Synthesis of Molecules in Modern Chemical Science: Challenge for Today

A design has been development that provides higher activity to darunavir, an antiretroviral drug, aiming a lower dose in the battle against HIV in children and adults. Globally this research paves the way to get a new darunavir: β-cyclodextrin complex driving future perspectives to new anti HIV drugs for clinical applications. β-cyclodextrins not only promote the solubility of darunavir, but can drive to development of new complexes able to combat HIV in lower doses and, therefore lower toxic effects. Analysis methods by chromatography, also, were developed to evaluated the quality of the complexed darunavir. All this effort to contemplate the patients of all ages and provide quality medicines as well as a better quality of life.

The bioactivation of drugs to Reactive Metabolites (RM) has been related to drug-induced liver injury and hypersensitivity reactions in patients. Therefore, many pharmaceutical companies are investigating the potential to form reactive metabolites in vitro as an integral part of the optimization of drug candidates. A computer assisted workflow to efficiently analyze larger numbers of compounds for the formation of glutathione trappable RM is presented here. A set of 95 compounds with known bioactivation potential was selected for this study. Incubations with human liver microsomes were prepared with GSH. The acquisition of MS/MS spectra was triggered by ion intensity. MS with singly and doubly charged ions were used for peak detection and MS/MS spectra were used for structural elucidation. A confidence classification system for the GSH peak detection (high, medium, low) was developed based on the detection of characteristic fragment ions or neutral losses and applied to remove potential false positive results. A comparative analysis of the HRMS results with literature data was carried out. The most frequently observed Neutral Loss (NL) found in singly charged GSH adducts (drug-glutathione conjugates) were, the Neutral Loss (NL, 129 Da) and Fragment Ion (FI, m/z 308) and in the doubly charged ones the Fragment Ion (FI, m/z 130). These NL and FI were used to identify GSH-related drug metabolites. MS/MS spectra were inspected to aid structural elucidations: 17% of drug substrates and 29 % of GSH adduct metabolites were identified with only doubly charged ions, stressing the importance of considering this charge state in the identification workflow. A total of 41 compounds that form GSH adducts were retrieved from literature (HRMS, identified 28 compounds (68%) in high confidence, and the same result was obtained using precursor ion scan). By the confidence analysis of GSH peaks, the quality of the each GSH adduct was determined.

We report herein, for the first time, the application of NH2 solid-phase extraction NH2 (NH2-SPE) cartridge for cleanup of enniatins (ENA, ENA1 , ENB, ENB1 ) and Beauvericin (BEA) in cereals. Samples were sequentially extracted with a solution containing 80% acetonitrile and 0.1% formic acid and the extracts were cleaned up with NH2-SPE cartridges before being analyzed by Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS). A CORTECS C18 column was used for separation of enniatins and beauvericin. Mass spectrometric analysis was conducted at the Positive Electrospray Ionization (ESI+) Mode with Multi Reactions Monitoring (MRM). Very good linear relationships between spiked levels of ENA, ENA1, ENB, ENB1, BEA in cereals and mass spectra were observed with regression coefficients of 0.995 to 0.999 and Detection Limits (LOD) range of 0.01 to 0.1 µg kg-1. Clean up with NH2-SPE cartridge gave more satisfactory recoveries ranging from 80.9% to 109.8% than with QuEChERS method that gave recoveries between 63.5% to 96.6%. Application of the NH2-SPE cartridge for the determination of enniatins and beauvericin showed detection levels ranging from 0.01 µg kg-1 to 127.87 µg kg-1 in corn and 0.01 µg kg-1 to 116.59 µg kg-1 for wheat.

Recent trends in the sensor community, indicates that one of the major challenges and opportunities of the field relies on developing smart sensor platforms, which are cheap, efficient, easy-to-use, and capable of minimizing tasks at the end user stage, in comparison to traditionally used methods which require bulky instrumentations and qualified personnel.

One of the negative consequences related to socioeconomic development in recent centuries has been the rise of environmental contamination. In light of this, human has sought to implement actions in all spheres (social, economic and cultural) aiming to minimize the impact on the environment. Concern about the pollution of bodies of water and industrial wastewater treatment is the biggest worry in this regard. Among various treatment methods highlights the adsorption solid phase, by being very efficient and economically feasible. The use of chitosan as an adsorbent makes the process more ecologically interesting, once chitosan is also retrieved from waste. In this study we evaluate the adsorption process of the bromothymol blue dye by the chitosan. The parameters that influence the sorption process were studied (pH, ionic strength, adsorbent mass and dye initial concentration), and the process thermodynamics.

A new kind of sorbent with high adsorption capacity and stability was prepared using chitosan and epichlorohydrin through a cross-linking reaction and assessed by using methyl orange. The sorption capability was evaluated by means of kinetics and equilibrium studies. Relevant factors for such sorption process were also assessed. After optimization of the relevant sorption factors, the percentages for methyl orange removal by chitosan and by modified chitosan were 82%, and 67%, respectively. Although the cross-linked chitosan offered the lowest removal percentage, this sorbent presented other relevant advantages when compared to non-modified chitosan, such as higher chemical and thermal stabilities.

The Directive 2013/39/EU has reviewed the list of priority substances under the European Water Framework Directive (WFD; Directive 2000/60/EC) and has strengthened the principle of flexibility for Member States in applying the Environmental Quality Standard (EQS) for alternative matrices. Coherently, it has established new EQS for biota and it has invited Member States to set EQS for more opportune matrices, able to advantage the monitoring strategy and offer the same level of protection, such as sediment. The present work developed a (HS)SPME-GC-MS/MS method for the analysis of Tributyltin (TBT) in sediment samples and, through an in depth validation process, it assessed the compliance with the technical specification required by the EU Directive 2009/90/EC for chemical status analysis under the scope of the WFD. The EQS established for TBT in sediment by the Italian Environmental Ministry was used as reference. The method fulfils the minimum performance criteria required by the EU Directive 2009/90/EC (Method Detection Limit (MDL) and Minimum Level Of Quantitation (ML), expressed as ng Sn g-1 d.w., were 0.2 and 0.5, respectively). More generally, the analytical figures of merit achieved, were satisfying for the target TBT concentration range (recovery: 90-111%, intermediate precision range: 6-12%).

A simple, rapid, sensitive and selective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the quantification of pravastatin in human plasma. Pravastatin-D3 was used as an internal standard. The analyte was extracted from human plasma samples by liquid-liquid extraction technique. Due to the presence of isobaric metabolites, 3α-iso-pravastatin and 6-epi-pravastatin, chromatographic conditions were optimized, with a C18 column by using a mixture of 0.1% acetic acid in water and acetonitrile/ methanol (43:57,v/v) as the mobile phase at a flow rate of 0.6 mL/min. The calibration curve obtained was linear (r2 ≥ 0.9900) over the concentration range of 0.500-500 ng/mL. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The method was suitable for supporting clinical studies.

In this paper we investigate the problem of tracking a moving but non-vibrating cylindrical object and estimating its size and shape using an artificial lateral line system, an d determine the lower bound that the estimator can be reached. Based on a nonlinear analytical model for the moving object-induced flow field, a two-stage extended Kalman filter is proposed to estimate the location, velocity, size, and shapes of the object. Simulation results on tracking an ellipsoidal cross-section are presented to illustrate the approach.

Medicinal plants contain a wide variety of chemicals which have very important roles in numerous applications including medicinal and those related with industry. Essential oils represent valuable sources for natural antioxidants. The aim of our study was to evaluate the chemical composition and antioxidant activity of the essential oils extracted from leaves of Syrian Vitex agnus-castus L. and Rosmarinus officinalis L., where is both essential oils were extracted and analyzed by gas chromatography-mass spectrometry. The antioxidant activities of these essential oils were determined by three different test systems, scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radical, total phenolic and flavonoids contents. The main constituents found in Vitex agnus-castus L. essential oil were 1,8-Cineole (19.34%) and Sabinene (12.50%), while the major constituents in Rosmarinus officinalis L. essential oil were 1,8-Cineole (28.03%) and α-Pinene (14.70%). The results showed that 2,2-diphenyl-1-picrylhydrazyl radical scavenging and total phenolic contents of Vitex agnus-castus L. essential oil were higher than Rosmarinus officinalis L. essential oil. Total flavonoids contents were not detected in both essential oils. The Vitex agnus-castus L. and Rosmarinus officinalis L. essential oils are sources of natural antioxidants. Therefore, further work is needed to identify the compound(s) responsible for the antioxidant activity of Vitex agnus-castus L. and Rosmarinus officinalis L. essential oils.