Pyrazolines are among the heterocyclic compounds, a class that exhibit a range of applications in a wide diversity of fields. We report here, a novel approach to the pyrazoline scaffold featuring an unprecedented substitution pattern. This synthesis is carried out from a diazoester and promoted by the addition of a phosphinyl chloride through a putative cyclic phosphinazine. The pyrazoline has been fully spectroscopically characterized and the structure has been further assessed by X-ray diffraction, as the new compound crystallized from toluene in a monoclinic crystal lattice.

A wide range of nano-objects is found in many applications of our everyday life. Recognition of their peculiar properties and ease of functionalization has prompted their engineering into multifunctional platforms that are supposed to afford efficient tools for the development of biomedical applications. However, bridging the gap between bench to bedside cannot be expected without a good knowledge of their behaviour in vivo, which can be obtained through non-invasive imaging techniques, such as positron emission tomography (PET). Their radiolabelling with [18F]-fluorine, a technique already well established and widely used routinely for PET imaging, with [18F]-FDG for example, and in preclinical investigation using [18F]-radiolabelled biological macromolecules, has, therefore, been developed. In this context, this review highlights the various nano-objects studied so far, the reasons behind their radiolabelling, and main in vitro and/or in vivo results obtained thereof. Then, the methods developed to introduce the radioelement are presented. Detailed indications on the chemical steps involved are provided, and the stability of the radiolabelling is discussed. Emphasis is then made on the techniques used to purify and analyse the radiolabelled nano-objects, a point that is rarely discussed despite its technical relevance and importance for accurate imaging. The pros and cons of the different methods developed are finally discussed from which future work can develop.

Background: N-methyl-D-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family. These ligand-gated channels are entwined with numerous fundamental neurological functions within the central nervous system (CNS), and numerous neuropsychiatric disorders may arise from their malfunction. Methods: The purpose of the present review is to provide a detailed description of NMDARs by addressing their molecular structures, activation mechanisms, and physiological roles in the mammalian brain. In the second part, their role in various neuropsychiatric disorders including stroke, epilepsy, anti-NMDA encephalitis, Alzheimer’s and Huntington’s diseases, schizophrenia, depression, neuropathic pain, opioid-induced tolerance, and hyperalgesia will be covered. Results: Finally, through a careful exploration of the main non-competitive NMDARs antagonists (channel-blockers). Conclusion: We discuss the strengths and limitations of the various molecular structures developed for diagnostic or therapeutic purposes.

A new one-pot approach for the synthesis of the Zn2+-sensitive probes 2-azahetaryl-2-(oxoindolin-2-ylidene)acetonitriles 3a-c and 4 is described. The method includes the in situ formation of imidoylchloride and its further condensation with azahetarylacetonitrile 1. The structure of the obtained compounds is studied using 1H nuclear magnetic resonance (NMR), 13C NMR, infrared (IR), high-resolution mass spectrometry (HRMS), and UV-Vis spectroscopy techniques. Two model ligands both exhibiting the highest extinction coefficient and the best solubility in a Tris buffer pH 7.2/dimethyl sulfoxide (DMSO) solution, namely 5-methyl-benzothiazole derivative 3b and benzoxazole derivative 4, are thoroughly studied as colorimetric probes for Zn2+. The probe 3b has the highest sensitivity to Zn2+, showing a limit of ion detection (LOD) calculated by the 3S criterion of 0.43 μM and selectivity upon masking Cu2+ ions with Na2S2O3. The composition of the complexes in the solution was determined by the limited logarithm method. The stability constant (lg K) values of 3b-Zn of 10.27 ± 0.02 and 4-Zn of 12.5 ± 0.2 indicate the formation of complexes of average stability.

Advances in personalized medicine are prompting the development of multimodal agents, that is, molecules that combine properties promoting various diagnostic and therapeutic applications. General approaches exploit chemical conjugation of therapeutic agents with contrast agents or the design of multimodal nanoplatforms. Herein, we report the design of a single molecule that exhibits potential for different diagnostic modes as well as the ability to sensitize oxygen, thus offering potential for photodynamic therapy. Exceptionally, this work involves the synthesis and chiral resolution of an enantiomeric pair of chiral monofluoroborates that contain a stereogenic boron atom. Combining experimental and theoretical chiroptical studies allowed the unambiguous determination of their absolute configuration. Photophysical investigations established the ability of this compound to sensitize oxygen even in the absence of heavy atoms within its structure. The synthesis of a chiral benzothiazole monofluoroborate paves a way to multimodal diagnostic tools (fluorescence and nuclear imaging) while also featuring potential therapeutic applications owing to its ability to activate oxygen to its singlet state for use in photodynamic therapy.

Le dysfonctionnement des récepteurs du N-méthyl-D-Aspartate (NMDARs) est présent dans de nombreuses pathologies psychiatriques et neurodégénératives. Le développement d’un traceur permettant l’objectivation des dysfonctionnements, in vivo, permettrait de mieux appréhender la physiopathologie de ces maladies. Les NMDARs sont des récepteurs ionotropiques et le développement d’un traceur capable de se lier à l’intérieur du canal ionique, au niveau du site PCP, permettrait d’imager spécifiquement les récepteurs activés et donc d’observer une activation anormale de ces récepteurs. L’objectif de notre étude est d’étudier l’affinité et la spécificité de plusieurs candidats traceurs TEP pour le site PCP des NMDARs : la fluoroéthylnormémantine (FNM), ainsi que des molécules appartenant à la famille des méthylguanidines. L’affinité de ces molécules pour le site PCP des NMDARs a été évaluée par des études de liaison ligand-récepteur à l’aide du [3H]-TCP sur des fractions membranaires préparées à partir de cerveaux de souris et de rats. La spécificité de ces molécules a aussi été évaluée en utilisant des ligands tritiés spécifiques d’autres récepteurs cérébraux sur lesquels les candidats sont susceptibles de se lier : la [3H]-glycine (site glycine des NMDARs, situé à l’extérieur du canal ionique), la [3H]-diprénorphine (récepteurs opioïdes), l’[3H]-AMPA (récepteurs AMPA), l’[3H]-acide kaïnique (récepteurs kaïnate), le [3H]SCH23390 (récepteurs dopaminergiques D1) et le [3H]raclopride (récepteurs dopaminergiques D2). Les candidats radiotraceurs sélectionnés pour la phase de radiofluoration seront donc ceux qui présentent la meilleure affinité et sélectivité pour la cible tout en étant peu métabolisé. La recherche de la molécule idéale est un enjeu majeur pour la mise au point de radiotraceurs performants utilisables en clinique et permettant de la quantification intracérébrale de l’activation du récepteur NMDA. Un tel traceur pourrait être un outil précieux pour étudier les maladies neurodégénératives et psychiatriques.

As balanced electron-rich P,C-chelating ligands, phosphine-phosphonium-ylides are considered for their ability to in situ promote palladium-catalysed direct C(sp2)H arylation. Using methyl phosphonium salts of 2,2'-bis(diphenylphosphino)-1,1'-binaphtyl ("methyl-BINAPIUM") as ylide precursors under optimized reaction conditions, arylation of benzoxazole was found to proceed in moderate to high yield to give functional 2-aryl benzoxazoles. A strong anion effect of the non-salt free ylide was evidenced (TfO− > I− > PF6− ≈ salt-free). This first example of phosphonium ylides as ligands in catalytic C–H activation extends the prospect of their general implementation in homogeneous transition metal catalysis.

A modular access to 2,4 disubstituted benzothiazoles has been achieved though the intermediacy of 4-bromo-2-iodobenzothiazole. The difference in reactivity of both halogens was advantageously exploited to achieve sequential Suzuki-Miyaura cross-coupling giving access to a range of polyaromatic derivatives featuring a central benzothiazole core.

The unprecedented reaction of organotrifluoroborates salts of unsymmetrical diaryliodoniums to give aryl fluorides is presented. This preliminary report describes the first synthesis of unsymmetrical diaryliodonium phenyltrifluoroborates along with an exemplary x-ray crystal structure, and explores their reactivity regarding the fluorination of the diaryliodonium cation. Fluorination was found to be chemoselective, providing exclusively hindered aryl fluoride products in moderate to good yields (up to 89%).

The title coordination polymer was obtained by combining an aqueous solution of copper(II) dichloride with the ligand {tert-butylmethyl[4-(6-{[4-(pyridin-2-yl-)1H-1,2,3-triazol-1-yl]methyl}-1,3-benzothiazol-2-yl)phenyl]carbamate in acetonitrile.

The structure of the title compound, C15H14Br2N2O, at 180 K has monoclinic (P21/n) symmetry. It was obtained unexpectedly from the decomposition of the parent 4-bromo-N-tert-butoxycarbonyl-N-methyl-aniline. It exhibits an `endo' conformation with angles between the two aromatic rings slightly lower than the average values found for similar compounds on the Cambridge Structural Database. In the crystal, C—H...O hydrogen bonds and short Br...Br halogen bonds [3.444 (1) Å] are observed.

[This corrects the article DOI: 10.1371/journal.pone.0161209.].

The selective mono-N-methylation of anilines using methanol as an alkylating reagent was achieved with high efficiency under the catalysis of well-defined rhenium complexes bearing tridentate diphosphinoamino ligands and in the presence of a base. The reaction proceeds well for a large scope of anilines (32 examples) with low loadings of both the catalyst (down to 0.5 mol%) and the base (Cs2CO3, down to 5 mol%). The mechanism of the reaction was investigated by DFT (PBEO-D3) calculations. (C) 2018 Elsevier Inc. All rights reserved.

The Balz-Schiemann reaction endures as a method for the preparation of (hetero)aryl fluorides yet is eschewed due to the need for harsh conditions or high temperatures along with the need to isolate potentially explosive diazonium salts. In a departure from these conditions, we show that various organotrifluoroborates (RBF3 - s) may serve as fluoride ion sources for solution-phase fluoro-dediazoniation in organic solvents under mild conditions. This methodology was successfully extended to a one-pot process obviating aryl diazonium salt isolation. Sterically hindered (hetero)anilines are fluorinated under unprecedentedly mild conditions in good-to-excellent yields. Taken together, this work expands the repertoire of RBF3 - s to act as fluorine ion sources in an update to the classic Balz-Schiemann reaction.

We report here an efficient and easily reproducible two-step approach to heterocycle-substituted amino-pyrazoles from heterocyclic acetonitriles and their unprecedented subsequent transformations to fully substituted pyrazoles. Such transformations include regioselective derivatization from polyamino derivatives, formation of tetracyclic compounds in up to 45% overall yield, and deaminative transformations through diazotization, followed by arylation through Suzuki-Miyaura cross-coupling and C-H activation, providing arylated pyrazoles in up to 71% yield over four steps. This strategy allows the swift introduction of significant molecular complexity to a range of scaffolds.

The coordination chemistry of a priori weakly sigma-donating nitroaromatic phosphines is addressed through a series of nitro-substituted (N-phenyl-benzimidazol-1-yl)diphenylphosphines in Rh-I complexes. From a set of seven such phosphines L = L-xyz((')) (x, y, z = 0 or 1 = number of NO2 substituents at the 5, 6 and N-Ph para positions, respectively), including the non-nitrated parent L-000 and its dicationic N-methyl counterpart L-000', three LRhCl(COD) and seven L2RhCl(CO) complexes have been obtained in 72-95% yield. Despite of a cis orientation of the L and CO ligands, the C=O IR stretching frequency nu(CO) varies in the expected sense, from 1967 +/- 1 cm(-1) for L-xy0 to 1978 +/- 1 cm(-1) for L-xy1, and 2005 cm(-1) for L-000. The Rh-103 NMR chemical shift delta(Rh) varies from -288 ppm for L-000 to -316 +/- 1 ppm for L-10z or L-01z, and -436 ppm for L-000'. The nu(CO) and delta(Rh) probes thus reveal moderate but systematic variations, and act as "orthogonal" spectroscopic indicators of the presence of nitro groups on the N-Ph group and the benzimidazole core, respectively. For the dicationic ligand L-000', a tight electrostatic sandwiching of the Rh-Cl bond by the benzimidazole moities is evidenced by X-ray crystallography (RhCl delta- center dot center dot center dot CN2+ approximate to 3.01 angstrom). Along with the LRhCl(CO) complexes, dinuclear side-products (mu-CO)(RhClL)(2) were also obtained in low spectroscopic yield: for the dinitro ligand L = L-011, a unique 1:6.7 clathrate structure, with dichloromethane as solvate, is also revealed by X-ray crystallography.

Artificial metalloenzymes, with their high selectivity and specificity combined with a wide scope of reactivity and substrates, constitute an original approach for catalyst development. Different strategies have been proposed for their elaboration, proceeding from modification of natural enzymes using bioengineering methods to de novo protein design. Another bio-inspired methodology for the development of hybrid catalysts consists in the incorporation of coordination complexes into biomolecules, with the aim to upgrade their catalytic abilities. In these systems, the reaction performed by the naked catalyst is modulated by the well-defined structure of the host biomolecule. This conveys added value to the catalyst, such as enantioselectivity or chemoselectivity. DNA, apo-enzymes, proteins and peptides have been engaged in this approach, affording a wide diversity of reactivities and substrates. The resulting systems can then be improved by combined chemical and bioengineering optimization, allowing access to powerful catalysts. Because this approach can virtually be applied to any biomolecule or coordination complex, the elaboration of bio-based hybrid catalysts seems promising for advance in catalysis. (C) 2015 Elsevier B.V. All rights reserved.