2-Diphenylphosphinomethyl-3-methylpyrazine

The lateral metalation-electrophilic trapping reaction of alkyl-substituted pyrazines has always been challenging and poorly regioselective, with the corresponding derivatives often being isolated in moderate yield. In this contribution, we first report on the preparation of an unsymmetrically-substituted pyrazine, that is 2-diphenylphosphinomethyl-3-methylpyrazine, by subjecting to metalation with n-BuLi the commercially available 2,3-dimethylpyrazine, followed by interception of the putative lithiated benzyl-type intermediate with Ph2PCl. Such a functionalization has been successfully carried out in the absence of additional ligands, working either in THF at −78 °C or in a more environmentally friendly solvent like cyclopentyl methyl ether at 0 °C, with the desired phosphine derivative being isolated in 70–85% yield. The newly synthesized adduct has been fully characterized by means of multinuclear magnetic resonance spectroscopic techniques, and also by preparing a selenium derivative, which furnished single crystals that were suitable for X-ray analysis

Climate variability during MIS 20–18 as recorded by alkenone-SST and calcareous plankton in the Ionian Basin (central Mediterranean)

This study shows the first Mediterranean high-resolution record of alkenone-derived sea surface temperature (SST) in the marine sediments outcropping at the Ideale section (IS) (southern Italy, central Mediterranean) from late marine isotope stage (MIS) 20 - through early MIS 18. The SST pattern evidences glacial-interglacial up to submillennial-scale temperature variation, with lower values (~13 °C) in late MIS 20 and substage 19b, and higher values (up to 21 °C) in MIS 19c and in the interstadials of MIS 19a. The SST data are combined with the new calcareous plankton analysis and the available, chronologically well-constrained carbon and oxygen isotope records in the IS. The multi-proxy approach, together with the location of the IS near the Italian coasts, the lower circalittoral-upper bathyal depositional setting, and high sedimentation rate allow to document long-and short-term paleoenvironmental modifications (sea level, rainfall, inorganic/organic/fresh water input to the basin), as a response to regional and global climate changes. The combined proxies reveal the occurrence of a terminal stadial event in late MIS 20 (here Med-HTIX), and warm-cold episodes (here Med-BATIX and Med-YDTIX) during Termination IX (TIX), which recall those that occurred through the last termination (TI). During these periods and the following ghost sapropel layer (insolation cycle 74, 784 ka) in the early MIS 19, high frequency internal changes are synchronously recorded by all proxies. The substage MIS 19c is warm but quite unstable, with several episodes of paleoenvironmental changes, associated with fluctuating tropical-subtropical water inflow through the Gibraltar Strait, variations of the cyclonic regime in the Ionian basin, and the southward shift of westerly winds and winter precipitation over southern Europe and Mediterranean basin. Three high-amplitude millennial-scale oscillations in the patterns of SST and calcareous plankton key taxa during MIS 19a are interpreted as linked to changes in temperature as well as in salinity due to periodical water column stratification and mixing. The main processes involved in the climate variability include changes in oceanographic exchanges through the Gibraltar Strait during modulations of Atlantic meridional overturning circulation and/or variations in atmospheric dynamics related to the influence of westerly and polar winds acting in the paleo-Ionian basin. A strong climate teleconnection between the North Atlantic and Mediterranean is discussed, and a prominent role of atmospheric processes in the central Mediterranean is evidenced by comparing data sets at the IS with Italian and extra-Mediterranean marine and terrestrial records

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose‐to‐Brain Delivery Application

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administratio

Oxidized alginate dopamine conjugate: In vitro characterization for nose-to-brain delivery application

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginatedopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and1H-NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 µg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration

Data for: Surface and deep water variability in the Western Mediterranean (ODP Site 975) during insolation cycle 74: high resolution calcareous plankton, biomarker and organic geochemical signals

Surface and deep water variability in the Western Mediterranean (ODP Site 975) during insolation cycle 74: high resolution calcareous plankton, biomarker and organic geochemical signal

Data for: Surface and deep water variability in the Western Mediterranean (ODP Site 975) during insolation cycle 74: high resolution calcareous plankton, biomarker and organic geochemical signals

Surface and deep water variability in the Western Mediterranean (ODP Site 975) during insolation cycle 74: high resolution calcareous plankton, biomarker and organic geochemical signal