The Physico-Chemical Properties of Glipizide: New Findings

The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.     

Mixing of electronic states in pentacene adsorption on copper

By combining experimental and theoretical approaches, we study the adsorption of pentacene on copper as a model for the coupling between aromatic molecules and metal surfaces. Our results for the interface electronic structure are not compatible with a purely physisorption picture, which is conventionally employed for such systems. Nay, we demonstrate electronic mixing between molecular orbitals and metal electronic states.     

Tunable Linear and Nonlinear Optical Properties from Room Temperature Phosphorescent Cyclic Triimidazole-Pyrene Bio-Probe

Organic materials with multiple emissions tunable by external stimuli represent a great challenge. TTPyr, crystallizing in different polymorphs, shows a very rich photophyisics comprising excitation-dependent fluorescence and phosphorescence at ambient conditions, and mechanochromic and thermochromic behavior. Transformation among the different species has been followed by thermal and X-ray diffraction analyses and the emissive features interpreted through structural results and DFT/TDDFT calculations. Particularly intriguing is the polymorph TTPyr(HT), serendipitously obtained at high temperature but stable also at room temperature, whose non-centrosymmetric structure guarantees an SHG efficiency 10 times higher than that of standard urea. Its crystal packing, where only the TT units are strongly rigidified by π-π stacking interactions while the Pyr moieties possess partial conformational freedom, is responsible for the observed dual fluorescence. The potentialities of TTPyr for bioimaging have been successfully established.     

Palladium nanoparticles on modified cellulose as a novel catalyst for low temperature gas reactions

Cellulose - Palladium was incorporated into carboxymethylated cellulose fibers as a support, thereby becoming an efficient and stable catalyst for low temperature gas phase reaction. Thus, NO was...     

Spin‐State Ordering on One Sub‐lattice of a Mononuclear Iron(III) Spin Crossover Complex Exhibiting LIESST and TIESST

The two‐step spin crossover in mononuclear iron(III) complex [Fe(salpm)₂]ClO₄ ? 0.5 EtOH ( 1 ) is shown to be accompanied by a structural phase transition as concluded from ⁵⁷Fe Mössbauer spectroscopy and single crystal X‐ray diffraction, with spin‐state ordering on just one of two sub‐lattices in the intermediate magnetic and structural phase. The complex also exhibits thermal‐ and light‐induced spin‐state trapping (TIESST and LIESST), and relaxation from the LIESST and TIESST excited states occurs via the broken symmetry intermediate phase. Two relaxation events are evident in both experiments, that is, two T(LIESST) and two T(TIESST) values are recorded. The change in symmetry which accompanies the TIESST effect was followed in real time using single crystal diffraction. After flash freezing at 15 K the crystal was warmed to 40 K at which temperature superstructure reflections were observed to appear and disappear within a 10 000 s time range. In the frame of the international year of crystallography, these results illustrate how X‐ray diffraction makes it possible to understand complex ordering phenomena.     

Copper-Free Halodediazoniation of Arenediazonium Tetrafluoroborates in Deep Eutectic Solvents-like Mixtures

Deep Eutectic Solvent (DES)-like mixtures, based on glycerol and different halide organic and inorganic salts, are successfully exploited as new media in copper-free halodediazoniation of arenediazonium salts. The reactions are carried out in absence of metal-based catalysts, at room temperature and in a short time. Pure target products are obtained without the need for chromatographic separation. The solvents are fully characterized, and a computational study is presented aiming to understand the reaction mechanism.     

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.     

New Promising Therapeutic Avenues of Curcumin in Brain Diseases

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called “spice of life”, in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer’s Diseases, Parkinson’s Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.     

Label-Free Quantitative Proteomics to Explore the Action Mechanism of the Pharmaceutical-Grade Triticum vulgare Extract in Speeding Up Keratinocyte Healing

Plant extracts have shown beneficial properties in terms of skin repair, promoting wound healing through a plethora of mechanisms. In particular, the poly-/oligosaccharidic aqueous extract of Triticum vulgare (TVE), as well as TVE-based products, shows interesting biological assets, hastening wound repair. Indeed, TVE acts in the treatment of tissue regeneration mainly on decubitus and venous leg ulcers. Moreover, on scratched monolayers, TVE prompts HaCat cell migration, correctly modulating the expression of metalloproteases toward a physiological matrix remodeling. Here, using the same HaCat-based in vitro scratch model, the TVE effect has been investigated thanks to an LFQ proteomic analysis of HaCat secretomes and immunoblotting. Indeed, the unbiased TVE effect on secreted proteins has not yet been fully understood, and it could be helpful to obtain a comprehensive picture of its bio-pharmacological profile. It has emerged that TVE treatment induces significant up-regulation of several proteins in the secretome (153 to be exact) whereas only a few were down-regulated (72 to be exact). Interestingly, many of the up-regulated proteins are implicated in promoting wound-healing-related processes, such as modulating cell–cell interaction and communication, cell proliferation and differentiation, and prompting cell adhesion and migration.