Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives

2,12-diaza[6]helicene: An efficient non-conventional stereogenic scaffold for enantioselective electrochemical interphases

The new configurationally stable, unsymmetrical 2,12-diaza[6]helicene was synthesized as a racemate and the enantiomers were separated in an enantiopure state by semi-preparative HPLC on chiral stationary phase. Under selected alkylation conditions it was possible to obtain both the enantiopure 2-N-mono- and di-N-ethyl quaternary iodides. Metathesis with bis(trifluoromethanesulfonyl)imide anion gave low-melting salts which were tested as inherently chiral additives to achiral ionic liquids for the electrochemical enantiodiscrimination of chiral organic probes in voltammetric experiments. Remarkable differences in the oxidation potentials of the enantiomers of two probes, a chiral ferrocenyl amine and an aminoacid, were achieved; the differences increase with increasing additive concentration and number of alkylated nitrogen atoms

Helicity: a non-conventional stereogenic element for designing inherently chiral ionic liquids for electrochemical enantiodifferentiation

Configurationally stable 5-aza[6]helicene (1) was envisaged as a promising scaffold for non-conventional ionic liquids (IL)s. It was prepared, purified, and separated into enantiomers by preparative HPLC on a chiral stationary phase. Enantiomerically pure quaternary salts of 1 with appropriate counterions were prepared and fully characterized. N-octyl-5-aza[6]helicenium bis triflimidate (2) was tested in very small quantities as a selector in achiral IL media to perform preliminary electrochemical enantiodifferentiation experiments on the antipodes of two different chiral probes. The new organic salt exhibited outstanding enantioselection performance with respect to these probes, thus opening the way to applications in the enantioselective electroanalysis of relevant bioactive molecules

Highly enantioselective “inherently chiral” electroactive materials based on a 2,2' -biindole atropisomeric scaffold

Chiral oligothiophene monomers with C2 symmetry, based on 3,30 -bithiophene atropisomeric cores with high racemization barriers, have recently been shown to provide excellent chiral starting materials with high electroactivity for the easy preparation of enantiopure electroactive films endowed with powerful chirality manifestations. We now introduce an inherently chiral monomer based on a 2,20 -biindole core, as the prototype of a new inherently chiral monomer family, whose properties could be modulable through functionalization of the pyrrolic N atoms. By fast, regular electrooligomerization the new monomer yields inherently chiral films with high, reversible electroactivity and, above all, impressive enantioselectivity towards very different chiral probes, some of pharmaceutical interest, as generalscope electrode surfaces. Such results, while opening the way to a new, attractive inherently chiral selector class, nicely confirm the general validity of the inherent chirality strategy for chiral electrochemistry. Furthermore, the enantioselectivity of the new selectors not only holds with electroactive chiral probes, but also with circularly polarized light components as well as electron spins, resulting in good chiroptical and spin filter performances, which suggests fascinating correlations between the three contexts

Latest Triassic onset of the Central Atlantic Magmatic Province (CAMP) volcanism in the Fundy Basin (Nova Scotia): New stratigraphic constraints

In this paper we investigate the stratigraphic relationship between the emplacement of the CAMP basalts and the Triassic–Jurassic (Tr–J) boundary in the Fundy Basin (Nova Scotia, Canada). This is one of the best exposed of the synrift basins of eastern North America (ENA) formed as a consequence of the rifting that led to the formation of the Atlantic Ocean. The Triassic palynological assemblages found in the sedimentary rocks below (uppermost Blomidon Formation) and just above the North Mountain Basalt (Scots Bay Member of the McCoy Brook Formation) indicate that CAMP volcanism, at least in Nova Scotia, is entirely of Triassic age, occurred in a very short time span, and may have triggered the T–J boundary biotic and environmental crisis. The palynological assemblage from the Blomidon Formation is characterised by the dominance of the Circumpolles group (e.g. Gliscopollis meyeriana, Corollina murphyae, Classopollis torosus) which crosses the previously established Tr–J boundary.The Triassic species Patinasporites densus disappears several centimetres below the base of the North Mountain basalt, near the previously interpreted Tr–J boundary. The lower strata of the Scots Bay Member yielded a palynological assemblage dominated by Triassic bisaccate pollens (e.g Lunatisporites acutus, L. rhaeticus Lueckisporites sp., Alisporites parvus) with minor specimens of the Circumpolles group. Examination of the state of preservation and thermal alteration of organic matter associated with the microfloral assemblages precludes the possibility of recycling of the Triassic sporomorphs from the older strata. Our data argue against the previous definition of the Tr–J boundary in the ENA basins, which was based mainly on the last occurrence of P. densus. Consequently, it follows that the late Triassic magnetostratigraphic correlations should be revised considering that chron E23r, which is correlated with the last occurrence of P. densus in the Newark basin, does not occur at the Tr–J boundary but marks rather a late Triassic (probably Rhaetian) reversal

Towards a standardized index of European rabbit abundance in Iberian Mediterranean habitats

European rabbits Oryctolagus cuniculus are a keystone species in Iberian Mediterranean ecosystems. However, the reliability of methods for estimating rabbit abundance, particularly when at low numbers, is not well understood. Further, better standardization of these methodologies would allow abundance estimates to be more reliably compared between areas and periods. Consequently, we compared several frequently used methods of estimating rabbit abundance and assessed their advantages and disadvantages. During the summers of 2008 and 2009, in 11 localities of central-southern Spain we undertook (a) driving transect counts of rabbits, either at dusk or at night, (b) linear transects on foot recording rabbit signs, (c) cleared-plot pellet counts at permanent plots, and (d) standing crop counts, both with and without habitat stratification. Density estimated at night from driving transects using the Distance Sampling method (the reference method against which all other indices were compared) varied from 0 to 2. 69 rabbits ha-1. Most pellet-count indices were significantly related to the reference method. In particular, cleared-plot pellet counts in permanent plots corrected for pellet persistence showed the best correlation with the reference method. In contrast, latrine counts were not related to the reference method index, and we recommend against their use. A standard methodology based on cleared-plot pellets counts could be used to monitor rabbit abundance on a large scale.This work is a partial result from the projects CGL2005-02340, CGL2009-10741, and CGL2009-11665 funded by the Spanish Ministry of Science and Innovation and EU-FEDER funds, and projects POII09-0099-2557 and 07/NAT/E/000742 funded by the Junta de Comunidades de Castilla-La Mancha with EU-FEDER and LIFE funds, respectively. Javier Fernandez-de-Simon benefits from a FPI scholarship and Miguel Delibes-Mateos is currently holding a Juan de la Cierva research contract, both funded by the Spanish Ministry of Science and Innovation and the European Social Fund.Peer Reviewe

Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes

Aging is a multifactorial phenomenon characterized by degenerative processes closely connected to oxidative damage and chronic inflammation. Recently, many studies have shown that natural bioactive compounds are useful in delaying the aging process. In this work, we studied the effects of an in vivo supplementation of the stilbenoid pterostilbene on lifespan extension in Drosophila melanogaster. We found that the average lifespan of flies of both sexes was increased by pterostilbene supplementation with a higher effect in females. The expression of longevity related genes (Sir2, Foxo, and Notch) was increased in both sexes but with different patterns. Pterostilbene counteracted oxidative stress induced by ethanol and paraquat and up-regulated the antioxidant enzymes Ho e Trxr-1 in male but not in female flies. On the other hand, pterostilbene decreased the inflammatory mediators dome and egr only in female flies. Proteomic analysis revealed that pterostilbene modulates 113 proteins in male flies and only 9 in females. Only one of these proteins was modulated by pterostilbene in both sexes: vacuolar H[+] ATPase 68 kDa subunit 2 (Vha68-2) that was strongly down-regulated. These findings suggest a potential role of pterostilbene in increasing lifespan both in male and female flies by mechanisms that seem to be different in the two sexes, highlighting the need to conduct nutraceutical supplementation studies on males and females separately in order to give more reliable results

40Ar/39Ar ages of CAMP in North America: implications for the Triassic-Jurassic boundary and the 40K decay constant bias

The Central Atlantic magmatic province (CAMP) is one of the largest igneous provinces on Earth (>107 km²) and spanning four continents. Recent high-precision 40Ar/39Ar dating of mineral separates has provided important constraints on the age, duration, and geodynamic history of CAMP. Yet, the North American CAMP is strikingly under-represented in this dating effort. Here we present 13 new statistically robust plateau, mini-plateau and isochron ages obtained on plagioclase and sericite separates from lava flows from the Fundy (n = 10; Nova Scotia, Canada) and Hartford and Deerfield (n = 3; U.S.A.) basins. Ages mostly range from 198.6 ± 1.1 to 200.1 ± 1.4 Ma (2σ), with 1 date substantially younger at 190.6 ± 1.0 Ma. Careful statistical regression shows that ages from the upper (199.7.0 ± 1.5 Ma) and bottom (200.1 ± 0.9 Ma) units of the lava pile in the Fundy basin are statistically indistinguishable, confirming a short duration emplacement (<< 1.8 Ma; ≤1 Ma). Three ages obtained on the Hartford (198.6 ± 2.0 Ma and 199.8 ± 1.1 Ma) and Deerfield (199.3 ± 1.2 Ma) basins were measured on sericite from the upper lava flow units. We interpret these dates as reflecting synemplacement hydrothermal activity within these units. Collectively, CAMP ages gathered so far suggest a short duration of the main magmatic activity (2-3 Ma), but also suggest the possibility of a temporal migration of the active magmatic centers from north to south. Such a migration challenges a plume model that would postulate a radial outward migration of the magmatism and is more compatible with other models such as the supercontinent global warming hypothesis. When compared to the age of the Triassic-Jurassic boundary, the filtered CAMP age database suggests that the onset of the magmatic activity precedes the limit by at least few hundred thousand years, therefore suggesting a causal relationship between CAMP and the end of Triassic mass extinction. An age at 191 Ma possibly suggests a minor CAMP late tailing activity (190-194 Ma) which has already observed for dykes and sills in Africa and Brazil. We speculate that, if real, this late activity can be due to a major extensional event, possibly heralding the oceanisation process at ~190 Ma. Comparison between high quality U/Pb and 40Ar/39Ar ages of pegmatite lenses from the North Mountain basalts confirms a ~1% bias between the two chronometers. This discrepancy is likely attributed to the miscalibration of the 40K decay constants, in particular the electron capture branch