Labdane Diterpenoids from Salvia tingitana Etl. Synergize with Clindamycin against Methicillin-Resistant Staphylococcus aureus

Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (1) and manool (2) extracted from Salvia tingitana were considered as potential QSI against methicillin-resistant Staphylococcus aureus. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC–MS analysis in the organs and in the calli of S. tingitana showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in Salvia species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in Salvia. Docking simulations suggested that 1 and 2 bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes.     

Different approaches to the study of the gravitational radiation emitted by astrophysical sources

Stars and black holes are sources of gravitational radiation in many phases of their life, and the signals they emit exhibit features that are characteristic of the generating process. Emitted since the beginning of star formation, these signals also contribute to create a stochastic background of gravitational waves. We shall show how the spectral properties of this background can be estimated in terms of the energy spectrum of each single event and of the star formation rate history, which is now deducible from astronomical observations. We shall further discuss the process of scattering of masses by stars and black holes, showing that, unlike black holes, stars emit signals that carry a clear signature of the nature of the source.     

A sinapic acid–calix[4]arene hybrid selectively binds Pb over Hg and Cd

The binding affinity for Pb²⁺, Cd²⁺ and Hg²⁺ of the sinapic acid–calix[4]arene hybrid 2, having four sinapyl pendants at the upper rim, has been investigated via an UV–Vis study. Compound 2 has better complexing ability than the monomeric p-phenetidine derivative 1. This highlights that the clustering of sinapyl units in a basket-like structure, dictated by the calixarene scaffold, greatly enhances the complexing properties. Ligand 2 forms complexes even with Hg²⁺, which is not complexed by 1 at all; the complexes formed by 2 with Pb²⁺ and Cd²⁺ are much stronger than the analogous complexes formed by 1. The UV–Vis investigation shows that the hybrid 2 markedly favors Pb²⁺ over Cd²⁺ and Hg²⁺. Information on the structural properties of the complex species was obtained by ¹H NMR spectroscopy. NMR data show that all three metal ions are placed into the cavity consisting of the calixarene scaffold and the sinapyl pendants, though their binding affects the coordinating regions to a different extent.     

Inclusion complexes of γ-cyclodextrin and carboxyl-modified γ-cyclodextrin with C60: synthesis, characterization and controlled release application via microgels

Carboxyl modified γ-cyclodextrin (CDSA) with a substitution degree of about 9.5 was prepared by the esterification of γ-cyclodextrin (CD) with succinic anhydride in pyridine at 90 °C. The chemical composition and the structure of CDSA were characterized by FT-IR, MALDI-TOF, X-ray diffraction pattern, potentiometric titration and TGA. Modified and native γ-cyclodextrin associate with fullerene (C₆₀) in DMF-toluene mixture resulting 1:1 CDSA:C₆₀ and CD:C₆₀ inclusion complexes. Aqueous solutions of native cyclodextrin, carboxyl-modified cyclodextrin and their inclusion complexes with C₆₀ were used as microgel solvent (or swelling agent) for controlled release application. The release of solutions was induced by shear stress and demonstrated using rheo-optical set-up.     

A novel second-order standard addition analytical method based on data processing with multidimensional partial least-squares and residual bilinearization

In the presence of analyte-background interactions and a significant background signal, both second-order multivariate calibration and standard addition are required for successful analyte quantitation achieving the second-order advantage. This report discusses a modified second-order standard addition method, in which the test data matrix is subtracted from the standard addition matrices, and quantitation proceeds via the classical external calibration procedure. It is shown that this novel data processing method allows one to apply not only parallel factor analysis (PARAFAC) and multivariate curve resolution-alternating least-squares (MCR-ALS), but also the recently introduced and more flexible partial least-squares (PLS) models coupled to residual bilinearization (RBL). In particular, the multidimensional variant N-PLS/RBL is shown to produce the best analytical results. The comparison is carried out with the aid of a set of simulated data, as well as two experimental data sets: one aimed at the determination of salicylate in human serum in the presence of naproxen as an additional interferent, and the second one devoted to the analysis of danofloxacin in human serum in the presence of salicylate.     

Theoretical conformational study of six-membered cyclic allyl epoxides

Accurate “ab initio” calculations (MP2 method) were performed to outline the conformational profile of a number of six-membered cyclic allyl epoxides differing either in the nature of the cycle fragment (Y) bound to the unsaturation, or in the substitution at the endocyclic carbon bound to the epoxy ring and bridging the epoxy ring with the Y fragment. In particular, we calculated structures 4 (Y=CH₂), 5 (Y=O), 6 (Y=NH), 7 (Y=S), 8 (Y=CF₂), 9 (Y=NH₂ ⁺), 10 (Y=CO), 11 (Y=BH) and 12 (Y=NCOOH), where the fragment of the endocyclic carbon bridging “Y” and the epoxy fragment is either non-substituted (4a – 12a) or bears a methyl side chain trans (4b–12b) or cis (4c–12c) to the epoxidic oxygen. Saturated analogs (Y=O and Y=CH₂) were also computed to test the method and to evaluate the conformational profile in the absence of the unsaturation. Minimum energy conformations were found which differ in the relative position of the Y group and the epoxy oxygen, with respect to a plane containing the epoxy ring carbons and the adjacent saturated endocyclic carbon: they may be on the same side (conformer A) or on opposite sides (conformer B). Conformers A are generally more stable. The conjugation effect of Y with the double bond lowers the barrier between the two conformers to the extent that in a few cases only conformer A is associated with a minimum of energy. On the basis of the elongation of the allylic oxirane C–O bond, we postulated the order of reactivity of epoxides 4–12 in the oxirane ring-opening process, and a mechanism based on the more reactive conformer A. A comparison was also made between MP2 and DFT calculation methods.     

Risk Analysis in Transport and Storage of Monomers: An Accident Investigation

Summary: In this work the analysis of an accident in transport of dangerous goods is proposed. The objective of this study is to contribute to the determination of the causes that brought about the self-polymerization of commercial divinylbenzene (DVB 63%) contained in an iso-container, in order to prevent this accident to happen in the future. Time and conditions during transport and storage of monomers (in particular the storage temperature) are very important factors, that affect the self-polymerization aptitude of these substances. To stabilize this monomer, usually 4-tert-Butylcatechol (TBC) is added at a level of 900–1200 ppm by weight to act as an inhibitor to prevent the self-initiated autopolymerization of the material. In particular one hypothesis has been investigated: probably the quantity of oxygen in the tanker was insufficient to activate properly the inhibition mechanism of TBC. From this consideration the self-polymerization of DVB and the inhibition mechanism of TBC have been studied as a function of temperature and monomer exposure to air. Different calorimetric techniques have been applied, in particular Differential Scanning Calorimetry and Adiabatic Calorimetry, to investigate the causes of the accident.     

Complete wetting of curved microscopic channels

We have measured the adsorption of argon films on arrays of microscopic nonlinear cusps and of semicircular channels. In the former case, we observe a distinct crossover from a planarlike to a geometry dependent growth behavior near liquid-vapor bulk coexistence, characterized by a growth exponent chi equal to -0.96+/-0.04 in very good agreement with the predictions of a recent scaling theory [C. Rascon and A. O. Parry, J. Chem. Phys. 112, 5175 (2000)]. The crossover location is also consistent with theory. Instead, on the concave channels we find a much steeper growth near saturation that may signal the formation of two menisci at both sides of the channel bottom.     

Trichloromethyl chloroformate ("diphosgene"), ClCOOCCl3: structure and conformational properties in the gaseous and condensed phases

The conformational properties of gaseous trichloromethyl chloroformate (or "diphosgene"), ClC(O)OCCl3, have been studied by vibrational spectroscopy [IR (gas), IR (matrix), and Raman (liquid)] and quantum chemical calculations (MP2 and B3LYP with 6-311G basis sets); in addition, the structure of a single crystal at low temperature has been determined by X-ray diffraction. ClC(O)OCCl3 exhibits only one conformational form having Cs symmetry with a synperiplanar orientation of the C-O single bond relative to the C=O double bond. The calculated energy difference between the syn and anti forms, 5.73 kcal mol(-1) (B3LYP) or 7.06 kcal mol(-1) (MP2), is consistent with the experimental findings for the gas and liquid phases. The crystalline solid at 150 K [monoclinic, P2(1)/n, a = 5.5578(5) angstroms, b = 14.2895(12) angstroms, c = 8.6246(7) angstroms, beta = 102.443(2) degrees, Z = 4] likewise consists only of molecules in the syn form.