Quantitative weight of evidence method for combining predictions of quantitative structure-activity relationship models

ABSTRACT

A method for combining statistical-based QSAR predictions of two or more binary classification models is presented. It was assumed that all models were independent. This facilitated the combination of positive and negative predictions using a quantitative weight of evidence (qWoE) procedure based on Bayesian statistics and the additivity of the logarithms of the likelihood ratios. Previous studies combined more than one prediction but used arbitrary strengths for positive and negative predictions. In our approach, the combined models were validated by determining the sensitivity and specificity values, which are performance metrics that are a point of departure for obtaining values that measure the weight of evidence of positive and negative predictions. The developed method was experimentally applied in the prediction of Ames mutagenicity. The method achieved a similar accuracy to that of the experimental Ames test for this endpoint when the overall prediction was determined using a combination of the individual predictions of more than one model. Calculating the qWoE value would reduce the requirement for expert knowledge and decrease the subjectivity of the prediction. This method could be applied to other endpoints such as developmental toxicity and skin sensitisation with binary classification models.     

Spectroscopic investigation of cyclodextrin monomers,derivatives, polymers and azo dyes (1)

Circular dichroism (CD) and visible spectra of inclusion compounds between Methyl Orange (MO) analogues and -, -, -cyclodextrin (cdx), 2,6-dimethyl-and 2,3,6-trimethyl--cdx, water soluble -, -, -cdx polymer products were investigated. In the CD-spectroscopic investigation, the complex with -cdx epichlorohydrin condensate showed a large amplitude and splitting of the induced ^* band. Fractions of glyceryl ether of less than 2000 and polymer of more than 10000 dalton molecular mass were separated. Complexes of above two fractions and MO showed the same splitting spectral pattern. Job's plots from visible spectra showed the formation of the 11 complex and CD-data suggested the co-existence of the 21 MO-cdx complex. This splitting pattern showed the reversal of the signs when -cdx-ethyleneglycol-bis(epoxypropyl) ether was used and disappeared when larger host molecules and azo dyes were used. The splitting was explained by exciton interaction.     

Efficient desulfurization of 2-thiopyrimidine nucleosides to the corresponding 4-pyrimidinone analogues using trans-2-(phenylsulfonyl)-3-phenyloxaziridine

A brief treatment of 2-thiopyrimidine nucleosides (s²U^∗) with trans-2-phenylsulfonyl-3-phenyloxaziridine (PSO) results in efficient substrate desulfurization leading to the corresponding 4-pyrimidinone analogues (H²U^∗). The key transformation proceeds through oxidation of the 2-thiocarbonyl group to a sulfur oxyacid derivative and subsequent elimination of sulfur dioxide. 4-Pyrimidinone 1-β-d-riboside (H²U) has been transformed into the respective phosphoramidite, a ready-to-use monomer for the introduction of a modified nucleoside into an oligonucleotide chain. Moreover, the effective desulfurization of the 2-thiouridine nucleotide could be achieved directly at the oligonucleotide level, by treatment of the TdA(s²U)dGdC oligonucleotide with PSO, as verified by MALDI-TOF mass spectrometry.     

Determination of fungicide residues in fruits by coupled-column liquid chromatography

Coupled-column liquid chromatography with fluorescence detection was applied to the determination of o-phenylphenol and bitertanol residues in orange and banana fruits. After extraction with a mixture of acetone, dichloromethane-petroleum ether, and ethyl acetate, an extract aliquot of 100 microL was injected directly without any additional clean-up into the chromatographic system using two reversed phase C18 coupled columns. The LC-LC approach allowed automated sample clean up of the vegetal extracts, leading to a simple and rapid analytical procedure, with limits of quantification between 0.01 and 0.05 mg kg(-1). Recovery experiments performed on orange and banana samples fortified at different concentrations (0.01 - 4 mg kg(-1)) gave average recoveries between 70 and 113% with relative standard deviations lower than 15%. The procedure developed was finally applied to orange and banana samples from different geographical locations and the results were confirmed by GC-MS.     

Direct, two-step synthetic pathway to novel dibenzo[a,c]phenanthridines

Novel dibenzo[a,c]phenanthridines are prepared regioselectively by the application of a straightforward synthetic pathway, starting from new 3,4-diaryl- and 3,4-dihydro-3,4-diarylisoquinolines prepared via Ritter-type heterocyclization and the more classical two-step reductive amination/Bischler-Napieralski cyclization of triarylethanones, respectively. A comparative study of nonphenolic oxidative coupling methodologies provides a highly efficient procedure, based on the hypervalent iodine reagent phenyliodine(III) bis(trifluoroacetate) (PIFA), to accomplish the final coupling step.     

Facile Desulfurization of Thioamides and Thioureas with Tetrabutylammonium Periodate under Mild Conditions

Summary. Thioamides and thioureas were reacted with tetrabutylammonium periodate at room temperature to afford the corresponding amides and ureas, respectively, under aprotic conditions.     

Flow injection on-line ultrasound-assisted extraction of iron in meat samples coupled to a flame atomic absorption spectrometric system

Iron was extracted on-line from solid meat samples by a simple and rapid continuous ultrasound-assisted extraction system (CUES). The CUES is connected to a flow injection manifold, which allows the on-line flame atomic absorption spectrometric determination of iron. A Plakett–Burman design was used for the optimisation of the CUES. The method achieved a total sampling frequency of 11 samples per hour with a relative standard deviation for the complete procedure of 0.4%. The detection limit was 0.6 g g^–1 (dry mass) for a sample amount of 30 mg. Accurate results were obtained by measuring the certified reference materials BCR-186 (pig kidney) and BCR-184 (bovine muscle). The analytical procedure was applied to different real meat samples with satisfactory results.     

Modifying the thermosensitivity of copolymers of sodium styrene sulfonate and<Emphasis Type="Italic"> N</Emphasis>-isopropylacrylamide with dodecyltrimethylammonium chloride

The interactions between copolymers of sodium styrene sulfonate (SSS) and N-isopropylacrylamide (NIPAM), anionic polyelectrolytes, and dodecyltrimethylammonium chloride (DTAC), a cationic surfactant, were studied in aqueous solutions of various ionic strengths. The copolymers were found to be thermoresponsive, showing a lower critical solution temperature (LCST). The influence of the polymer composition, the surfactant concentration, and the ionic strength on the LCST was studied. The surfactant was found to interact strongly with the polymer, forming mixed polymer-surfactant micelles. The critical aggregation concentration (cac) of the polymer-surfactant system was found from fluorescence spectroscopy using pyrene as a fluorescent probe. A strong dependence of the anionic polyelectrolyte-cationic surfactant interactions on the structure of the ionic comonomer was observed.     

Unique tautomeric properties of isoguanine

The tautomeric properties of isoguanine (also named 2-oxoadenine or 2-hydroxyadenine) have been studied in the gas phase, in different pure solvents, and in the DNA environment using state of the art theoretical methods. Our results show that isoguanine constitutes an unique example of how tautomerism can be modulated by the environment. Compared to the tautomeric preference in the gas phase, both polar solvents and the DNA microenvironment dramatically change the intrinsic tautomeric properties of isoguanine. Tautomers which are important in physiological conditions are less than 1/10(5) of the total population of isoguanine in the gas phase. The impact of the present findings in the understanding of spontaneous mutations and in the design of new nucleobases with multiple recognition properties is discussed.