A new biphenol-dipicolylamine based ligand and its dinuclear Zn2+ complex as fluorescent sensors for ibuprofen and ketoprofen in aqueous solution.

In this work, the study of the new ligand 3,3'-bis[N,N-bis(pyridine-2-ylmethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L) is reported, where a central 2,2'-biphenol (BPH) fluorophore was functionalized at 3,3'-positions with two dipicolylamine (DPA) side arms as receptor units. Following the synthesis and full chemical-physical characterization, the acid-base and Zn2+-coordination abilities of L were investigated through a combination of potentiometric, UV-Vis, fluorescence, NMR, XRD and DFT measurements. The optical properties of the ligand turned out to be strongly dependent on the pH, being straightforwardly associated with the protonation state of the BPH moiety, whereas its peculiar design allowed to form stable mono and dinuclear Zn2+ complexes. In the latter species, the presence of two Zn2+ ions coordinatively unsaturated and placed at close distance to each other, prompted us to test their usefulness as metallo-receptors for two environmental pollutants of great relevance, ibuprofen and ketoprofen. Potentiometric and fluorescence investigations evidenced that these important non-steroidal anti-inflammatory drugs (NSAIDs) are effectively coordinated by the metallo-receptors and, of relevance, both the stability and the fluorescence properties of the resulting ternary adducts are markedly affected by the different chemical architectures of the two substrates. This study aims at highlighting the promising perspectives arising from the use of polyamino phenolic ligands as chemosensors for H+/Zn2+ and other additional anionic targets in their metal-complexed forms.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.

Flow cytometric analysis of hepatopancreatic cells from Armadillidium vulgare highlights terrestrial isopods as efficient environmental bioindicators in ex vivo settings.

Several studies have reported the high bioindication capacity of Isopoda (Crustacea, Oniscidea), which is related to their important ability to accumulate contaminants, usefulness in soil ecotoxicology and bioindication activities. Any change in the isopod population, diversity and life cycle can indicate relevant pollution levels. The analysis of target tissues, such as the hepatopancreas, is another emerging approach (from a cytologic/histological level) to detect contaminant accumulation from different sources. In this study, tissue disaggregation procedures were optimised in the hepatopancreas, and flow cytometry (FC) was applied to detect cell viability and several cell functions. After disaggregation, two hepatopancreatic cell types, small (S) and big (B), were still recognisable: they differed in morphology and behaviour. The analyses were conducted for the first time on isopods from sites under different conditions of ecological disturbance through cytometric re-interpretation of ecological-environmental parameters. Significant differences in cell functional parameters were found, highlighting that isopod hepatopancreatic cells can be efficiently analysed by FC and represent standardisable, early biological indicators, tracing environmental-induced stress through cytologic/histologic analyses.

Sub-THz wireless transmission based on graphene-integrated optoelectronic mixer.

Optoelectronics is a valuable solution to scale up wireless links frequency to sub-THz in the next generation antenna systems and networks. Here, we propose a low-power consumption, small footprint building block for 6 G and 5 G new radio wireless transmission allowing broadband capacity (e.g., 10-100 Gb/s per link and beyond). We demonstrate a wireless datalink based on graphene, reaching setup limited sub-THz carrier frequency and multi-Gbit/s data rate. Our device consists of a graphene-based integrated optoelectronic mixer capable of mixing an optically generated reference oscillator approaching 100 GHz, with a baseband electrical signal. We report >96 GHz optoelectronic bandwidth and -44 dB upconversion efficiency with a footprint significantly smaller than those of state-of-the-art photonic transmitters (i.e., <0.1 mm2). These results are enabled by an integrated-photonic technology based on wafer-scale high-mobility graphene and pave the way towards the development of optoelectronics-based arrayed-antennas for millimeter-wave technology.

Polyethylene pipes exposed to chlorine dioxide in drinking water supply system: A critical review of degradation mechanisms and accelerated aging methods.

Polyethylene (PE) pipes have been widely used in drinking water distribution systems across the world. In many cases, chlorine dioxide (ClO2) is used to maintain a residual disinfectant concentration in potable water. Practical experiences have shown that the lifetime of PE pipes is significantly reduced due to exposure to drinking water with ClO2. Recently, many companies have proposed new PE pipes with a modified formulation, which are more resistant to chlorine dioxide. However, a standardized test method for evaluating the long-term performances of PE pipes is still missing. This literature review was performed to provide a description of chlorine dioxide uses and degradation mechanisms of polyethylene pipes in real water distribution systems. Current accelerated aging methods to evaluate long-term performances of PE pipes exposed to ClO2 are described and discussed along with the common technics used to characterize the specimens. Accelerate aging methods can be distinguished in immersion aging tests and pressurized pipe loop tests. Wide ranges of operational conditions (chlorine dioxide concentration, water pressure, water temperature, etc.) are applied, resulting in a great variety of results. It was concluded that pressurized looping tests applying semi-realistic operational conditions could better replicate the aging mechanisms occurring in service. Despite this, the acceleration and the evaluation of the long-term performance are still difficult to determine precisely. Further experimentation is needed to correlate chemical-mechanical characterization parameters of PE pipes with their lifetime in service.

Fluorescent sensing of non-steroidal anti-inflammatory drugs naproxen and ketoprofen by dansylated squaramide-based receptors.

Bis-squaramide receptors L1-L4 bearing a dansyl moiety were synthesised and their potential applications as fluorescent probes towards non steroidal anti-inflammatory drugs naproxen and ketoprofen was investigated. A detailed photophysical characterization in CH3CN/DMSO solution (9 : 1 v/v) was conducted and demonstrated that the two macrocyclic receptors L1 and L2 show good sensitivity towards ketoprofen with an ON-OFF fluorescent response, while the two open chain receptors L3 and L4 behave similarly with the three guests considered. DFT theoretical calculations carried out on L2 and L4 as model receptors allowed to propose a possible coordination mode towards the guests. Finally, 1H-NMR spectroscopy in DMSO-d6/0.5% water solution demonstrated that the four receptors interact with the considered guests via H-bonds.

A New Family of Macrocyclic Polyamino Biphenolic Ligands: Acid-Base Study, Zn(II) Coordination and Glyphosate/AMPA Binding.

In this study, the ligands 23,24-dihydroxy-3,6,9,12-tetraazatricyclo[17.3.1.1(14,18)]eicosatetra-1(23),14,16,18(24),19,21-hexaene, L1, and 26,27-dihidroxy-3,6,9,12,15-pentaazatricyclo[20.3.1.1(17,21)]eicosaepta-1(26),17,19,21(27),22,24-hexaene, L2, were synthesized: they represent a new class of molecules containing a biphenol unit inserted into a macrocyclic polyamine fragment. The previously synthesized L2 is obtained herein with a more advantageous procedure. The acid-base and Zn(II)-binding properties of L1 and L2 were investigated through potentiometric, UV-Vis, and fluorescence studies, revealing their possible use as chemosensors of H+ and Zn(II). The new peculiar design of L1 and L2 afforded the formation in an aqueous solution of stable Zn(II) mono (LogK 12.14 and 12.98 for L1 and L2, respectively) and dinuclear (LogK 10.16 for L2) complexes, which can be in turn exploited as metallo-receptors for the binding of external guests, such as the popular herbicide glyphosate (N-(phosphonomethyl)glycine, PMG) and its primary metabolite, the aminomethylphosphonic acid (AMPA). Potentiometric studies revealed that PMG forms more stable complexes than AMPA with both L1- and L2-Zn(II) complexes, moreover PMG showed higher affinity for L2 than for L1. Fluorescence studies showed instead that the L1-Zn(II) complex could signal the presence of AMPA through a partial quenching of the fluorescence emission. These studies unveiled therefore the utility of polyamino-phenolic ligands in the design of promising metallo-receptors for elusive environmental targets.

A novel 2,6-bis(benzoxazolyl)phenol macrocyclic chemosensor with enhanced fluorophore properties by photoinduced intramolecular proton transfer.

Macrocyclic ligand L, in which a 2,6-bis(2-benzoxazolyl)phenol (bis-HBO) group is incorporated in triethylenetetramine, was designed and synthesized with the aim of creating a chemosensor with high selectivity and specificity for metal cations in an aqueous environment. The availability of several proton acceptors and donors, and amine and phenol hydroxy groups, respectively, affects the keto-enol equilibrium in both the ground and excited states, and the ligand properties show dependence on the pH of the solution. L is fluorescent in the visible range, through an excited-state intramolecular proton transfer (ESIPT) mechanism. The results of an exhaustive characterization of L by spectroscopic techniques and DFT calculations, as well as of its Zn(II), Cd(II) and Pb(II) complexes, show promising properties of L as a ratiometric metal cation chemosensor, since metal coordination prevents the ESIPT and gives rise to a peculiar displacement of the fluorescence emission from green to blue with Zn(II) and Cd(II), while with Pb(II) the fluorescence is quenched.

A Tetranuclear Copper(II)/Calcium(II) Complex as Dual Chemosensor for Colorimetric and Fluorescent Detection of Non-Steroidal Anti-Inflammatory Drugs.

The tetranuclear Cu2+ /Ca2+ /Ca2+ /Cu2+ complex based on Malten ligand has been investigated as a platform for anion binding. Simple organic carboxylates and non-steroidal anti-inflammatory drugs (NSAIDs) have been tested, revealing the ability of the platform to bind them. The receiving platform hosts at least two guests in solution although a third anion can be bound, as suggested by X-ray diffraction analysis. The addition of the anions is accompanied by a color change of the solution, making the system a colorimetric sensor for carboxylates (LOD values comprised between 3.6 and 20.7 ppm). A fluorescent system consisting of the 2-(3-oxido-6-oxoxanthen-9-yl)benzoate (fluorescein anion) linked to the tetranuclear platform has been also prepared and used in a chemosensing ensemble approach to signal the presence of the selected anions (Log K between 2.6 and 5.6 for the addition of two guests). The latter also works in a paper strip test, offering the chemosensor a possible practical application.

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation.

Acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia (AML) in which the PML/RARα fusion protein exerts oncogenic activities by recruiting repressive complexes to the promoter of specific target genes. Other epigenetic perturbations, as alterations of histone H3 lysine 9 trimethylation (H3K9me3), have been frequently found in AMLs and are associated with leukemogenesis and leukemia progression. Here, we characterized the epigenomic effects of maltonis, a novel maltol-derived molecule, in APL cells. We demonstrate that maltonis treatments induce a profound remodulation of the histone code, reducing global H3K9me3 signal and modulating other histone post-translational modifications. Transcriptomic and epigenomic analyses revealed that maltonis exposure induces changes of genes expression associated with a genomic redistribution of histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 acetylation (H3K27ac). Upregulation of interferon alpha and gamma response and downregulation of c-MYC target genes, in function of c-MYC reduced expression (monitored in all the hematopoietic neoplasms tested), represent the most significant modulated pathways. These data demonstrate the ability of maltonis to epigenetically reprogram the gene expression profile of APL cells, inducing an intriguing antiviral-like response, concomitantly with the downregulation of c-MYC-related pathways, thus making it an attractive candidate for antileukemic therapy.

A Multidisciplinary Approach in Examining the Susceptibility to Microbial Attack of Polyacrylic and Polyurethane Resins Used in Art Restoration.

The synthetic polymers used to protect artworks from deterioration process can be colonized by the fungi and bacteria responsible for the biodeterioration process. In this study, the susceptibility of synthetic polyacrylics and polyurethane resins to microorganisms (Aspergillus niger ATCC 9642, Aureobasidium pullulans ATCC 15233, Chaetomium globosum ATCC 6205, Cladosporium cladosporioides ATCC 16022, Alternaria alternata BC01, Penicillium citrinum LS1 and Pseudomonas aeruginosa ATCC 9027) was investigated. The microbial attack was simulated alone and with a biocide and the related growth was observed up to 21 days for bacteria and 28 days for fungi. The polyacrylic and polyurethane resins were subjected to microbial attack, regardless of the biocide treatment, with a fungal growth from 60% to the complete coverage of the plate surface. Penicillium citrinum showed the greatest adaptation ability and was found in all the examined resins. P. aeruginosa was visible in all the different resins, regardless of the presence of biocide. An environmental scanning electron microscope (ESEM) revealed the presence of fungal conidia and hyphae in the inoculated resins and the Fourier transform IR spectroscopy (FTIR-ATR) indicated chemical transformations in the IR spectra, particularly the hydrolysis of esters, with some differences between the polyacrylic and polyurethane resins, which were probably due to their different chemical features. Overall, our data stress that the chemical, physical and biological deterioration caused by microorganisms capable of degrading synthetic polymers is still a problem in art restoration and that new strategies must be considered to counteract this phenomenon.

Selective Detection of Mg2+ for Sensing Applications in Drinking Water.

A new series of ligands containing the 2-(2-hydroxy-3- naphthyl)-4-methylbenzoxazole (HNBO) fluorophore showed selectivity for Mg2+ ions, without the interference of Ca2+ . The most promising representative L3 resulted the best performing sensor for Mg2+ both in solution and embedded in an all-solid-state optode, especially towards real samples of drinkable water.

Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells.

The activity and interacting ability of a polyamidoamine (PAMAM) dendrimer modified with 4-N-methylpiperazine-1,8-naphthalimide units (termed D) and complexed by Cu(ii) ions, towards healthy and cancer cells were studied. Comparative electron paramagnetic resonance (EPR) studies of the Cu(ii)-D complex are presented: coordination mode, chemical structure, flexibility and stability of these complexes, in the absence and presence of myeloid cancer cells and peripheral blood mononuclear cells (PBMC). The interactions of Cu(ii) ions in the biological media at different equilibrium times were studied, highlighting different stability and interacting conditions with the cells. Furthermore, flow cytometry and confocal analysis, trace the peculiar properties of the dendrimers in PBMC and U937 cells. Indeed, a new probe (Fly) was used as a potential fluorescent tool for biological imaging of Cu(ii). The study highlights that dendrimer and, mainly, the Cu(ii) metallodendrimer are cytotoxic agents for the cells, specifically for U937 tumor cells, inducing mitochondrial dysfunction, ROS increase and lysosome involvement. The metallodendrimer shows antitumor selectivity, fewer affecting healthy PBMC, inducing a massive apoptotic cell death on U937 cells, in line with the high stability of this complex, as verified by EPR studies. The results underline the potentiality of this metallodendrimer to be used as anticancer drug.

A selective fluorescent probe for gadoliniumIII in water based on a PdII-preorganized chromone-receptor.

The synthesis, solution studies, photochemical properties and the X-ray structure of a chromone based fluorescent PdII complex are reported. The ligand contains two chromone units linked as side arms to an ethylenediamine moiety; in the PdII complex the metal ion preorganizes the two hydroxychromone units forming a rigid structure with a negatively charged pocket formed by four oxygen atoms that is able to interact with hard metal cations, such as ions, giving rise to stable bimetallic complexes. Upon interaction with LaIII and GdIII, in particular, the emission intensity at 423 nm increases by a factor of 2 and 8, respectively, while the other rare earth ions quench the fluorescence. Spectrofluorimetric studies on real matrices showed the possibility to use this system as a selective fluorescence probe to detect and trace the presence of Gadolinium in environmental water acting as an OFF-ON chemosensor, with a LOD of 0.4 ppm and a LOQ of 1.2 ppm.

Synthesis and biological characterization of a new fluorescent probe for vesicular trafficking based on polyazamacrocycle derivative.

The fluorescent probes represent an important tool in the biological study, in fact characterization of cellular structures and organelles are an important tool-target for understanding the mechanisms regulating most biological processes. Recently, a series of polyamino-macrocycles based on 1,4,7,10-tetraazacyclododecane was synthesized, bearing one or two NBD units (AJ2NBD·4HCl) useful as sensors for metal cations and halides able to target and to detect apolar environment, as lipid membranes. In this paper, we firstly illustrate the chemical synthesis of the AJ2NBD probe, its electronic absorption spectra and its behavior regarding pH of the environment. Lack of any cellular toxicity and an efficient labelling on fresh, living cells was demonstrated, allowing the use of AJ2NBD in biological studies. In particular, this green fluorescent probe may represent a potential dye for the compartments involved in the endosomal/autophagic pathway. This research's field should benefit from the use of AJ2NBD as a vesicular tracer, however, to ensure the precise nature of vesicles/vacuoles traced by this new probe, other more specific tests are needed.

Hetero-Tetranuclear Cu2+ /Ca2+ /Ca2+ /Cu2+ Architectures Based On Malten Ligand: Scaffold for Anion Binding.

The hetero-tetranuclear Cu2+ /Ca2+ /Ca2+ /Cu2+ complex obtained with the N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N'-dimethylethylendiamine (Malten) ligand has been studied in solid and solution states as scaffold to bind anions. Three crystal structures showing the same metal ions sequence have been examined; they display a tetracharged complex cation neutralized by four monocharged anions. The anions play two different roles: as coordinated (two ClO4- , Cl- or NO3- ) or ancillary (two ClO4- ) guests. The tetranuclear scaffold hosts two anions also in aqueous and ethanol solutions. Spectrophotometric studies in ethanol allowed to determine the addition constant values for Cl- and Br- (Log K1-2 =4.43(4), 4.39(3) for Cl- , 3.80(3), 3.54(2) for Br- ) while the others, although bound, showed lower affinity for the scaffold. Both the crystals and the solutions change their color depending on the added anion, namely pink, dark green or blue in the presence of ClO4- , Cl- or NO3- , respectively, thus the presence of the different anions is visible to the naked eye. The hetero-tetranuclear Cu2+ /Ca2+ /Ca2+ /Cu2+ complex is a versatile architecture to be used as scaffold for anion binding.

Zn(ii) detection and biological activity of a macrocycle containing a bis(oxadiazole)pyridine derivative as fluorophore.

The synthesis, photochemical properties, biological effects and the X-ray crystal structure of a fluorescent polyamine macrocycle L are reported. L is a polyamine cyclophane macrocycle in which 2,6-bis(5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl)pyridine (POXAPy) acts as a fluorescent sensor and the polyamine as a metal ion binding unit. L performs as a PET-mediated chemosensor, with a maximum emission wavelength close to 360 nm. This gives rise to a signal that is visible to the naked eye in the blue visible range. L is able to detect the Zn(ii) and Cd(ii) metal ions in an aqueous solution at pH = 7, with the coordination of the ions switching the emission ON through a CHEF effect. In contrast, paramagnetic metal ions like Cu(ii) and Ni(ii) completely quench the already low emission of L at this pH value. L affects the cell survival of a leukemic cellular model (U937) at micromolar concentrations with cell death starting after only 24 h of exposure; starting from a final concentration of 5 µM, L almost completely abrogates the survival of the leukemic cells over 72 h, with a mechanism that is compatible with a genomic DNA interaction.

Isolation and molecular identification of a strain belonging to the new species Zalaria obscura from a deteriorated wooden artwork.

We report the case of an outdoor deteriorated wooden sculpture of Madonna, completely blackened in the face, and thus suspected of fungal attack. A multi-disciplinary approach, including microbiological analysis, molecular biology, and Fourier transform infrared (FT-IR) spectroscopy, was applied to understand the real nature of the observed alteration. FT-IR showed that the blackening was due to the application of a natural terpene resin subjected to alteration over time. The microbiological assay allowed to isolate a particular black fungus that has been recovered in the vegetative phase, growing as the only species adapted to the examined substrate. Basic Local Alignment Search Tool (BLAST) analysis of the ITS (internal transcribed spacer) region sequence identified the fungus (LS31012019) as Zalaria obscura, a black yeast belonging to the new genus Zalaria, family Dothideales. Overall, this study evidenced the importance of a multi-disciplinary approach to understand the real causes of observed deterioration of artworks. More interestingly, the recovery of a strain identified as Z. obscura from this type of substrate is never reported in the literature and this finding could offer the possibility to investigate the role of this microorganism in the deterioration process of cultural heritage.

Playing with Structural Parameters: Synthesis and Characterization of Two New Maltol-Based Ligands with Binding and Antineoplastic Properties.

Two maltol-based ligands, N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-1,4-piperazine (L1) and N,N',N'-tris((3-hydroxy-4-pyron-2-yl)methyl)-N-methylethylendiamine (L2), were synthesized and characterized. L1 and L2, containing, respectively, two and three maltol units spaced by a diamine fragment, were designed to evaluate how biological and binding features are affected by structural modifications of the parent compound malten. The acid-base behavior and the binding properties towards transition, alkaline-earth (AE) and rare-earth (RE) cations in aqueous solution, studied by potentiometric, UV-Vis and NMR analysis, are reported along with biological studies on DNA and leukemia cells. Both ligands form stable complexes with Cu(II), Zn(II) and Co(II) that were studied as metallo-receptors for AE and RE at neutral pH. L1 complexes are more affected than L2 ones by hard cations, the L1-Cu(II) system being deeply affected by RE. The structural modifications altered the mechanism of action: L1 partially maintains the ability to induce structural alterations of DNA, while L2 provokes single strand (nicks) and to a lesser extent double strand breaks of DNA.

A Fluorescent Sensor Array Based on Heteroatomic Macrocyclic Fluorophores for the Detection of Polluting Species in Natural Water Samples.

The development of a novel all-solid-state optical sensor array based on heteroatomic macrocyclic fluorophores (diaza-crown ether, metallocorrole and pyridinophans) for the photographic analysis of liquid media, is presented. The sensitivity of the new optical system toward a number of different species (cations: Li+, K+, Na+, NH4+ , Mg2+, Ca2+, Co2+, Cu2+, Zn2+, Cd2+, Pb2+ and anions: NO2- , NO3- , Cl-, Br-, HCO3- ) was evaluated both in single selective sensor mode and in multisensory arrangement. The satisfactory PLS1 regression models between sensor array optical response and analyte concentration were obtained for Cd2+, Cu2+, Zn2+, and NO2- ions in all the range of tested concentrations. Among these species the highest attention was focused onto detection of cadmium and nitrite ions, for which the detection limits, DL, estimated by 3σ method were found 0.0013 mg/L and 0.21 mg/L respectively, and these values are lower than the corresponding WHO guideline values of 0.003 mg/L (Cd2+) and 2 mg/L ( NO2- ). The suitability of the developed sensors implemented with familiar devices for signal acquisition (Light Emitting Diode, LED, as light source and a digital camera as a signal detector), and chemometric methods for data treatment to perform fast and low-cost monitoring of species under interest, in real samples of environmental importance, is demonstrated.