U and Th thin film neutron dosimetry for fission-track dating: application to the age standard Moldavite

Neutron dosimetry based on U and Th thin films was used for fission-track dating of the age standard Moldavite, the central European tektite, from the Middle Miocene deposit of Jankov (southern Bohemia, Czech Republic). Our fission-track age () agrees with a recent ⁴⁰Ar/³⁹Ar age, , based on several determinations on Moldavites from different sediments, including the Jankov deposit. This result indicates that the U and Th thin film neutron dosimetry represents a reliable alternative for an absolute approach in fission-track dating.     

Synthetic Cathinones: Recent Developments,Enantioselectivity Studies and Enantioseparation Methods

New psychoactive substances represent a public health threat since they are not controlled by international conventions, are easily accessible online and are sold as a legal alternative to illicit drugs. Among them, synthetic cathinones are widely abused due to their stimulant and hallucinogenic effects. To circumvent the law, new derivatives are clandestinely synthesized and, therefore, synthetic cathinones keep emerging on the drug market, with their chemical and toxicological properties still unknown. In this review, a literature assessment about synthetic cathinones is presented focusing on the recent developments, which include more than 50 derivatives since 2014. A summary of their toxicokinetic and toxicodynamic properties are also presented. Furthermore, synthetic cathinones are chiral compounds, meaning that they can exist as two enantiomeric forms which may present different biological and toxicological activities. To analyze the enantiomers, the development of enantiomeric resolution methods for synthetic cathinones is crucial. Many methods have been reported over the years that include mostly chromatographic and electromigration techniques, with liquid chromatography using chiral stationary phases being the technique of choice. This review intended to present an overview of enantioselectivity studies and enantioseparation analysis regarding synthetic cathinones, highlighting the relevance of chirality and current trends.     

Structure factor of ferrofluids with chain aggregates: Theory and computer simulations

In this paper we present theoretical and simulation results on the structure factor of mono- and bidisperse ferrofluids with chain aggregates, both with and without an applied external magnetic field. Chain distribution is obtained by the density functional theory (DFT). The radial distribution function (RDF) is calculated directly on the basis of the chain distribution and Fourier transformed to calculate the structure factor. An extensive comparison of the theoretical predictions to the results of the molecular dynamics computer simulations is provided. The proposed combined approach allows to elucidate the connection between experimentally observed small angle neutron scattering (SANS) images and the ferrofluid microstructure.     

Search of ligands for the amyloidogenic protein beta2-microglobulin by capillary electrophoresis and other techniques

Beta2-microglobulin (beta2-m) is a small amyloidogenic protein normally present on the surface of most nucleated cells and responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of beta2-m through the binding to a small molecule, and consequent inhibition of protein misfolding and amyloid fibril formation. A few compounds have been described to weakly bind beta2-m, including the drug suramin. The lack of a binding site for nonpolypeptidic ligands on the beta2-m structure makes it difficult for both the identification of functional groups responsible for the binding and the search of hits to be optimized. The characterization of the binding properties of suramin for beta2-m by using three different techniques (surface plasmon resonance, affinity CE (ACE), ultrafiltration) is here described and the results obtained are compared. The common features of the chemical structures of the compounds known to bind the protein led us to select 200 sulfonated/suramin-like molecules from a wider chemical library on the basis of similarity rules, so as to possibly single out some interesting hits and to gain more information on the functional groups involved in the binding. The development of screening methods to test the compounds by using ultrafiltration and ACE is described.     

Squeezing the [Cu-OH...H2O-Cu]3+ bridge by cryptate encapsulation

Treatment of cryptand L(1) with Cu(II) generates a H3O2(-)-bridged dicopper(II) cryptate, 2, where the guest anion has responded to steric constraint by a significant shortening of the O-O distance to 2.325(9) A; computational optimization at the B3LYP/6-31(d) level suggests that the bridging O-H...O H-bond is bent (approximately 157 degrees) but that the barrier to interchange of the bridging H atom is low (<4 kJ mol(-1)). This cryptate, rather than the [Cu2L(1)muCN]3+ species recently claimed to derive from cleavage of the C-C bond of the solvent, is the product of acetonitrile recrystallization of the initially formed reaction product, 1.     

Novel anti-Plasmodial hits identified by virtual screening of the ZINC database

Increased resistance of Plasmodium falciparum to most available drugs challenges the control of malaria. Studies with protease inhibitors have suggested important roles for the falcipain family of cysteine proteases. These enzymes act in concert with other proteases to hydrolyze host erythrocyte hemoglobin in the parasite food vacuole. In order to find potential new antimalarial drugs, we screened in silico the ZINC database using two different protocols involving structure- and ligand-based methodologies. Our search identified 19 novel low micromolar inhibitors of cultured chloroquine resistant P. falciparum. The most active compound presented an IC₅₀ value of 0.5 μM against cultured parasites and it also inhibited the cysteine protease falcipain-2 (IC₅₀ = 25.5 μM). These results identify novel classes of antimalarials that are structurally different from those currently in use and which can be further derivatized to deliver leads suitable for optimisation.     

Dihydroxamate based siderophore model, piperazine-1,4-bis-(N-methyl-acetohydroxamic acid (PIPDMAHA), as a chelating agent of molybdenum(VI)

Equilibrium studies based on pH-potentiometric and spectrophotometric measurements as well as some theoretical simulations are reported for the complexes of Mo(VI) with a dihydroxamate type siderophore analogue, the piperazine-1,4-bis-(N-methyl-acetohydroxamic acid) (PIPDMAHA). It has been found that the complexation process starts below pH 2 and that PIPDMAHA forms more stable O,O-hydroxamate bis-chelated complexes with Mo(VI) than any of the formerly studied dihydroxamic acids. The experimental data were fitted with two complexation models based either on dinuclear or on mononuclear species. However, ESI-MS showed that the dimmer is much more abundant than the monomer. This feature was further suggested by theoretical simulation studies, which indicated the dimeric species is more stable than the monomeric one.