Geometric Singular Perturbation Theory for Systems with Symmetry

Journal of Dynamics and Differential Equations - In this paper we focus on a class of symmetric vector fields in the context of singularly perturbed fast-slow dynamical systems. Our main question...     

Catalytic Nitrene Transfer by an FeIV-Imido Complex Generated by a Comproportionation Process

Nitrene transfer reactions have emerged as one of the most powerful and versatile ways to insert an amine function to various kinds of hydrocarbon substrates. However, the mechanisms of nitrene generation have not been studied in depth albeit their formation is taken for granted in most cases without definitive evidence of their occurrence. In the present work, we compare the generation of tosylimido iron species and NTs transfer from Fe^II and Fe^III precursors where the metal is embedded in a tetracarbene macrocycle. Catalytic nitrene transfer to reference substrates (thioanisole, styrene, ethylbenzene and cyclohexane) revealed that the same active species was at play, irrespective of the ferrous versus ferric nature of the precursor. Through combination of spectroscopic (UV-visible, Mössbauer), ESI-MS and DFT studies, an Fe^IV tosylimido species was identified as the catalytically active species and was characterized spectroscopically and computationally. Whereas its formation from the Fe^II precursor was expected by a two-electron oxidative addition, its formation from an Fe^III precursor was unprecedented. Thanks to a combination of spectroscopic (UV-visible, EPR, Hyscore and Mössbauer), ESI-MS and DFT studies, we found that, when starting from the Fe^III precursor, an Fe^III tosyliodinane adduct was formed and decomposed into an Fe^V tosylimido species which generated the catalytically active Fe^IV tosylimide through a comproportionation process with the Fe^III precursor.     

Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serum

Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10–1000 ng/mL), with adequate accuracy (90.1–114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.     

Vinylic MIDA Boronates: New Building Blocks for the Synthesis of Aza‐Heterocycles

A two‐step synthesis of structurally diverse pyrrole‐containing bicyclic systems is reported. ortho‐Nitro‐haloarenes coupled with vinylic N‐methyliminodiacetic acid (MIDA) boronates generate ortho‐vinyl‐nitroarenes, which undergo a “metal‐free” nitrene insertion, resulting in a new pyrrole ring. This novel synthetic approach has a wide substrate tolerance and it is applicable in the preparation of more complex “drug‐like” molecules. Interestingly, an ortho‐nitro‐allylarene derivative furnished a cyclic β‐aminophosphonate motif.     

Influence of Polarity and Activation Energy in Microwave–Assisted Organic Synthesis (MAOS)

The aim of this work was to determine the parameters that have decisive roles in microwave-assisted reactions and to develop a model, using computational chemistry, to predict a priori the type of reactions that can be improved under microwaves. For this purpose, a computational study was carried out on a variety of reactions, which have been reported to be improved under microwave irradiation. This comprises six types of reactions. The outcomes obtained in this study indicate that the most influential parameters are activation energy, enthalpy, and the polarity of all the species that participate. In addition to this, in most cases, slower reacting systems observe a much greater improvement under microwave irradiation. Furthermore, for these reactions, the presence of a polar component in the reaction (solvent, reagent, susceptor, etc.) is necessary for strong coupling with the electromagnetic radiation. We also quantified that an activation energy of 20–30 kcal mol⁻¹ and a polarity (μ) between 7–20 D of the species involved in the process is required to obtain significant improvements under microwave irradiation.     

Sensitive targeted multiple protein quantification based on elemental detection of Quantum Dots

A generic strategy based on the use of CdSe/ZnS Quantum Dots (QDs) as elemental labels for protein quantification, using immunoassays with elemental mass spectrometry (ICP-MS), detection is presented. In this strategy, streptavidin modified QDs (QDs-SA) are bioconjugated to a biotinylated secondary antibody (b-Ab₂). After a multi-technique characterization of the synthesized generic platform (QDs-SA-b-Ab₂) it was applied to the sequential quantification of five proteins (transferrin, complement C3, apolipoprotein A1, transthyretin and apolipoprotein A4) at different concentration levels in human serum samples. It is shown how this generic strategy does only require the appropriate unlabeled primary antibody for each protein to be detected. Therefore, it introduces a way out to the need for the cumbersome and specific bioconjugation of the QDs to the corresponding specific recognition antibody for every target analyte (protein). Results obtained were validated with those obtained using UV–vis spectrophotometry and commercial ELISA Kits.     

Thermal,morphostructural and spectrometric characterization of an antibacterial kaolinite-based filter modified with silver for water treatment

Journal of Thermal Analysis and Calorimetry - The aim of this work is to synthesize and characterize a new structured silver–clay dried, calcined or sintered at different temperatures...     

Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates

The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT.