Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

A robust, click‐chemistry‐inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable for all carbon isotopes (¹¹C, ¹³C, ¹⁴C), is based on the direct functionalization of carbon dioxide: the universal building block for carbon radiolabeling. The strategy is operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity as compared to previously reported systems. With this procedure, a variety of pharmaceuticals and an unprotected peptide were labeled with high radiochemical efficiency.     

Room‐Temperature Functionalization of N2 to Borylamine at a Molybdenum Complex

Intermolecular, stepwise functionalization by BH bonds of a (triphosphine)Mo^IV–nitrido complex generated by N₂ splitting is reported. The imido–hydride and di‐hydride–amido Mo^IV complexes have been isolated and characterized. Addition of PinBH to the [Mo(H)₂(N(BPin)₂)]⁺ complex at room temperature results in the liberation of borylamines from the metal center.     

Reversible CO2 Addition to a Si=O Bond and Synthesis of a Persistent SiO2–CO2 Cycloadduct Stabilized by a Lewis Donor–Acceptor Ligand

The donor‐stabilized sila‐β‐lactone 1 reacts with CO₂ via a remarkable reversible [2+2]‐cycloaddition reaction to form the spiro‐cyclic silicon carbonate derivative 2 . Furthermore, photolysis of 2 under pressure of CO₂ affords the first persistent SiO₂–CO₂ cycloadduct 3 , presenting a Si₂O₄‐like structure, which is stabilized by a Lewis donor–acceptor type ligand. As predicted by theoretical calculations, in marked contrast to the thermodynamically stable SiO₂ dimer, the SiO₂–CO₂ mixed cycloadduct 3 is labile and readily releases CO₂.     

A Survey of Orbitrap All Ion Fragmentation Analysis Assessed by an R MetaboList Package to Study Small-Molecule Metabolites

Leukemia cell and melanoma tumor tissue extracts were studied for small (mostly m/z?<?250) polar metabolites by LC-ESI-HRMSⁿ analysis powered by a hybrid Quadrupole-Orbitrap. MS data were simultaneously acquired in fast polarity switching mode operating in MS¹ and MS/MS (All Ion Fragmentation, AIF) full-scan analyses at high mass resolution. Positive metabolite assignments were achieved by AIF analysis considering at least two characteristic transitions. Targeted metabolite profiling was achieved by the relative quantification of 18 metabolites through spiking of their respective deuterated counterparts. Manual data processing of MS¹ and AIF scans were compared for the accurate determination of natural metabolites and their deuterated analogs by chromatographic alignment and peak area integration. Evaluation of manual and automated (MetaboList R package) AIF data processing yielded comparable results. The versatility of AIF analysis also enabled the untargeted metabolite profiling of leukemia and melanoma samples in which 22 and 53 compounds were, respectively, identified outside those studied by labeling. The main limitation of this method was that low abundance metabolites with scan rates below 8 scans/peak could not be accurately quantified by AIF analysis. The combination of AIF analysis with MetaboList R package represents an opportunity to move towards automated, faster, and more global metabolomics approaches supported by an entirely flexible open source data processing platform freely available from Comprehensive R Archive Network (CRAN, https://CRAN.R-project.org/package=MetaboList).     

Vinylmercury Hydrides: Synthesis and Spectroscopic Characterization

The first vinylmercury hydrides, and among them the parent compound, have been prepared by a chemoselective reduction of the corresponding vinylmercury chlorides with tributylstannane in the presence of a radical inhibitor. These hydrides have been characterized on the basis of their spectral data ((1)H, (13)C, and (199)Hg NMR spectroscopy and mass spectrometry). The photoelectron spectra of the ethenylmercury hydride displays bands at 9.79, 10.13, 11.41, and 13.20 eV. On the basis of photoelectron spectra and ab initio quantum chemical calculations some (d-p)pi interaction between the vinyl pi-system and the mercury d-orbitals could be concluded. Vinylmercury hydrides have been condensed and then revaporized in vacuum at low temperature, but they exhibit a very low stability at room temperature even diluted in toluene (tau(1/2) approximately 1 min); elemental mercury and the corresponding divinylmercury were formed under these conditions.     

The Double Exchange Phenomenon Revisited: The [Re2OCl10]3− Compound

Correlated ab initio calculations have been performed on the [Re₂OCl₁₀]³⁻ anion. The calculated spectrum does not respect the intervals given by the usually accepted double exchange Hamiltonian. Surprisingly enough the ground-state happens to be of intermediate spin multiplicity (i.e. a quartet) at any level of correlation treatment. A model that combines the Anderson and Hasegawa method and the usually used double exchange one rationalizes the spectrum calculated both by a configuration interaction restricted to the open shell molecular orbitals and at a more correlated level of calculation. An alternative analysis of the double exchange phenomenon, based on a molecular orbital language, is presented. The specific effects of the electronic correlation brought by extended active space and by a difference dedicated configuration interaction are also analyzed.     

Very large swelling in hybrid frameworks: a combined computational and powder diffraction study

Using a combination of simulations and powder diffraction, we report here the study of the very large swelling of a three-dimensional nanoporous iron(III) carboxylate (MIL-88) which exhibits almost a reversible doubling (approximately 85%) of its cell volume while fully retaining its open-framework topology. The crystal structure of the open form of MIL-88 has been successfully refined and indicates that atomic displacements larger than 4 angstroms are observed when water or various alcohols are adsorbed in the porous structure, revealing an unusually flexible crystallized framework. X-ray thermodiffractometry shows that only a displacive transition occurs during the swelling phenomenon, ruling out any bond breaking.     

Potent inhibitors of the hepatitis C virus NS3 protease: design and synthesis of macrocyclic substrate-based beta-strand mimics

The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring beta-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.     

Desymmetrised pentaporphyrinic gears mounted on metallo-organic anchors

Mastering intermolecular gearing is crucial for the emergence of complex functional nanoscale machineries. However, achieving correlated motion within trains of molecular gears remains highly challenging, due to the multiple degrees of freedom of each cogwheel. In this context, we designed and synthesised a series of star-shaped organometallic molecular gears incorporating a hydrotris(indazolyl)borate anchor to prevent diffusion on the surface, a central ruthenium atom as a fixed rotation axis, and an azimuthal pentaporphyrinic cyclopentadienyl cogwheel specifically labelled to monitor its motion by non-time-resolved Scanning Tunneling Microscopy (STM). Desymmetrisation of the cogwheels was first achieved sterically, i.e. by introducing one tooth longer than the other four. For optimal mechanical interactions, chemical labelling was also investigated as a preferential way to induce local contrast in STM images, and the electronic properties of one single paddle were modulated by varying the porphyrinic scaffold or the nature of the central metal. To reach such a structural diversity, our modular synthetic approach relied on sequential cross-coupling reactions on a penta(p-halogenophenyl)cyclopentadienyl ruthenium(ii) key building block, bearing a single pre-activated p-iodophenyl group. Chemoselective Sonogashira or more challenging Suzuki–Miyaura reactions allowed the controlled introduction of the tagged porphyrinic tooth, and the subsequent four-fold cross-couplings yielded the prototypes of pentaporphyrinic molecular gears for on-surface studies, incorporating desymmetrised cogwheels over 5 nm in diameter.

Star-shaped cogwheel prototypes incorporating one sterically- or chemically-labelled porphyrinic paddle were designed and synthesised with the aim of achieving intermolecular gearing on surfaces.     

Charge assisted chiral hybrid H-bonded molecular networks

The co-crystallisation of [Fe(CN)5NO]2- and cyclic achiral 1(2+) and chiral 2(2+) or 3(2+) bisamidinium tectons leads in the crystalline phase to the formation of 1-D H-bonded achiral and chiral molecular networks respectively. In all cases, the network is formed by mutual bridging of the anionic and cationic units through a chelate mode of H-bonding.