Design, synthesis, evaluation, and structure of vitamin D analogues with furan side chains

Based on the crystal structures of human vitamin D receptor (hVDR) bound to 1α,25-dihydroxy-vitamin D(3) (1,25 D) and superagonist ligands, we previously designed new superagonist ligands with a tetrahydrofuran ring at the side chain that optimize the aliphatic side-chain conformation through an entropy benefit. Following a similar strategy, four novel vitamin D analogues with aromatic furan side chains (3a, 3b, 4a, 4b) have now been developed. The triene system has been constructed by an efficient stereoselective intramolecular cyclization of an enol triflate (A-ring precursor) followed by a Suzuki-Miyaura coupling of the resulting intermediate with an alkenyl boronic ester (CD-side chain, upper fragment). The furan side chains have been constructed by gold chemistry. These analogues exhibit significant pro-differentiation effects and transactivation potency. The crystal structure of 3a in a complex with the ligand-binding domain of hVDR revealed that the side-chain furanic ring adopts two conformations.     

In Vitro Antioxidant,Antitumor and Photocatalytic Activities of Silver Nanoparticles Synthesized Using Equisetum Species: A Green Approach

The ethanolic extracts of three Equisetum species (E. pratense Ehrh., E. sylvaticum L. and E. telmateia Ehrh.) were used to reduce silver ions to silver nanoparticles (AgNPs). The synthesized AgNPs were characterized using UV-Vis spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), Energy Dispersive X-ray (EDX), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) measurements. FTIR data revealed the functional groups of biomolecules involved in AgNPs synthesis, such as O-H, C-H, C=O, C-O, and C-C. EDX spectroscopy was used to highlight the presence of silver, while DLS spectroscopy provided information on the mean diameter of AgNPs, that ranged from 74.4 to 314 nm. The negative Zeta potential values (−23.76 for Ep–AgNPs, −29.54 for Es–AgNPs and −20.72 for Et–AgNPs) indicate the stability of the obtained colloidal solution. The study also focused on establishing the photocatalytic activity of AgNPs, which is an important aspect in terms of removing organic dyes from the environment. The best photocatalytic activity was observed for AgNPs obtained from E. telmateia, which degraded malachite green in a proportion of 97.9%. The antioxidant action of the three AgNPs samples was highlighted comparatively through four tests, with the best overall antioxidant capacity being observed for AgNPs obtained using E. sylvaticum. Moreover, the biosynthesized AgNPs showed promising cytotoxic efficacy against cancerous cell line MG63, the AgNPs obtained from E. sylvaticum L. providing the best result, with a LD₅₀ value around 1.5 mg/mL.     

Chiral Nano-Liquid Chromatography and Dispersive Liquid-Liquid Microextraction Applied to the Analysis of Antifungal Drugs in Milk

A novel chromatographic application in chiral separation by using the nano-LC technique is here reported. The chiral recognition of 12 antifungal drugs was obtained through a 75 µm I.D. fused-silica capillary, which was packed with a CSP-cellulose 3,5-dichlorophenylcarbamate (CDCPC), by means of a lab-made slurry packing procedure. The mobile phase composition and the experimental conditions were optimized in order to find the optimum chiral separation for some selected racemic mixtures of imidazole and triazole derivatives. Some important parameters, such as retention faction, enantioresolution, peak efficiency, and peak shape, were investigated as a function of the mobile phase (pH, water content, type and concentration of both the buffer and the organic modifier, and solvent dilution composition). Within one run lasting 25 min, at a flow rate of approximately 400 nL min⁻¹, eight couples of enantiomers were baseline-resolved and four of them were separated in less than 25 min. The method was then applied to milk samples, which were pretreated using a classical dispersive liquid–liquid microextraction technique preceded by protein precipitation. Finally, the DLLME-nano-LC–UV method was validated in a matrix following the main FDA guidelines for bioanalytical methods.     

The role of nuclear chemistry and radiochemistry in nanosafety studies

ABSTRACT

Nowadays there is an increasing demand of engineering nanoparticles – ENPs – thanking the excellent characteristics and properties of the products in which nanoparticles (NPs) are used. On the other hand, many are the unresolved questions about their potential adverse health and environmental impacts arising from exposure to these innovative materials. The growing utilisation of ENPs in consumer and industrial products have led to a potential increase of human exposure, thus raising concerns of many scientists and governments regarding health risks to workers and the public. Research on the impact of ENPs is strongly hampered by a lack of reliable tools to detect, visualise, and quantitatively trace particles movement and transfer in complex environmental and biological systems. The research tries to give some answers in this field using many different analytical techniques. In this paper, the types of information that can be obtained using nuclear techniques will be presented, with some examples of applications related to studies with metallic NPs.     

NP-completeness results for edge modification problems

The aim of edge modification problems is to change the edge set of a given graph as little as possible in order to satisfy a certain property. Edge modification problems in graphs have a lot of applications in different areas, and many polynomial-time algorithms and NP-completeness proofs for this kind of problems are known. In this work we prove new NP-completeness results for these problems in some graph classes, such as interval, circular-arc, permutation, circle, bridged, weakly chordal and clique-Helly graphs.     

Analysis of ν2 of H233S and H234S

We have extended our analysis of the (010) vibrational state of H₂S, this time using Watson's A-reduced Hamiltonian (through P⁸ terms) in the I′ rotational representation. We have determined separate sets of (010) upper state constants for each isotopomer (H₂³²S, H₂³³S, and H₂³⁴S) by fitting the ν₂ spectral lines, keeping the ground state constants fixed to the values determined by Flaud, Camy-Peyret, and Johns. Determinable coefficients for H₂³²S and a slightly revised set of ν₂ line assignments for H₂³³S and H₂³⁴S are also reported.     

A New Water Soluble Calixarene: 5,11,17,23-tetrasulphonato-25,27-di(hydroxycarbonylmethoxy)-26, 28-dihydroxycalix[4]arene. A Thermodynamic and Spectroscopic Investigation of Its Proton and Copper(II) Complexes

A new water soluble receptor 5,11,17,23-tetrasulphonato-25,27-di(hydroxycarbonylmethoxy)-26,28-dihydroxycalix[4]arene was synthesized andcharacterized and its proton and copper(II) complexes were studied andcompared with the analogous species of the fully carboxylated ligand5,11,17,23-tetrasulphonato-25,26,27,28-tetrakis(hydroxycarbonylmethoxy)calix[4]arene. H° and S° values are crucial for understanding thepeculiar acid-base properties of the ligand. EPR spectra together with theUV-VIS spectral data reveal the coordination stereochemistry of thecopper(II) species.     

Response of a designed metalloprotein to changes in metal ion coordination, exogenous ligands, and active site volume determined by X-ray crystallography

The de novo protein DF1 is a minimal model for diiron and dimanganese metalloproteins, such as soluble methane monooxygenase. DF1 is a homodimeric four-helix bundle whose dinuclear center is formed by two bridging Glu side chains, two chelating Glu side chains, and two monodentate His ligands. Here, we report the di-Mn(II) and di-Co(II) derivatives of variants of this protein. Together with previously solved structures, 23 crystallographically independent four-helix bundle structures of DF1 variants have been determined, which differ in the bound metal ions and size of the active site cavity. For the di-Mn(II) derivatives, as the size of the cavity increases, the number and polarity of exogenous ligands increases. This collection of structures was analyzed to determine the relationship between protein conformation and the geometry of the active site. The primary mode of backbone movement involves a coordinated tilting and sliding of the first helix in the helix-loop-helix motif. Sliding depends on crystal-packing forces, the steric bulk of a critical residue that determines the dimensions of the active site access cavity, and the intermetal distance. Additionally, a torsional motion of the bridging carboxylates modulates the intermetal distance. This analysis provides a critical evaluation of how conformation, flexibility, and active site accessibility affect the geometry and ligand-binding properties of a metal center. The geometric parameters defining the DF structures were compared to natural diiron proteins; DF proteins have a restricted active site cavity, which may have implications for substrate recognition and chemical stability.