Phosphoinositide-3-kinases (PI3Ks): combined comparative modeling and 3D-QSAR to rationalize the inhibition of p110alpha

The p110alpha isoform of the class IA PI3Ks was recently genetically validated as a promising target for anticancer therapy. However, up to now, only one compound (PIK75 = 1) has been reported as a very potent and selective inhibitor of this isoform. The lack of a 3D structure for this enzyme has clearly hindered the discovery of new p110alpha selective compounds. In view of this, we combined target-based (homology modeling) and ligand-based (3D-QSAR) approaches in an attempt to define an integrated interaction model for p110alpha inhibition. Twenty-five analogues of 1 were docked within the putative p110alpha binding site, and the molecular alignment generated was subsequently used to derive QSAR models based on scoring function, free energy of binding, CoMFA. and CoMSIA. The predictive power of these models was then analyzed using a challenging test set of 5 compounds. CoMSIA, and particularly CoMFA, models were found to outperform the other methods, predicting accurately the potency of 100% of the compounds in the test set, thereby validating our p110alpha homology model for use in further drug development.     

Selective partial hydrogenation of hydroxy aromatic derivatives with palladium nanoparticles supported on hydrophilic carbon

Selective hydrogenation of phenol to cyclohexanol in the aqueous phase was achieved using a new catalytic system based on palladium particles supported on hydrophilic carbon prepared by one-pot hydrothermal carbonisation.     

Electrochemical fabrication and characterization of thin films of redox-active molecular wires based on extended Rh-Rh bonded chains

An original electrochemical synthesis of {[Rh4(mu-OOCCH3)4(phen)4]2+}n (1) molecular wire films from a solution of binuclear bridged Rh complexes [Rh2(mu-OOCCH3)2(phen)2(X)2](Y)2 (X = H2O, Y = BF4(-) (2a) and X = CH3CN, Y = BF4(-) (2b)) in MeCN electrolyte is reported. UV-vis spectroscopy and quartz crystal microbalance electrochemical coupled techniques have been used to demonstrate the electrosynthesis process. The resulting polymetallic compound has been characterized on the basis of its physicochemical properties, which have been compared with those of a chemically synthesized sample. Furthermore, according to EPR, 1H NMR and electrochemical behaviour, the mechanism of the oxidation of this polymetallic wire, containing mixed valent rhodium centers and alternatively acetate bridged Rh-Rh bonds, has been investigated in detail.     

A stereodivergent synthesis of beta-hydroxy-alpha-methylene lactones via vinyl epoxides

A catalytic diastereoselective sulfonium ylide epoxidation of aldehydes furnished original vinyl epoxides, having an MBH backbone. These highly functionalized building blocks were used for a formal synthesis of the antibiotic conocandin, and opened up a stereodivergent route towards beta-hydroxy-alpha-methylene lactones, core units of naturally occurring compounds. Under acidic conditions, the oxiranes were mainly transformed, with moderate to good yields, into trans beta-hydroxy-alpha-methylene lactones. On the other hand, a user-friendly palladium-catalysed CO2 insertion and cyclisation sequence gave the cis beta-hydroxy-alpha-methylene lactone counterparts along with an interesting cis-trans equilibration of the pi-allyl intermediates.     

A dramatic difference between the electron-driven dissociation of alcohols and ethers and its relation to Rydberg states

A difference was observed in the reactivity of alcohols and ethers toward free electrons. Whereas the lowest core-excited state of the negative ion-a (2)(n,3s(2)) Feshbach resonance-of the alcohols readily dissociates by losing a hydrogen atom, ethers show no observable signal from this resonance. This difference in reactivity has a parallel in the anomalous shapes and energies of the parent states of the Feshbach resonances, the (1)(n,3s) Rydberg states of the neutral alcohols. We explained this anomaly using potential surfaces of the alcohols and ethers calculated using the TD-DFT method as a function of the dissociation coordinate. The lowest excited state of alcohols was found to be repulsive, whereas a barrier to dissociation was found in the ethers. Rydberg-valence mixing and avoided crossings are decisive in determining the shapes of the potential surfaces. It is concluded that the reactivities of alcohols and ethers toward free electrons are rationalized by assuming that the potential surfaces of the daughter Feshbach resonances closely follow those of the parent Rydberg states, i.e., the lowest Feshbach resonance is repulsive, but a barrier occurs in ethers. The potential surfaces of both the Rydberg states and the Feshbach resonances thus differ dramatically from the non-dissociative surface of the grandparent (2)(n(-1)) positive ions, despite the nominally non-bonding character of the Rydberg electrons.     

A new quantitative and low-cost determination method of nitrate in vegetables, based on deconvolution of UV spectra

A new UV-spectrophotometric method for the determination of nitrate in vegetables is presented. The method is based on the spectral deconvolution: UV spectrum of a sample is considered as a linear combination of absorption spectra, named reference spectra. The combination of a small number of spectra of reference allows to reconstitute the shape of UV spectrum of an unknown sample. There have been several fresh vegetables (lettuce, curly lettuce, oak-leaf lettuce), as well as frozen spinaches that have been tested. The results obtained were comparable to those obtained with the reference HPLC method (official European reference method for the determination of nitrate in foodstuffs). The nitrate content varied from 377 to 3240 mg kg⁻¹ of fresh vegetables, and 545 to 1190 mg kg⁻¹ of frozen spinach. The recovery of added nitrate ranged from 91 to 99%. The results were obtained with a laboratory spectrophotometer and also with a dedicated field-type spectrophotometer. This method does not require almost any consumable, is quantitative and very fast reading with easy and low maintenance.     

Trends in UV irradiance of tanning devices in Norway: 1983-2005

Abstract Indoor tanning increases skin cancer risk, but the importance of different parts of the UV spectrum is unclear. We assessed irradiance of tanning devices in Norway for the period 1983-2005. Since 1983, all tanning models needed approval before being sold or used. UV Type 3 limits were valid from late 1992 (<0.15 W m(-2) for CIE-weighted, i.e. erythemally weighted, short and long wave irradiances). We analyzed data from 90% of the approved tanning models (n = 446 models) and two large inspection surveys in 1998/1999 and 2003 (n = 1341 tanning devices). Mean CIE-weighted short wave irradiance of approved models increased from 0.050 W m(-2) (95% confidence interval [CI] 0.045-0.055) in 1983-1992 to 0.101 W m(-2) (95% CI 0.098-0.105) in 1993-2005, and mean long wave from 0.091 W m(-2) (95% CI 0.088-0.095) to 0.112 W m(-2) (95% CI 0.109-0.115), respectively. Inspection surveys revealed short wave irradiances much higher than that approved. In 1998-1999, only 28% (293/1034) of the devices were equipped with correct sunlamps and only 1 out of 130 inspected establishments fulfilled all requirements. In 2003, corresponding numbers were 59% (180/307) of devices and 2 out of 52 establishments. Mean short and long wave irradiances of the inspected tanning devices in 2003 were 1.5 and 3.5 times, respectively, higher than the irradiance of natural summer sun in Oslo. In conclusion, the short wave irradiance has increased in indoor tanning devices in Norway over the last 20 years. Due to the high long wave irradiance throughout this period, the percentage of short wave irradiance was much lower than for natural sun.     

Evaluation of some parameters affecting troublesome pesticide analysis in gas chromatography-ion-trap mass spectrometry

Nowadays, multiresidue methods for pesticides monitoring in food commodities are commonly employed. It is also well known that the presence of several compounds from the matrix introduces a bias during the detection and the quantification steps. The so-called matrix effect phenomenon is related to the masking or formation of active sites. In GC, this phenomenon occurs in the injector port, and in the separative system (retention gap and/or analytical column) and also causes ionization potential modification of analytes. The main consequence of matrix effect is an increasing or decreasing analyte signal in the presence of the matrix (real sample) in respect to the same analyte in solvent (standard solution). In standard mixture, pesticides themselves interact with the active present sites among analytical chain from injector to the detector. Some matrix components, sometimes at trace amounts, are inevitably present in analyzed samples even after numerous and diverse clean-up procedures. In this paper, the influence of some analytical parameters on pesticide signal response is explored using gas chromatography with ion-trap mass-selective detection (GC-IT-MS). Moreover, the responses of characteristic troublesome analytes are analyzed in various kinds of matrices. Finally, matrix compound identification is initiated to study analyte-matrix relationship. Sample acidification with 0.1% acetic acid was the most appropriate for the majority of pesticides, while 0.1% formic acid was more suitable for base-sensitive ones (amitraz, imazalil, thiabendazole). Among tested calibration methods, matrix matched calibration provides the best results. In green bean matrix model, a matrix/pesticide ratio of 1/1 induces the best detected signal for almost every investigated analytes. Presence and quantity of some identified matrix co-extracted compounds like sterols could be partially a cause of signal enhancement.