Converting Strain Release into Aromaticity Loss for Activation of Donor-Acceptor Cyclopropanes: Generation of Quinone Methide Traps for C-Nucleophiles.

Here, we present a new approach for the activation of donor-acceptor cyclopropanes in ring-opening reactions, which does not require the use of a Lewis or Brønsted acid as a catalyst. Donor-acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and isomerization to form the corresponding quinone methides. This innovative strategy was applied to achieve (4 + 1)-annulation of cyclopropanes with sulfur ylides, affording functionalized dihydrobenzofurans. Additionally, the generated ortho- and para-(aza)quinone methides can be trapped by various CH-acids.

Application of mixed phosphorus/sulfur ligands based on terpenoids in Pd-catalyzed asymmetric allylic substitution and Rh-catalyzed hydrogenation.

A small library of easily prepared diamidophosphite-sulfides based on 1,3-thioether alcohols, primarily of terpenoid nature, was developed. Upon complexation with Pd(II) ions, these hemilabile ligands showed the ability to form both P,S-chelates and complexes with two ligands P-monodentately bonded to the metal. The structures of the ligands and their complexes were determined by 2D NMR spectroscopy and X-ray diffraction. The use of these stereoselectors provided up to 95% ee in the classic Pd-catalyzed asymmetric allylic substitution reactions of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 80% ee in the Pd-mediated allylic alkylation of cinnamyl acetate with ß-ketoesters. In addition, ee values of up to 90% with quantitative conversion were achieved in the Rh-catalyzed asymmetric hydrogenation of methyl esters of unsaturated acids. The effects of the structural parameters, reaction conditions and ligand-to-metal ratio on the catalytic results are discussed.

Dual Optoelectronic Organic Field-Effect Device: Combination of Electroluminescence and Photosensitivity.

Merging the functionality of an organic field-effect transistor (OFET) with either a light emission or a photoelectric effect can increase the efficiency of displays or photosensing devices. In this work, we show that an organic semiconductor enables a multifunctional OFET combining electroluminescence (EL) and a photoelectric effect. Specifically, our computational and experimental investigations of a six-ring thiophene-phenylene co-oligomer (TPCO) revealed that this material is promising for OFETs, light-emitting, and photoelectric devices because of the large oscillator strength of the lowest-energy singlet transition, efficient luminescence, pronounced delocalization of the excited state, and balanced charge transport. The fabricated OFETs showed a photoelectric response for wavelengths shorter than 530 nm and simultaneously EL in the transistor channel, with a maximum at ~570 nm. The devices demonstrated an EL external quantum efficiency (EQE) of ~1.4% and a photoelectric responsivity of ~0.7 A W-1, which are among the best values reported for state-of-the-art organic light-emitting transistors and phototransistors, respectively. We anticipate that our results will stimulate the design of efficient materials for multifunctional organic optoelectronic devices and expand the potential applications of organic (opto)electronics.

The Copper Reduction Potential Determines the Reductive Cytotoxicity: Relevance to the Design of Metal-Organic Antitumor Drugs.

Copper-organic compounds have gained momentum as potent antitumor drug candidates largely due to their ability to generate an oxidative burst upon the transition of Cu2+ to Cu1+ triggered by the exogenous-reducing agents. We have reported the differential potencies of a series of Cu(II)-organic complexes that produce reactive oxygen species (ROS) and cell death after incubation with N-acetylcysteine (NAC). To get insight into the structural prerequisites for optimization of the organic ligands, we herein investigated the electrochemical properties and the cytotoxicity of Cu(II) complexes with pyridylmethylenethiohydantoins, pyridylbenzothiazole, pyridylbenzimidazole, thiosemicarbazones and porphyrins. We demonstrate that the ability of the complexes to kill cells in combination with NAC is determined by the potential of the Cu+2 → Cu+1 redox transition rather than by the spatial structure of the organic ligand. For cell sensitization to the copper-organic complex, the electrochemical potential of the metal reduction should be lower than the oxidation potential of the reducing agent. Generally, the structural optimization of copper-organic complexes for combinations with the reducing agents should include uncharged organic ligands that carry hard electronegative inorganic moieties.

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines.

An easy synthesis of novel highly functionalized 5,6-dihydroindolo[2,1-a]isoquinolines was developed via a pseudo four-component domino reaction of 1-aroyl-3,4-dihydroisoquinolines, terminal α,ß-ynones, and malononitrile. The selective formation of this biologically relevant heterocyclic core was achieved using a one-pot approach under microwave irradiation. The formation of the same skeleton through the reaction of 5,6-dihydropyrrolo[2,1-a]isoquinolines with malonic acid dinitrile supports the proposed mechanism, involving the intermediate product of the three-component reaction. Furthermore, the disproval of an alternative reaction pathway, which involved the dimerization of malononitrile followed by three-component transformation, was demonstrated. Introducing the malononitrile dimer as a CH acid resulted in the formation of a different pyrido[3',4':4,5]pyrrolo[2,1-a]isoquinoline core. Additionally, the synthesized 5,6-dihydroindolo[2,1-a]isoquinolines were examined for their photophysical properties, revealing their attractive luminescent characteristics.

TADDOL-based P,S-bidentate phosphoramidite ligands in palladium-catalyzed asymmetric allylic substitution.

A series of easy-to-prepare and modular chiral P,S-bidentate phosphoramidites were synthesized. With respect to Pd(II), these ligands showed the ability to form stable P,S-chelate allylic complexes. The structures of the ligands and their complexes were confirmed by 2D NMR spectroscopy and single-crystal X-ray diffraction. These chiral inducers provided up to 99% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 94% ee in the Pd-mediated allylic alkylation of cinnamyl esters with ß-ketoesters and 2,5-dimethylpyrrole. Furthermore, up to 92% ee with quantitative conversion and chemo- and regioselectivity was achieved in the rare reaction between 2-(diethoxyphosphoryl)-1-phenylallyl acetate and aniline. The effects of the structural parameters, reaction conditions and ligand-to-metal ratio on the catalytic results are discussed. It was shown that the ligands surpass their analogues with different denticity.

Structural Motifs in Aryl Organogermanium Ge-O Derivatives for Material Design.

The aim of this work was to understand the main structural features and ways of formation of Ge-O bonds in organogermanium compounds under the conditions of ArnGeHal4-n (Hal = halide) hydrolysis. The structural types of these compounds were considered, providing 11 blocks (A-K). The molecular structures of the novel compounds [(p-FC6H4)3Ge]2O (1), [(p-F3CC6H4)3Ge]2O (2), and cyclo-[(p-F3CC6H4)2GeO]4 (3) were studied through XRD (X-ray diffraction) analysis. The molecular structure of [(p-F3CC6H4)3GeO]4Ge (4), representing a novel structural type, was also investigated. The data presented in this study will be important in the design of materials with useful properties based on group 14 element derivatives with element-oxygen bonding.

Synthesis and Self-Assembly of ß-Octa[(4-Diethoxyphosphoryl)phenyl]porphyrins.

The ß-substituted porphyrinoids commonly used to form functional assembled systems in nature yet are still scarcely used in material chemistry probably due to the laborious synthesis of these compounds. In this work, ß-octa[(4-diethoxyphosphoryl)phenyl]porphyrin (2HOPPP) and its metal (Zn(II), Cd(II), Cu(II), and Ni(II)) complexes were prepared in good yields. These highly soluble chromophores were characterized in solution using spectroscopic (NMR, UV-vis, fluorescence), electrochemical, and spectroelectrochemical methods. Attachment of the electron-deficient residue (ArP(O)(OEt)2) to the porphyrin macrocycle leads to easier reductions and harder oxidations of the macrocycle for all complexes studied as compared to corresponding meso-tetra[4-(diethoxyphosphoryl)phenyl]porphyrin derivatives reported previously. We demonstrated that the strong electron-deficient character of the MOPPP porphyrins results principally from the increase in the number of electron-withdrawing groups at the periphery of the tetrapyrrolic macrocycle. Electron-deficient porphyrins are highly required in supramolecular and material chemistry in part due to their ability to form supramolecular assemblies via the coordination of axial ligands to the central metal atom. According to single-crystal X-ray data, ZnOPPP forms in the crystalline phase dimers in which each of the two tetrapyrrolic macrocycles is connected through an unusual combination of hydrogen bonding of two phosphoryl groups and the water molecules axially coordinated to the zinc atom of the partner molecule. The involvement of water molecules in porphyrin binding allows for an increase of distance between two porphyrin mean N4 planes, up to 4.478 Å. The offset of phosphoryl groups attached to the macrocycle through a 1,4-phenylene spacer withdraws the whole porphyrin macrocycle of one molecule from spatial overlap with the macrocycle of a partner molecule and increases the Zn-Zn distance up to 10.372 Å. This still unknown type of porphyrin dimers allows one to get deeper insights into the organization of naturally occurring tetrapyrrolic macrocycles. ZnOPPP also forms a labile dimeric complex in 5.3 × 10-7-5.8 × 10-5 M chloroform solutions. In contrast, other complexes prepared in this work exist as monomeric species under these experimental conditions. The self-association constant of ZnOPPP has been determined by electronic absorption spectroscopy.

A Promising 1,3,5-Triazine-Based Anion Exchanger for Perrhenate Binding: Crystal Structures of Its Chloride, Nitrate and Perrhenate Salts.

The reaction of pyridine with cyanuric chloride was studied under microwave activation as well as in the presence of silver nitrate. The product of hydrolysis containing two pyridinium rings and chloride anion was isolated. The structures of these anion exchanger salts with chloride, nitrate and perrhenate anions are discussed.

Biological Activity of Novel Organotin Compounds with a Schiff Base Containing an Antioxidant Fragment.

A series of novel organotin(IV) complexes on the base of 2-(N-3',5'-di-tert-butyl-4'-hydroxyphenyl)-iminomethylphenol (L) of formulae Me2SnBr2(L)2 (1), Bu2SnCl2(L)2(2), Ph2SnCl2(L) (3), Ph2SnCl2(L)2 (4) Ph3SnBr(L)2 (5) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. The crystal structures of initial L and complex 2 were determined by XRD method. It was found that L crystallizes in the orthorhombic syngony. The distorted octahedron geometry around Sn center is observed in the structure of complex 2. Intra- and inter-molecular hydrogen bonds were found in both structures. The antioxidant activity of new complexes as reducing agents, radical scavengers and lipoxygenase inhibitors was estimated spectrophotometrically in CUPRAC and DPPH tests (compounds 1 and 5 were found to be the most active in both methods), and in the process of enzymatic oxidation in vitro of linoleic acid under the action of lipoxygenase LOX 1-B (EC50 > 33.3 µM for complex 2). Furthermore, compounds 1-5 have been investigated for their antiproliferative activity in vitro towards HCT-116, MCF-7 and A-549 and non-malignant WI-38 human cell lines. Complexes 2 and 5 demonstrated the highest activity. The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase.

Copper coordination compounds with (5Z,5Z')-2,2'-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones. Comparison with sulfur analogue.

A series of new organic ligands (5Z,5Z')-2,2'-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones (L) consisting of two 5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-one units linked with polymethylene chains of various lengths (n = 2-10, where n is the number of CH2 units) have been synthesized. The reactions of these ligands with CuCl2·2H2O and CuClO4·6H2O gave Cu2+ or Cu1+ containing mono- and binuclear complexes with Cu2LCl x (x = 2-4) or CuL(ClO4) y (y = 1, 2) composition. It was shown that the agents reducing Cu2+ to Cu1+ in the course of complex formation can be both a ligand and an organic solvent in which the reaction is carried out. This fundamentally distinguishes the selenium-containing ligands L from their previously described sulfur analogs, which by themselves are not capable of reducing Cu2+ during complexation under the same conditions. A higher cytotoxicity and reasonable selectivity to cancer cell lines for synthesized complexes of selenium-containing ligands was shown; unlike sulfur analogs, ligands L themselves demonstrate a high cytotoxicity, comparable in some cases to the toxicity of copper-containing complexes.

Carbene functionalization of porphyrinoids through tosylhydrazones.

Here, we investigated methods for carbene functionalization of porphyrinoids through metal catalyst-free thermal decomposition of their tosylhydrazones. For the first time, tetrapyrrolyl substituted carbenes were obtained via thermolysis of tosylhydrazones of the corresponding tetrapyrrolyl aldehydes and ketones in the presence of a base. The carbenes formed reacted thermally with substrates without a metal catalyst or light irradiation. Carbenes at the ß-pyrrolic position of porphyrinoids reacted with styrene leading to cyclopropane derivatives of tetrapyrroles. Carbenes also reacted with 1,4-dioxane with their insertion into the C-H bond yielding a tetrapyrrole 1,4-dioxane conjugate. Thermolysis of tosylhydrazones of meso-formyl-ß-octaalkylporphyrinoids led exclusively to the corresponding cyclopentane fused porphyrinoids via intramolecular carbene C-H insertion. A plausible reaction mechanism was discussed based on DFT calculations of the intermediates. The tetrapyrrolyl carbenes were found to be considerably more stable than other carbenes. The products of the functionalization of porphyrinoids via hydrazone formation and subsequent carbene reactions exhibited modified optical spectra. The method for carbene functionalization of porphyrinoids through thermal decomposition of their tosylhydrazones created a new synthetic pathway for tailoring the perimeter of tetrapyrrolic macrocycles. Moreover, this method allows the obtainment of dyes with controllable spectral optical properties. In particular, new tetrapyrrole derivatives possessing phytoporphyrin carbon skeletons which have not been accessible were obtained using a convenient straightforward procedure.

cis-Diastereoselective Synthesis of Spirooxindolo-ß-Lactams by Staudinger Cycloaddition with TsCl as Activating Co-reagent.

A convenient and versatile one-pot method for synthesis of 1,3-bis-aryl spirooxindolo-ß-lactams from isatin Schiff bases and substituted phenylacetic acids using ketene-imine cycloaddition reaction with TsCl for a ketene generation has been developed. The reaction procedure does not require absolute solvents and unstable starting reagents. The studied reactions lead to cis-diastereoselective ß-lactam formation for all tested phenylacetic acids except 4-MeOC6H4CH2COOH. An increase of trans-diastereomers yields with increasing temperature and solvent polarity was demonstrated.

Amiridine-piperazine hybrids as cholinesterase inhibitors and potential multitarget agents for Alzheimer's disease treatment.

We synthesized eleven new amiridine-piperazine hybrids 5a-j and 7 as potential multifunctional agents for Alzheimer's disease (AD) treatment by reacting N-chloroacetylamiridine with piperazines. The compounds displayed mixed-type reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Conjugates were moderate inhibitors of equine and human BChE with negligible fluctuation in anti-BChE activity, whereas anti-AChE activity was substantially dependent on N4-substitution of the piperazine ring. Compounds with para-substituted aromatic moieties (5g, 5h, and bis-amiridine 7) had the highest anti-AChE activity in the low micromolar range. Top-ranked compound 5h, N-(2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-yl)-2-[4-(4-nitro-phenyl)-piperazin-1-yl]-acetamide, had an IC50 for AChE = 1.83 ± 0.03 µM (Ki = 1.50 ± 0.12 and αKi = 2.58 ± 0.23 µM). The conjugates possessed low activity against carboxylesterase, indicating a likely absence of unwanted drug-drug interactions in clinical use. In agreement with analysis of inhibition kinetics and molecular modeling studies, the lead compounds were found to bind effectively to the peripheral anionic site of AChE and displace propidium, indicating their potential to block AChE-induced ß-amyloid aggregation. Similar propidium displacement activity was first shown for amiridine. Two compounds, 5c (R = cyclohexyl) and 5e (R = 2-MeO-Ph), exhibited appreciable antioxidant capability with Trolox equivalent antioxidant capacity values of 0.47 ± 0.03 and 0.39 ± 0.02, respectively. Molecular docking and molecular dynamics simulations provided insights into the structure-activity relationships for AChE and BChE inhibition, including the observation that inhibitory potencies and computed pKa values of hybrids were generally lower than those of the parent molecules. Predicted ADMET and physicochemical properties of conjugates indicated good CNS bioavailability and safety parameters comparable to those of amiridine and therefore acceptable for potential lead compounds at the early stages of anti-AD drug development.

Diamidophosphites from ß-hydroxyamides: readily assembled ligands for Pd-catalyzed asymmetric allylic substitution.

Two groups of modular chiral diamidophosphite ligands were easily synthesised from accessible N-Boc-amino alcohols and pseudodipeptides. The reaction of these compounds with [Pd(allyl)Cl]2 in the presence of AgBF4 yielded complexes [Pd(allyl)(L)2]BF4. In addition, metallochelates [Pd(allyl)(L)]BF4 with (S)-methioninol-based P,S-bidentate ligands were prepared. The structures of the novel ligands and complexes were elucidated by means of 2D-NMR and were confirmed by single-crystal X-ray diffraction, as well as by DFT calculations. Asymmetric inducers of this type exhibited high enantioselectivities in the Pd-mediated allylic substitution of (E)-1,3-diphenylallyl ethyl carbonate with CH2(CO2Me)2 (up to 98% ee) and (CH2)4NH (up to 92% ee). Ee values of up to 86% and 73% were obtained in the Pd-catalyzed allylic alkylation of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate and ethyl 2-oxocyclopentane-1-carboxylate, respectively. The effects of the structural modules, such as the nature of the phosphorus-containing ring or exocyclic substituent, on the catalytic activity and enantioselectivity were investigated.

Ullmann-type C-Se Cross-Coupling in the Hydantoin Family: Synthesis, Mechanistic Studies, and Tests of Biological Activity.

An attractive strategy for C-Se bond formation by Ullmann-type copper(I)-promoted cross-coupling is developed. A wide range of aryliodides reacts with various disubstituted 2-selenohydantoins under mild conditions and provides Se-arylated imidazolines in moderate to high yields. Computational mechanistic studies show the oxidative addition/intramolecular reductive elimination likely to be the lowest-energy pathway. Cytotoxic activity of all 43 reaction products has been tested in vitro against MCF7 and A549 cancer cell lines with VA13 and MCF10a control cells.

Structural explanation of the spectral features of the nonsymmetrical complex {2,3,7,8,12,13,17,18-octaethyl-5-[(methylimino)methyl]porphyrinato-κ4N21,N22,N23,N24}palladium(II).

The features of porphyrins defining their functionality are related to their conformational flexibility. The degree of nonplanarity of metalloporphyrins depends directly on the number of substituents, their size and their location. The introduction of substituents in the meso positions of ß-substituted porphyrins increases the steric interaction and leads to distortions of the porphyrin core. Increasing the distortion of the porphyrin core would augment the bathochromic (red) shift of the electronic absorption spectra. A new nonsymmetrical 2,3,7,8,12,13,17,18-octaethyl-5-[(methylimino)methyl]porphyrin complex of palladium(II), [Pd(C38H47N5)], was synthesized and characterized by NMR, mass spectrometry and X-ray analysis. The features of the electronic absorption spectrum of the synthesized complex are explained by the planarity of the porphyrin core and the π-system of the imino group orthogonal to it.

Molecular structure of clonidine: gas-phase electron diffraction, single-crystal X-ray diffraction and quantum chemical studies.

This study presents the first determination of the molecular structure of the antihypertensive drug clonidine in the gas phase using gas electron diffraction (GED). The refinement was supported by quantum chemical calculations (QCs). The tautomeric and conformational distribution was investigated theoretically, providing an explanation for the presence of the single conformer in the gas phase. The molecular conformation of clonidine has been shown to have a nearly perpendicular arrangement of the phenyl and imidazolidine rings as described by the torsion angle C2-N6-C7-C8 = -72(6)°. The following structural parameters were obtained (bond lengths in Angstroms and bond angles in degrees with 3σ in parentheses): r(CHH-CHH) = 1.549(7), r(CHH-NH)av = 1.470(7), r(NH-C)av = 1.388(2), r(C[double bond, length as m-dash]N) = 1.286(7), r(C-N) = 1.388(2), r(C[partial double bond, bottom dashed]C)av = 1.403(2), r(C-Cl)av = 1.737(2); ∠(NH-C-NH) = 108.1(11), ∠(CHH-NH-C)av = 109.7(12), ∠(CHH-CHH-NH)av = 100.9(12), ∠(C-N[double bond, length as m-dash]C) = 122.5(12), ∠(CCl[partial double bond, bottom dashed]C[partial double bond, bottom dashed]CCl) = 114.9(2), and ∠(CH[partial double bond, bottom dashed]CCl[partial double bond, bottom dashed]C)av = 123.1(2). The standard enthalpy of formation of clonidine in the gas phase was calculated using G4 theory with both atomisation and isodesmic reaction approaches, yielding the corresponding value of . The molecular structure of clonidine in the solid phase was determined using X-ray diffraction (XRD). Clonidine crystallizes in the monoclinic space group P21/c as a twinned crystal. The imino-tautomer, as an equimolar mixture of the two conformers with geometries close to the enantiomeric pair, is present in the solid phase. The identical conformers are linked into centrosymmetric dimers by paired N-HN hydrogen bonds. The geometries of gaseous and solid clonidine differ especially in the immediate vicinity of the intermolecular hydrogen bonds formed in the crystal.

Cobalt-Based Single-Ion Magnets on an Apatite Lattice: Toward Patterned Arrays for Magnetic Memories.

Single-ion magnets (SIMs) that can maintain magnetization direction on an individual transition metal atom represent the smallest atomic-scale units for future magnetic data storage devices and molecular electronics. Here we present a robust extended inorganic solid hosting efficient SIM centers, as an alternative to molecular SIM crystals. We show that unique dioxocobaltate(II) ions, confined in the channels of strontium hydroxyapatite, exhibit classical SIM features with a large energy barrier for magnetization reversal (Ueff) of 51-59 cm-1. The samples have been tuned such that a magnetization hysteresis opens below 8 K and Ueff increases by a factor of 4 and can be further enhanced to the highest values among 3d metal complexes of 275 cm-1 when Ba is substituted for Sr. The SIM properties are preserved without any tendency toward spin ordering up to a high Co concentration. At a maximal Co content, a hypothetical regular hexagonal grid of SIMs with a 1 nm interspacing on the (001) crystal facet would allow a maximal magnetic recording density of 105 Gb/cm2.

Synthesis and X-ray Characterization of Alkali Metal 2-Acyl-1,1,3,3-tetracyanopropenides.

A novel route for synthesis of 2-acyl-1,1,3,3-tetracyanopropenides (ATCN) salts in high yields and excellent purities starting from readily available methyl ketones, malononitrile, bromine, and alkali metal acetates is reported. The starting aryl(heteroaryl) methyl ketones were oxidized to the corresponding α-ketoaldehydes by new a DMSO-NaBr-H2SO4 oxidation system in yields up to 90% within a short reaction time of 8-10 min. The subsequent stages of ATCN preparation are realized in aqueous media without use of any toxic solvents, in accordance with principle 5 of "green chemistry". Lithium, sodium, potassium, rubidium, and cesium 2-benzoyl-1,1,3,3-tetracyanopropenides were characterized by X-ray diffraction analysis. These salts show a good potential for synthesis of five- and six-membered heterocycles and may serve as potentially useful ligands in coordination and supramolecular chemistry.