N-acylazinium salts: a new source of iminium ions for Ugi-type processes

A multicomponent reaction involving the interaction of azines (quinolines, isoquinolines, and phenanthridine) with activating agents (chloroformates, acid halides, and sulfonyl halides), isocyanides, and water is described. The products of this process, alpha-carbamoylated-1,2-dihydroazines, are the result of the addition of the isocyanide partner to the N-acylazinium salt formed in situ. This represents a new source of iminium ion equivalents for Ugi-type reactions.     

Ultrasonic Extraction–Ozonation Sequential Sample Treatment for the Determination of Arsenic in Environmental Certified Reference Materials by Hydride Generation–Atomic Fluorescence Spectrometry

Abstract

A sample pretreatment method based on ultrasound‐assisted extraction followed by ozonation is developed for sensitive determination of total As in biological and environmental certified reference materials and an unknown plant sample (Acacia dealbata) by flow injection and continuous‐flow hydride generation–atomic fluorescence spectrometry. The method is meant to minimize the use of corrosive and oxidizing acids for sample decomposition and common errors in trace analysis. Problems derived from introduction of sonicated extracts in continuous flow and flow injection manifolds in combination with an atomic fluorescence detector, such as excessive foaming and flame instability, are addressed. The following certified reference materials (CRMs) were employed for method assessment: BCR CRM 482 lichen; BCR CRM 60 and 61 aquatic plants; BCR CRM 279 sea lettuce; NIST 1633b fly ash; BCR 320 river sediment; RTC CRM 024‐050 soil. Effect of variables such as extraction time, ultrasound amplitude, concentration of extractant acid, sample mass, drying mode, and particle size was investigated. Leaves of Acacia dealbata were also employed for method development. Limits of detection ranged from 0.03 to 0.15 µg/g As depending on the sample. Between‐batch precision values ranged from 2% to 11%. Sample throughput was 40 hr^?1 with flow injection.     

A paper‐based gas sensor for simultaneous noninstrumental colorimetric detection of nitrite and sulfide in waters

The use of paper‐based devices in combination with noninstrumental detection systems is becoming increasingly important in the analytical field due to its simplicity, rapidity, and low cost. However, their use for determination of volatile analyte derivatives is still relatively scarce. The present work reports on the assessment of a paper‐based gas‐sensing approach for the simultaneous noninstrumental colorimetric detection of nitrite and sulfide. Colorimetric systems based on the Griess and methylene blue assays, formation of colored metallic sulfides, and interaction/reaction with in situ generated metallic nanoparticles were preliminary evaluated. Then, the effect of experimental variables affecting the analytical performance of the paper‐based gas sensor was studied with two digitization systems, namely a scanner and a smartphone. Under optimal conditions, the developed system yielded limits of detection of 0.055 and 0.005 mg/L for nitrite and sulfide, respectively. The repeatability, expressed as relative standard deviation, was found to be 5.9 and 6.7% for nitrite and sulfide, respectively. The proposed method was finally applied to the analysis of water samples, showing recoveries in the range of 95–105%.     

Determination of selenium in marine biological tissues by transverse heated electrothermal atomic absorption spectrometry with longitudinal Zeeman background correction and automated ultrasonic slurry sampling.

A fast, sensitive, and reliable method for determination of selenium in marine biological tissues by electrothermal atomic absorption spectrometry with slurry sampling was developed. Slurries were prepared from fresh and frozen seafood samples that were previously homogenized, dried, and ground; particle sizes <100 microm were taken for analysis. A 3% (v/v) HNO3 solution containing 0.01% (v/v) Triton X-100 was used as slurry diluent. Slurries were mixed on an automated ultrasonic slurry sampler at 20% amplitude for 30 s just before an aliquot was injected into the furnace. The method was successfully validated against the following certified reference materials: NRCC CRM DORM-2 (Dogfish muscle); NRCC CRM TORT-2 (Lobster hepatopancreas); NRCC CRM DOLT-2 (Dogfish liver); and BCR CRM 278 (Mussel tissue), and was subsequently applied to determination of Se in 10 marine biological samples. The influences of the drying procedure (oven-, microwave-, and freeze-drying), matrix modifier amount, mass of solid material in cup, and pipetting sequence are discussed. The limit of determination of Se was 0.16 microg/g and the repeatability, estimated as between-batch precision, was in the range of 4-8%. Se contents in the samples ranged from 0.6 to 2.8 microg/g. The proposed method should be useful for fast assessment of the daily dietary intake of Se.     

1,4-Dihydropicolinic acid derivatives: novel NADH analogues with an altered connectivity pattern

Sodium dithionite reduction of α-substituted N-alkylpyridinium salts (derived from picolinic acid derivatives) afforded the corresponding 1,4-dihydropyridines with a new substitution pattern, in which the electron-withdrawing group is at the α-position. These compounds promote biomimetic reductions and are hence considered functional NADH analogues.     

Assessment of ultrasound-assisted extraction as sample pre-treatment for the measurement of lead isotope ratios in marine biological tissues by multicollector inductively coupled plasma-mass spectrometry

In this work, ultrasound-assisted extraction (UAE) was evaluated as a sample preparation procedure for lead isotope ratio measurements in marine biological tissues by multicollector inductively coupled plasma-mass spectrometry. 20 mg of marine biological tissue and 1 mL of acid extractant were sonicated for 3 min at 60% ultrasound amplitude. Matrix separation was performed in the supernatant using a chromatographic exchange resin (Sr-Spec™). Total elimination of organic matter was achieved during the separation step. Microwave-assisted digestion and dry-ashing were used for comparative purposes. No significant differences were found in lead isotope ratios at 95% of confidence level. UAE emerges as an advantageous alternative to classical methods for sample preparation owing to its simplicity and rapidity (i.e. operation steps were reduced), low reagent consumption and low contamination risks.     

Theoretical study of GSK−3<Emphasis Type="Italic">α</Emphasis>: neural networks QSAR studies for the design of new inhibitors using 2D descriptors

Glycogen synthase kinase-3 (GSK-3) targets encompass proteins implicated in AD and neurological disorders. The functions of GSK-3 and its implication in various human diseases have triggered an active search for potent and selective GSK-3 inhibitors. In this sense, QSAR could play an important role in studying these GSK-3 inhibitors. For this reason, we developed QSAR models for GSK−3α, linear discriminant analysis (LDA), and artificial neural networks (ANNs) from nearly 50,000 cases with more than 700 different GSK−3α inhibitors obtained from ChEMBL database server; in total we used more than 20,000 different molecules to develop the QSAR models. The model correctly classified 237 out of 275 active compounds (86.2%) and 14,870 out of 15,970 non-active compounds (93.2%) in the training series. The overall training performance was 93.0%. Validation of the model was carried out using an external predicting series. In these series, the model classified correctly 458 out of 549 (83.4%) compounds and 29,637 out of 31,927 non-active compounds (83.4%). The overall predictability performance was 92.7%. In this study, we propose three types of non-linear ANN as alternative to already existing models, such as LDA. Linear neural network: LNN: 236:236-1-1:1 which had an overall training performance of 96% proved to be the best model. In addition, we did a study of the different fragments of the molecules of the database to see which fragments had more influence in the activity. This can help design new inhibitors of GSK−3α. This study reports the attempts to calculate, within a unified framework probabilities of GSK−3α inhibitors against different molecules found in the literature.     

Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca²⁺-regulation of myocardial contraction. Here, we report the molecular basis of a human mutation in cTnC''s αD-helix (TNNC1-p.C84Y) that impacts conformational dynamics of the D/E central-linker and sampling of discrete states in the N-domain, favoring the “primed” state associated with Ca²⁺ binding. We demonstrate cTnC''s αD-helix normally functions as a central hub that controls minimally frustrated interactions, maintaining evolutionarily conserved rigidity of the N-domain. αD-helix perturbation remotely alters conformational dynamics of the N-domain, compromising its structural rigidity. Transgenic mice carrying this cTnC mutation exhibit altered dynamics of sarcomere function and hypertrophic cardiomyopathy. Together, our data suggest that disruption of evolutionary conserved molecular frustration networks by a myofilament protein mutation may ultimately compromise contractile performance and trigger hypertrophic cardiomyopathy.

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca²⁺-regulation of myocardial contraction.     

Comparison between conventional and ultrasound accelerated Tessier sequential extraction schemes for metal fractionation in sewage sludge

Chemical sequential extraction for metal fractionation in sewage sludge using the Tessier method has been accelerated by ultrasound. The two sequential extraction schemes (conventional and ultrasound accelerated) were compared in terms of extraction efficiency, precision, treatment time and partitioning patterns of metals. Extractable contents of Cu, Cr, Ni, Pb and Zn were measured by flame atomic absorption spectrometry, and the analytical results obtained by the two procedures were statistically compared (P = 0.95). No significant differences were found in the two first fractions (i.e. exchangeable and carbonate-bound), however, in the third and fourth extracts (i.e. Fe-Mn oxides-bound and organic matter-bound) the extraction capability of the two methods differed significantly. Received: 15 June 1998 / Revised: 10 November 1998 / Accepted: 11 November 1998