Metallohosts with a heart of carbon

Single-crystal X-ray diffraction studies have confirmed that Ni(3)S(3)-based molecular bowls prepared in one-pot reactions capture either CH(2)Cl(2) or C(60). The nature of the pendant substituents (naphthalen-2-ylmethyl, benzyl, or ethyl) around the rim of the bowl dictates the formation of a 1:1 (bowl host-C(60) guest) or 2:1 (capsule host-C(60) guest) architecture. In CDCl(3), the trimeric complexes were found to be in equilibrium with dimeric analogues. For the naphthalen-2-ylmethyl-substituted host, NMR spectroscopic titration data confirmed a 1:1 host-C(60) guest complex in 1,2-Cl(2)C(6)D(4) solution.     

Size and sequence and the volume change of protein folding

The application of hydrostatic pressure generally leads to protein unfolding, implying, in accordance with Le Chatelier's principle, that the unfolded state has a smaller molar volume than the folded state. However, the origin of the volume change upon unfolding, ΔV(u), has yet to be determined. We have examined systematically the effects of protein size and sequence on the value of ΔV(u) using as a model system a series of deletion variants of the ankyrin repeat domain of the Notch receptor. The results provide strong evidence in support of the notion that the major contributing factor to pressure effects on proteins is their imperfect internal packing in the folded state. These packing defects appear to be specifically localized in the 3D structure, in contrast to the uniformly distributed effects of temperature and denaturants that depend upon hydration of exposed surface area upon unfolding. Given its local nature, the extent to which pressure globally affects protein structure can inform on the degree of cooperativity and long-range coupling intrinsic to the folded state. We also show that the energetics of the protein's conformations can significantly modulate their volumetric properties, providing further insight into protein stability.     

Photocatalytic α‐Tertiary Amine Synthesis via C−H Alkylation of Unmasked Primary Amines

A practical, catalytic entry to α,α,α‐trisubstituted (α‐tertiary) primary amines by C?H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom‐economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α‐tertiary amines, or their corresponding γ‐lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α‐tertiary primary amines.     

Polyesters by a Radical Pathway: Rationalization of the Cyclic Ketene Acetal Efficiency

Radical ring‐opening polymerization (rROP) of cyclic ketene acetals (CKAs) combines the advantages of both ring‐opening polymerization and radical polymerization thereby allowing the robust production of polyesters coupled with the mild polymerization conditions of a radical process. rROP was recently rejuvenated by the possibility to copolymerize CKAs with classic vinyl monomers leading to the insertion of cleavable functionality into a vinyl‐based copolymer backbone and thus imparting (bio)degradability. Such materials are suitable for a large scope of applications, particularly within the biomedical field. The competition between the ring‐opening and ring‐retaining propagation routes is a major complication in the development of efficient CKA monomers, ultimately leading to the use of only four monomers that are known to completely ring‐open under all experimental conditions. In this article we investigate the radical ring‐opening polymerization of model CKA monomers and demonstrate by the combination of DFT calculations and kinetic modeling using PREDICI software that we are now able to predict in silico the ring‐opening ability of CKA monomers.     

A First-Principles Study of C3N Nanostructures: Control and Engineering of the Electronic and Magnetic Properties of Nanosheets,Tubes and Ribbons

Using first-principles calculations we systematically investigate the atomic, electronic and magnetic properties of novel two-dimensional materials (2DM) with a stoichiometry C₃N which has recently been synthesized. We investigate how the number of layers affect the electronic properties by considering monolayer, bilayer and trilayer structures, with different stacking of the layers. We find that a transition from semiconducting to metallic character occurs which could offer potential applications in future nanoelectronic devices. We also study the affect of width of C₃N nanoribbons, as well as the radius and length of C₃N nanotubes, on the atomic, electronic and magnetic properties. Our results show that these properties can be modified depending on these dimensions, and depend markedly on the nature of the edge states. Functionalization of the nanostructures by the adsorption of H adatoms is found induce metallic, half-metallic, semiconducting and ferromagnetic behavior, which offers an approach to tailor the properties, as can the application of strain. Our calculations give insight into this new family of C₃N nanostructures, which reveal unusual electronic and magnetic properties, and may have great potential in applications such as sensors, electronics and optoelectronic at the nanoscale.     

Design of Advanced Functional Materials Using Nanoporous Single‐Site Photocatalysts

Nanoporous silica solids can offer opportunities for hosting photocatalytic components such as various tetra‐coordinated transition metal ions to form systems referred to as “single‐site photocatalysts”. Under UV/visible‐light irradiation, they form charge transfer excited states, which exhibit a localized charge separation and thus behave differently from those of bulk semiconductor photocatalysts exemplified by TiO₂. This account presents an overview of the design of advanced functional materials based on the unique photo‐excited mechanisms of single‐site photocatalysts. Firstly, the incorporation of single‐site photocatalysts within transparent porous silica films will be introduced, which exhibit not only unique photocatalytic properties, but also high surface hydrophilicity with self‐cleaning and antifogging applications. Secondary, photo‐assisted deposition (PAD) of metal precursors on single‐site photocatalysts opens up a new route to prepare nanoparticles. Thirdly, visible light sensitive photocatalysts with single and/or binary oxides moieties can be prepared so as to use solar light, the ideal energy source.     

Porphyrin Containing Polymersomes with Enhanced ROS Generation Efficiency: In Vitro Evaluation

Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano‐assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20‐tetrakis(1‐(6‐ethoxy‐6‐oxohexyl)‐4‐pyridin‐1‐io)‐21H,23H‐porphyrin tetrabromide porphyrin is inserted into polymersomes in order to demonstrate that the encapsulation enhances its ability to generate highly reactive singlet oxygen (¹O₂) upon irradiation in vitro. The photoactivation of the free and polymersome‐encapsulated porphyrin is evaluated by electron spin resonance and cell viability assays on three different mammalian cell lines. The results indicate that by encapsulating the porphyrin, a controlled ROS delivery within the cells is achieved, at the same time avoiding side effects such as dark toxicity, non‐specific porphyrin release and over time decreased activity in vitro. This work focuses on showing a not‐toxic model system for modern therapeutic nanomedicine, which works under mild irradiation and dosage conditions.     

Preparing to read the ubiquitin code: a middle‐out strategy for characterization of all lysine‐linked diubiquitins

Multiple studies demonstrate that ubiquitination of proteins codes for regulation of cell differentiation, apoptosis, endocytosis and many other cellular functions. There is great interest in and considerable effort being given to defining the relationships between the structures of polyubiquitin modifications and the fates of the modified proteins. Does each ubiquitin modification achieve a specific effect, much like phosphorylation, or is ubiquitin like glycosylation, where there is heterogeneity and redundancy in the signal? The sensitive analytical tools needed to address such questions readily are not yet mature. To lay the foundation for mass spectrometry (MS)‐based studies of the ubiquitin code, we have assembled seven isomeric diubiquitins with all‐native sequences and isopeptide linkages. Using these compounds as standards enables the development and testing of a new MS‐based strategy tailored specifically to characterize the number and sites of isopeptide linkages in polyubiquitin chains. Here, we report the use of Asp‐selective acid cleavage, separation by reverse phase high‐performance liquid chromatography and characterization by tandem MS to distinguish and characterize all seven isomeric lysine‐linked ubiquitin dimers. Copyright © 2014 John Wiley & Sons, Ltd.     

A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced‐Fit Pocket Stabilized by a Cation–π Interaction

The benzoxazinone and dihydroquinoxalinone fragments were employed as novel acetyl lysine mimics in the development of CREBBP bromodomain ligands. While the benzoxazinone series showed low affinity for the CREBBP bromodomain, expansion of the dihydroquinoxalinone series resulted in the first potent inhibitors of a bromodomain outside the BET family. Structural and computational studies reveal that an internal hydrogen bond stabilizes the protein‐bound conformation of the dihydroquinoxalinone series. The side chain of this series binds in an induced‐fit pocket forming a cation–π interaction with R1173 of CREBBP. The most potent compound inhibits binding of CREBBP to chromatin in U2OS cells.     

Phosphorus-containing cyclodextrin polymers: metal cations and hydroxyapatite affinities

The aim of this study was to highlight the properties of novel phosphorus-containing β-cyclodextrin polymers (CDP) and mainly their dual complexing abilities toward hydrophobic guests and (bio)minerals. Affinity of CDP toward divalent metal cations, calcium, magnesium and zinc, has been investigated by isothermal titration microcalorimetry (ITC). The complexation constants K were around 1.1–6.2 × 10⁴ L mol^?1 and were in the order Ca²⁺ < Mg²⁺ < Zn²⁺. The K regular increase with the CDP molecular weights could be attributed to a cooperative binding of the cations by the monophosphate groups carried by the CDPs. Regarding their CD and phosphorus functionalities, the dual complexing abilities toward amphiphilic guests and divalent cations can occur independently as evidenced from ITC experiments performed in presence of both species. Finally, strong interactions between CDPs and hydroxyapatite have been highlighted by X-ray photoelectron spectrometry with adsorbed amount in the range of 2 mg/m². CDPs are thus promising materials endowed with dual functionalities which could serve in biomaterials to simultaneously entrap bioactive molecules and capture (bio)minerals.