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Adsorption layers at the air-water interface formed from the soluble zwitterionic surfactant dodecylphosphorylcholine (DPC) serving as a soluble model substance for phospho-lipids were characterized with respect to their equilibrium and dynamic surface properties. To clarify the effect of ionic interactions with electrolyte present in the bulk phase, surface rheological properties upon addition of Ce(NO 3 ) 3 and Yb(NO 3 ) 3 were determined. In order to account for the surface activity of the nitrate ion, comparative measurements using NaNO 3 were carried out additionally. Further experimental information on the bulk hydration characteristics of the aqueous solutions was obtained using dielectric relaxation spectroscopy (DRS). A possible mechanism causing the deviating surface dilatational modulus E in terms of ion specificity is suggested., (Copyright © 2019. Published by Elsevier Inc.)

This review summarizes work done on triply, or higher, interpenetrating polymer network materials prepared in order to widen the properties of double polymer network hydrogels (DN), doubly interpenetrating polymer networks with enhanced mechanical properties. The review will show that introduction of a third, or fourth, polymeric component in the DNs would further enhance the mechanical properties of the resulting materials, but may also introduce other useful functionalities, including electrical conductivity, low-friction coefficients, and (bio)degradability.

Over the last decade there has been a significant boost towards the use of electronic cigarettes (e-cigarettes), especially among youth. Different concentrations of propylene glycol (PG) or vegetable glycerin (VG), flavors and nicotine are mixed in plastic cartridges and commercially offered or privately produced by the vapers. During vaping, a mixture of air and vapors is inhaled to the lungs. Since the ingredients of the e-cigarettes are not burned but vaporized (heated), fewer chemicals are emitted. The levels of potentially toxic compounds (e.g. volatile organic compounds (VOCs), particulate matter (PM), metals, radicals, nitrosamines, etc.) emitted from vaping appear to be lower compared to that of tobacco smoking (from combustible cigarettes). Nevertheless, measurable toxic elements and VOCs are still released (e.g. acetaldehyde, formaldehyde, acrolein, benzene, etc.) along with other volatiles associated with e-liquid flavoring and device variability with PG and VG. The wide range of available flavors at various purities along with the heating temperature are important parameters affecting the evolution of VOCs and aerosols. There is lack of standardized short- and long-term epidemiological medical data (chronic exposure) on e-cigarettes effects to users, non-users and the human micro-environment (second- or third-hand exposure). Therefore, the potential health, safety and environmental effects of vaping are reviewed, examined and discussed., (Copyright © 2019. Published by Elsevier Ltd.)

D-pinitol (3-O-methyl-D-chiro-inositol) is a well-known bioactive compound with anti-diabetic and anti-oxidant biological functions. A gas chromatography-mass spectrometry (GC-MS) method was developed for its quantitation in carob syrup, flesh and seed samples originated from Cyprus. The analysis was performed after derivatization of carbohydrates and polyols into trimethylsilyl ether derivatives. D-pinitol was determined in 13 carob syrup samples, in concentrations ranging 65.71 ± 4.60 - 77.72 ± 5.44 mg/g (mean: 68.58 ± 4.80 mg/g, n = 13). In two commercial samples, it was determined in relative medium-low concentrations (21.96 ± 1.54 and 44.71 ± 3.13 mg/g), revealing possible adulteration; however, this needs further investigation. Similarly, it was determined in high concentrations in carob flesh samples, in concentrations ranging 53.20 ± 3.72 - 54.58 ± 3.82 mg/g (mean: 53.81 ± 3.76 mg/g, n = 3). On the other hand, seed samples proved very poor in D-pinitol (

Ceratonia siliqua, known as the carob, is considered to be of high nutritional value and of great economic significance due to its unique composition. The beneficial effects of carob against cancer, metabolic syndrome, diabetes, diarrhea, hyperlipidemia and gastro esophageal reflux disease are only a few of its therapeutic actions. Metabolomics-based analysis provides an ultimate tool, for the deciphering of nutritional intervention derived metabolic alterations. In the present study, 16 male Wistar rats were treated with carob powder for a 15-day period. Fecal and urine samples were collected at 5 time points (0, 1, 5, 10 and 15 days). By the applied HILIC-MS/MS method, 63 and 67 hydrophilic metabolites were detected in the fecal and urine samples, respectively, including amino acids, organic acids, sugars, vitamins and other endogenous compounds. A clear group separation based on fecal metabolome was observed after 1 day and 15 days treatment, while only a mild differentiation at day 1 was observed based on urine metabolome. Twenty-one fecal metabolites were responsible for the separation including amino acids and their derivatives, vitamins and organic acids. However, only 7 metabolites were altered in rat urine samples. Metabolic alterations in fecal samples could be attributed to physiological and biochemical adaptations derived from the nutritional intervention. Fecal targeted metabolomics were proven to be suitable for uplifting and highlighting such alterations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bisazafullerene (C 59 N) 2 has been functionalized under aerobic conditions with cyclo-[2]-octylmalonate through a Mannich-type reaction, furnishing the corresponding monoadduct. A regioselective tether-directed Bingel cyclopropanation reaction was then carried out on the azafullerene core to yield a single bisadduct. Spectroscopic analysis of the formed bisadduct showed it to have a C 1 symmetrical structure, making it inherently chiral. Single-crystal X-ray analysis revealed the addition pattern of the azafullerene bisadduct to be equatorial face . Examination of the optical properties showed the evolution of new absorption bands, which can be used as signatures for the characterization of equatorial face bisadducts of C 59 N. Finally, redox assays showed that the LUMO level of the equatorial face bisadduct was increased compared to that of the parent (C 59 N) 2 ., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the synthesis, crystal structures and magnetic properties of the giant heterometallic [Mn 36 Ni 4 ] 2-/0 (compounds 1 , 2 )/[Mn 32 Co 8 ] (compound 3 ) "loops-of-loops-and-supertetrahedra" molecular aggregates and of a [Mn 2 Ni 6 ] 2+ compound (cation of 4 ) that is structurally related with the cation co-crystallizing with the anion of 1 . In particular, after the initial preparation and characterization of compound [Mn 2 Ni 6 (μ 4 -O) 2 (μ 3 -OH) 3 (μ 3 -Cl) 3 (O 2 CCH 3 ) 6 (py) 8 ] 2+ [Mn 36 Ni 4 (μ 4 -O) 8 (μ 3 -O) 4 (μ 3 -Cl) 8 Cl 4 (O 2 CCH 3 ) 26 (pd) 24 (py) 4 ] 2- ( 1 ) we targeted the isolation of (i) both the cationic and the anionic aggregates of 1 in a discrete form and (ii) the Mn/Co analog of [Mn 36 Ni 4 ] 2- aggregate. Our synthetic efforts toward these directions afforded the discrete [Mn 36 Ni 4 ] "loops-of-loops-and-supertetrahedra" aggregate [Mn 36 Ni 4 (μ 4 -O) 8 (μ 3 -O) 4 (μ 3 -Cl) 8 Cl 2 (O 2 CCH 3 ) 26 (pd) 24 (py) 4 (H 2 O) 2 ] ( 2 ), the heterometallic Mn/Co analog [Mn 32 Co 8 (μ 4 -O) 8 (μ 3 -O) 4 (μ 3 -Cl) 8 Cl 2 (μ 2 -OCH 2 CH 3 ) 2 (O 2 CCH 3 ) 28 (pd) 22 (py) 6 ] ( 3 ) and the discrete [Mn 2 Ni 6 ] 2+ cation [Mn 2 Ni 6 (μ 4 -O) 2 (μ 3 -OH) 4 (μ 3 -Cl) 2 (O 2 CCH 3 ) 6 (py) 8 ](ClO 4 )(OH) ( 4 ). The structure of 1 consists of a mixed valence [ Mn 28 III Mn 8 II Ni 4 II ] 2- molecular aggregate that contains two Mn 8 III Ni 2 II loops separated by two Mn 6 III Mn 4 II supertetrahedral units and a [ Mn 2 III Ni 6 II ] 2+ cation based on two [Mn III Ni 3 II (μ 4 -O)(μ 3 -OH) 1.5 (μ 3 -Cl) 1.5 ] 4+ cubane sub-units connected through both mono- and tri-atomic bridges provided by the μ 4 -O 2- and carboxylate anions. The structures of 2 - 4 are related to those of the compounds co-crystallized in 1 exhibiting however some differences that shall be discussed in detail in the manuscript. Magnetism studies revealed the presence of dominant ferromagnetic interactions in 1 - 3 that lead to large ground state spin (S T ) values for the "loops-of-loops-and-supertetrahedra" aggregates and antiferromagnetic exchange interactions in 4 that lead to a low (and possibly zero) S T value. In particular, dc and ac magnetic susceptibility studies revealed that the discrete [Mn 36 Ni 4 ] aggregate exhibits a large S T value ~ 26 but is not a new SMM. The ac magnetic susceptibility studies of the [Mn 32 Co 8 ] analog revealed an extremely weak beginning of an out-of-phase tail indicating the presence of a very small relaxation barrier assignable to the anisotropic Co 2+ ions and a resulting out-of-phase ac signal whose peak is at very low T.

In this work, we computationally explored the ability of water-swollen, model ionizable ABA triblock copolymer-based amphiphilic polymer conetworks (APCNs) to solubilize a water-immiscible organic solvent (oil), via Gibbs free energy minimization. This was done as a function of the conetwork hydrophobe (A-blocks) mol fraction and the degree of ionization of the hydrophilic B-blocks. Expectedly, highest oil solubilization capacities were calculated for the most hydrophobic and least ionized APCNs, which could absorb up to 6.4 times more oil than water and exhibited a lamellar morphology. Our results also included a phase diagram, which indicated transitions from spheres to cylinders, lamellae, and unimers in oil, as the hydrophobe content increased and the degree of ionization decreased. All of these transitions were accompanied by discontinuous changes in the degrees of swelling in the aqueous and oil nanophases, discontinuous changes in the asymmetry ratios (for the anisotropic morphologies), and discontinuous changes in the oil solubilization capacities. This is the first time that a dual discontinuous volume phase transition is reported within a polymer gel., Competing Interests: The authors declare no competing financial interest.

The effect of the tail length of Triton-X surfactants on the surface properties of ceria prepared by means of reversed micelles and Ce(O i Pr) 4 has been systematically studied. Generally, solids with increased surface areas (up to 136 m 2 g -1 ) were synthesised. It was shown that the tail length strongly affects the surface characteristics. Further studies were carried out using UV-Vis, ATR-FTIR, XRD and TGA/DSC studies of the precursor gels as well as N 2 -isothermal adsorption BET, XRD, FT-IR, UV-Vis diffuse reflectance and SEM investigations of the final solids samples. An interaction mechanism between the ceria precursor molecules and the polar tail of the reversed Triton X micelles and the formation of ceria (CeO 2 ) particles in the aqueous nucleus of the reversed microemulsions is proposed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

β-Thalassemia (β-thal) is a hemoglobinopathy characterized by reduced or absent β-globin production. Pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (Hb F) presents an attractive treatment strategy. In an effort to identify promising therapeutic agents, we evaluated 80 analogues of the histone deacetylase inhibitor MS-275, a known Hb F inducer. The chemical analogues were identified via molecular modeling and targeted chemical modifications. Nine novel agents exhibited significant hemoglobin (Hb)-inducing and erythroid differentiation activities in the human K562 erythroleukemia cell line. Five of them appeared to be stronger inducers than the lead compound, MS-275, demonstrating the effectiveness of our method.

The combined use of chiral ionic liquids (CILs) and conventional chiral selectors (CSs) in CE, to establish a synergistic system, has proven to be an effective approach for the separation of enantiomeric pairs. In this study, a new CE method was developed, employing a binary system of a CS, either a cyclodextrin (CD) or a cyclofructan (CF), and a chiral amino acid ester-based ionic liquid (AAIL), for the chiral separation of four basic, acidic and zwitterionic drug compounds. In particular, the enantioseparation of two anticoagulants, warfarin (WAR) and coumachlor (COU), a non-opioid analgesic, nefopam (NEF) and a third-generation antihistamine, fexofenadine (FXD), was examined, by supporting the BGE with a CS and the chiral AAIL L-alanine tert butyl ester lactate (L-AlaC 4 Lac). Parameters, such as the type of the CS, the concentration of both the CS and L-AlaC 4 Lac, and the BGE pH, were methodically examined in order to optimize the chiral separation of each analyte. It was observed that, in some cases, the addition of the AAIL into the BGE improved both resolution (R s ) and efficiency (N) significantly. In other cases, the synergistic effect enabled baseline separation of analyte enantiomers, at a much lower concentration of the CS. Finally, after optimization of separation conditions, baseline separations (R s >1.5) of all four analytes were achieved in less than 5 min., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

7-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this article, we provide the first synthesis of fluorinated derivatives. Fluorination using Selectfluor of benzo[1,2,4]triazin-7-ones occurs regioselectively and in high yield at the enamine-activated position. This electron N-lone pair activation overrides the activation/deactivation effects of some other substituents. The reaction time was significantly reduced with the use of microwave irradiation at 120 °C and 7 bar. The cytotoxicity and cyclic voltammetry measurements for 8-fluoro-1,3-diphenylbenzo[ e ][1,2,4]triazin-7(1 H )-one ( 2 ) are presented and compared with its synthetic precursor, 1,3-diphenylbenzo[ e ][1,2,4]triazin-7(1 H )-one ( 1a ).

Carob (Ceratonia Siliqua L., tree of the pea family Fabaceae) and its products have recently attracted great interest due to their polyphenolic composition. This review summarizes the polyphenolic compounds that are contained in different carob parts (leaves, pod, seeds, barks) and products (syrup, flour, fiber). It also states the main differences of polyphenolic composition due to environmental and natural reasons, such as region, variety, and gender, and due to the processes used for preparation, extraction and analysis. The gender, along with the extraction procedure, proved to be the most important factors affecting the polyphenolic composition. Supercritical fluid extraction is the most efficient technique used because it protects polyphenols from decomposition. Due to the relatively low number of publications, it is concluded that further development of optimum methods for extraction, analysis and isolation of polyphenols should be carried over to assess their antioxidant capacity and their food technological and pharmaceutical industry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Coffee is perhaps one of the most vital ingredients in humans' daily life in modern world. However, this causes the production of million tons of relevant wastes, i.e., plastic cups, aluminum capsules, coffee chaff (silver skin), and spent coffee grounds (SCG), all thrown untreated into landfills. It is estimated that 1 kg of instant coffee generates around 2 kg of wet SCG; a relatively unique organic waste stream, with little to no contamination, separated directly in the source by the coffee shops. The produced waste has been under researchers' microscope as a useful feedstock for a number of promising applications. SCG is considered a valuable, nutrients rich source of bioactive compounds (e.g., phenolics, flavonoids, carotenoids, lipids, chlorogenic and protocatechuic acid, melanoidins, diterpenes, xanthines, vitamin precursors, etc.) and a useful resource material in other processes (e.g., soil improver and compost, heavy metals absorbent, biochar, biodiesel, pellets, cosmetics, food, and deodorization products). This paper aims to provide a holistic approach for the SCG waste management, highlighting a series of processes and applications in environmental solutions, food industry, and agricultural sector. Thus, the latest developments and approaches of SCG waste management are reviewed and discussed.

Twenty traditional carob products were measured for their nutritional composition, and their results were compared with the pulp of Cypriot carob cultivars. Moisture, ash, fat, proteins, sugars, dietary fibers, minerals, caffeine-theobromine, carbohydrates, and energy value were determined. Fluctuations of the nutritional composition values based on the ingredients' chemical synthesis and product manufacturing process were noted. Only 60% of the products had a label indicating their nutritional value, and the majority of them (75%) were consistent with that of labeling. Chemometric analyses distinguished the carob products according to their type and the discriminator components highlighted their particular nutritional value. Carobs can be characterized as functional foods with low-fat content, high content in dietary fibers, and high content and/or source of minerals; however, carob products partially satisfied those health and nutritional claims as expected. This pilot research contributes to the nutritional estimation of carob and highlights the traditional carob products.

Nanoporous titania was prepared from non-ionic surfactant reverse micelles ( e.g. Triton-X) and the effects of the chain length of the surfactants and calcination temperature of the precursor gels on the surface properties of the product (mesoporous titania) were investigated. The studies included sample characterization of the precursor gels from the titania samples characterized by UV-Vis, ATR-FTIR, XRD, TGA/DSC and the titania samples by N 2 -adsorption BET, XRD, FT-IR, UV-Vis diffuse reflectance and SEM measurements after calcination at 400 °C, 500 °C, 600 °C, 700 °C and 800 °C. According to the experimental results, generally increasing the length of the polar tail of Triton-X results in an increased specific surface area and volume, and an average pore diameter of the solids. Moreover, increasing the length of the polar tail is associated with a smaller crystallite size and higher thermal stability of the materials. Finally, a nucleation mechanism of the titania particles within the aqueous centre of the reversed micelles is proposed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Modifying the para-quinonimine 1,3-diphenyl-1,2,4-benzotriazin-7(1 H)-one (2a) ( E 1/2 -1/0 ∼ -0.65 V) involved combining the ylidenemalononitrile groups at C7 with the trifluoromethyl groups at C3. 1,2,5-Thiadiazolo fusion at C5-C6 did not affect the redox behavior but did enhance the UV-vis absorption profile. During the synthesis of the thiadiazolo analogues, 1,4-thiazino-fused analogues 6 were obtained in low yield, which thermally ring contract to the triazafluoranthenones 7. Compounds are fully characterized, and X-ray data are provided for selected analogues.1/2 -1/0 ∼ -0.65 V) involved combining the ylidenemalononitrile groups at C7 with the trifluoromethyl groups at C3. 1,2,5-Thiadiazolo fusion at C5-C6 did not affect the redox behavior but did enhance the UV-vis absorption profile. During the synthesis of the thiadiazolo analogues, 1,4-thiazino-fused analogues 6 were obtained in low yield, which thermally ring contract to the triazafluoranthenones 7. Compounds are fully characterized, and X-ray data are provided for selected analogues.

Two known tin-based polymers of formula {[R₃Sn(CH₃COO)] n } where R = n -Bu⁻ ( 1 ) and R = Ph⁻ ( 2 ),were evaluated for their in vitro biological properties. The compounds were characterized via their physical properties and FT-IR, 119 Sn Mössbauer, and ¹H NMR spectroscopic data. The molecular structures were confirmed by single-crystal X-Ray diffraction crystallography. The geometry around the tin(IV) ion is trigonal bi-pyramidal. Variations in O⁻Sn⁻O···Sn' torsion angles lead to zig-zag and helical supramolecular assemblies for 1 and 2 , respectively. The in vitro cell viability against human breast adenocarcinoma cancer cell lines: MCF-7 positive to estrogens receptors (ERs) and MDA-MB-231 negative to ERs upon their incubation with 1 and 2 was investigated. Their toxicity has been studied against normal human fetal lung fibroblast cells (MRC-5). Compounds 1 and 2 exhibit 134 and 223-fold respectively stronger antiproliferative activity against MDA-MB-231 than cisplatin. The type of the cell death caused by 1 or 2 was also determined using flow cytometry assay. The binding affinity of 1 and 2 towards the CT-DNA was suspected from the differentiation of the viscosity which occurred in the solution containing increasing amounts of 1 and 2 . Changes in fluorescent emission light of Ethidium bromide (EB) in the presence of DNA confirmed the intercalation mode of interactions into DNA of both complexes 1 and 2 which have been ascertained from viscosity measurements. The corresponding apparent binding constants ( K ) of app ) of 1 and 2 towards CT-DNA calculated through fluorescence spectra are 4.9 × 10⁴ ( 1 ) and 7.3 × 10⁴ ( 2 respectively. Finally, the type of DNA binding interactions with -1 respectively. Finally, the type of DNA binding interactions with 1 and 2 was confirmed by docking studies.

The development of ligands with high selectivity and affinity for uranium is critical in the extraction of uranium from human body, radioactive waste, and seawater. A scientific challenge is the improvement of the selectivity of chelators for uranium over other heavy metals, including iron and vanadium. Flat ligands with hard donor atoms that satisfy the geometric and electronic requirements of the U VI O 2 2+ exhibit high selectivity for the uranyl moiety. The bis(hydroxylamino)(triazine) ligand, 2,6-bis[hydroxy(methyl)amino]-4-morpholino-1,3,5-triazine (H 2 bihyat), a strong binder for hard metal ions (Fe III , Ti IV , V V , and Mo VI ), reacted with [U VI O 2 (NO 3 ) 2 (H 2 O) 2 O in aqueous solution and resulted in the isolation of the complexes [U 2 O in aqueous solution and resulted in the isolation of the complexes [U VI O 2 (bihyat)(H 2 O)], [U VI O 2 (bihyat) 2 ] 2- , and {[U VI O 2 . These three species are in equilibrium in aqueous solution, and their abundance varies with the concentration of H 2 bihyat and the pH. Reaction of H 2- . These three species are in equilibrium in aqueous solution, and their abundance varies with the concentration of H 2 bihyat and the pH. Reaction of H 2 bihyat with [U VI O 2 (NO 3 ) 2 (H 2 O) 2 ]·4H 2 O in CH 3 CN gave the trinuclear complex [U VI 3 O 6 (bihyat) 2 (μ-bihyat) 2 ] 2- bihyat in aqueous and dimethyl sulfoxide solutions; the metal binding ability of the H VI O 2 2+ and the free ligand H 2 , and the selectivity of the H 2 bihyat over pyridine-2,6-dicarboxylic acid (H 2 dipic) or glutarimidedioxime for U VI O 2 2+ , and the selectivity of the H 2 bihyat to bind U VI O 2 2+ in comparison to V V O 4 3- and Fe III in either U VI O 2 2+ /V V O 4 3- , which increases at higher pHs. Thus, this type of ligand might find applications in the extraction of uranium from the sea and its removal from the environment and the human body.VI O 2 2+ /Fe III solutions were examined by NMR and UV-vis spectroscopies. The results revealed that H 2 bihyat is a superior ligand for U VI O 2 2+ with high selectivity compared to Fe III and V V O 4 3- , which increases at higher pHs. Thus, this type of ligand might find applications in the extraction of uranium from the sea and its removal from the environment and the human body.

Thermolysis of 4,4'-dichloro-, 4,4'-diaryl-, and 4,4'-di(thien-2-yl)-5,5'-bi(1,2,3-dithiazol-ylidenes) affords the respective 3,6-dichloro-, 3,6-diaryl- and 3,6-di(thien-2-yl)isothiazolo[5,4- d ]-isothiazoles in low to high yields. The transformation of the 4,4'-diaryl- and 4,4'-di(thien-2-yl)-5,5'-bi(1,2,3-dithiazolylidenes) occurs at lower temperatures in the presence of the thiophiles triphenylphosphine or tetraethylammonium iodide. Optimized reaction conditions and a mechanistic rationale for the thiophile-mediated ring transformation are presented.

We demonstrate for the first time that 4 H -1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4 H -1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors.

Isodiphenylfluorindone 6 and isodiphenylfluorindinone 7 are synthesized. The former reacts with NaOMe to give the 13-methoxyisodiphenylfluorindone 22 (95%), while the latter reacts with 70% perchloric acid to give the bisperchlorate 21 (87%) and with MnO 2 dimerizes to give 13,13'-bi(isodiphenylfluorindone) 4 (60%). UV-vis, NMR, CV, and DFT computational studies support the structural assignments of all products. Single-crystal X-ray diffraction studies are reported for isodiphenylfluorindinone 7.

Earthquakes are lethal natural disasters frequently burying people alive under collapsed buildings. Tracking entrapped humans from their unique volatile chemical signature with hand-held devices would accelerate urban search and rescue (USaR) efforts. Here, a pilot study is presented with compact and orthogonal sensor arrays to detect the breath- and skin-emitted metabolic tracers acetone, ammonia, isoprene, CO 2 , and relative humidity (RH), all together serving as sign of life. It consists of three nanostructured metal-oxide sensors (Si-doped WO 3 , Si-doped MoO 3 , and Ti-doped ZnO), each specifically tailored at the nanoscale for highly sensitive and selective tracer detection along with commercial CO 2 and humidity sensors. When tested on humans enclosed in plethysmography chambers to simulate entrapment, this sensor array rapidly detected sub-ppm acetone, ammonia, and isoprene concentrations with high accuracies (19, 21, and 3 ppb, respectively) and precision, unprecedented by portable sensors but required for USaR. These results were in good agreement (Pearson's correlation coefficients ≥0.9) with benchtop selective reagent ionization time-of-flight mass spectrometry (SRI-TOF-MS). As a result, an inexpensive sensor array is presented that can be integrated readily into hand-held or even drone-carried detectors for first responders to rapidly screen affected terrain.

Mixed-valent polyoxometalate (POM) clusters are one of the most interesting host species, showing a wide range of structural features and properties. The facile preparation and functionalisation of a mixed-valent polyoxofluorovanadates is reported, where two electrons are trapped to antipodal sites of the clusters. The first members of this family of clusters with the general formula, [V V 12 V IV 2 O 16 (μ-O) 10 (μ 3 -O) 10 (μ 3 -F) 2 , where L: py=pyridine (1); pyr=pyrazine (2); im=imidazole (3), are unique organic-inorganic hybrids with the addition of a N-donor ligand at either end of the polyoxofluorovanadate. The composition and connectivity of 1-3 were characterised by single-crystal X-ray diffraction and electrospray ionisation mass spectrometry. Electron paramagnetic resonance spectroscopy revealed that the two well-separated V 2 ions in each cluster are fully uncoupled with J=0, giving a degenerate singlet-triplet ground state. This attenuation of the exchange interaction is probed with density functional theoretical calculations that reveal that the inclusion of the fluoride ion in the cluster produces a bond pathway biased toward destructive interference between competing ferromagnetic and antiferromagnetic interactions. These robust molecular materials are the ideal combination of desirable electronic properties, with an organic handle with which they can be integrated into spintronic circuitry for molecular devices.6- , where L: py=pyridine (1); pyr=pyrazine (2); im=imidazole (3), are unique organic-inorganic hybrids with the addition of a N-donor ligand at either end of the polyoxofluorovanadate. The composition and connectivity of 1-3 were characterised by single-crystal X-ray diffraction and electrospray ionisation mass spectrometry. Electron paramagnetic resonance spectroscopy revealed that the two well-separated V IV ions in each cluster are fully uncoupled with J=0, giving a degenerate singlet-triplet ground state. This attenuation of the exchange interaction is probed with density functional theoretical calculations that reveal that the inclusion of the fluoride ion in the cluster produces a bond pathway biased toward destructive interference between competing ferromagnetic and antiferromagnetic interactions. These robust molecular materials are the ideal combination of desirable electronic properties, with an organic handle with which they can be integrated into spintronic circuitry for molecular devices., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cell viability studies for benzo[1,2,4]triazin-7-ones and 1,2,4-benzotriazinyl (Blatter-type) radical precursors are described with comparisons made with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). All of the stable free radicals were several orders of magnitude less cytotoxic than the benzo[1,2,4]triazin-7-ones. The synthesis and evaluation of two new pyrid-2-yl benzo[1,2,4]triazin-7-ones are described, where altering the 1,3-substitution from phenyl to pyrid-2-yl increased cytotoxicity against most cancer cell lines, as indicated using National Cancer Institute (NCI) one-dose testing. COMPARE analysis of five-dose testing data from the NCI showed very strong correlations to the naturally occurring anti-cancer compound pleurotin. COMPARE is program, which analyzes similarities in cytotoxicity data of compounds, and enables quantitative expression as Pearson correlation coefficients. Compounds were also evaluated using the independent MTT assay, which was compared with SRB assay data generated at the NCI., Competing Interests: The authors declare no conflict of interest.

Human smuggling and associated cross-border crimes have evolved as a major challenge for the European Union in recent years. Of particular concern is the increasing trend of smuggling migrants hidden inside shipping containers or trucks. Therefore, there is a growing demand for portable security devices for the non-intrusive and rapid monitoring of containers to detect people hiding inside. In this context, chemical analysis of volatiles organic compounds (VOCs) emitted from the human body is proposed as a locating tool. In the present study, an in-house made ion mobility spectrometer coupled with gas chromatography (GC-IMS) was used to monitor the volatile moieties released from the human body under conditions that mimic entrapment. A total of 17 omnipresent volatile compounds were identified and quantified from 35 ion mobility peaks corresponding to human presence. These are 7 aldehydes (acrolein, 2-methylpropanal, 3-methylbutanal, 2-ethacrolein, n-hexanal, n-heptanal, benzaldehyde), 3 ketones (acetone, 2-pentanone, 4-methyl-2-pentanone), 5 esters (ethyl formate, ethyl propionate, vinyl butyrate, butyl acetate, ethyl isovalerate), one alcohol (2-methyl-1-propanol) and one organic acid (acetic acid). The limits of detection (0.05-7.2 ppb) and relative standard deviations (0.6-11%) should be sufficient for detecting these markers of human presence in field conditions. This study shows that GC-IMS can be used as a portable field detector of hidden or entrapped people., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The heme-based aerotactic transducer (HemAT) is an oxygen-sensor protein consisting of a sensor and a signaling domain in the N- and C-terminal regions, respectively. Time-resolved step-scan FTIR spectroscopy was employed to characterize protein intermediate states obtained by photolysis of the carbon monoxide complexes of sensor-domain, full-length HemAT, and the Y70F (B-helix), L92A (E-helix), T95A (E-helix), and Y133F (G-helix) HemAT mutants. We assign the spectral components to discrete substructures, which originate from a helical structure that is solvated (1638 cm -1 ) and a native helix that is protected from solvation by interhelix tertiary interactions (1654 cm -1 ). The full-length protein is characterized by an additional amide I absorbance at 1661 cm -1 , which is attributed to disordered structure suggesting that further protein conformational changes occur in the presence of the signaling domain in the full-length protein. The kinetics monitored within the amide I absorbance of the polypeptide backbone in the sensor domain exhibit two distinct relaxation phases (t 1  = 24 and t 2  = 694 μs), whereas that of the full-length protein exhibits monophasic behavior for all substructures in a time range of t = 1253-2090 μs. These observations can be instrumental in monitoring helix motion and the role of specific mutants in controlling the dynamics in the communication pathway from the sensor to the signaling domain. The kinetics observed for the amide I relaxation for the full-length protein indicate that the discrete substructures within full-length HemAT, unlike those of the sensor domain, relax independently., (Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Isodiphenylfluorindine (5) reacts with K 2 Cr 2 O 7 /H + to give 13-oxoisodiphenylfluorindinium perchlorate (7) (75%), but with phenyliodine bis(trifluoroacetate) (PIFA) or MnO 2 it gives the zwitterionic and quinoidal cruciform 13,13'-dimers 11 (85%) and 12 (89%), respectively. The zwitterionic 13,13'-dimer 11 can be rapidly converted with MnO 2 into the quinoidal 13,13'-dimer 12 (100%). UV-vis, NMR, single-crystal X-ray diffraction, and density functional theory studies support the structural assignments of all products. The electrochemical behavior of the compounds is also presented.

This work explores the potential for development of a lupanine valorization process evaluating different isolated microorganisms for their capacity to metabolize the alkaloid. Ecotoxicological assessment demonstrated that lupanine is toxic for Vibrio fischeri and Daphnia magna exhibiting EC 50 values of 89 mg L -1 and 47 mg L -1 respectively, while acting both as growth inhibitor for a monocotyledonous and as promoter for a dicotyledonous plant. Among the eight aerobic and anaerobic strains isolated and identified Rhodococcus rhodochrous LPK211 achieved 81% removal for 1.5 g L -1 lupanine, while no end-products were detected by NMR constituting a promising microorganism for lupanine biodegradation. Moreover, Rhodococcus ruber LPK111 and Rhodococcus sp. LPK311 exhibited 66% and 71% of removal respectively, including potential formation of lupanine N-oxide. Pseudomonas putida LPK411 reached 80% of lupanine removal and generated three fermentation products potentially comprising 17-oxolupanine and lupanine derivatives with open ring structures enabling the development of alkaloid valorization processes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The antiproliferative activity of the gold complex [Au(tpp)Cl] (1) (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic pathway, especially though the mitochondrion damage was concluded by cell cycle arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and Propidium Iodide (PI) as indicators, assays and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action of 1 was further studied by: (i) its catalytic activity on the oxidation of linoleic acid (an acid that partakes in membrane fluidity) to hyperoxolinoleic acid by oxygen and (ii) its binding affinity towards the calf thymus (CT) DNA. Since the deactivation of cisplatin by glutathione (GSH), is related with the development of cell resistance, the reaction of 1 with GSH was investigated by UV absorption spectroscopy. The absence of micronucleus in cells confirms that the complex has no in vitro toxicity. The in vivo genotoxicity caused by 1 was evaluated by Allium cepa test., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The non steroidal anti-inflammatory drugs (NSAID's)-silver(I) metallodrugs of aspirin (aspH), salicylic acid (salH 2 ), naproxen (napH) acid or p-hydrobenzoic acid (pHbzaH) and the mitochondriotropic triphenylarsine (tpAs) with the formulae [Ag(asp)(tpAs) 3 ] (1), [Ag(salH)(tpAs) 3 ] (2), [Ag(nap)(tpAs) 3 ] (3) and {[Ag(pHbza)(tpAs) 3 ]∙(dmf)} (4) and [Ag(tpAs) 3 (NO 3 )] (5) have been synthesized and characterized by m.p., FT-IR, UV-vis and 1 H NMR, spectroscopic techniques and X-ray crystallography. The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer cells: MCF-7 (positive to estrogen receptors (ERs)) and MDA-MB-231 (negative to estrogen receptors (ERs)) was evaluated. Compound 4 exhibits the stronger activity against MCF-7 (2.5 ± 0.1 μΜ), while 1 the strongest one against MDA-MB-231 (3.2 ± 0.3 μΜ). The IC 50 values against normal human fetal lung fibroblast cells lie between 3.0 and 3.7 μΜ. The toxic effect of 1-5 was evaluated against normal human fetal lung fibroblast cells (MRC-5 cells). The IC 50 values of 1-5 lie between 2.9 and 3.7 μΜ. The genotoxicity or not of 1-5 against MRC-5 cells was detected from the presence or absence of micronucleus using fluorescence microscopy. The presence of micronucleus in MRC-5 cells (3.0-3.7% in contrast to 1% of the untreated cells) confirms the in vitro toxic behaviour of the compounds. The apoptotic pathway, though the mitochondrion, was confirmed by cell cycle arrest (increasing of the apoptotic cells, in sub-G 1 phase (3.5 (5) - 13.3% (4)) in contrast of 1.8% in the control group) and permeabilization of the mitochondrial membrane test (MMP assay). Moreover, the ability of 1-5 to interact with Calf Thymus (CT)-DNA was also studied. Compound 4 exhibits the highest DNA binding constant (K b = (25.0 ± 9.7) × 10 4  M -1 ). The inhibitory activity of 1-5 against the enzyme lipoxygenase (LOX) is also investigated. The activity order is 1 > 4 > 3 > 2,5., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

In recent years, the design and discovery of new metal-organic framework (MOF) platforms with distinct structural features and tunable chemical composition has remarkably enhanced by applying reticular chemistry rules and the molecular building block (MBB) approach. We targeted the synthesis of new rare earth (RE)-MOF platforms based on a rectangular-shaped 4-c linker, acting as a rigid organic MBB. Accordingly, we designed and synthesized the organic ligand 1,2,4,5-tetrakis(4-carboxyphenyl)-3,6-dimethyl-benzene (H 4 L), in which the two methyl groups attached to the central phenyl ring lock the four peripheral carboxyphenyl groups to an orthogonal/vertical position. We report here a new family of RE-MOFs featuring the novel inorganic building unit, RE 4 (μ 3 -O) 2 (RE: Y 3+ , Tb 3+ , Dy 3+ , Ho 3+ , Er 3+ , and Yb 3+ ), with planar D 2h symmetry. The rigid 4-c linker, H 4 L, directs the in situ assembly of the unique 8-c RE 4 (μ 3 -O) 2 (COO) 8 cluster, resulting in the formation of the first (4, 8)-c RE-MOFs with csq topology, RE-csq-MOF-1. The structures of the yttrium (Y-csq-MOF-1) and holmium (Ho-csq-MOF-1) analogues were determined by single-crystal X-ray diffraction analysis. Y-csq-MOF-1 was successfully activated and tested for Xe/Kr separation. The results show that Y-csq-MOF-1 has high isosteric heat of adsorption for Xe (33.8 kJ mol -1 ), with high Xe/Kr selectivity (IAST 12.1, Henry 12.9) and good Xe uptake (1.94 mmol g -1 at 298 K and 1 bar), placing this MOF among the top-performing adsorbents for Xe/Kr separation.

Carob samples from seven different Mediterranean countries (Cyprus, Greece, Italy, Spain, Turkey, Jordan and Palestine) were analyzed using Fourier Transform Infrared (FTIR) spectroscopy. Seed and flesh samples of indigenous and foreign cultivars, both authentic and commercial, were examined. The spectra were recorded in transmittance mode from KBr pellets. The data were compressed and further processed statistically using multivariate chemometric techniques, including Principal Component Analysis (PCA), Cluster Analysis (CA), Partial Least Squares (PLS) and Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA). Specifically, unsupervised PCA framed the importance of the variety of carobs, while supervised analysis highlighted the contribution of the geographical origin. Best classification models were achieved with PLS regression on first derivative spectra, giving an overall correct classification. Thus, the applied methodology enabled the differentiation of carobs flesh and seed per their origin. Our results appear to suggest that this method is a rapid and powerful tool for the successful discrimination of carobs origin and type.

Oligomeric compounds, constituted of consecutive N , O -heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C-H activation of the formed oxazoles and their subsequent C-C cross-coupling to 2-bromopyridines in order to assemble a library of variable-length, 'head-to-tail'-connected, pyridyl-oxazole ligands. Through investigation of the interaction of the three longer ligands (5-mer, 6-mer, 7-mer) with cancer-relevant G-quadruplex structures (human telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22), the asymmetric pyridyl-oxazole motif has been demonstrated to be a prominent recognition element for G-quadruplexes. Fluorescence titrations reveal excellent binding affinities of the 7-mer and 6-mer for a Na⁺-induced antiparallel 22AG G-quadruplex (K D = 0.6 × 10 -7 M -1 and 0.8 × 10 -7 M -1 , respectively), and satisfactory (albeit lower) affinities for the 22AG/K⁺ and Myc2345-Pu22/K⁺ G-quadruplexes. All ligands tested exhibit substantial selectivity for G-quadruplex versus duplex (ds26) DNA, as evidenced by competitive Förster resonance energy transfer (FRET) melting assays. Additionally, the 7-mer and 6-mer are capable of promoting a sharp morphology transition of 22AG/K⁺ G-quadruplex., Competing Interests: The authors declare no conflicts of interest.

The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [ 3 H]histidine in exchange with intraliposomal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100µM concentration, were subjected to dose-response analysis. Two of them exhibited IC 50 lower than 1µM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular docking of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect., (Copyright © 2017 Elsevier Inc. All rights reserved.)

HemAT is a heme-containing oxygen sensor protein that controls aerotaxis. Time-resolved step-scan FTIR studies were performed on the isolated sensor domain and full-length HemAT proteins as well as on the Y70F (B-helix), L92A (E-helix), T95A (E-helix), and Y133F (G-helix) mutants to elucidate the effect of the site-specific mutations on the ligand dynamics subsequent to CO photolysis. The mutations aimed to perturb H-bonding and electrostatic interactions near the heme Fe-bound gaseous ligand (CO) and the heme proximal environment. Rebinding of CO to the heme Fe is biphasic in the sensor domain and full-length HemAT as well as in the mutants, with the exception of the Y133F mutant protein. The monophasic rebinding of CO in Y133F suggests that in the absence of the H-bond between Y133 and the heme proximal H123 residue the ligand rebinding process is significantly affected. The role of the proximal environment is also probed by resonance Raman photodissociation experiments, in which the Fe-His mode of the photoproduct of sensor domain HemAT-CO is detected at a frequency higher than that of the deoxy form in the difference resonance Raman spectra. The role of the conformational changes of Y133 (G-helix) and the role of the distal L92 and T95 residues (E-helix) in regulating ligand dynamics in the heme pocket are discussed.

A novel dynamic method for the investigation of the phenols activity in early stage oxidation of edible oils based on the formation of α-tocopheryl radicals initiated by oil-soluble vanadium complexes is developed. Two new vanadium complexes in oxidation states V and IV were synthesized by reacting 2,2'-((2-hydroxyoctadecyl)azanediyl)bis(ethan-1-ol) (C18DEA) with [VO(acac) 2 ] and 1-(bis(pyridin-2-ylmethyl)amino)octadecan-2-ol (C18DPA) with VOCl 2 . Addition of a solution of either complex in edible oils resulted in the formation of α-tocopheryl radical, which was monitored by electron paramagnetic resonance (EPR) spectroscopy. The intensity of the α-tocopheryl signal in the EPR spectra was measured versus time. It was found that the profile of the intensity of the α-tocopheryl signal versus time depends on the type of oil, the phenolic content, and the storage time of the oil. The time interval until the occurrence of maximum peak intensity be reached (t m ), the height of the maximum intensity, and the rate of the quenching of the α-tocopheryl radical were used for the investigation of the mechanism of the edible oils oxidation. 19 F NMR of the 19 F labeled phenolic compounds (through trifluoroacetate esters) and radical trap experiments showed that the vanadium complexes in edible oil activate the one electron reduction of dioxygen to superperoxide radical. Superperoxide reacts with the lipids to form alkoperoxyl and alkoxyl lipid radicals, and all these radicals react with the phenols contained in oils.

The employment of di-2-pyridyl ketone, (py) 2 CO, in heterometallic Mn/4f and homometallic Mn cluster chemistry has yielded six Mn III 4 Ln 2 and two Mn III 4 Mn II 2 structurally related clusters, namely, [Mn 4 Ln 2 O 2 {(py) 2 CO 2 } 4 (NO 3 ) 2 (RCO 2 ) 2 (H 2 O) 6 ](NO 3 ) 2 (Ln = Gd, 1, 5; Dy, 2; Tb, 3; R = Et, 1-3; Me, 5), [Mn 4 Dy 2 O 2 {(py) 2 CO 2 } 4 (NO 3 ) 4 (EtCO 2 ) 2 (H 2 O) 3 (MeOH)]·0.7MeOH·0.8H 2 O (4·0.7MeOH·0.8H 2 O), [Mn 4 Gd 2 O 2 {(py) 2 CO 2 } 4 (NO 3 ) 4 (C 6 H 4 ClCO 2 ) 2 (MeOH) 2 (py) 2 ]·2MeOH (6·2MeOH), [Mn 6 O 2 {(py) 2 CO 2 } 4 (py) 4 (H 2 O) 4 ](ClO 4 ) 4 ·4H 2 O (7·4H 2 O), and [Mn 6 O 2 {(py) 2 CO 2 } 4 (NO 3 ) 4 is the dianion of the gem-diol derivative of (py) 4 CO. The compounds possess a new type of cross-shaped structural core, which in the case of 1-6 is essentially planar, whereas in 7 and 8 it deviates from planarity. Clusters 1-6 are rare examples of Mn/4f species bearing (py) 2 CO or its derivatives, despite the fact that this ligand has been well-studied and proven a rich source of more than 200 metal compounds so far. Variable-temperature, solid-state direct-current and alternating-current magnetization studies were performed on complexes 1-5, 7, and 8 revealing that the dominant exchange interactions between the metal ions are antiferromagnetic and indicating ground-state spin values of S = 5 (for 1), 6 (for 5), and 2 (for 7 and 8).2 2- is the dianion of the gem-diol derivative of (py) 2 CO. The compounds possess a new type of cross-shaped structural core, which in the case of 1-6 is essentially planar, whereas in 7 and 8 it deviates from planarity. Clusters 1-6 are rare examples of Mn/4f species bearing (py) 2 CO or its derivatives, despite the fact that this ligand has been well-studied and proven a rich source of more than 200 metal compounds so far. Variable-temperature, solid-state direct-current and alternating-current magnetization studies were performed on complexes 1-5, 7, and 8 revealing that the dominant exchange interactions between the metal ions are antiferromagnetic and indicating ground-state spin values of S = 5 (for 1), 6 (for 5), and 2 (for 7 and 8).

From the ion point-of-view specific ion effects (SIE) arise as an interplay of ionic size and shape and charge distribution. However in aqueous systems SIE invariably involve water, and at surfaces they involve both interacting surface groups and local fields emanating from the surface. In this review we highlight the fundamental importance of ionic size and hydration on SIE, properties which encompass all types of interacting forces and ion-pairing phenomena and make the Hofmeister or lyotropic series of ions pertinent to a broad range of systems and phenomena. On the other hand ionic hydrophobicity and complexation capacity also determine ionic behavior in a variety of contexts. Over the years we have carried out carefully designed experiments on a few selected soft matter model systems, most involving zwitterionic phospholipids, to assess the importance of fundamental ionic and interfacial properties on ion specific effects. By tuning down direct Coulomb interactions, working with different interfacial geometries, and carefully tuning ion-lipid headgroup interactions it is possible to assess the importance of different parameters contributing to ion specific behavior. We argue that the majority of specific ion effects involving relatively simple soft matter systems can be at least qualitatively understood and demystified., (Copyright © 2017. Published by Elsevier B.V.)

Accumulation of mechanical stresses during cancer progression can induce blood and lymphatic vessel compression, creating hypo-perfusion, hypoxia and interstitial hypertension which decrease the efficacy of chemo- and nanotherapies. Stress alleviation treatment has been recently proposed to reduce mechanical stresses in order to decompress tumor vessels and improve perfusion and chemotherapy. However, it remains unclear if it improves the efficacy of nanomedicines, which present numerous advantages over traditional chemotherapeutic drugs. Furthermore, we need to identify safe and well-tolerated pharmaceutical agents that reduce stress levels and may be added to cancer patients' treatment regimen. Here, we show mathematically and with a series of in vivo experiments that stress alleviation improves the delivery of drugs in a size-independent manner. Importantly, we propose the repurposing of tranilast, a clinically approved anti-fibrotic drug as stress-alleviating agent. Using two orthotopic mammary tumor models, we demonstrate that tranilast reduces mechanical stresses, decreases interstitial fluid pressure (IFP), improves tumor perfusion and significantly enhances the efficacy of different-sized drugs, doxorubicin, Abraxane and Doxil, by suppressing TGFβ signaling and expression of extracellular matrix components. Our findings strongly suggest that repurposing tranilast could be directly used as a promising strategy to enhance, not only chemotherapy, but also the efficacy of cancer nanomedicine.

Benzene, toluene, ethylbenzene, o-, m-, and p-xylenes (BTEX) are ubiquitous outdoor and indoor air pollutants associated with both environmental and health effects. The objective of this exploratory study was to determine the magnitude and variability of urinary BTEX levels among residents of two areas located in the same city (Nicosia, Cyprus). The two areas differed with respect to their proximity to an industrial cluster and an intercity-highway. First morning urine voids were collected during a random campaign from selected households in the two urban areas (n = 48). Urinary BTEX measurements were obtained using headspace solid phase micro extraction coupled with gas chromatography-mass spectrometry. The majority of participants were females (65%) and non-smokers (85%) with a mean age of 49 years. Median urinary BTEX levels were: 118 ng L -1 , 124 ng L -1 , 9 ng L -1 , 29 ng L -1 and 28 ng L -1 for benzene, toluene, ethylbenzene, (p + m)-xylene and o-xylene, respectively. With the exception of benzene, participants from area 2 (closer to the industrial cluster and an intercity road than area 1) had significantly (p < 0.05) higher urinary BTEX levels than those from area 1 (regression analysis). The residence location (in area 2) was the sole significant (p < 0.05) predictor of urinary BTEX levels after adjusting for sex, smoking, age, body mass index, and educational level. This observational study showed differences in BTEX exposures between two urban areas of the same city. This baseline BTEX dataset may prove useful for future activities of natural gas extraction and handling nearby urban settings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Nitrite is a powerful oxidant that affects the activity of peroxidases towards various substrates and leads to heme macrocycle modifications in members of the peroxidase family, such as the horseradish peroxidase (HRP). We have applied resonance Raman spectroscopy to investigate the structural properties of the species formed in the reaction of NO 2 with the ferric form of HRP. Our data demonstrate that the heme nitrovinyl group is partially formed at near neutral pH, without coordination of NO - to the heme Fe. Nitrite coordinates to the heme Fe at acidic pH in the nitro binding mode, characterized by the detection of the ν(Fe-NO 2 - to the heme Fe. Nitrite coordinates to the heme Fe at acidic pH in the nitro binding mode, characterized by the detection of the ν(Fe-NO 2 ) at 563cm -1 , δ(FeNO 2 ) at 822cm -1 and ν sym . The sensitivity of the vibrations of the heme Fe-nitro complex to H/D exchange indicates H-bonding interaction of the heme-bound ligand with the distal environment that determines the NO 2 binding mode. A model describing the different modes of NO -1 . The sensitivity of the vibrations of the heme Fe-nitro complex to H/D exchange indicates H-bonding interaction of the heme-bound ligand with the distal environment that determines the NO 2 - binding mode. A model describing the different modes of NO 2 - binding in HRP is presented., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A new two-electron photosensitizer, H 2 BBQ 2+ [ZnCl 4 ] 2- /[(ZnCl) 2 (μ-BBH)] (BBQ stands for 2,5-bis[bis(pyridin-2-ylmethyl)amino]-1,4-quinone and BBH stands for 2,5-bis[bis(pyridin-2-ylmethyl)amino]-1,4-hydroquinone), has been synthesized and the oxidation state of the ligand was determined by X-ray crystallography and NMR spectroscopy. Under light illumination the H 2 BBQ 2+ [ZnCl 4 ] 2- + ZnCl 2 is reduced quantitatively to [(ZnCl) 2 (μ-BBH)] (pH ∼ 5) oxidizing H 2 O to H 2 O 2 as is evident by trap experiments. Electrochemistry gave a reversible two-electron ligand-centered redox wave for [(ZnCl) 2 (μ-BBH)]. UV-Vis, luminescence and EPR spectroscopies reveal the slow formation of a stable quinone diradical, intermediate of the reaction. DFT calculations are in agreement with the proposed mechanism. Based on this property an aqueous {[(ZnCl) 2 (μ-BBH)]||H 2 O 2 } solar rechargeable galvanic cell has been constructed.

The initial use of ligands 2'-hydroxyacetophenone (HL 1 ), 2-hydroxybenzophenone (HL 2 ) and 2,2'-dihydroxybenzophenone (H 2 L 3 ) in iron(iii) chemistry is described. The syntheses and crystal structures are reported for five iron(iii) clusters: [Fe 10 O 4 (OMe) 14 (L 1 ) 6 (MeOH) 2 ](NO 3 ) 2 ·3MeOH (1·3MeOH), [Fe 12 O 4 (OH)(OMe) 17 (L 1 ) 8 ](ClO 4 ) 2 ·2H 2 O (2·2H 2 O), [Fe 10 O 4 (OMe) 14 Cl 4 (L 2 ) 4 (MeOH) 2 ] (3), [Fe 10 O 4 (OMe) 14 (L 2 ) 6 (py) 2 ](ClO 4 ) 2 ·MeOH (4·MeOH), where py = pyridine, and [Fe 6 O 2 (OEt) 6 (O 2 CMe) 2 (L 3 ) 2 (HL 3 ) 2 ] (5). The molecular structures of the decanuclear clusters 1, 3 and 4 are organized around a {Fe 10 (μ 4 -O) 4 (μ 3 -OMe) 2 (μ-OMe) 12 } 8+ core consisting of ten {Fe 3 O 4 } face-sharing defective cubane units. The core of 2 consists of a {Fe 12 (μ 4 -O) 4 (μ 3 -OMe) 4 (μ-OH)(μ-OMe) 13 } 10+ unit composed of twelve {Fe 3 O 4 } face-sharing defective cubanes. The ligands (L 1 ) - and (L 2 ) - in 1-4 adopt the O,O'-bidentate chelating coordination mode and their roles are to terminate the further aggregation of the Fe III /O 2- /RO - cores. Complex 5 contains the {Fe 6 (μ 4 -O) 2 (μ-OEt) 6 (μ-O carbonyl ) 2 } 4+ core, where the μ-O carbonyl atoms are the bridging carbonyl oxygens of the two η 1 :η 2 :η 1 :μ (L 3 ) 2- ligands; the (HL 3 ) - groups behave as O phenolate , O carbonyl -bidentate chelating ligands with the neutral hydroxyl group being unbound to the Fe III atoms. The core is composed of four {Fe 3 O 4 } face-sharing defective cubanes. The Fe III atoms in 1-5 are all six-coordinate with distorted octahedral geometries. The IR spectra of the complexes are discussed in terms of the known coordination modes of the ligands and the ionic character of nitrates and perchlorates. Variable-temperature magnetic susceptibility and variable-field magnetization measurements establish that 2, 3 and 5 have S = 3, 0 and 5 ground states, respectively. The susceptibility data for 5 were fitted using a 3-J model indicating the simultaneous presence of both antiferromagnetic and ferromagnetic Fe III Fe III exchange interactions. Known magnetostructural correlations in oxido-bridged iron(iii) systems have been applied to rationalise the magnetic behaviour of the three clusters. The results of the present study demonstrate the utility of HL 1 , HL 2 and H 2 L 3 in the stabilisation of robust iron(iii)/oxido/alkoxido clusters.

This report, which is a sequence of a series of reviews, records the most important chiral selectors (CSs) applied in CE. It highlights the CSs that were used during the period 2014 to mid-2016. In this review, method developments, validations, and pharmaceutical along with biomedical applications are presented. The different CSs include CDs, antibiotics, cyclofructants, linear and branched oligo- and polysaccharides, and polymeric surfactants. In addition, the advantages of these CSs, along with their chiral recognition mechanisms, and their performance, are discussed., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Myoglobin (Mb) is known to react slowly with nitirite to form the green pigment by NO 2 cordination to the heme Fe in the O-binding nitrito (O1NO2) mode and to the heme 2-vinyl position. Nitrite is a powerful oxidizing agent and a biological reservoir for NO that has been implicated in a variety of aerobic biological systems. Accordingly, it is important to elucidate the nature and variety of NO - reaction mechanisms with Mb. We have performed principal component analysis (PCA, or essential dynamics) on Molecular Dynamics trajectories of all MbNO 2 coordination states to resolve the most important motions in the protein at 298K. We show that the coordination or removal of NO - to/from the heme iron is associated mainly with a motion of helix E and the coordination of NO 2 to the 2-vinyl is associated with a motion of helix F and a correlated motion of helices E-F. This latter correlated motion can be attributed to the interaction of Val68 and Ile107 with the 2-nitrovinyl moiety. The resonance Raman results show that coordination of NO 2 to the 2-vinyl is increased at pH6.0 demonstrating that the amide protons in the F helix are not protected from access of solvent water and the helix F motion allows solvent access to the 2-vinyl group, without affecting the coordination to the heme Fe.- to/from the heme iron is associated mainly with a motion of helix E and the coordination of NO 2 - to the 2-vinyl is associated with a motion of helix F and a correlated motion of helices E-F. This latter correlated motion can be attributed to the interaction of Val68 and Ile107 with the 2-nitrovinyl moiety. The resonance Raman results show that coordination of NO 2 - to the 2-vinyl is increased at pH6.0 demonstrating that the amide protons in the F helix are not protected from access of solvent water and the helix F motion allows solvent access to the 2-vinyl group, without affecting the coordination to the heme Fe., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Platinum(ii) complexes of the formula PtLCl 2 [L = 2-(2'-pyridyl)quinoxaline, (pqx) (1), 2,(2'-pyridyl)benzo[g]quinoxaline, (pbqx) (3) and 2,(2'-pyridyl)quinoline, (pqn) (5)] were synthesized and characterized by spectroscopic and X-ray diffraction methods. Also, monodentate coordination of the ligands pqx and pbqx formed the complexes trans-Pt(DMSO)pqxCl 2 (2) and trans-Pt(DMSO)pbqxCl 2 (4) as it is indicated from X-ray crystal structure and NMR studies. The reaction of the complexes (1), (3) and (5) with DMSO-d 6 revealed a ligand-release solvolysis, which was studied by means of NMR techniques. Correlation between the crystal structures of (1), (3), and (5) and the kinetic or thermodynamic parameters of the solvolysis reactions showed that the tendency of the ligands pqx, pbqx, and pqn to return to the anti-configuration in addition to their ability to form non-classical H-bonds are crucial factors for the ligand-release solvolysis. Instantaneous DMSO-d 6 solvolysis for the complexes (1) and (3) and slow kinetics solvolysis for (5) (k = 10 -4 ± 6.4 × 10 -6 s -1 ) reflect their structural differences in ligand planarity. Based on NMR techniques a two-step mechanism of the chelate ring opening was suggested with equilibrium constants of the overall reaction at 298 K, K eq = 4.1 ± 0.2 × 10 -4 M -1 (1) and K eq = 1.7 ± 0.2 × 10 -4 M -1 (2).

A Pd(0)-catalyzed double C-N coupling of 5,5'-dibromo-2,2'-bithiazoles with (het)arylamines and subsequent in situ Ag 2 O-mediated oxidation provides access to cross-conjugated quinoidal 5,5'-diarylimino-2,2'-bithiazoles in moderate to high yield. The highly colored quinoidal 2,2'-bithiazoles were studied by UV/vis spectroscopy, cyclic voltammetry and computational methods.

The coordination of nitrite in myoglobin (Mb) has been characterized by resonance Raman spectroscopy and the frequencies of the nitrite bound to the heme Fe as well to the 2-vinyl have been computed by density functional theory (DFT) calculations. The DFT Natural Bond Orbital (NBO) analysis and the extensive isotope-labeling in the resonance Raman experiments indicate that NO 2 (O1NO2) is bound to the heme Fe via O1. Based on the vibrational characterization of the reversible transition between low and high spin FeONO/2-nitrovinyl species, we suggest that the key step that triggers the spin-change is the increase of the proximal FeN - bond length. The frequencies of the O and N sensitive bands of the FeONO/2-nitrovinyl species remained largely unchanged in the low- to high-spin transition. Therefore the "greening" process in the reaction of ferric Mb with NO His93 bond length. The frequencies of the O and N sensitive bands of the FeONO/2-nitrovinyl species remained largely unchanged in the low- to high-spin transition. Therefore the "greening" process in the reaction of ferric Mb with NO 2 - proceeds through the FeONO/2-nitrovinyl species, which can exist in either the high or low-spin state., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Atomic force microscope (AFM) is a powerful and invaluable tool for imaging and probing the mechanical properties of biological samples at the nanometric scale. The importance of nano-scale characterization and nanomechanics of soft biological tissues is becoming widely appreciated, and AFM offers unique advantages in this direction. In this chapter, we describe the procedure to collect data sets (imaging and mechanical properties measurement) of collagen gels and tumor tissues. We provide step-by-step instructions throughout the procedure, from sample preparation to cantilever calibration, data acquisition, analysis, and visualization, using two commercial AFM systems (PicoPlus and Cypher ES) and software that accompanied the AFM systems and/or are freeware available (WSxM, AtomicJ). Our protocols are written specifically for these two systems and the mentioned software; however, most of the general concepts can be readily translated to other AFM systems and software.