Photo‐Organocatalysis of Atom‐Transfer Radical Additions to Alkenes

We have found that an organic molecule as simple as p‐anisaldehyde efficiently catalyzes the intermolecular atom‐transfer radical addition (ATRA) of a variety of haloalkanes onto olefins, one of the fundamental carbon–carbon bond‐forming transformations in organic chemistry. The reaction requires exceptionally mild reaction conditions to proceed, as it occurs at ambient temperature and under illumination by a readily available fluorescent light bulb. Initial investigations support a mechanism whereby the aldehydic catalyst photochemically generates the reactive radical species by sensitization of the organic halides by an energy‐transfer pathway.     

Probing the Compound I-like reactivity of a bare high-valent oxo iron porphyrin complex: the oxidation of tertiary amines

The mechanisms of oxidative N-dealkylation of amines by heme enzymes including peroxidases and cytochromes P450 and by functional models for the active Compound I species have long been studied. A debated issue has concerned in particular the character of the primary step initiating the oxidation sequence, either a hydrogen atom transfer (HAT) or an electron transfer (ET) event, facing problems such as the possible contribution of multiple oxidants and complex environmental effects. In the present study, an oxo iron(IV) porphyrin radical cation intermediate 1, [(TPFPP)*+ Fe(IV)=O]+ (TPFPP = meso-tetrakis (pentafluorophenyl)porphinato dianion), functional model of Compound I, has been produced as a bare species. The gas-phase reaction with amines (A) studied by ESI-FT-ICR mass spectrometry has revealed for the first time the elementary steps and the ionic intermediates involved in the oxidative activation. Ionic products are formed involving ET (A*+, the amine radical cation), formal hydride transfer (HT) from the amine ([A(-H)]+, an iminium ion), and oxygen atom transfer (OAT) to the amine (A(O), likely a carbinolamine product), whereas an ionic product involving a net initial HAT event is never observed. The reaction appears to be initiated by an ET event for the majority of the tested amines which included tertiary aliphatic and aromatic amines as well as a cyclic and a secondary amine. For a series of N,N-dimethylanilines the reaction efficiency for the ET activated pathways was found to correlate with the ionization energy of the amine. A stepwise pathway accounts for the C-H bond activation resulting in the formal HT product, namely a primary ET process forming A*+, which is deprotonated at the alpha-C-H bond forming an N-methyl-N-arylaminomethyl radical, A(-H)*, readily oxidized to the iminium ion, [A(-H)]+. The kinetic isotope effect (KIE) for proton transfer (PT) increases as the acidity of the amine radical cation increases and the PT reaction to the base, the ferryl group of (TPFPP)Fe(IV)=O, approaches thermoneutrality. The ET reaction displayed by 1 with gaseous N,N-dimethylaniline finds a counterpart in the ET reactivity of FeO+, reportedly a potent oxidant in the gas phase, and with the barrierless ET process for a model (P)*+ Fe(IV)=O species (where P is the porphine dianion) as found by theoretical calculations. Finally, the remarkable OAT reactivity of 1 with C6F5N(CH3)2 may hint to a mechanism along a route of diverse spin multiplicity.     

Enantioselective determination of the organochlorine pesticide bromocyclen in spiked fish tissue using solid-phase microextraction coupled to gas chromatography with ECD and ICP-MS detection

A method for enantioselective determination of bromocyclen enantiomers in fish tissue has been developed. The enantiomers were resolved by capillary gas chromatography (GC) using a commercial chiral column (CP-Chirasil-Dex CB) and a temperature program from 50 degrees C (held for 1 min), raised to 140 degrees C at 40 degrees C min(-1) and then raised at 0.2 degrees C min(-1) to 155 degrees C. This enantioselective gas chromatographic separation was combined with a clean-up/enrichment procedure based on solid-phase microextraction (SPME). Under SPME optimized conditions, precision, linearity range and detection limits of the developed SPME-enantioselective GC procedure were evaluated and compared using two different detection systems: a classical electron-capture detection (ECD) and an element specific detection using inductively coupled plasma mass spectrometry (ICP-MS). The SPME-GC-ECD method exhibited an excellent sensitivity, with detection limits of 0.2 ng L(-1) for each enantiomer of bromocyclen. Although ICP-MS offered poorer detection limits (7 ng L(-1) as Br, equivalent to 36 ng L(-1) of each enantiomer) than conventional ECD detector, it proved to be clearly superior in terms of selectivity. The relative potential and performance of the two compared methods for real-life analysis has been illustrated by the determination of enantiomers of bromocyclen in spiked tissue extracts of trout.     

Ionic Nickel Embedded in Ceria with High Specific CO2 Methanation Activity

CO₂ hydrogenation to methane is gaining increasing interest as one of the most promising ways to store intermittent renewable energy in the form of chemical fuels. Ni particles supported on CeO₂ represent a highly efficient, stable and inexpensive catalyst for this reaction. Herein, Ni-doped CeO₂ nanoparticles were tested for CO₂ methanation showing an extremely high Ni mass-specific activity and CH₄ selectivity. Operando characterization reveals that this performance is tightly associated with ionic Νi and Ce³⁺ surface sites, while formation of metallic Ni does not seem to considerably promote the reaction. Theoretical calculations confirmed the stability of interstitial ionic Ni sites on ceria surfaces and highlighted the role of Ce-O frustrated Lewis pair (FLP), Ni-O classical Lewis pair (CLP) and Ni-Ce pair sites to the activation of H₂ and CO₂ molecules. To a large extent, the theoretical predictions were validated by in situ spectroscopy under H₂ and CO₂ : H₂ gaseous environments.     

Combining Solid-State NMR with Structural and Biophysical Techniques to Design Challenging Protein-Drug Conjugates

Several protein-drug conjugates are currently being used in cancer therapy. These conjugates rely on cytotoxic organic compounds that are covalently attached to the carrier proteins or that interact with them via non-covalent interactions. Human transthyretin (TTR), a physiological protein, has already been identified as a possible carrier protein for the delivery of cytotoxic drugs. Here we show the structure-guided development of a new stable cytotoxic molecule based on a known strong binder of TTR and a well-established anticancer drug. This example is used to demonstrate the importance of the integration of multiple biophysical and structural techniques, encompassing microscale thermophoresis, X-ray crystallography and NMR. In particular, we show that solid-state NMR has the ability to reveal effects caused by ligand binding which are more easily relatable to structural and dynamical alterations that impact the stability of macromolecular complexes.     

Electrochemical Nickel-Catalyzed Selective Inter- and Intramolecular Arylations of Cysteine-Containing Peptides**

Here we report a simple electrochemical route towards the synthesis of S-arylated peptides by a site selective coupling of peptides with aryl halides under base free conditions. This approach demonstrates the power of electrochemistry to access both highly complex peptide conjugates and cyclic peptides.     

A Porous Gelatin Methacrylate-Based Material for 3D Cell-Laden Constructs

3D constructs are fundamental in tissue engineering and cancer modeling, generating a demand for tailored materials creating a suitable cell culture microenvironment and amenable to be bioprinted. Gelatin methacrylate (GelMA) is a well-known functionalized natural polymer with good printability and binding motifs allowing cell adhesion; however, its tight micropores induce encapsulated cells to retain a non-physiological spherical shape. To overcome this problem, blended GelMa is here blended with Pluronic F-127 (PLU) to modify the hydrogel internal porosity by inducing the formation of larger mesoscale pores. The change in porosity also leads to increased swelling and a slight decrease in Young's modulus. All blends form stable hydrogels both when cast in annular molds and bioprinted in complex structures. Embedded cells maintain high viability, and while Neuroblastoma cancer cells typically aggregate inside the mesoscale pores, Mesenchymal Stem Cells stretch in all three dimensions, forming cell–cell and cell–ECM interactions. The results of this work prove that the combination of tailored porous materials with bioprinting techniques enables to control both the micro and macro architecture of cell-laden constructs, a fundamental aspect for the development of clinically relevant in vitro constructs.     

Heavy metal separation with polymer inclusion membranes

Using functionalized calix[4]arene carrier 1 in a PIM system, Hg(II) is transported with high selectivity from acidic aqueous source phase solutions of Cd(II), Hg(II) and Pb(II) with high NaNO₃ concentration into aqueous receiving solutions containing EDTA. To gain insight into this transport selectivity, complexation studies of the three heavy metal perchlorate species by ligand 1 were conducted in acetonitrile. Although 1:1 complexation of the divalent heavy metal cation by 1 was observed for Cd(II), the stoichiometries were more complicated for Hg(II) and Pb(II). Selective Hg(II) transport across the PIM is attributed to both the strength and stoichiometry of the metal ion-carrier species forming at the source phase-membrane interphase and its stripping from the membrane into the receiving phase by EDTA.