of a chemical model that mimics the His-57...