Synthesis, characterisation and solution behaviour of fluoroalkyl phosphoryl complexes of tin tetrachloride

The synthesis, characterisation and solution behaviour of a series of octahedral complexes SnCl₄·2L (L = R₂NP(O)(OCH₂CF₃)₂; R = Me (1); Et (2) or L = P(O)(OCH₂R_f)₃; R_f = CF₃ (3); C₂F₅ (4)) are described. Complexes 1-4 were prepared from SnCl₄ and 2 equiv. of the ligand, L, in anhydrous CH₂Cl₂ solution. The adducts have been characterised by multinuclear (¹H, ³¹P and ¹¹⁹Sn) NMR, IR spectroscopy and elemental analysis. In dichloromethane solution, the NMR data showed the presence of a mixture of cis and trans isomers for 1 and 2 and only the cis isomer for 3 and 4. The difference could be interpreted in terms of the electronic effects of the substituents on the phosphorus atom of the ligand. In addition, the solution structure of the complexes studied by variable temperature ³¹P-{¹H} and ¹H NMR in the presence of excess ligand indicated that the ligand exchange on the cis isomer dominates the chemistry. The metal-ligand exchange barriers were estimated to be 13.38 and 11.39 kcal/mol for 1 and 3, respectively. The results are discussed and compared with those previously reported for the related hexamethylphosphoramide adduct, SnCl₄·2HMPA.     

Theoretical study of Escherichia coli peptide deformylase inhibition by several drugs

Because peptide deformylase (PDF) is essential for the initiation of translation in eubacteria but not in eukaryotes, it is a potentially interesting target for antibiotics. Computer simulation using docking software can be used to model protein-ligand interactions, and in this brief report we describe its use in optimizing the design in PDF-directed inhibitors. PDF was used as target for a set of five inhibitors with substantial structural differences. Docking results show that the compound 1BB2 (actinonin) binds with high affinity to the enzyme and produces the most stable complex, forming nine hydrogen bonds with the enzyme active site. Its binding energy is DeltaG = -31.880 kJ/mol. The modeling study shows that when the methyl group of 1BB2 is replaced with an amine group, the binding energy is increased to -35.316 kJ/mole. This enhancement is more marked (DeltaG = -41.141 kJ/mol) when the propyl group and the five-membered ring of 1BB2 are replaced by an amide group and a phenyl ring, respectively. We describe an attempt to design better antibiotics on the basis of a computer-aided simulation of the interaction between a drug and its target molecule.     

Nonselective cation transport in native esophageal epithelia

Rabbit esophageal epithelia actively transport Na(+) in a manner similar to that observed in classic electrically tight Na(+)-absorbing epithelia, such as frog skin. However, the nature of the apical entry step is poorly understood. To address this issue, we examined the electrophysiological and biochemical nature of this channel. Western blotting experiments with epithelial Na(+) channel (ENaC) subunit-specific antibodies revealed the presence of all three ENaC subunits in both native and immortalized esophageal epithelial cells. The amino acid sequence of the rabbit alpha-ENaC cloned from native rabbit esophageal epithelia was not significantly different from that of other published alpha-ENaC homologs. To characterize the electrophysiological properties of this native apical channel, we utilized nystatin permeabilization to eliminate the electrical contribution of the basolateral membrane in isolated native epithelia mounted in Ussing-type chambers. We find that the previously described apical Na(+) channel is nonselective for monovalent cations (Li(+), Na(+), and K(+)). Moreover, this channel was not blocked by millimolar concentrations of amiloride. These findings document the presence of a nonselective cation channel in a native Na(+) transporting epithelia, a finding that hereto has been thought to be limited to artificial culture conditions. Moreover, our data are consistent with a potential role of ENaC subunits in the formation of a native nonselective cation channel.     

Comparative evaluation of vacuum-based surface sampling methods for collection of Bacillus spores

In this study, four commonly-used sampling devices (vacuum socks, 37 mm 0.8 μm mixed cellulose ester (MCE) filter cassettes, 37 mm 0.3 μm polytetrafluoroethylene (PTFE) filter cassettes, and 3M™ forensic filters) were comparatively evaluated for their ability to recover surface-associated spores. Aerosolized spores (~ 10⁵ CFU cm^− 2) of a Bacillus anthracis surrogate were allowed to settle onto three material types (concrete, carpet, and upholstery). Ten replicate samples were collected using each vacuum method, from each material type. Stainless steel surfaces, inoculated simultaneously with test materials, were sampled with pre-moistened wipes. Wipe recoveries were utilized to normalize vacuum-based recoveries across trials. Recovery (CFU cm^− 2) and relative recovery (vacuum recovery/wipe recovery) were determined for each method and material type. Recoveries and relative recoveries ranged from 3.8 × 10³ to 7.4 × 10⁴ CFU cm^− 2 and 0.035 to 1.242, respectively. ANOVA results indicated that the 37 mm MCE method exhibited higher relative recoveries than the other methods when used for sampling concrete or upholstery. While the vacuum sock resulted in the highest relative recoveries on carpet, no statistically significant difference was detected. The results of this study may be used to guide selection of sampling approaches following biological contamination incidents.     

MicroRNAs and hepatitis C virus: Toward the end of miR-122 supremacy

ABSTRACT: The most common etiologic agents causing chronic hepatitis are hepatitis C and B viruses(HCV and HBV, respectively). Chronic infection caused by HCV is considered one of themajor causative agents of liver cirrhosis and hepatocellular carcinoma worldwide. Incombination with the increasing rate of new HCV infections, the lack of a current vaccineand/or an effective treatment for this virus continues to be a major public health challenge.The development of new treatments requires a better understanding of the virus and itsinteraction with the different components of the host cell. MicroRNAs (miRNAs) are smallnon-coding RNAs functioning as negative regulators of gene expression and represent aninteresting lead to study HCV infection and to identify new therapeutic targets. Until now,microRNA-122 (miR-122) and its implication in HCV infection have been the focus ofdifferent published studies and reviews. Here we will review recent advances in therelationship between HCV infection and miRNAs, showing that some of them emerge inpublications as challengers against the supremacy of miR-122.     

Chemical Variability and Biological Activities of Brassica rapa var. rapifera Parts Essential Oils Depending on Geographic Variation and Extraction Technique

In the present work, the Brassica rapa var. rapifera parts essential oils and their antioxidant and antimicrobial activities were investigated for the first time depending on geographic origin and extraction technique. Gas‐chromatography (GC) and GC/mass spectrometry (MS) analyses showed several constituents, including alcohols, aldehydes, esters, ketones, norisoprenoids, terpenic, nitrogen and sulphur compounds, totalizing 38 and 41 compounds in leaves and root essential oils, respectively. Nitrogen compounds were the main volatiles in leaves essential oils and sulphur compounds were the main volatiles in root essential oils. Qualitative and quantitative differences were found among B. rapa var. rapifera parts essential oils collected from different locations and extracted by hydrodistillation and microwave‐assisted hydrodistillation techniques. Furthermore, our findings showed a high variability for both antioxidant and antimicrobial activities. The highlighted variability reflects the high impact of plant part, geographic variation and extraction technique on chemical composition and biological activities, which led to conclude that we should select essential oils to be investigated carefully depending on these factors, in order to isolate the bioactive components or to have the best quality of essential oil in terms of biological activities and preventive effects in food.