Campione M.,Piazza della Science
Advanced Materials | Year: 2013
Organic droplet epitaxy is presented as a method for growing nanopatterned crystalline heterostructures, thanks to the transport of molecules of an amorphous first-layer on top of a crystalline second-layer, where they form an epitaxial interface. Such heterostructures may be transferred to any substrates, raising particular interest for applications (e.g., for organic photovoltaics), where crystallinity and nanopatterning constitute well recognized advantages. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Haynes R.K.,Hong Kong University of Science and Technology |
Chan W.-C.,Hong Kong University of Science and Technology |
Wong H.-N.,Hong Kong University of Science and Technology |
Li K.-Y.,Hong Kong University of Science and Technology |
And 8 more authors.
ChemMedChem | Year: 2010
The antimalarial drug methylene blue (MB) affects the redox behaviour of parasite flavin-dependent disulfide reductases such as glutathione reductase (GR) that control oxidative stress in the malaria parasite. The reduced flavin adenine dinucleotide cofactor FADH2 initiates reduction to leucomethylene blue (LMB), which is oxidised by oxygen to generate reactive oxygen species (ROS) and MB. MB then acts as a subversive substrate for NADPH normally required to regenerate FADH2 for enzyme function. The synergism between MB and the peroxidic antimalarial artemisinin derivative artesunate suggests that artemisinins have a complementary mode of action. We find that artemisinins are transformed by LMB generated from MB and ascorbic acid (AA) or N-benzyldihydronicotinamide (BNAH) in situ in aqueous buffer at physiological pH into single electron transfer (SET) rearrangement products or two-electron reduction products, the latter of which dominates with BNAH. Neither AA nor BNAH alone affects the artemisinins. The AA-MB SET reactions are enhanced under aerobic conditions, and the major products obtained here are structurally closely related to one such product already reported to form in an intracellular medium. A ketyl arising via SET with the artemisinin is invoked to explain their formation. Dihydroflavins generated from riboflavin (RF) and FAD by pretreatment with sodium dithionite are rapidly oxidised by artemisinin to the parent flavins. When catalytic amounts of RF, FAD, and other flavins are reduced in situ by excess BNAH or NAD(P)H in the presence of the artemisinins in the aqueous buffer, they are rapidly oxidised to the parent flavins with concomitant formation of twoelectron reduction products from the artemisinins; regeneration of the reduced flavin by excess reductant maintains a catalytic cycle until the artemisinin is consumed. In preliminary experiments, we show that NADPH consumption in yeast GR with redox behaviour similar to that of parasite GR is enhanced by artemisinins, especially under aerobic conditions. Recombinant human GR is not affected. Artemisinins thus may act as antimalarial drugs by perturbing the redox balance within the malaria parasite, both by oxidising FADH2 in parasite GR or other parasite flavoenzymes, and by initiating autoxidation of the dihydroflavin by oxygen with generation of ROS. Reduction of the artemisinin is proposed to occur via hydride transfer from LMB or the dihydroflavin to O1 of the peroxide. This hitherto unrecorded reactivity profile conforms with known structure-activity relationships of artemisinins, is consistent with their known ability to generate ROS in vivo, and explains the synergism between artemisinins and redox-active antimalarial drugs such as MB and doxorubicin. As the artemisinins appear to be relatively inert towards human GR, a putative model that accounts for the selective potency of artemisinins towards the malaria parasite also becomes apparent. Decisively, ferrous iron or carbon-centered free radicals cannot be involved, and the reactivity described herein reconciles disparate observations that are incompatible with the ferrous iron-carbon radical hypothesis for antimalarial mechanism of action. Finally, the urgent enquiry into the emerging resistance of the malaria parasite to artemisinins may now in one part address the possibilities either of structural changes taking place in parasite flavoenzymes that render the flavin cofactor less accessible to artemisinins or of an enhancement in the ability to use intra-erythrocytic human disulfide reductases required for maintenance of parasite redox balance. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
Silvestri L.,University of New South Wales |
Campione M.,Piazza della Science
Chemistry of Materials | Year: 2011
Great effort is being devoted to the fabrication of electronic devices based on rubrene thin films, because its outstanding charge transport properties make it one of the most promising organic semiconducting materials. Nonetheless, charge transport is strongly affected by the degree of crystallinity and degradation by photo-oxidation of rubrene. In the present work, in order to understand the dynamics of oxidation of rubrene when in the crystalline thin-film form, a combination of scanning probe techniques, such as Kelvin probe, phase contrast, and surface morphology atomic force microscopy, is used to study the oxidation process under ambient conditions of rubrene crystalline ultrathin films grown by organic molecular beam epitaxy on tetracene substrates. These films have a thickness of one or two molecular layers and consist of separated, island-like, epitaxial domains, whose orientation is determined by organic epitaxy. Theoretical calculations of the rubrene peroxide molecular dipole and structural data of rubrene and of purposely grown rubrene peroxide crystals, are exploited to determine the oxidation dynamics of such thin films and its connection with morphological, structural, and dielectric properties of the films. We demonstrate the formation of a native crystalline rubrene peroxide layer on top of the pristine rubrene crystalline domains. © 2011 American Chemical Society.
Zampella G.,Piazza della Science |
Bertini L.,Piazza della Science |
De Gioia L.,Piazza della Science
Chemical Communications | Year: 2014
Bromoperoxidase catalytic activity exerted by oxidated amavadin [V(HIDPA)2]- (HIDPA = 2,2′-(hydroxyimino) dipropionate) in mono- and bis-protonated forms has been investigated by DFT. Possible reaction pathways for formation of peroxido/hydroperoxido complexes and subsequent bromide oxidation have been systematically dissected. The effect of increasing [H+] on catalytically active species and on halogenide oxidation has been also studied. Similarly to vanadium haloperoxidase (VHPO), the results point to a hydroperoxido amavadin adduct as the most reactive species toward bromide oxidation. However, comparison of the reactivity of amavadin and VHPO reveals also crucial differences in the catalytic mechanism of such natural V complexes. © 2013 The Royal Society of Chemistry.
Matteis M.D.,Piazza della Science |
Resta F.,Piazza della Science |
Richter R.,Max Planck Institute for Physics |
Kroha H.,Max Planck Institute for Physics |
And 5 more authors.
Journal of Instrumentation | Year: 2016
The Phase-II Upgrade of the ATLAS Muon Detector requires new electronics for the readout of the MDT drift tubes. The first processing stage, the Amplifier-Shaper-Discriminator (ASD), determines the performance of the readout for crucial parameters like time resolution, gain uniformity, efficiency and noise rejection. An 8-channel ASD chip, using the IBM 130 nm CMOS 8RF-DM technology, has been designed, produced and tested. The area of the chip is 2.2 × 2.9 mm2 size. We present results of detailed measurements as well as a comparison with simulation results of the chip behavior at three different levels of detail. © 2016 IOP Publishing Ltd and Sissa Medialab srl.