Direct Synthesis of 2-Hydroxytrifluoroethylacetophenones via Organophotoredox-Mediated Net-Neutral Radical/Polar Crossover.

Alkene difunctionalization is a very attractive tool in synthetic organic chemistry. Herein, we disclose an operationally and practically simple method to access 2-hydroxytrifluoroethylacetophenones from styrene derivatives via photoredox catalysis. This light-mediated transformation promotes the generation of the 1-hydroxy-2,2,2-trifluoroethyl carbon-centered radical as key synthon, which undergoes Giese addition with styrenes followed by a Kornblum oxidation process. The presented method is not only mild and cost-effective, but also utilizes an organic photocatalyst and DMSO as oxidant. Experimental investigations support the operative mechanism via net-neutral radical/polar crossover.

Using electric fields to control insects: current applications and future directions.

Chemical-based interventions are mostly used to control insects that are harmful to human health and agriculture or that simply cause a nuisance. An overreliance on these insecticides however raises concerns for the environment, human health, and the development of resistance, not only in the target species. As such, there is a critical need for the development of novel nonchemical technologies to control insects. Electrocution traps using UV light as an attractant are one classical nonchemical approach to insect control but lack the specificity necessary to target only pest insects and to avoid harmless or beneficial species. Here we review the fundamental physics behind electric fields (EFs) and place them in context with electromagnetic fields more broadly. We then focus on how novel uses of strong EFs, some of which are being piloted in the field and laboratory, have the potential to repel, capture, or kill (electrocute) insects without the negative side effects of other classical approaches. As EF-insect science remains in its infancy, we provide recommendations for future areas of research in EF-insect science.

Air- and Water-Stable Heteroleptic Copper (I) Complexes Bearing Bis(indazol-1-yl)methane Ligands: Synthesis, Characterisation, and Computational Studies.

A series of four novel heteroleptic Cu(I) complexes, bearing bis(1H-indazol-1-yl)methane analogues as N,N ligands and DPEPhos as the P,P ligand, were synthesised in high yields under mild conditions and characterised by spectroscopic and spectrometric techniques. In addition, the position of the carboxymethyl substituent in the complexes and its effect on the electrochemical and photophysical behaviour was evaluated. As expected, the homoleptic copper (I) complexes with the N,N ligands showed air instability. In contrast, the obtained heteroleptic complexes were air- and water-stable in solid and solution. All complexes displayed green-yellow luminescence in CH2Cl2 at room temperature due to ligand-centred (LC) phosphorescence in the case of the Cu(I) complex with an unsubstituted N,N ligand and metal-to-ligand charge transfer (MLCT) phosphorescence for the carboxymethyl-substituted complexes. Interestingly, proper substitution of the bis(1H-indazol-1-yl)methane ligand enabled the achievement of a remarkable luminescent yield (2.5%) in solution, showcasing the great potential of this novel class of copper(I) complexes for potential applications in luminescent devices and/or photocatalysis.

A novel series of pyrazole derivatives toward biological applications: experimental and conceptual DFT characterization.

A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents.

Uracil Derivatives for Halogen-Bonded Cocrystals.

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied.

Studies on the Enantioselective Synthesis of E-Ethylidene-bearing Spiro[indolizidine-1,3'-oxindole] Alkaloids.

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3'-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared.

New Sensitive and Selective Chemical Sensors for Ni2+ and Cu2+ Ions: Insights into the Sensing Mechanism through DFT Methods.

We report the synthesis and theoretical study of two new colorimetric chemosensors with special selectivity and sensitivity to Ni2+ and Cu2+ ions over other metal cations in the CH3CN/H2O solution. Compounds (E)-4-((2-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (A) and (E)-4-((3-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (B) exhibited a drastic color change from yellow to colorless, which allows the detection of the mentioned metal cations through different techniques. The interaction of sensors with these metal ions induced a new absorption band with a hypsochromic shift to the characteristic signal of the free sensors. A theoretical study via time-dependent density functional theory (TD-DFT) was performed. This method has enabled us to reproduce the hypsochromic shift in the maximum UV-vis absorption band and explain the selective sensing of the ions. For all of the systems studied, the absorption band is characterized by a π → π* transition centered in the ligand. Instead of Ni2+ and Cu2+ ions, the transition is set toward the σ* molecular orbital with a strong contribution of the 3dx2-y2 transition (π → 3dx2-y2). These absorptions imply a ligand-to-metal charge transfer (LMCT) mechanism that results in the hypsochromic shift in the absorption band of these systems.

Energetic, Topological and Electric Field Analyses of Cation-Cation Nucleic Acid Interactions in Watson-Crick Disposition.

A theoretical study of the effect of the diprotonation on the nucleic acid bases (A : U, A : T and G : C) in Watson-Crick conformation has been carried out by means of DFT computational methods in vacuum. In addition, the corresponding neutral and monoprotonated binary complexes have been considered. Most of the diprotonated species studied are stable, even though the binding energy is positive due to the overall repulsive electrostatic term. Local electrostatic attractive forces in the regions of hydrogen bonds (HBs) are responsible for equilibrium geometries, as shown by the electric field lines connecting the electrophilic and nucleophilic sites involved in the HB interactions. Secondary electrostatic effects also affect the assembling of the nucleic acid complexes in either neutral or cationic form. In particular, the electric field lines flowing from electrophilic sites in one base to nucleophilic sites in the other reinforce the linking between them. Hence, when the nucleophilic site concerns the free lone pair of the heteroatom involved in the HB interaction as acceptor, the HB distance shortens. However, if the free lone pair of the HB acceptor interacts with an electrophilic site in the same molecule, the HB distance elongates, weakening the HB interaction. The topological analysis of the electron density distribution in HB regions indicates that neutral, monoprotonated and diprotonated complexes show no differences in the nature of their HB's.

A Straightforward Synthesis of Functionalized cis-Perhydroisoquinolin-1-ones.

Base-catalyzed annulation reactions of 5,6-dihydro-2(1H)-pyridones with Nazarov-type reagents are reported. The effect of the solvent polarity and the concentration of the reagents is studied. The process involves two successive Michael additions and stereoselectively provides functionalized cis-perhydroisoquinolin-1-ones.

Synthesis of Au Nanoparticles Assisted by Linker-Modified TiO2 Nanoparticles.

Plasmonic nanoparticles, especially gold ones, have been widely employed as photosensitizers in photoelectrovoltaic or photocatalytic systems. To improve the system's performance, a greater interaction of the nanoparticles with the semiconductor, generally TiO2, is desired. Moreover, this performance is enhanced when an efficient covering of TiO2 surface by the sensitizer is achieved. The Brust-Schiffrin-like methods are of the most employed approaches for nanoparticles synthesis. In a traditional approach, the reduction of the gold precursor is performed in the presence of a stabilizer (typically a thiol molecule) free in solution. A second step in which the obtained nanoparticles are anchored to the semiconductor surface is necessary in the case of photosensitive applications. Drawbacks like steric hindrance turn more difficult the covering of the semiconductor's surface by nanoparticles. In this paper, we report a variation of this methodology, where the linker is previously anchored to the TiO2 nanoparticles surface. The resulting system is employed as the stabilizer in the gold reduction step. This strategy is carried out in aqueous media in two simple steps. A great covering of the titania surface by gold nanoparticles is achieved in all cases and the gold nanoparticles in the resulting nanoaggregate might be useful for photoelectrovoltaic or photocatalytic applications.

Studies on the Synthesis of Phlegmarine-Type Lycopodium Alkaloids: Enantioselective Synthesis of (-)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline.

The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between ( R)- or ( S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from ( R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline.

X-ray Crystal Structure of a Metalled Double-Helix Generated by Infinite and Consecutive C*-AgI -C* (C*:N1 -Hexylcytosine) Base Pairs through Argentophilic and Hydrogen Bond Interactions.

The synthesis of a metalled double-helix containing exclusively silver-mediated C*-C* base pairs is reported herein (C*=N1 hexylcytosine). Remarkably, it is the first crystal structure containing infinite and consecutive C*-AgI -C* base pairs that form a double helix. The AgI ion occupies the center between two C* residues with N(3)-Ag bond lengths of 2.1 Šand short AgI -AgI distances (3.1 Å) suggesting an interesting argentophilic attraction as a stabilization source of the helical disposition. The solid-state structure is further stabilized by metal-mediated base-pairs, hydrogen bonding and π-stacking interactions. Moreover, the angle N(3)-Ag-N(3) is almost linear in the [Ag(N1 hexylcytosine)2 ]+ motif and the bases are not coplanar, thus generating a double-strand helical aggregate in the solid state. The noncovalent and argentophilic interactions have been rationalized based on DFT calculations.

Charged versus Neutral Hydrogen-Bonded Complexes: Is There a Difference in the Nature of the Hydrogen Bonds?

A theoretical study on some carboxylic acid dimers formed by positively or negatively charged molecules has been carried out by using DFT methods. The resulting dimers possess either a charge of +2 or -2. In addition, the corresponding neutral complexes have also been considered. The electron density distribution described by the atoms in molecules and the natural bond orbital methods, as well as the electric field maps of the systems, have been analyzed and compared without finding significant differences between the neutral and ionic complexes. The interaction energy along the dissociation path of the charged dimers shows both a local minimum and a local maximum, defining a stability region between them. When this energetic profile is recalculated by removing the repulsion between the charged groups, it resembles to those of the neutral molecules. Hence, the characteristics of the charged dimers are similar to those of the neutral ones: the addition of a repulsion term for the charged groups permits to retrieve the energetic profiles dependence with the distance in the charged system. The interacting quantum atom (IQA) method has been used to calculate the interaction energy terms, including the classic Coulombic term between the whole molecules and the corresponding of the carboxylic acid groups. The IQA results show repulsive electrostatic interactions when the whole molecules are considered in the ionic complexes, but attractive ones between the carboxylic groups in both neutral and ionic complexes.

The paradox of hydrogen-bonded anion-anion aggregates in oxoanions: a fundamental electrostatic problem explained in terms of electrophilic···nucleophilic interactions.

A theoretical study of anionic complexes formed by two partly deprotonated oxoacids joined by hydrogen bonds has been carried out at the MP2 computational level. In spite of the ionic repulsion, local energy minima are found both in the gas phase and in aqueous solution. Electrostatic potential and electron density topologies, and the comparison with neutral complexes formed by oxoacids, reveal that the ionization has no significant effect on the properties of the hydrogen bonds. The stability of the complexes in the gas phase is explained by attractive forces localized in a volume situated in the hydrogen bond and defined as the electrostatic attraction region (EAR) and determined by the topological analyses of the electron density and the electrostatic potential, and by the electric field lines. In solution, the strong anionic repulsion is mostly screened by the effect of the surrounding polar solvent, which only leads to a weak destabilizing interaction in the hydrogen bond region and finally favors the overall stability of the complexes. The anion-anion complexes have been compared with the corresponding neutral ones (as salts or protonated forms), showing that EAR remains unchanged along the series.

Exploring ortho-dianthrylbenzenes for molecular solar thermal energy storage.

Molecular solar thermal systems, which absorb light, store it, and release it as heat, have been extensively researched, yet many potential candidates remain unexplored. To expand this range, five specifically designed ortho-dianthrylbenzenes were investigated. Anthracene dimers have been underexplored due to issues like photooxidation and varying photodimerization efficiency. The presented systems address these challenges by aryl-linking two anthracene moieties, achieving photodimerization quantum yields ranging from 11.5% to 16% in mesitylene. The impact of donor or acceptor groups on energy storage time (9-37 years), energy storage density (0.14-0.2 MJ kg-1), and solar energy storage efficiency (0.38-0.66%) was evaluated. The experimental results, supported by density functional theory-based modeling, highlight the potential of anthracene-based photoswitches for molecular solar thermal applications and encourage further exploration of similar systems.

Enantio- and diastereoconvergent cyclocondensation reactions: synthesis of enantiopure cis-decahydroquinolines.

Up to four stereocenters with a well-defined configuration are generated in a single synthetic step by the cyclocondensation of (R)-phenylglycinol or (1S,2R)-1-amino-2-indanol with stereoisomeric mixtures (racemates, meso forms, diastereoisomers) of cyclohexanone-based δ-keto-acid and δ-keto-diacid derivatives in enantio- and diastereoconvergent processes that involve dynamic kinetic resolution and/or desymmetrization of enantiotopic groups. A detailed analysis of the stereochemical outcome of this process is presented. This method provides easy access to enantiopure 8- and 6,8-substituted cis-decahydroquinolines, including alkaloids of the myrioxazine family.

First diastereoselective [3 + 2] cycloaddition reaction of diethyl isocyanomethylphosphonate and maleimides.

Bicyclic α-iminophosphonates were prepared via the first diastereoselective silver catalyzed [3 + 2] cycloaddition reaction of diethyl isocyanomethylphosphonate and diversely N-substituted maleimides. The reduction of the resulting imine by catalytic hydrogenation led to cyclic α-aminophosphonates, which are α-aminoester surrogates. The relative stereochemistry of the adducts was confirmed by X-ray crystallographic analysis of . The diastereoselectivity of the cycloaddition reaction was rationalised by theoretical studies.

Cocrystallization of Antifungal Compounds Mediated by Halogen Bonding.

The application of halogen bonding in pharmaceutical chemistry remains a challenge. In this work, novel halogen-bonded cocrystals based on azole antifungal active pharmaceutical ingredients (APIs) and the ditopic molecule 1,4-diiodotetrafluorobenzene are reported. Their crystal structural features, spectroscopic properties, and thermal stability were studied. The components are bound through I···N from the triazole moieties present in all of the compounds. The molecular electrostatic potential (MEP) surfaces and quantum theory of atoms in molecules (QTAIM) calculations are used to rationalize the presence of hydrogen and halogen bonds in the resulting structures and their energetic analysis. The relative halogen bond ability of the different groups of voriconazole, fluconazole, and itraconazole was analyzed using MEP surfaces, demonstrating this approach to be an interesting tool to predict halogen-bonding preferences.

Electrostatics at the origin of the stability of phosphate-phosphate complexes locked by hydrogen bonds.

Stronger than you'd think: Ab initio calculations reveal that hydrogen bonds can lock phosphates into stable gas-phase complexes, showing that hydrogen bonding can overcome anion-anion repulsion. These complexes present a large energetic barrier of dissociation. The stability of the complexes can be explained in terms of the electrostatic interaction in the hydrogen-bond region.

Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines.

A practical enantioselective protecting group-free four-step route to the key quinolizidinone 6 from phenylglycinol-derived bicyclic lactam 1 is reported. The Grignard addition reaction to 6 takes place stereoselectively to give 1-ethyl-4-substituted quinolizidines 4-epi-207I and 7-9. Following a similar synthetic sequence, 9a-epi-6 is also accessed. However, the addition of Grignard reagents to 9a-epi-6 proceeds in a non-stereoselective manner. In order to gain insight into the different stereochemical outcome in the two series, theoretical calculations on the iminium salts A and B have been performed. The study concludes that the addition of the hydride, which is the step that determines the configuration of the final products, occurs in a stereoelectronic controlled manner. The theoretical study is in agreement with the experimental results.