Direct regio- and stereoselective synthesis of squalene 2,3;22,23-dioxide using dioxiranes

Dimethyldioxirane (1a) and its trifluoro analog (1b) were employed to achieve selectively the direct transformation of squalene 2,3(S)-oxide and of squalene 2,3(R)-oxide into the corresponding 2,3(S);22(S),23-dioxide and 2,3(R);22(R),23-dioxide, respectively. These transformations were found to occur with convenient regio- and diastereoselectivity, providing easy access to the valuable dioxides metabolites. The powerful methyl(trifluoromethyl)dioxirane (1b) is the reagent of choice to achieve optimum yields of the target compounds.     

Time-resolved microspectrofluorimetry and fluorescence lifetime imaging of hypericin in human retinal pigment epithelial cells

Hypericin is the active ingredient of the off-the-shelf antidepressant St. John's Wort. It is an effective phototoxic agent and its systemic administration at therapeutic doses could induce particular damage in the eye due to continuous light exposure. Hypercin is strongly fluorescent and its fluorescence properties can be monitored to investigate noninvasively its localization and interactions. To this aim, time-resolved microspectrofluorimetry and fluorescence lifetime imaging were used to assess the spectral and temporal properties as well as the spatial distribution of the fluorescence emitted by retinal pigment epithelium (RPE) cells treated with Hyp at concentrations in the micromolar range (0.5-10 microM). In the presence of hypericin, the emission peaks at 600-605 nm and the fluorescence decay is best fitted with three lifetimes (5.5-7 ns, 1.9-2.5 ns and <0.8 ns). Spectral and temporal differences were observed between high (> or =5 microM) and low hypericin concentrations. In particular, upon increasing concentration, the emission spectrum of the slow component broadens and its lifetime shortens. The latter change is observed also when high concentrations are reached locally, due to more efficient localization within the cell.     

Application of liquid chromatography/electrospray ionization tandem mass spectrometry to the analysis of polyphenolic compounds from an infusion of Byrsonima crassa Niedenzu

A fast and reliable method, based on high-performance liquid chromatography coupled to electrospray ionization ion trap tandem mass spectrometry (HPLC/ESI-ITMS), was developed to investigate the infusion prepared from the leaves of Byrsonima crassa Niedenzu (Malpighiaceae), a native plant used in Brazil against gastric disorders. The use of on-line reverse-phase HPLC/ESI-ITMS allowed separation of three major classes of compounds and identification of over 20 very polar compounds characterized as galloylquinic acids, proanthocyanidins, and flavonoid glycosides, as well as the dimeric flavonoid amentoflavone and minor amounts of galloyl hexose and galloyl saccharose. This approach provided data that will allow establishment of a method for a future standardization of the infusion.     

Effect of the gelation process on the production of alginate microbeads by microfluidic chip technology

The present paper reports the production of Ba-alginate microspheres by microfluidic chip technology. The general production strategy is based on the formation of an alginate multiphase flow by a 'Y' junction squeezing mechanism. Special emphasis is given to the relationship existing between the gelation process and the final morphological characteristics of the produced microbeads. A series of different gelation strategies, namely: 'external gelation', 'internal gelation' and 'partial gelation' were compared in terms of size, size distribution and morphology of the produced microbeads.     

Synthetic strategies to alpha-trifluoromethyl and alpha-difluoromethyl substituted alpha-amino acids

The combination of the unique physical and chemical properties of fluorine with proteinogenic amino acids represents a new approach to the design of biologically active compounds including peptides with improved pharmacological parameters. Therefore, the development of routine synthetic methods which enable the effective and selective introduction of fluorine into the desired amino acids from readily available starting materials is of significant synthetic importance. The scope of this critical review is to summarize the most frequently employed strategies for the synthesis of alpha-difluoromethyl and alpha-trifluoromethyl substituted alpha-amino acids (114 references).     

Reactivity of a phosphinito-bridged PtI-PtI complex with nucleophiles: substitution versus addition

As a result of the strong electrophilic character of the Pt bound to O, the phosphinito-bridged PtI complex [(PHCy2)Pt(micro-PCy2){kappa2P,O-micro-P(O)Cy2}Pt(PHCy2)](Pt-Pt) (1) undergoes attack at the O-bound Pt atom by molecules such as di- and tricyclohexylphosphane, dicyclohexylphosphane oxide, and dicyclohexylphosphane sulfide. Thus, reaction of 1 with PHCy2 gives the symmetric PtI dimer [(PHCy2)Pt(micro-PCy2)]2(Pt-Pt) (2), while the hydrido-bridged complex syn-[(PHCy2){kappaP-P(O)Cy2}Pt(micro-PCy2)(micro-H)Pt(PHCy2){kappaP-P(O)Cy2}](Pt-Pt) (4) is obtained from reaction of 1 with P(O)HCy2; the thiophosphinito complex [(PHCy2)Pt(micro-PCy2){kappa2P,S-micro-P(S)Cy2}Pt(PHCy2)](Pt-Pt) (8) forms selectively in reaction of 1 with P(S)HCy2. For comparison, the reaction with PCy3 results only in ligand substitution, affording [(PCy3)Pt(micro-PCy2){kappa2P,O-micro-P(O)Cy2}Pt(PHCy2)](Pt-Pt) (5). DFT studies confirmed the remarkable electrophilicity of the oxygen-bound Pt and shed light on the nature of the metal-metal bond in Pt dimers.     

New Antifungal Terpenoid Glycosides from Alibertia edulis (Rubiaceae)

Phytochemical investigation from the stems of Alibertia edulis led to the isolation and identification of a new iridoid 6β‐hydroxy‐7‐epigardoside methyl ester ( 1 ) and a new saponin 3β‐O‐[α‐L ‐rhamnopyranosyl‐(1→2)‐O‐β‐D ‐glucopyranosyl‐(1→2)‐O‐β‐D ‐glucopyranosyl]‐28‐O‐β‐D ‐glucopyranoside pomolate ( 2 ), along with three known compounds, shanzhiside methyl ester ( 3 ), ixoside ( 4 ), and 3,4,5‐trimethoxyphenyl 1‐O‐β‐D ‐apiofuranosyl‐(1→6)‐O‐β‐D ‐glucopyranoside ( 5 ). The structures of 1 and 2 were established on the basis of their spectroscopic data. Iridoid 1 and saponin 2 exhibited moderate inhibitory activities against Candida albicans and C. krusei in a dilution assay.     

Nanocomposite Fibers for Cosmetotextile Applications

In this work, a series of nylon 6 nanocomposites with different nanoclay/jojoba oil contents have been prepared by direct melt compounding. Nanocomposite morphologies were characterized by means of WAXS analysis. Thermal and mechanical fibers properties were studied as well. The kinetic desorption of the cosmetic oil through the polymer matrix was evaluated by FT-IR microscopy. It was found that the state of the clay particles affected the thermal behaviour and the tensile mechanical properties of each polymer/clay hybrid. On the other hand, the release of the cosmetic oil, tested by FT-IR microscopy, is a good perspective for the application of polyamide 6 nanocomposite fibers as textiles in cosmetic field.     

DNA Binding Studies and Cytotoxicity of a Dinuclear PtII Diazapyrenium‐Based Metallo‐supramolecular Rectangular Box

The interaction with native DNA of a 2,7‐diazapyrenium‐based ligand 1 and its Pt^II rectangular metallacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal‐free ligand 1 binds through intercalation, with a binding constant of approximately 5×10⁵ M ^?1, whereas the metallacycle 2 binds and bends the DNA with a binding constant of 7×10⁶ M ^?1. PCR assays show that metallo‐supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC₅₀ values ranging between 3.1 and 19.2 μM and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin.     

HCN channels and heart rate

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.