Mass spectrometry-based "omics" technologies for the study of gestational diabetes and the discovery of new biomarkers.

Gestational diabetes (GDM) is one of the most common complications occurring during pregnancy. Diagnosis is performed by oral glucose tolerance test, but harmonized testing methods and thresholds are still lacking worldwide. Short-term and long-term effects include obesity, type 2 diabetes, and increased risk of cardiovascular disease. The identification and validation of sensitidve, selective, and robust biomarkers for early diagnosis during the first trimester of pregnancy are required, as well as for the prediction of possible adverse outcomes after birth. Mass spectrometry (MS)-based omics technologies are nowadays the method of choice to characterize various pathologies at a molecular level. Proteomics and metabolomics of GDM were widely investigated in the last 10 years, and various proteins and metabolites were proposed as possible biomarkers. Metallomics of GDM was also reported, but studies are limited in number. The present review focuses on the description of the different analytical methods and MS-based instrumental platforms applied to GDM-related omics studies. Preparation procedures for various biological specimens are described and results are briefly summarized. Generally, only preliminary findings are reported by current studies and further efforts are required to determine definitive GDM biomarkers.

Positively Charged Organosilanes Covalently Linked to the Silica Network as Modulating Tools for the Salinity Correction of pH Values Obtained with Colorimetric Sensor Arrays (CSAs).

Seven increasing levels of water salinity from 0.029 to 0.600 M (as NaCl) were used to investigate the dependence of pH measurement, performed using colorimetric sensor arrays (CSAs), on ionic strength. The CSAs were arrays of sensing spots prepared in the form of sol-gel-embedding Bromothymol Blue (BB) and Bromocresol Green (BCG) in a porous nitrocellulose support. The support was impregnated over the entire thickness (≈100 µm), allowing for the signal (Hue) acquisition on the opposite side to the contact with the sample solution. Three CSAs were prepared, M1, M2, and M3. M1 contained a free cationic surfactant, hexadecyltrimethylammonium p-toluenesulfonate (CTApTs), for modulating the pKa of the indicators. In M2, the surfactant dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DTSACl) was covalently bonded to the sol-gel. M3 was prepared like M2 but using a larger amount of ethanol as the solvent for the synthesis. The modulation of the CTApTs or the DTSACl concentration enabled the tuning of the pKa. In general, the pKa modulation ability decreased with the increase in salinity. The presence of a surfactant covalently linked to the backbone partially reduced the competitiveness of the anionic species, improving the results. Nevertheless, the salt effect was still present, and a correction algorithm was required. Between pH 5.00 and 12.00, this correction could be made automatically by using spots taken as references to produce sensors independent of salinity. As the salt effect is virtually absent above 0.160 M, M2 and M3 can be used for future applications in seawater.

Tuning the Framework of Thioether-Functionalized Polyazamacrocycles: Searching for a Chelator for Theranostic Silver Radioisotopes.

Silver-111 is an attractive unconventional candidate for targeted cancer therapy as well as for single photon emission computed tomography and can be complemented by silver-103 for positron emission tomography noninvasive diagnostic procedures. However, the shortage of chelating agents capable of forming stable complexes tethered to tumor-seeking vectors has hindered their in vivo application so far. In this study, a comparative investigation of a series of sulfur-containing structural homologues, namely, 1,4,7-tris[2-(methylsulfanyl)ethyl)]-1,4,7-triazacyclononane (NO3S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetraazacyclotetradecane (TE4S) was conducted to appraise the influence of different polyazamacrocyclic backbones on Ag+ complexation. The performances of these macrocycles were also compared with those of the previously reported Ag+/[111Ag]Ag+-chelator 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S). Nuclear magnetic resonance data supported by density functional theory calculations and X-ray crystallographic results gave insights into the coordination environment of these complexes, suggesting that all of the donor atoms are generally involved in the metal coordination. However, the modifications of the macrocycle topology alter the dynamic binding of the pendant arms or the conformation of the ring around the metal center. Combined pH/pAg-potentiometric and spectroscopic experiments revealed that the 12-member N4 backbone of DO4S forms the most stable Ag+ complex while both the enlargement and the shrinkage of the macrocyclic frame dwindle the stability of the complexes. Radiolabeling experiments, conducted with reactor-produced [111Ag]Ag+, evidenced that the thermodynamic stability trend is reflected in the ligand's ability to incorporate the radioactive ion at high molar activity, even in the presence of a competing cation (Pd2+), as well as in the integrity of the corresponding complexes in human serum. As a consequence, DO4S proved to be the most favorable candidate for future in vivo applications.

Pterodon emarginatus Seed Preparations: Antiradical Activity, Chemical Characterization, and In Silico ADMET Parameters of ß-caryophyllene and Farnesol.

The study of medicinal plants and their active compounds is relevant to maintaining knowledge of traditional medicine and to the development of new drugs of natural origin with lower environmental impact. From the seeds of the Brazilian plant Pterodon emarginatus, six different preparations were obtained: essential oil (EO), ethanol extract (EthE) prepared using the traditional method, and four extracts using solvents at different polarities, such as n-hexane, chloroform, ethyl acetate, and methanol (HexE, ChlE, EtAE, and MetE). Chemical characterization was carried out with gas chromatography, allowing the identification of several terpenoids as characteristic components. The two sesquiterpenes ß-caryophyllene and farnesol were identified in all preparations of Pterodon emarginatus, and their amounts were also evaluated. Furthermore, the total flavonoid and phenolic contents of the extracts were assessed. Successively, the antiradical activity with DPPH and ORAC assays and the influence on cell proliferation by the MTT test on the human colorectal adenocarcinoma (HT-29) cell line of the preparations and the two compounds were evaluated. Lastly, an in silico study of adsorption, distribution, metabolism, excretion, and toxicity (ADMET) showed that ß-caryophyllene and farnesol could be suitable candidates for development as drugs. The set of data obtained highlights the potential medicinal use of Pterodon emarginatus seeds and supports further studies of both plant preparations and isolated compounds, ß-caryophyllene and farnesol, for their potential use in disease with free radical involvement as age-related chronic disorders.

Exploring volatile organic compound emission from thermally modified wood by PTR-ToF-MS.

Thermal modification of wood is a well-known industrial process performed to increase the durability and dimensional stability or to change the colour of natural wood. The treatment influences many other properties of wood including the emission of volatile organic compounds (VOCs). VOC release ultimately affects the quality of indoor air and the capability of having low VOC emission is often included as a key parameter for the attribution of quality labels. In the present work, wood from six tree species was subjected to different types of treatment and VOC profiling was carried out on both treated and untreated samples by means of PTR-ToF-MS. Different types of thermal treatment were tested, involving either overpressure or vacuum and the effect of different temperature profiles was evaluated. Hardwood and softwood showed different release profiles under all tested conditions: the headspace of softwood was richer in several VOCs, such as terpenes, phenols and C6-C9 aldehydes and carboxylic acids. Upon thermal treatment, terpene emissions decreased, whereas several other VOCs, such as formic acid, formaldehyde, furfural and acetic acid, were released in higher amounts. With its high sensitivity and throughput, PTR-ToF-MS appears to be a very powerful analytical tool, useful in supporting the selection of wood materials for different end uses.

Single-Walled Carbon Nanohorns as Boosting Surface for the Analysis of Low-Molecular-Weight Compounds by SALDI-MS.

Limits of Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry (MS) in the study of small molecules are due to matrix-related interfering species in the low m/z range. Single-walled carbon nanohorns (SWCNH) were here evaluated as a specific surface for the rapid analysis of amino acids and lipids by Surface-Assisted Laser Desorption Ionization (SALDI). The method was optimized for detecting twenty amino acids, mainly present as cationized species, with the [M+K]+ response generally 2-time larger than the [M+Na]+ one. The [M+Na]+/[M+K]+ signals ratio was tentatively correlated with the molecular weight, dipole moment and binding affinity, to describe the amino acids' coordination ability. The SWCNH-based surface was also tested for analyzing triglycerides in olive oil samples, showing promising results in determining the percentage composition of fatty acids without any sample treatment. Results indicated that SWCNH is a promising substrate for the SALDI-MS analysis of low molecular weight compounds with different polarities, enlarging the analytical platforms for MALDI applications.

Kinetically Stable Nonequilibrium Gold-Cobalt Alloy Nanoparticles with Magnetic and Plasmonic Properties Obtained by Laser Ablation in Liquid.

Nonequilibrium nanoalloys are metastable solids obtained at the nanoscale under nonequilibrium conditions that allow the study of kinetically frozen atoms and the discovery of new physical and chemical properties. However, the stabilization of metastable phases in the nanometric size regime is challenging and the synthetic route should be easy and sustainable, for the nonequilibrium nanoalloys to be practically available. Here we report on the one-step laser ablation synthesis in solution (LASiS) of nonequilibrium Au-Co alloy nanoparticles (NPs) and their characterization on ensembles and at the single nanoparticle level. The NPs are obtained as a polycrystalline solid solution stable in air and water, although surface cobalt atoms undergo oxidation to Co(II). Since gold is a renowned plasmonic material and metallic cobalt is ferromagnetic at room temperature, these properties are both found in the NPs. Besides, surface conjugation with thiolated molecules is possible and it was exploited to obtain colloidally stable solutions in water. Taking advantage of these features, an array of magnetic-plasmonic dots was obtained and used for surface-enhanced Raman scattering experiments. Overall, this study confirms that LASiS is an effective method for the formation of kinetically stable nonequilibrium nanoalloys and shows that Au-Co alloy NPs are appealing magnetically responsive plasmonic building blocks for several nanotechnological applications.

Copper Coordination Chemistry of Sulfur Pendant Cyclen Derivatives: An Attempt to Hinder the Reductive-Induced Demetalation in 64/67Cu Radiopharmaceuticals.

The Cu2+ complexes formed by a series of cyclen derivatives bearing sulfur pendant arms, 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), and 1,7-bis[2-(methylsulfanyl)ethyl]-4,10-diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S), were studied in aqueous solution at 25 °C from thermodynamic and structural points of view to evaluate their potential as chelators for copper radioisotopes. UV-vis spectrophotometric out-of-cell titrations under strongly acidic conditions, direct in-cell UV-vis titrations, potentiometric measurements at pH >4, and spectrophotometric Ag+-Cu2+ competition experiments were performed to evaluate the stoichiometry and stability constants of the Cu2+ complexes. A highly stable 1:1 metal-to-ligand complex (CuL) was found in solution at all pH values for all chelators, and for DO2A2S, protonated species were also detected under acidic conditions. The structures of the Cu2+ complexes in aqueous solution were investigated by UV-vis and electron paramagnetic resonance (EPR), and the results were supported by relativistic density functional theory (DFT) calculations. Isomers were detected that differed from their coordination modes. Crystals of [Cu(DO4S)(NO3)]·NO3 and [Cu(DO2A2S)] suitable for X-ray diffraction were obtained. Cyclic voltammetry (CV) experiments highlighted the remarkable stability of the copper complexes with reference to dissociation upon reduction from Cu2+ to Cu+ on the CV time scale. The Cu+ complexes were generated in situ by electrolysis and examined by NMR spectroscopy. DFT calculations gave further structural insights. These results demonstrate that the investigated sulfur-containing chelators are promising candidates for application in copper-based radiopharmaceuticals. In this connection, the high stability of both Cu2+ and Cu+ complexes can represent a key parameter for avoiding in vivo demetalation after bioinduced reduction to Cu+, often observed for other well-known chelators that can stabilize only Cu2+.

Thermal Desorption-Vocus Enables Online Nondestructive Quantification of 2,4,6-Trichloroanisole in Cork Stoppers below the Perception Threshold.

2,4,6-Trichloroanisole (TCA) contamination of wine determines huge economic losses for the wine industry estimated to amount to several billion dollars yearly. Over 50 years of studies have determined that this problem is often caused by TCA contamination of the cork stopper, which releases TCA into the wine. The human threshold for TCA is extremely low. A wine contaminated by 1-2 ng/L TCA can be perceived as tainted. Contaminations with <0.5 ng/L TCA are commonly considered negligible and are not perceivable. The possibility of prescreening cork stoppers for TCA contamination would be an enormous advantage. Therefore, the demand for a fast, nondestructive method capable of quantifying the TCA contamination in cork stoppers is impelling. Vastly used analytical methods have so far struggled to provide a fast and reliable solution, whereas sensory analysis by trained panelists is expensive and time-consuming. Here we propose a novel approach based on chemical ionization-time-of-flight (CI-TOF) mass spectrometry employing the "Vocus" ion source and ion-molecule reactor. The technique proved capable of nondestructively quantifying TCA contamination in a single cork stopper in 3 s, with a limit of quantification below the perception threshold. A real test on the industrial scale, quantifying TCA contamination in more than 10000 cork stoppers in a few hours is presented, representing the largest data set of TCA analysis on cork stoppers within the literature and proving the possibility to apply the technique in an industrial environment. The correlation with standard methods for releasable TCA quantification is also discussed.

Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals.

With a half-life of 7.45 days, silver-111 (ßmax 1.04 MeV, Eγ 245.4 keV [Iγ 1.24%], Eγ 342.1 keV [Iγ 6.7%]) is a promising candidate for targeted cancer therapy with ß- emitters as well as for associated SPECT imaging. For its clinical use, the development of suitable ligands that form sufficiently stable Ag+-complexes in vivo is required. In this work, the following sulfur-containing derivatives of tetraazacyclododecane (cyclen) have been considered as potential chelators for silver-111: 1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO4S), (2S,5S,8S,11S)-2,5,8,11-tetramethyl-1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO4S4Me), 1,4,7-tris(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris(2-(methylsulfanyl)ethyl)-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), and 1,7-bis(2-(methylsulfanyl)ethyl)-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). Natural Ag+ was used in pH/Ag-potentiometric and UV-vis spectrophotometric studies to determine the metal speciation existing in aqueous NaNO3 0.15 M at 25 °C and the equilibrium constants of the complexes, whereas NMR and DFT calculations gave structural insights. Overall results indicated that sulfide pendant arms coordinate Ag+ allowing the formation of very stable complexes, both at acidic and physiological pH. Furthermore, radiolabeling, stability in saline phosphate buffer, and metal-competition experiments using the two ligands forming the strongest complexes, DO4S and DO4S4Me, were carried out with [111Ag]Ag+ and promising results were obtained.

pH Colorimetric Sensor Arrays: Role of the Color Space Adopted for the Calculation of the Prediction Error.

A pH colorimetric sensor array was prepared and characterized by combining tetrabromophenol blue (TBB) and bromothymol blue (BB) embedded in organically modified silicate (OrMoSil) spots polyvinylidene fluoride (PVDF)-supported. The signal was based on the Hue profile (H). The individual calibrations of TBB and BB showed precisions with minimum values of 0.012 pH units at pH = 2.196 for TBB and 0.018 at pH = 6.692 for BB. The overall precision of 10 spots of the mixture TBB/BB increased in the pH range of 1.000-8.000 from a minimum value of pH precision of 0.009 at pH = 2.196 to 0.012 at pH = 6.692, with the worst value of 0.279 pH units at pH = 4.101. The possibility to produce an array with much more than 10 spots allows for improving precision. The H analytical performance was compared to those of other color spaces such as RGB, Lab, and XYZ. H was the best one, with prediction error in the range of 0.016 to 0.021 pH units, at least three times lower than the second-best (x coordinate), with 0.064 pH units. These results were also confirmed by the calculation of the main experimental contributions to the pH prediction error, demonstrating the consistency of the proposed calculation approach.

Comparative Evaluation of Intestinal Absorption and Functional Value of Iron Dietary Supplements and Drug with Different Delivery Systems.

Iron is a fundament micronutrient, whose homeostasis is strictly regulated. Iron deficiency anemia is among the most widespread nutritional deficiencies and its therapy, based on dietary supplement and drugs, may lead to severe side effects. With the aim of improving iron bioavailability while reducing iron oral therapy side effects, novel dietary supplements based on innovative technologies-microencapsulation, liposomes, sucrosomes-have been produced and marketed. In the present work, six iron dietary supplements for different therapeutic targets were compared in terms of bioaccessibility, bioavailability, and safety by using an integrated in vitro approach. For general-purpose iron supplements, ME + VitC (microencapsulated) showed a fast, burst intestinal iron absorption kinetic, which maintained iron bioavailability and ferritin expression constant over time. SS + VitC (sucrosomes), on the other side, showed a slower, time-dependent iron absorption and ferritin expression trend. ME + Folate (microencapsulated) showed a behavior similar to that of ME + VitC, albeit with a lower bioavailability. Among pediatric iron supplements, a time-dependent bioavailability increase was observed for LS (liposome), while PIC (polydextrose-iron complex) bioavailability is severely limited by its poor bioaccessibility. Finally, except for SS + VitC, no adverse effects on intestinal mucosa vitality and barrier integrity were observed. Considering obtained results and the different therapeutic targets, microencapsulation-based formulations are endowed with better performance compared to the other formulations. Furthermore, performances of microencapsulated products were obtained with a lower iron daily dose, limiting the potential onset of side effects.

Exploring the Phase-Selective, Green, Hydrothermal Synthesis of Upconverting Doped Sodium Yttrium Fluoride: Effects of Temperature, Time, and Precursors.

The aim of this work was i) to develop a hydrothermal, low-temperature synthesis protocol affording the upconverting hexagonal phase NaYF4 with suitable dopants while adhering to the "green chemistry" standards and ii) to explore the effect that different parameters have on the products. In optimizing the synthesis protocol, short reaction times and low temperatures (below 150 °C) were considered. Yb3+ and Er3+ ions were chosen as dopants for the NaYF4 material. Within the context of the second goal, parameters including nature of the precursors, treatment temperature, and treatment time were investigated to afford a pure hexagonal crystalline phase, both in the doped and undoped materials. To fully explore the synthesis results, the prepared materials were characterized from a structural (XRD), compositional (XPS, ICP-MS), and morphological (SEM) point of view. The upconverting properties of the compounds were confirmed by photoluminescence measurements.

Seawater acidification and emerging contaminants: A dangerous marriage for haemocytes of marine bivalves.

The combined effects of seawater acidification and the non-steroidal anti-inflammatory drug diclofenac on haemocyte parameters of the mussel Mytilus galloprovincialis and the clam Ruditapes philippinarum were investigated for the first time. Animals were maintained for one week (T0) in natural pH condition (8.1) and two reduced pH values (pH -0.4 units and pH -0.7 units). Bivalves were then exposed for additional 14 days (T1 and T2) to the three experimental pH values in both the presence and absence of environmentally realistic concentrations of diclofenac (0.05 and 0.50 µg/L). To assess potential impairment in immunosurveillance, haemocyte parameters (total haemocyte count, haemocyte volume and diameter, Neutral Red uptake, haemocyte proliferation and lysozyme activity) were measured after 7, 14 and 21 days of exposure to differing pH value or pH/diclofenac combinations. In both species, pH affected the whole haemocyte data set at all sampling times, influencing most of the parameters measured at T0 and T1 in clams, and at T2 in mussels. Conversely, in both species diclofenac affected the overall haemocyte response at T2 only. However, in R. philippinarum a higher number of haemocyte parameters were significantly influenced even at T1. A significant interaction between pH and diclofenac was mainly evident in mussels, affecting haemocyte size and lysozyme activity at both T1 and T2. Overall, the results obtained demonstrated that the experimental conditions tested can alter markedly haemocyte parameters in marine bivalves.

Effects of aminomethylphosphonic acid, the main breakdown product of glyphosate, on cellular and biochemical parameters of the mussel Mytilus galloprovincialis.

The effects of the breakdown products of herbicides on aquatic species are largely unknown. In a recent study, we evaluated the effects of glyphosate on the mussel Mytilus galloprovincialis. This study was designed to evaluate for the first time the impact of aminomethylphosphonic acid (AMPA) - the main breakdown product of glyphosate - on cellular and biochemical parameters of the mussel Mytilus galloprovincialis. Bivalves were exposed for 7, 14 and 21 days to 1, 10 and 100 µg/L of AMPA and various biomarkers were measured in haemolymph (total haemocyte counts, haemocyte diameter and volume, haemolymph pH, haemocyte proliferation, haemolymph lactate dehydrogenase activity, haemocyte lysate lysozyme and acid phosphatase activities), as well as in gills and digestive gland (superoxide dismutase, catalase, glutathione S-transferase and acetylcholinesterase activities). AMPA concentrations in seawater samples from the experimental tanks were also measured in order to correlate the biomarker responses of mussels with their exposure to the actual concentrations of AMPA. The MANOVA analysis demonstrated that the experimental variables considered (exposure dose, exposure duration, and their interaction) affected significantly biomarker responses. Nevertheless, the two-way ANOVA analysis revealed significant effects of AMPA on most of the biomarkers measured. The overall results of this study demonstrated that AMPA can affect cellular and biochemical parameters in mussels, similarly to glyphosate.

Study and Development of a Fluorescence Based Sensor System for Monitoring Oxygen in Wine Production: The WOW Project.

The importance of oxygen in the winemaking process is widely known, as it affects the chemical aspects and therefore the organoleptic characteristics of the final product. Hence, it is evident the usefulness of a continuous and real-time measurements of the levels of oxygen in the various stages of the winemaking process, both for monitoring and for control. The WOW project (Deployment of WSAN technology for monitoring Oxygen in Wine products) has focused on the design and the development of an innovative device for monitoring the oxygen levels in wine. This system is based on the use of an optical fiber to measure the luminescent lifetime variation of a reference metal/porphyrin complex, which decays in presence of oxygen. The developed technology results in a high sensitivity and low cost sensor head that can be employed for measuring the dissolved oxygen levels at several points inside a wine fermentation or aging tank. This system can be complemented with dynamic modeling techniques to provide predictive behavior of the nutrient evolution in space and time given few sampled measuring points, for both process monitoring and control purposes. The experimental validation of the technology has been first performed in a controlled laboratory setup to attain calibration and study sensitivity with respect to different photo-luminescent compounds and alcoholic or non-alcoholic solutions, and then in an actual case study during a measurement campaign at a renown Italian winery.

Magnetically Assembled SERS Substrates Composed of Iron-Silver Nanoparticles Obtained by Laser Ablation in Liquid.

The widespread application of surface-enhanced Raman scattering (SERS) would benefit from simple and scalable self-assembly procedures for the realization of plasmonic arrays with a high density of electromagnetic hot-spots. To this aim, the exploitation of iron-doped silver nanoparticles (NPs) synthesized by laser ablation of a bulk bimetallic iron-silver target immersed in ethanol is described. The use of laser ablation in liquid is key to achieving bimetallic NPs in one step with a clean surface available for functionalization with the desired thiolated molecules. These iron-silver NPs show SERS performances, a ready response to external magnetic fields and complete flexibility in surface coating. All these characteristics were used for the magnetic assembly of plasmonic arrays which served as SERS substrates for the identification of molecules of analytical interest. The magnetic assembly of NPs allowed a 28-fold increase in the SERS signal of analytes compared to not-assembled NPs. The versatility of substrate preparation and the SERS performances were investigated as a function of NPs surface coating among different thiolated ligands. These results show a simple procedure to obtain magnetically assembled regenerable plasmonic arrays for repeated SERS investigation of different samples, and it can be of inspiration for the realization of other self-assembled and reconfigurable magnetic-plasmonic devices.

Characterization of lipopeptides produced by Bacillus licheniformis using liquid chromatography with accurate tandem mass spectrometry.

RATIONALE: The plant endophyte Bacillus licheniformis, isolated from leaves of Vitis vinifera, was studied to individuate and characterize the presence of bioactive lipopeptides having amino acidic structures. METHODS: Crude extracts of liquid cultures were analyzed by ultra-high-performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight (QTOF) mass analyzer. Chromatographic conditions were optimized in order to obtain an efficient separation of the different isobaric lipopeptides, avoiding merged fragmentations of co-eluted isomeric compounds and reducing possible cross-talk phenomena. Composition of the amino acids was outlined through the interpretation of the fragmentation behavior in tandem high-resolution mass spectrometry (HRMS/MS) mode, which showed both common-class and peculiar fragment ions. Both [M + H](+) and [M + Na](+) precursor ions were fragmented in order to differentiate some isobaric amino acids, i.e. Leu/Ile. Neutral losses characteristic of the iso acyl chain were also evidenced. RESULTS: More than 90 compounds belonging to the classes of surfactins and lichenysins, known as biosurfactant molecules, were detected. Sequential LC/HRMS/MS analysis was used to identify linear and cyclic lipopeptides, and to single out the presence of a large number of isomers not previously reported. Some critical issues related to the simultaneous selection of different compounds by the quadrupole filter were highlighted and partially solved, leading to tentative assignments of several structures. Linear lichenysins are described here for the first time. CONCLUSIONS: The approach was proved to be useful for the characterization of non-target lipopeptides, and proposes a rationale MS experimental scheme aimed to investigate the difference in amino acid sequence and/or in the acyl chain of the various congeners, when standards are not available. Results expanded the knowledge about production of linear and cyclic bioactive compounds from Bacillus licheniformis, clarifying the structures of isomeric forms, and enabling the use of selected endophytes to produce fungicides for eco-friendly biocontrol. Copyright © 2016 John Wiley & Sons, Ltd.

Reversible Electrochemical Modulation of a Catalytic Nanosystem.

A catalytic system based on monolayer-functionalized gold nanoparticles (Au NPs) that can be electrochemically modulated and reversibly activated is reported. The catalytic activity relies on the presence of metal ions (Cd(2+) and Cu(2+) ), which can be complexed by the nanoparticle-bound monolayer. This activates the system towards the catalytic cleavage of 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP), which can be monitored by UV/Vis spectroscopy. It is shown that Cu(2+) metal ions can be delivered to the system by applying an oxidative potential to an electrode on which Cu(0) was deposited. By exploiting the different affinity of Cd(2+) and Cu(2+) ions for the monolayer, it was also possible to upregulate the catalytic activity after releasing Cu(2+) from an electrode into a solution containing Cd(2+) . Finally, it is shown that the activity of this supramolecular nanosystem can be reversibly switched on or off by oxidizing/reducing Cu/Cu(2+) ions under controlled conditions.

"One-shot" analysis of PDE-5 inhibitors and analogues in counterfeit herbal natural products using an LC-DAD-QTOF system.

A highly selective and robust method for simultaneous screening and confirmation of target and non-target phosphodiesterase type 5 (PDE-5) inhibitor analogues within a single chromatographic run in counterfeit herbal products was developed. The protocol, based on an easy and rapid extraction with a water/acetonitrile 1 % formic acid solution, followed by sonication and centrifugation, exploits an LC-diode array detector-quadrupole-time-of-flight (DAD-QTOF) system. The extraction method was optimized both at high concentrations and at trace levels. These two situations are typically encountered in pharmaceutical formulations and herbal food supplements. Carryover effects, never reported before and occurring mainly for vardenafil, were overcome using a polymer-based column. An in-house validation was carried out using five blanks of different bulk matrices spiked with seven standard analytes, namely yohimbine, sildenafil, vardenafil, tadalafil, homosildenafil, pseudovardenafil and hydroxyhomovardenafil. Reliable quantitation was possible using a conventional standard solution for all the pharmaceutical and herbal samples considered, as matrix effects were eliminated. Accuracy ranged from 80.9 to 108.1 % with overall relative standard deviation (RSD) <11 % (N = 15), measured at 1.0, 5.0 and 10.0 µg/g. Limits of detection (LODs) obtained ensured the determination of cross contaminations at nanogram per gram levels. A database with 82 PDE-5 inhibitor analogues was implemented for automatic non-target analysis. Among the 26 samples of dietary supplements and herbal remedies bulk marketed for erectile dysfunctions, three samples were found to be contaminated with both registered and unregistered synthetic PDE-5 inhibitors, i.e. yohimbine, sildenafil, dimethylsildenafil and thiodimethylsildenafil or thiomethisosildenafil. The occurrence of such contaminations, both at trace levels and at pharmaceutical dosage, indicates the illicit use of synthetic PDE-5 analogues. Graphical Abstract Examples of pharmaceutical formulations and herbal natural products marketed for the erectile dysfunction.