Synthesis of new 1,2,3-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetraazapentalenes

Some new v-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetraazapentalenes were prepared according to previously employed synthetic routes concerning deoxycyclization reactions of appropriate nitrophenyl-1,2,3-triazole derivatives and/or thermal decompositions of appropriate azidophenyl-1,2,3-triazoles. The nitration of 9-phenyl-1,2,3-triazolo[1,2-a]benzotriazoles allowed the isolation of some mononitro- and trinitro-derivatives, whose structures were assigned by chemical and spectroscopic methods.     

Synthesis,characterization and assignment of the absolute configuration of 4,4-dimethyl-5-oxo-tetrahydrofuran-3-carboxylic acid and its esters: a combined experimental and theoretical investigation

The synthesis of a new, optically active, paraconic-acid derivative 4,4-dimethyl-5-oxo-tetrahydrofuran-3-carboxylic acid and its methyl and ethyl esters was accomplished by a procedure involving the kinetic enzymatic resolution of the racemic ethyl ester. Thus, ethyl (+)-4,4-dimethyl-5-oxo-tetrahydrofuran-3-carboxylate, derived from a ring fission, was isolated at low conversion values, with 94% ee using HLAP as the enzymatic source. The corresponding enantiomerically pure acid was also obtained.The absolute configuration of the products was determined based on the results of an extensive computational study of the specific rotation of the acid and methyl ester. Four different wavelengths were considered and comparisons with the sign and magnitude of the corresponding experimental observations were carried out. Solvent effects on both the conformational space and the specific rotation were included in the computations using the Polarizable Continuum Model.The assigned absolute configuration of the title compounds is (R)-(+), which is in agreement with a tentative experimental assignment based on an analysis of the circular dichroism curves.     

A Novel LC–MS/MS-Based Method for the Diagnosis of ADA2 Deficiency from Dried Plasma Spot

Adenosine Deaminase 2 Deficiency (DADA2) (OMIM: 607575) is a monogenic, autoinflammatory disease caused by the loss of functional homozygous or heterozygous mutations in the ADA 2 gene (previously CECR1, Cat Eye Syndrome Chromosome Region 1). A timely diagnosis is crucial to start Anti-TNF therapies that are efficacious in controlling the disease. The confirmation of DADA2 is based on DNA sequencing and enzymatic assay. It is, thus, very important to have robust and reliable assays that can be rapidly utilized in specialized laboratories that can centralize samples from other centers. In this paper, we show a novel enzymatic assay based on liquid chromatography-tandem mass spectrometry that allows the accurate determination of the ADA2 enzyme activity starting from very small amounts of plasma spotted on filter paper (dried plasma spot). The method allows significantly distinguishing healthy controls from affected patients and carriers and could be of help in implementing the diagnostic workflow of DADA2.     

Nano-hybrids incorporation into poly(ε-caprolactone) for multifunctional applications: Mechanical and barrier properties

Intercalation compounds of ZnAl-Layered Double Hydroxide (LDH) with Benzoate (Bz), 2,4-dichlorobenzoate (BzDC), para-hydroxybenzoate (p-BzOH) and ortho-hydroxybenzoate (o-BzOH) anions, have been prepared via anion exchange procedure. The obtained inorganic-organic nano-hybrids were incorporated by High Energy Ball Milling (HEBM) into polycaprolactone (PCL), processed on laboratory scale and thin films were obtained. X-ray diffraction analyses of the samples indicated that both the nature and the position of the aromatic ring substituents affect the value of the interlayer distance and the hydrogen bonds of the nano-hybrids. Physical and barrier properties of water vapor were conducted on all the nanocomposite films, showing the influence of the exfoliation on the mechanical and barrier properties. A preliminary study on the release kinetic of the Bz anions bound to LDH was also performed, enlightening very good perspectives in the field of controlled release of active species.     

von Willebrand Factor multimers profiling with a semi‐automated system

Abnormalities in plasma von Willebrand factor (vWF) concentration and function result in von Willebrand disease (vWD). The diagnosis requires a battery of tests such as screening procedures, confirmatory tests, phenotypic characterization, and genotyping. The phenotypic testing (multimer pattern analysis) is important in order to subclassify the hereditary and the acquired forms of vWD. Only few laboratories are skilled to perform this analysis. The extreme range of protein size from 250 kDa monomer to over 20 000 kDa multimers requires a time‐consuming procedure (3–4 days) and presents many technical difficulties. To standardize the method and to overcome technical difficulties, we developed a rapid and sensitive semi‐automated method to visualize the multimeric structure of vWF. The semi‐automated method we present performs the electrophoresis of patient's plasma in 120 min on a precast gel. Gels are suitable for the G26 Interlab instrumentation. After gel blotting, the method allows visualization of the vWF multimer pattern directly on the membrane. We reduced the time required from 72 to 8 h and we propose this test for the first level screening of vWF multimer deficiency.     

Mathematical Models in Landscape Ecology: Stability Analysis and Numerical Tests

In the present paper a review of some mathematical models for the ecological evaluation of environmental systems is considered. Moreover a new model, capable to furnish more detailed information at the level of landscape units, is proposed. Numerical tests are then performed for a case study in the province of Viterbo (central Italy).     

Study on the stereochemical control of dihydroxylation of vinyl epoxides and their derivatives

The results obtained from a study on the stereochemical control in the dihydroxylation of the double bond of vinyl epoxides and their derivatives (bromo derivatives, azido derivatives and vinyl aziridines) are presented herein. A significant diastereoselectivity was observed for the bromo derivatives, azido derivatives and N-protected vinyl aziridines, whereas vinyl epoxides and unprotected vinyl aziridines showed no diastereoselectivity. The results obtained are generally consistent with the Kishi model.     

A cardinality-constrained robust model for the assignment problem in Home Care services

Home Care includes medical, paramedical and social services which are delivered to patients at their domicile rather than in hospital. Managing human and material resources in Home Care services is a difficult task, as the provider has to deal with peculiar constraints (e.g., the continuity of care, which imposes that a patient is always cared for by the same nurse) and to manage the high variability of patients’ demands. One of the main issues encountered in planning Home Care services under continuity of care requirement is the nurse-to-patient assignment. Despite the importance of this topic, the problem is only marginally addressed in the literature, where continuity of care is usually treated as a soft-constraint rather than as a hard one. Uncertainty is another relevant feature of nurse-to-patient assignment problem, and it is usually managed adopting stochastic programming or analytical policies. However, both these approaches proved to be limited, even if they improve the quality of the assignments upon those actually provided in practice. In this paper, we develop a cardinality-constrained robust assignment model, which allows exploiting the potentialities of a mathematical programming model without the necessity of generating scenarios. The developed model is tested on real-life instances related to a relevant Home Care provider operating in Italy, in order to evaluate its capability of reducing the costs related to nurses’ overtimes.     

Linear Stability Analysis for a Korteweg Fluid

Linear stability analysis of the homogeneous equilibrium solution of Euler equations for an isothermal, inviscid, compressible fluid endowed with a Korteweg-type stress tensor, in a harmonic potential field, is performed. We show that, by perturbing the fluid at rest, the transition from stability to instability takes place via a marginal state exhibiting a stationary cellular pattern of motions. By analyzing the disturbances in normal modes we obtain threshold values of the harmonic angular frequency that, in correspondence of a given temperature, could trigger fluid’s fragmentation. In the picture of initial stage of a volcano eruption, this model could describe the transition from the two-phase system magma-dissolved gas, at supersaturation pressure in the chamber, to the rising foam at conduit’s base induced by an external stress of elastic-type.     

Comparison of two SPME fibers for the extraction of some off-flavor cork-taint compounds in bottled wines investigated by GC–HRMS

Headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography with high-resolution mass spectrometry (GC–HRMS) was used to determine 2,4,6-trichloroanisole, 2,3,6-trichloroanisole, 2,3,4-trichloroanisole, 2,3,5,6-tetrachloroanisole, pentachloroanisole, 2,4,6-tribromoanisole, 2-methylisoborneol, and 4-ethylguaiacol in wine samples. Two types of fiber coating commonly employed for sampling trichloroanisoles in wine and cork stoppers, viz. a polar mixed 50/30 μm divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) and a nonpolar 100 μm polydimethylsiloxane (PDMS), both 1 cm in length, were compared. This study demonstrates that the most employed polar mixed fiber should not be used with ethanol–water solutions, viz. wine samples, as its coating is not chemically and mechanically robust for sample extractions, as confirmed by environmental scanning electron microscopy. Much more effective and reliable results were obtained with the PDMS fiber, which remained functional for more than 80 analyses of red and white wine samples with satisfactory extraction efficiencies. Detection limits of investigated compounds, under optimized experimental conditions, ranged from 0.2 to 0.4 ng/L at a signal-to-noise ratio of 3 and quantification limits from 0.8 to 1.5 ng/L. The proposed method was successfully applied to commercially available Italian white and red wines using 2,4,6-TCA-d₅ as the internal standard. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Presented, in part, at the XXI Congresso Nazionale di Chimica Analitica, 21–25 September 2008, Arcavacata di Rende, CS (Italy).