Self-assembly of a copper(II)-based metallosupramolecular hexagon

The self-assembly of a 1:1 mixture of copper(II) ions and a rigid heteroditopic ligand L containing phen and terpy binding units gives rise in the solid state to green crystals of a hexanuclear metallamacrocycle 1. X-ray crystallography reveals that 1 consists of molecular hexagons of the grid-type family in which each metal ion is bound to two different ligands through the phen and terpy units, plus a weakly coordinated PF6 (-) anion in a highly distorted octahedral geometry. ES-MS studies of acetonitrile solutions of L and copper(II) in a 1:1 ratio show mixtures of polynuclear complexes in which trinuclear L3Cu3 species are predominant.     

Stabilization and Binding of [V4O12]4− and Unprecedented [V20O54(NO3)]n− to Lysozyme upon Loss of Ligands and Oxidation of the Potential Drug VIVO(acetylacetonato)2

High-resolution crystal structures of lysozyme in the presence of the potential drug V^IVO(acetylacetonato)₂ under two different experimental conditions have been solved. The crystallographic study reveals the loss of the ligands, the oxidation of V^IV to V^V and the subsequent formation of adducts of the protein with two different polyoxidovanadates: [V₄O₁₂]⁴⁻, which interacts with lysozyme non-covalently, and the unprecedented [V₂₀O₅₄(NO₃)]ⁿ⁻, which is covalenty bound to the side chain of an aspartate residue of symmetry related molecules.     

Seeded Multicolor FEL Pulses: Status and Future Plans

The advent of FEL sources delivering two synchronized pulses of different wavelengths has made available a whole range of novel pump-probe experiments [1 E. Ferrari, Nat. Commun. 7, 10343 (2016).[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]], allowing the exploration of the dynamics of matter driven to extreme non-equilibrium states by an intense ultrashort X-ray pulse and then probing the sample response at variable time delay with a second pulse [2 E. Allaria, Nat. Commun. 4, 2476 (2013).[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]].     

QSAR model for alignment-free prediction of human breast cancer biomarkers based on electrostatic potentials of protein pseudofolding HP-lattice networks

Network theory allows relationships to be established between numerical parameters that describe the molecular structure of genes and proteins and their biological properties. These models can be considered as quantitative structure-activity relationships (QSAR) for biopolymers. The work described here concerns the first QSAR model for 122 proteins that are associated with human breast cancer (HBC), as identified experimentally by Sj?blom et al. (Science 2006, 314, 268) from over 10,000 human proteins. In this study, the 122 proteins related to HBC (HBCp) and a control group of 200 proteins that are not related to HBC (non-HBCp) were forced to fold in an HP lattice network. From these networks a series of electrostatic potential parameters (xi(k)) was calculated to describe each protein numerically. The use of xi(k) as an entry point to linear discriminant analysis led to a QSAR model to discriminate between HBCp and non-HBCp, and this model could help to predict the involvement of a certain gene and/or protein in HBC. In addition, validation procedures were carried out on the model and these included an external prediction series and evaluation of an additional series of 1000 non-HBCp. In all cases good levels of classification were obtained with values above 80%. This study represents the first example of a QSAR model for the computational chemistry inspired search of potential HBC protein biomarkers.     

Detection of PEGylated proteins in polyacrylamide gels by reverse staining with zinc and imidazole salts

The reverse staining, with imidazole-SDS-zinc, of PEG-linked proteins separated by SDS-PAGE was studied. Using model conjugates (interferon-alpha 2b (IFN-alpha2b) reacted with either a branched-chain (40,000) PEG (PEG2,40) or a linear monomethoxy PEG polymer (Mr of 12,000) and chromatographically purified monoPEG2,40-IFN-alpha2b), conventional small-format analytical gels (<1 mm thick) showed typical detection patterns (i.e., transparent, colorless bands clearly discernible against a zinc imidazolate-generated white gel background), in less than 20 min. Nonreacted (free) PEG was almost undetected, as expected. The reverse-stained PEGylated IFN-alpha2b patterns were qualitatively indistinguishable from those of parallel gels stained with iodine (I2). The LOD was estimated in the low nanogram range (e.g., at about 7 ng for mono- or bi-PEG2,40 IFN-alpha2b per lane on gradient (4-17%) gels). Also, this stain allowed the visualization of Coomassie blue-undetected PEG-IFN bands, and could be restained with I2. PEGylated species of lysozyme, a low-molecular-weight peptide, ovalbumin, and chymotrypsin were used to demonstrate the generality of this stain. We also show (i) how to counteract the adverse effect of some parameters (e.g., gel thickness above 1 mm, long gel length, low (e.g., 4-6%) acrylamide concentration) on the reverse staining process and (ii) that the properties of the reverse-stained PEGylated proteins remain unchanged, as judged by analyzing both the ion exchange chromatography-based positional isomer separation profile and enzyme-linked immunosorbent response of PEG-IFN recovered from gels. Consequently, this technique may be useful for the rapid analysis or the small-scale preparation of PEGylated proteins.     

Monitoring benzene formation from benzoate in model systems by proton transfer reaction-mass spectrometry

The presence of benzene in food and in particular in soft drinks has been reported in several studies and should be considered in fundamental investigations about formation of this carcinogen compound as well as in quality control.Proton transfer reaction-mass spectrometry (PTR-MS) has been used here for rapid, direct quantification of benzene and to monitor its formation in model systems related to the use of benzoate, a common preservative, in presence of ascorbic acid: a widespread situation that yields benzene in, e.g., soft drinks and fruit juices.Firstly, we demonstrate here that PTR-MS allows a rapid determination of benzene that is in quantitative agreement with independent solid phase micro-extraction/gas chromatography (SPME/GC) analysis. Secondly, as a case study, the effect of different sugars (sucrose, fructose and glucose) on benzene formation is investigated indicating that they inhibit its formation and that this effect is enhanced for reducing sugars. The sugar-induced inhibition of benzene formation depends on several parameters (type and concentration of sugar, temperature, time) but can be more than 80% in situations that can be expected in the storage of commercial soft drinks. This is consistent with the reported observations of higher benzene concentrations in sugar-free soft drinks.     

A novel mixed valent Cu(II)-Cu(I) 2D framework made of a hydrazone and μ-SCN bridged metallacyclic loops cross-linked by μ(3)-SCN chains

A mixed valent copper complex [Cu(II)Cu(I)(L)(μ-SCN)(μ(3)-SCN)](n) (LH = N'-((pyridin-2-yl)methylene)acetohydrazide) has been synthesized and characterized. It is a unique example of a 2D mixed valent Cu(II)-Cu(I) interlinked molecular assembly with a very unusual bridging property of the hydrazone ligand. An extraordinary in situ partial Cu(II)→ Cu(I) reduction is observed in this system at room temperature.     

Cord blood metabolomic profiling in intrauterine growth restriction

A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis of cord blood collected soon after birth. Samples were collected from 22 IUGR and 21 appropriate for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001). Serum samples were immediately obtained and deproteinized by mixing with methanol at room temperature and centrifugation; supernatants were lyophilized and reconstituted in water for analysis. LC-HRMS analyses were performed on an Orbitrap mass spectrometer linked to a Surveyor Plus LC. Samples were injected into a 1.0 × 150-mm Luna C18 column. Spectra were collected in full-scan mode at a resolution of approximately 30,000. Data were acquired over the m/z range of 50–1,000, with measurements performed in duplicate. To observe metabolic variations between the two sets of samples, LC-HRMS data were analyzed by a principal component analysis model. Many features (e.g., ionic species with specific retention times) differed between the two classes of samples: among these, the essential amino acids phenylalanine, tryptophan, and methionine were identified by comparison with available databases. Logistic regression coupled to a receiver-operating characteristic curve identified a cut-off value for phenylalanine and tryptophan, which gave excellent discrimination between IUGR and AGA fetuses. Non-targeted LC-HRMS analysis of cord blood collected at birth allowed the identification of significant differences in relative abundances of essential amino acids between IUGR and AGA fetuses, emerging as a promising tool for studying metabolic alterations.     

Detection of phosphorylation states by intermolecular sensitization of lanthanide-peptide conjugates

The luminescence of a designed peptide equipped with a coordinatively-unsaturated lanthanide complex is modulated by the phosphorylation state of a serine residue in the sequence. While the phosphorylated state is weakly emissive, even in the presence of an external antenna, removal of the phosphate allows coordination of the sensitizer to the metal, yielding a highly emissive supramolecular complex.     

The effect of the functional,basis set,and solvent in the simulation of the geometry and spectroscopic properties of VIVO2+ complexes. chemical and biological applications

The geometry of 32 V^IVO²⁺ complexes with different donor set, electric charge, geometry, arrangement of the ligands with respect to the V?O bond and type of ligand was calculated by density functional theory methods. 32 V?O, 45 V? O, 16 V? OH, 40 V? N, 24 V? S, and 14 V? Cl bonds were examined. The performance of several functionals (B3LYP, B3P86, B3PW91, HCTH, TPSS, PBE0, and MPW1PW91), keeping constant the Pople triple‐zeta basis sets 6‐311g, was tested. The order of accuracy of the functional in the prediction of the bond distances, expressed in terms of mean of the deviation Δd (Δd = d^calcd ? d^exptl) and absolute deviation |Δd| (|Δd| = |d^calcd ? d^exptl|) from the experimental values and of the corresponding standard deviations (SD(Δd) and SD(|Δd|)), is: B3P86 ～ PBE0 ～ MPW1PW91 > B3PW91 ? TPSS > B3LYP ? HCTH. In the gas phase the prediction of V?O, V? O, V? N bond lengths is rather good, but that of V? OH, V? S and V? Cl distances is by far worse. An improvement in the optimization of V? S and V? Cl lengths is reached by adding polarization and diffuse functions on the sulfur and chlorine atoms. Finally, a general improvement in the prediction of all the calculated bond lengths and angles is obtained by simulating the structures in the solvent where they are isolated within the framework of the polarizable continuum model. The last choice allows also to improve the prediction of structural (the deviation of a penta‐coordinate geometry toward the trigonal bipyramid) and spectroscopic parameters (⁵¹V and ¹⁴N hyperfine coupling constants and ¹⁴N nuclear quadrupolar coupling constant). In most of the cases, the structures optimized in solution closely approach the experimental ones and this can be of great help in the simulations of naturally occurring vanadium compounds and metal site of V‐proteins, like amavadin and the reduced form of vanadium bromoperoxidase (VBrPO). © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011