Bidimensional Polyiodide Netting Stabilized by a Cu(II) Macrocyclic Complex

Iodine-dense polyiodide phases are interesting materials for a number of potential uses, including batteries and solid-state conductors. The incorporation of transition metal cations is considered a promising way to enhance the stability, tune the properties, and influence the architecture of polyiodides. However, several interesting metals, including Cu(II), may suffer redox processes, which generally make them not compatible with the I2/I− redox couple. Herein L, a simple derivative of cyclen, is proposed as a Cu(II) ligand capable of protecting the +2 oxidation state of the metal even in the presence of polyiodides. With a step by step approach, we report the crystal structure of free L; then we present spectrophotometric verification of Cu(II) complex stability, stoichiometry, and formation kinetic in DMF solution, together with Cu(II) binding mode elucidation via XRD analysis of [Cu(L)Cl]ClO4∙CH3CN crystals; afterwards, the stability of the CuL complex in the presence of I− is demonstrated in DMF solution, where the formation of a Cu:L:I− ternary complex, rather than reduction to Cu(I), is observed; lastly, polyiodide crystals are prepared, affording the [Cu(L)I]2I3I5 crystal structure. This layered structure is highly peculiar due to its chiral arrangement, opening further perspective for the crystal engineering of polyiodide phases.

Degradation of Components of the Lpt Transenvelope Machinery Reveals LPS-Dependent Lpt Complex Stability in Escherichia coli

Lipopolysaccharide (LPS) is a peculiar component of the outer membrane (OM) of many Gram-negative bacteria that renders these bacteria highly impermeable to many toxic molecules, including antibiotics. LPS is assembled at the OM by a dedicated intermembrane transport system, the Lpt (LPS transport) machinery, composed of seven essential proteins located in the inner membrane (IM) (LptB2CFG), periplasm (LptA), and OM (LptDE). Defects in LPS transport compromise LPS insertion and assembly at the OM and result in an overall modification of the cell envelope and its permeability barrier properties. LptA is a key component of the Lpt machine. It connects the IM and OM sub-complexes by interacting with the IM protein LptC and the OM protein LptD, thus enabling the LPS transport across the periplasm. Defects in Lpt system assembly result in LptA degradation whose stability can be considered a marker of an improperly assembled Lpt system. Indeed, LptA recruitment by its IM and OM docking sites requires correct maturation of the LptB2CFG and LptDE sub-complexes, respectively. These quality control checkpoints are crucial to avoid LPS mistargeting. To further dissect the requirements for the complete Lpt transenvelope bridge assembly, we explored the importance of LPS presence by blocking its synthesis using an inhibitor compound. Here, we found that the interruption of LPS synthesis results in the degradation of both LptA and LptD, suggesting that, in the absence of the LPS substrate, the stability of the Lpt complex is compromised. Under these conditions, DegP, a major chaperone–protease in Escherichia coli, is responsible for LptD but not LptA degradation. Importantly, LptD and LptA stability is not affected by stressors disturbing the integrity of LPS or peptidoglycan layers, further supporting the notion that the LPS substrate is fundamental to keeping the Lpt transenvelope complex assembled and that LptA and LptD play a major role in the stability of the Lpt system.

Phosphorylation of interfacial phosphosite leads to increased binding of Rap-Raf complex

The effect of phosphorylation of a serine residue in the Rap protein, residing at the complex interface of Rap-Raf complex is studied using atomistic molecular dynamics simulations. As the phosphosite of interest (SER39) is buried at the interface of the Rap-Raf complex, phosphorylation of only Rap protein was simulated and then complexed with the RBD of Raf for further analysis of complex stability. Our simulations reveal that the phosophorylation increases the binding of complex through strong electrostatic interactions and changes the charge distribution of the interface significantly. This is manifested as an increase in stable salt-bridge interactions between the Rap and Raf of the complex. Network analysis clearly shows that the phosphorylation of SER39 reorganizes the community network to include the entire region of Raf chain, including, Raf L4 loop potentially affecting downstream signalling.

Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants

Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.

Study on Manufacturing Environmentally Friendly Alkyd Paint

The article presents results of studying and manufacturing environmentally friendly alkyd paint. By producing a polysaccharide intermediate emulsion (LPR), about 20% of water to total paint volume was added. Mechanical properties (impact resistance, flexural strength, adhesion) of paint films were studied. In addition, the paper presents results of thermal stability, 10-cycle UV-thermo-humidity complex stability of paint film. Ability of films to withstand 03-cycle heat shocking of films at temperatures of + 50 oC and -50 oC was investigated. The properties of studying paint were compared with those of an alkyd paint of Hanoi Synthetic Paint Company. Results show that the environmentally friendly alkyd paint has less volatile organic compounds (VOC), uses a smaller amount of toxic solvents, while its properties are comparable to common alkyd paint.

Complex Activity and Sensor Potential toward Metal Ions in Environmental Water Samples of N-Phthalimide Azo-Azomethine Dyes

Herein, the spectral and electrochemical characterizations of three different substituted N-phthalimide azo-azomethine (NAA) dyes (L) containing an o-hydroxy group and their NAA-M(II) chelates [M(II): Cu, Ni, Co, Pb] were reported by using UV–Vis and fluorescence spectroscopy and potentiometric and voltamperometric techniques. The pK value of the dyes as well as the stoichiometry and stability of the NAA-metal chelates were studied, and the stoichiometry was found to be mostly 1:2 (ML2) with high complex stability constant values. The sensor activity of N-phthalimide azo-azomethine derivatives toward pH and metal ions has been also investigated and tested for indicator application in acid–base analysis and detection of Cu(II) ions in real samples of surface river water using voltamperometric detection. The results showed that one of the ligands possesses the highest electrochemical response upon binding to copper ions and could be successfully used in the analysis of copper in water at a concentration range of the analyte from 3.7 × 10−7 to 5.0 × 10−6 mol L−1, with analytical characteristics of the method being Sr = 1.5%, LOD = 3.58 µg L−1 and LOQ =11.9 µg L−1

Metal–ligand interactions in complexes of cyclen-based ligands with Bi and Ac

The structural and bonding properties of Bi and Ac complexes with cyclen-based chelating ligands have been studied using relativistic DFT calculations in conjunction with TZ2P all-electron basis sets. Besides the parent cyclen ligand, the study has covered its extensions with pyridine-type (Lpy), carboxylate (DOTA, DOTPA), picolinate (MeDO2PA) and phosphonate (DOTMP) pendant arms. The effect of the cyclen ring size has been probed by increasing it from [12]aneN4 to [16]aneN4. Additional extensions in the DOTA complexes included the H2O ligand at the 9th coordination site as well as the p-SCN-Bn substituent (a popular linker to the targeting vector). The study focuses on the complex stability, the nature of bonding and the differences between Ac and Bi in the complexes. The metal–ligand interactions have been analysed by the Extended Transition State method combined with Natural Orbitals of Chemical Valence theory and Quantum Theory of Atoms in Molecules models.

A rare MSH2 variant as a candidate marker for Lynch Syndrome II screening in Tunisia: A case of Diffuse Gastric Carcinoma

BACKGROUND Inherited syndromic forms of digestive cancers with age occurrence before 50 seem to be relatively in higher proportions in Tunisia suggesting genetic susceptibility. Several syndromic forms are known to predispose to early onset gastric tumors such as Hereditary Diffuse Gastric Cancer (HDGC) and Lynch Syndrome (LS). LS II is an extracolonic cancer syndrome characterized by a tumor spectrum including gastric cancer (GC). In the current work, our main aim was to identify the mutational spectrum underlying the genetic predisposition to diffuse gastric tumors occurring in a Tunisian family suspected with both HDGC and LS II syndromes. PATIENTS AND METHODS The index case was a woman diagnosed with Diffuse Gastric Carcinoma (DGC) fulfilling the international guidelines for both HDGC and LSII syndromes. Genomic DNA was used for the search of CDH1 and CTNNA1 germ mutations. We performed, also a DNA repair custom panel targeting candidate genes recovering the four DNA repair systems. Structural bioinformatics analysis was conducted to predict the effect of the revealed mutations. RESULTS No deleterious variants have been identified neither in CDH1 nor in CTNNA1 coding and their flanking regions. DNA repair genes panel screening identified two variants: a rare MSH2 c.728G > A classified as a variant with uncertain significance and a novel FANCD2 variant c.1879G > T. The structural prediction model of MSH2 mutation and electrostatic potential calculation showed for the first time that MSH2 c.728G > A is likely pathogenic and is involved in the MSH2-MLH1 complex stability. This mutation appears to affect the MSH2-MLH1 complex as well as DNA-complex stability. The c.1879G > T FANCD2 variant was predicted to destabilize the protein structure. CONCLUSIONS Our results showed that MSH2 p.R243Q variant is likely pathogenic and is involved in the MSH2-MLH1 complex stability with a putative impact on the binding with MLH1 by disrupting the electrostatic potential suggesting the revision of its status from VUS to likely pathogenic. This variant seems to be a shared variant in Mediterranean region. These findings emphasize the importance of testing DNA repair genes for patients diagnosed with DGC with suspicion of LSII as well as colorectal cancer allowing better clinical surveillance for more personalized medicine.