First synthesis and full characterization of mexiletine N-carbonyloxy β-d-glucuronide

A simple, convergent synthesis of the N-carbonyloxy β-d-glucuronide of mexiletine (sodium salt) in moderate yield is described. The compound is now available as an authentic reference standard for analytical studies, enabling more detailed investigation on the metabolism of mexiletine.     

Economical,Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

A new electrochemical methodology has been developed for the generation of oxycarbonyl radicals under mild and green conditions from readily available hemioxalate salts. Mono‐ and multi‐functionalised γ‐butyrolactones were synthesised through exo‐cyclisation of these oxycarbonyl radicals with an alkene, followed by the sp³–sp³ capture of the newly formed carbon‐centred radical. The synthesis of functionalised valerolactone derivatives was also achieved, demonstrating the versatility of the newly developed methodology. This represents a viable synthetic route towards pharmaceutically important fragments and further demonstrates the practicality of electrosynthesis as a green and economical method to activate small organic molecules.     

Gravitational Collapse in Quantum Einstein Gravity

The existence of spacetime singularities is one of the biggest problems of nowadays physics. According to Penrose, each physical singularity should be covered by a “cosmic censor” which prevents any external observer from perceiving their existence. However, classical models describing the gravitational collapse usually results in strong curvature singularities, which can also remain “naked” for a finite amount of advanced time. This proceedings studies the modifications induced by asymptotically safe gravity on the gravitational collapse of generic Vaidya spacetimes. It will be shown that, for any possible choice of the mass function, quantum gravity makes the internal singularity gravitationally weak, thus allowing a continuous extension of the spacetime beyond the singularity.     

Analysis of corticosteroids by high performance liquid chromatography-electrospray mass spectrometry

A high performance liquid chromatography electrospray mass spectrometry (HPLC-ESI-MS) method, for the detection of corticosteroids in cosmetics has been developed. A water-acetonitrile linear gradient on a C-18 reversed-phase column was found to be suitable in separating triamcinolone and its main derivatives, which greatly differ in lipophilicity. Detection was performed in negative electrospray ionisation mode. Good correlation between peaks areas and solutions concentration was found in the range 0.05-10.0 micro g ml(-1) and the detection limits resulted in the range of 20-45 pg injected. The method was successfully applied to the analysis of real samples of shampoo.     

Effects of polymorphic differences for sulfanilamide, as seen through 13C and 15N solid-state NMR, together with shielding calculations

We recorded both carbon-13 and nitrogen-15 NMR spectra of the three solid forms of sulfanilamide most commonly known. This study led to an interpretation of the solid-state effects seen in cross-polarization magic angle spinning spectra. Relaxation times for the different forms were measured. These show different behaviour for the three forms, arising from mobility variations. To obtain information on local environments, static spectra and spinning sideband manifolds were recorded and analysed for the 15N resonances, using isotopically enriched samples. Shielding asymmetries and anisotropies for the two nitrogen nuclei were obtained, showing very different behaviour for the two sites. Shielding calculations were carried out for both 13C and 15N nuclei, and the results are discussed in relation to the experimental values.     

Iridoid glucosides from Lamium garganicum flowers

In the flowers of Lamium garganicum L. a single iridoid is present, as main glycosidic component, the 8-acetyl-shanzhiside methyl ester, 1. The structure of 1 was established by spectroscopic studies and chemical evidence.     

Synthesis and structural characterization of copper(II) complexes with the 2′-[1-(2-pyridinyl)ethylidene]oxalohydrazide ligand

The octahedral copper(II) complex with two 2-[1-(2-pyridinyl)ethylidene]oxalohydrazide molecules was synthesized from bis(acetylacetonato)copper(II) and 2-[1-(2-pyridinyl)ethylidene]oxamohydrazide (Hapsox). The complex is unstable when not in solution. X-ray analysis confirmed the tridentate coordination of the ligands in the monoanionic form. In addition, the stable tetrahedral copper(II) complex with one ligand molecule coordinated as a tridentate in the dianionic form was prepared by direct synthesis from Cu(NO₃)₂·3H₂O and Hapsox, and characterized by elemental analysis, magnetic measurements and by i.r. and u.v./vis. spectrophotometry.     

Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose-based chiral stationary phase under normal- and green reversed-phase conditions

Normal-phase and reversed-phase high-performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)-enantiomer impurity have been developed on the cellulose-based Chiralcel OJ-H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol–water–diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)-enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 μg mL⁻¹, respectively.     

New Coumarin Derivatives as Cholinergic and Cannabinoid System Modulators

In the last years, the connection between the endocannabinoid system (eCS) and neuroprotection has been discovered, and evidence indicates that eCS signaling is involved in the regulation of cognitive processes and in the pathophysiology of Alzheimer’s disease (AD). Accordingly, pharmacotherapy targeting eCS could represent a valuable contribution in fighting a multifaceted disease such as AD, opening a new perspective for the development of active agents with multitarget potential. In this paper, a series of coumarin-based carbamic and amide derivatives were designed and synthesized as multipotent compounds acting on cholinergic system and eCS-related targets. Indeed, they were tested with appropriate enzymatic assays on acetyl and butyryl-cholinesterases and on fatty acid amide hydrolase (FAAH), and also evaluated as cannabinoid receptor (CB1 and CB2) ligands. Moreover, their ability to reduce the self-aggregation of beta amyloid protein (Aβ₄₂) was assessed. Compounds 2 and 3, bearing a carbamate function, emerged as promising inhibitors of hAChE, hBuChE, FAAH and Aβ₄₂ self-aggregation, albeit with moderate potencies, while the amide 6 also appears a promising CB1/CB2 receptors ligand. These data prove for the new compounds an encouraging multitarget profile, deserving further evaluation.