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Pyrrolidines are important heterocyclic organic compounds which show biological effects. Many of them are successfully used in medicine. These compounds can also be applied in industry, for example as dyes or agrochemical substances. Therefore, the study of pyrrolidines chemistry is important for modern science. In this paper the pyrrolidines synthesis in [3+2] cycloaddition between N-methyl azomethine ylide and trans-3,3,3-trichloro-1-nitroprop-1-ene was studied. The reaction was carried out experimentally and based on computational research. The obtained results show the reaction may be of a polar nature, and proceed under mild conditions leading to (3SR,4RS)-1-methyl-3-nitro-4-(trichloromethyl)pyrrolidine as a single reaction product. Probably, a similar protocol can be applied for analogous reactions involving other 2-substituted nitroethene analogues.

The enantiomerically pure ligand BisNap-Phos was obtained in a straightforward sequence of reactions beginning with inexpensive starting materials under the readily affordable conditions in high overall yield. An asymmetric BisNap-Phos-palladium complex-catalyzed Suzuki–Miyaura coupling leading to axially chiral biaryl compounds was described. The reactions were carried out under mild conditions in aqueous and organic media. A series of atropisomeric biaryls were synthesized with excellent yields and high enantioselectivities (up to 86% ee). The methodology provides an efficient and practical strategy for the synthesis of novel multifunctionalized axially chiral biaryl compounds under mild environmentally friendly and easily affordable conditions.

Lauric acid was used to synthesize the low-molecular-weight organogelators (LMOGs), derivatives of two endogenous (L)-alanine, (L)-leucine, and three exogenous (L)-valine, (L)-phenylalanine, and (L)-proline amino acids. The nature of processes responsible for the gel formation both in polar and in apolar solvents of such compounds is still under investigation. Knowing that the organization of surfactant molecules affects the properties of nano scale materials and gels, we decided to elucidate this problem using crystallographic diffraction and energy frameworks analysis. The single crystals of the mentioned compounds were produced successfully from heptane/tBuOMe mixture. The compounds form lamellar self-assemblies in crystals. The energetic landscapes of single crystals of a series of studied amphiphilic gelators have been analyzed to explore the gelling properties. The presented results may be used as model systems to understand which supramolecular interactions observed in the solid state and what energy contributions are desired in the designing of new low-molecular-weight organic gelators.

The adsorption characteristics of amino acid surfactants, synthesized as substances with different volumes and hydrophilic head properties, have been previously described experimentally, without robust theoretical explanation. A theoretical model enabling the characterization of the adsorption behavior and physicochemical properties of this type of biodegradable surfactants, based on molecular structure, would be beneficial for assessment of their usefulness in colloids and interface science in comparison with typical surface-active substances. In this paper, the adsorption behaviour of synthesized amino acid surfactants at the liquid/gas interface was analyzed experimentally (by surface tension measurements using two independent techniques) and theoretically by means of an elaborate model, considering the volume of the surfactant hydrophilic "head" and its ionization degree. It was shown that the adsorption behavior of the synthesized compounds can be successfully described by the proposed model, including the Helfand-Frisch-Lebowitz isotherm based on the equation of state of 2D hard disk-like particles, with molecular properties of surfactant particles obtained using molecular dynamics simulations (MDS). Model parameters allow for direct comparison of physicochemical properties of synthesized amino acid surfactants with other ionic and non-ionic surface-active substances. Furthermore, it was revealed that intermolecular hydrogen bonds allow the formation of surfactant dimers with high surface activity.

(E)-3,3,3-Trichloro-1-nitroprop-1-ene undergoes [3+2] cycloaddition reaction with N-aryl(pyridin-3-yl) nitrones under mild conditions. The reaction is fully regio- and stereoselective and gives expected nitro-substituted nicotine analogs with 3,4-cis-4,5-trans-stereoconfiguration.

The process of searching for new antibacterial agents is more and more challenging due to the increasing drug resistance which has become a major concern in the field of infection management. Our study presents a synthesis and characterization by IR, UV, 1H NMR and 13C NMR spectra of a homogenous series of 1-EWG functionalized 2-aryl-1-nitroethenes which could prove good candidates for the replacement of traditional antibacterial drugs In vitro screening against a panel of the reference strains of bacteria and fungi and their cytotoxicity towards cultured human HepG2 and HaCaT cells was performed. Antimicrobial results indicated that four of the synthesized compounds exhibited a significant antimicrobial activity against all tested reference bacteria and fungi belonging to yeasts with a specific and strong activity towards B. subtilis ATCC 6633. Two of these compounds had no detectable cytotoxicity towards the cultured human cell lines, making them promising candidates for new antibacterial drugs. Keywords: Conjugated nitroalkenes, Antimicrobial activity, Fungicidal activity, Cytotoxicity, B. subtilis ATCC 6633, HepG2 cells, HaCaT cells

A series of novel cationic trimethine oxonol dyes with pyridinium substituents in the β-position of polymethine chain have been synthesized via an easy and efficient methodology by the condensation of 1,3-indandione with various substituted vinamidinium salts in ethanol as a green solvent without formation of any byproducts. The chemical structure of the synthesized dyes was investigated by FTIR, 1H NMR, 13C NMR, and HRMS techniques. The solutions of the new dyes in DMF absorbed visible light wavelengths at about 524–530 nm with narrow band widths and high molar absorption coefficients (around 1–2 × 105 dm3 mol−1 cm−1). They also exhibited fluorescence with a maximum emission intensity at about 700 nm and a relatively large (about 171–176 nm) Stokes shift. An optimized geometrical configuration of the dyes has been determined by using the density functional theory (DFT) at B3LYP/6-311G(d,p) theoretical level.

A highly efficient synthesis of new chiral bisphosphanes derived from the renowned NORPHOS ligand is presented. The synthesis involves ring-opening metathesis of NORPHOS dioxide with an external olefin, followed by saturation of the new double bonds and adjustment of the oxidation level of phosphorus centers oxidation level. The synthesized bisphosphanes retain the configuration and enantiomeric purity of the starting NORPHOS. Their utility as ligands in asymmetric catalysis is exemplified using an open-NORPHOS ligand in some benchmark Rh-catalyzed hydrogenations of enamides where excellent chemical yields and enantiomeric purities of the products have been secured. The proposed protocol demonstrated the possibility of a straightforward synthesis of new chiral catalysts to be utilized in the asymmetric synthesis of pharmaceutically important compounds, such as amino acid derivatives.

A library of new spiro[diindeno[1,2-b:2′,1′-e]pyridine-11,3′-indoline]-2′,10,12-trione derivatives has been prepared in an efficient, one-pot pseudo four-component method mediated by a reusable heterogeneous nano-ordered mesoporous SO3H functionalized-silica (MCM-41-SO3H) catalyst. Excellent yields, short reaction times, as well as convenient non-chromatographic purification of the products and environmental benefits such as green and metal-free conditions constitute the main advantages of the developed synthetic methodology. The obtained fused indole-indenone dyes would be of interest to pharmaceutical and medicinal chemistry. Furthermore, due to their sensitivity to pH changes, they could be used as novel pH indicators.

In the light of the increasing occurrence of antifungal resistance, there is an urgent need to search for new therapeutic strategies to overcome this phenomenon. One of the applied approaches is the synthesis of small-molecule compounds showing antifungal properties. Here we present a continuation of the research on the recently discovered anti-Candida albicans agent 4-AN. Using next generation sequencing and transcriptional analysis, we revealed that the treatment of C. albicans with 4-AN can change the expression profile of a large number of genes. The highest upregulation was observed in the case of genes involved in cell stress, while the highest downregulation was shown for genes coding sugar transporters. Real-time PCR analysis revealed 4-AN mediated reduction of the relative expression of genes engaged in fungal virulence (ALS1, ALS3, BCR1, CPH1, ECE1, EFG1, HWP1, HYR1 and SAP1). The determination of the fractional inhibitory concentration index (FICI) showed that the combination of 4-AN with amphotericin B is synergistic. Finally, flow cytometry analysis revealed that the compound induces mainly necrosis in C. albicans cells.

1-Phenylphosphol-2-ene 1-oxide is effectively resolved by L-menthyl bromoacetate to afford both SP and RP enantiomers of 1-phenylphosphol-2-ene 1-oxide on a multigram scale. The resolved 1-phenylphosphol-2-ene oxide has been found to undergo face-selective and endo-selective cycloadditions with a series of acyclic and cyclic dienes to produce enantiopure P-stereogenic C-P heterocycles of hexahydrophosphindole and hexahydrobenzophosphindole as well as phospha[5 .2.1.02,6]decene and phospha[5.2.2.02,6]undecene structures. Conversions of these cycloadducts to the fully saturated heterocyclic systems as well as to their P (III), P = S, P = Se and P-BH3 derivatives have been demonstrated to occur with retention of configuration and preservation of configurational homogeneity at P. A perplexing case of stereomutation at P during reduction of a tricyclic &beta, hydroxy phosphine oxide by PhSiH3 at 80 &deg, C has been recorded.

A green approach for the one-pot four-component sonochemical synthesis of 5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylic esters from the reaction of 2-cyano-guanidine, sodium azide, various aromatic aldehydes and methyl or ethyl acetoacetate in the presence of a catalytic amount of Fe2O3@SiO2-(CH2)3NHC(O)(CH2)2PPh2 as a new hybrid organic–inorganic core–shell nanomagnetic catalyst is described. This is the first design, preparation, characterization and application of the present nanomaterial and also the first ultrasound irradiated synthesis of the biologically and pharmaceutically important heterocyclic compounds in water as a green solvent. This novel sonocatalysis/nanocatalysis protocol offers several advantages such as high yields, short reaction times, environmentally-friendly reaction media, easily isolation of the products, simple preparation, full characterization and recoverability of the nanocatalyst by an external magnet and reusing several times without significant loss of activity.

Microtubules and actin filaments are cytoskeletal protein assemblies that are engaged in motility, mitosis, and regulate cell signalling with an essential role in the control of protein synthesis and accordingly, cell growth. Inhibition of cytoskeletal organelles, in particular tubulin polymerization, is important in cancer therapy due to their antimitotic role. Considering protein structure variations, we conducted a molecular docking study followed by a series of molecular dynamics (MD) simulations at different binding sites to investigate how a known α-/β-tubulin dimerization inhibitor, Glaziovianin A, and its analogue Gatastatin target human γ-tubulin subunit. The results of our MD simulations reproduced these protein-ligand interactions, demonstrating that Glaziovianin A is selective against β-tubulin's colchicine site and Gatastatin hits γ-tubulin's GTP binding site. Further analyses shed light on the reasons for subunit-focused selectivity for these structurally similar compounds, provided mechanistic insights into some of the tubulin functions such as the conformational transitions and subsequent microtubule disruption. The information combined from energy and structural analysis of MD, with all represented validation steps, and detailed study of specific protein-protein interaction features potentially could facilitate the early identification of γ-tubulin-specific inhibitors.

Simple, efficient, clean, and stereospecific protocols of protection of phosphorus atom with borane and deprotection from the borane complexes of the tertiary phosphines in mild conditions are reported. The proposed protection/deprotection reactions tolerate a range of functional groups and lead to pure products with excellent yield with no need for application of chromatographic or crystallisation purification procedures. For the first time mechanisms of the reactions of phosphine protection and deprotection have been studied based on experimental kinetic data as well as quantumchemical calculations, which allows designing reaction conditions suitable for a given substrate.

Organic ionic gel (OIG) electrolytes, also known as gel electrolytes or ionogels are one example of modern functional materials with the potential to use in wide range of electrochemical applications. The functionality of OIGs arises from the thermally reversible solidification of electrolytes or ionic liquids and their superior ionic conductivity. To understand and to predict the properties of these systems it is important to get the knowledge about the interactions on molecular level between the solid gelator matrix and the electrolyte solution. This paper reports the spectroscopic studies (FT-IR, UV–Vis and Raman) of the gel electrolyte based on low molecular weight gelator methyl-4,6-O-(p-nitrobenzylidene)-α- d -glucopyranoside and solution of quaternary ammonium salt, tetramethylammonium bromide. The solidification process was based on sol-gel technique. Below characteristic temperature, defined as gel to sol phase transition temperature, T gs , the samples were solid-like and showed high conductivity values of the same order as observed for pure liquid electrolytes. The investigations were performed for a OIGs in a wide range of molar concentrations of the electrolyte solution.

This work explores the behavior of chiral compound mixtures enriched in one of the enantiomers whilst a typical chromatography on the achiral stationary phase is employed. The influence of several factors, such as the eluent composition, ratio of the compound to the stationary phase, and the initial enatiomeric purity of the compound used on the distribution of the enantiomers in the collected chromatographic fraction, was studied. The obtained results indicate that the phenomenon of Self Disproportionation of Enantiomer (SDE) occurred in all cases, and some of the collected fractions got higher optical purities than the initial one. Thus, achiral column chromatography could be applied in some cases as the simplest approach for chiral purification. Based on the experimental results and DFT calculations, an alternative concept explaining the SDE phenomenon was proposed. Due to its generality and simplicity, SDE may also be responsible for the formation of the first chiral non-racemic compounds on the early Earth.

International audience; Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.

The “green” and selective methodology for the preparation of precursors of cyclopropene-type inhibitors for the maturation of fruits or vegetables was described. It was found out that 2-nitroprop-1-ene undergoing reactions with diaryldiazomethanes under mild conditions yields 3,3-diphenyl-5-methyl-5-nitro-Δ1-pyrazolines. Under the applied conditions the primary reaction products are spontaneously transformed via nitrogen extrusion to form respective 1,1-diaryl-2-methyl-2-nitrocyclopropanes. All synthetized compounds were fully characterized by spectral methods and structural roentgenography (X-ray). The reaction course was explored in detail at molecular scale using advanced quantumchemical calculations. A Bonding Evolution Theory (BET) study along with the [3 + 2] cycloaddition (32CA) reaction of the 2-nitroprop-1-ene with diphenyldiazomethane as well as nitrogen elimination from 3,3-diphenyl-5-methyl-5-nitro-Δ1-pyrazoline allows an explanation of the molecular mechanism. As a consequence the programming of a wide range of synthesis of similar compounds will be possible.

A variety of tertiary phosphine sulfides have been reduced by Raney-Ni to give the corresponding phosphines with high efficiency and under mild conditions. Alkyl, aryl, acyclic, cyclic, as well as ...

Naphthalene-1,4-dione derivatives were synthesized and tested against selected bacterial strains. All the tested compounds were prepared by direct introduction of corresponding substituents into the naphthoquinone core in oxidative conditions. In this study, eight strains of bacteria (Proteus, Escherichia, Klebsiella, Staphylococcus, Enterobacter, Pseudomonas, Salmonella, Enterococcus) were used for determination of antimicrobial activity of synthesized compounds with the Minimal Inhibitory Concentration (MIC) method. Additionally, selected compounds were tested for haemolytic activity using human erythrocytes. All naphthalene-1,4-dione derivatives exhibited significant antimicrobial activity with MIC values between 7.8 and 500 μg/ml. A majority of the synthesized compounds showed the strongest antibacterial properties towards S. aureus, with a high level of selectivity. None of the tested naphthalene-1,4-dione derivatives exhibited haemolytic activity.

Results of the single crystal X-ray diffraction analysis of tris(acetonitrile)chloropalladium tetrafluoroborate [PdCl(CH3CN)3]BF4 are presented in details. It was found that the title compound crystallises in the monoclinic system, in the space group C2/c. The role of charge-assisted C–H⋅⋅⋅F–B interactions in crystal architecture was investigated. Due to its untypical properties the prepared [PdCl(CH3CN)3]BF4 has proved to be an excellent palladium source in the synthesis of phosphine-palladium complexes.

A straightforward synthesis of a sterically hindered and electron rich bidentate monophosphine biaryl ligand Sym-Phos of C,P-type of complexation was realised in a high yield starting from simple substrates in easily affordable conditions. In combination with a palladium source, the obtained ligand formed a highly active catalyst mediating sterically demanding Suzuki–Miyaura coupling reactions in aqueous media even at 60 °C and with no need to protect the reaction mixture by an inert gas.

The first synthesis of rigid pentacyclic NORPHOS derivatives by a tandem cross-coupling/cross-dehydrogenative-coupling according to the Catellani reaction protocol is reported. Mediated by palladium complexes of C,P-chelating monophosphine ligands, the readily available enantiopure NORPHOS oxide underwent a stereo- and regio-selective cyclocondensation reaction with arylhalides involving the activation of two unreactive C–H bonds.

To explain an extremely low reactivity of (2E)-3-[4-(dimethylamino)phenyl]-2-nitroprop-2-enenitrile (1) in regard to other similar derivatives, the molecular structure of the title compound has been studied by experimental and theoretical methods. The crystal structure analysis provided the evidence, that the title compound exists in a solid state as a stable E-isomer in a zwitterionic form. Based on NMR, IR, UV/VIS spectroscopic and DFT calculations data, this structure has been also proposed for 1 dissolved in organic solvents.

The application of important organophosphorus ligand-based complex catalysts in potentially environmentally benign processes was overviewed. In particular, the focus was put on the phosphoorganic s...

Atroposelective synthesis of axially chiral biaryls mediated by palladium complexes of chiral phosphorus ligands is discussed. Analysis of the literature data allowed us to compare the activity and...

The domino sequence of pseudocyclic reactions involving 4-methoxybenzonitrile N-oxide and trans-2-phenyl-1-cyano-1-nitroethene proceeding in mild (r.t.; atm. pressure) non-catalytic (without participation of palladium or other transition metals (TM)) conditions yielded a bis-heterobiarylic molecular system containing an oxadiazole moiety with an almost 40% yield. The presented methodology represents therefore an evident contrast to the existing methods of preparation of bis-heterobiarylic systems, which require the presence of TMs. This reaction should be considered stereochemically “clean” and contains a stage of cycloaddition to the C N bond. It should be underlined that this is the first case of non-catalyzed [3 + 2] cycloaddition involving the nitrile C N bond. Our comprehensive study shows that the described protocol can be applied as a general methodology for preparation of a wide group of bis-heterobiarylic molecules. The self-adjusted cascade of transformations, which is unique and valuable from the practical point of view, leads to formation of a single isomeric product (from many possible) as a consequence of three pseudocyclic tandem reactions performed in agreement with the fundamental principles of green chemistry and sustainable development with a maximal level of atom economy and good overall yields. A self-adjustment phenomenon observed in the studied smart technology leading to production of a material with special properties was explained by it deep quantum nature confirmed undoubtedly by the modern Molecular Electron Density Theory.