On the Fragmentation of Ni(II) ß-Diketonate-Diamine Complexes as Molecular Precursors for NiO Films: A Theoretical and Experimental Investigation.

NiO-based nanomaterials have attracted considerable interest for different applications, which have stimulated the implementation of various synthetic approaches aimed at modulating their chemico-physical properties. In this regard, their bottom-up preparation starting from suitable precursors plays an important role, although a molecular-level insight into their reactivity remains an open issue to be properly tackled. In the present study, we focused on the fragmentation of Ni(II) diketonate-diamine adducts, of interest as vapor-phase precursors for Ni(II) oxide systems, by combining electrospray ionization mass spectrometry (ESI-MS) with multiple collisional experiments (ESI-MSn) and theoretical calculations. The outcomes of this investigation revealed common features in the fragmentation pattern of the target compounds: (i) in the first fragmentation, the three complexes yield analogous base-peak cations by losing a negatively charged diketonate moiety; in these cations, Ni-O and Ni-N interactions are stronger and the Ni positive charge is lower than in the parent neutral complexes; (ii) the tendency of ligand electronic charge to migrate towards Ni further increases in the subsequent fragmentation, leading to the formation of a tetracoordinated Ni environment featuring an interesting cation-π intramolecular interaction.

Interplay between coordination sphere engineering and properties of nickel diketonate-diamine complexes as vapor phase precursors for the growth of NiO thin films.

NiO-based films and nanostructured materials have received increasing attention for a variety of technological applications. Among the possible strategies for their fabrication, atomic layer deposition (ALD) and chemical vapor deposition (CVD), featuring manifold advantages of technological interest, represent appealing molecule-to-material routes for which a rational precursor design is a critical step. In this context, the present study is focused on the coordination sphere engineering of three heteroleptic Ni(II) ß-diketonate-diamine adducts of general formula [NiL2TMEDA] [L = 1,1,1-trifluoro-2,4-pentanedionate (tfa), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedionate (fod) or 2,2,6,6-tetramethyl-3,5-heptanedionate (thd), and TMEDA = N,N,N',N'-tetramethylethylenediamine]. Controlled variations in the diketonate structure are pursued to investigate the influence of steric hindrance and fluorination degree on the chemico-physical characteristics of the compounds. A multi-technique investigation supported by density functional calculations highlights that all complexes are air-insensitive and monomeric and that their thermal properties and fragmentation patterns are directly dependent on functional groups in the diketonate ligands. Preliminary thermal CVD experiments demonstrate the precursors' suitability for the obtainment of NiO films endowed with flat and homogeneous surfaces, paving the way to future implementation for CVD end-uses.

Insights into the Photoelectrocatalytic Behavior of gCN-Based Anode Materials Supported on Ni Foams.

Graphitic carbon nitride (gCN) is a promising n-type semiconductor widely investigated for photo-assisted water splitting, but less studied for the (photo)electrochemical degradation of aqueous organic pollutants. In these fields, attractive perspectives for advancements are offered by a proper engineering of the material properties, e.g., by depositing gCN onto conductive and porous scaffolds, tailoring its nanoscale morphology, and functionalizing it with suitable cocatalysts. The present study reports on a simple and easily controllable synthesis of gCN flakes on Ni foam substrates by electrophoretic deposition (EPD), and on their eventual decoration with Co-based cocatalysts [CoO, CoFe2O4, cobalt phosphate (CoPi)] via radio frequency (RF)-sputtering or electrodeposition. After examining the influence of processing conditions on the material characteristics, the developed systems are comparatively investigated as (photo)anodes for water splitting and photoelectrocatalysts for the degradation of a recalcitrant water pollutant [potassium hydrogen phthalate (KHP)]. The obtained results highlight that while gCN decoration with Co-based cocatalysts boosts water splitting performances, bare gCN as such is more efficient in KHP abatement, due to the occurrence of a different reaction mechanism. The related insights, provided by a multi-technique characterization, may provide valuable guidelines for the implementation of active nanomaterials in environmental remediation and sustainable solar-to-chemical energy conversion.

Spray-drying Microencapsulation of an Extract from Tilia tomentosa Moench Flowers: Physicochemical Characterization and in Vitro Intestinal Activity.

Silver linden (Tilia tomentosa Moench, TtM) flowers possess several health-promoting properties, especially at the neurological level, such as intestinal relaxation activity associated with specific flavonols, particularly quercetin and kaempferol derivatives. However, such molecules are susceptible to degradation upon different triggers like heat, light and extreme pH values. To overcome the scarce stability of TtM flowers bioactive molecules and make them suitable for developing functional food and supplements, we applied microencapsulation. Spray-drying microencapsulation of TtM flowers extract was performed using three starch-derived wall materials: maltodextrin 12 DE (MD12) and 19 DE (MD19), and OSA-modified starch (OSA-S). The stability of total phenols, flavanols, and antioxidant capacity was monitored for 70 days under accelerated stress conditions (40 °C/70% RH) by HPLC and spectrophotometric methods, and the intestinal contractile activity was tested in a murine model. In comparison to MD12 and MD19, OSA-S stood out for the higher encapsulation efficiency of quercetin and kaempferol glycosides (+ 36-47% compared to MD12 and + 18-24% compared to MD19) and stability thereof (half-life on average + 30% compared to MD12 and + 51% compared to MD19). The intestinal contractile activity of OAS-S powders resulted comparable to the original extract, indicating that flavonols were biologically active and accessible. Our results underly the potential advantages of OSA-S encapsulated formulation as a functional ingredient for the development of nutraceutical products.

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.

Facile preparation of a cobalt diamine diketonate adduct as a potential vapor phase precursor for Co3O4films.

Co3O4 thin films and nanosystems are implemented in a broad range of functional systems, including gas sensors, (photo)catalysts, and electrochemical devices for energy applications. In this regard, chemical vapor deposition (CVD) is a promising route for the fabrication of high-quality films in which the precursor choice plays a key role in the process development. In this work, a heteroleptic cobalt complex bearing fluorinated diketonate ligands along with a diamine moiety [Co(tfa)2·TMEDA; tfa = 1,1,1-trifluoro-2,4-pentanedionate and TMEDA = N,N,N',N'-tetramethylethylenediamine] is investigated as a potential Co molecular precursor for the CVD of Co3O4 systems. For the first time, the compound is characterized by crystal structure determination and comprehensive analytical studies, focusing also on its thermal properties and fragmentation patterns, important figures of merit for a CVD precursor. The outcomes of this investigation, accompanied by detailed theoretical studies, highlight its very favorable properties for CVD applications. In fact, growth experiments under oxygen atmospheres containing water vapor revealed the suitability of Co(tfa)2·TMEDA for the fabrication of high-quality, phase-pure Co3O4 thin films. The versatility of the proposed strategy in tailoring Co3O4 structural/morphological features highlights its potential to obtain multi-functional films with controllable properties for a variety of eventual technological end-uses.

In vitro chronic glycation induces AGEs accumulation reducing insulin-stimulated glucose uptake and increasing GLP1R in adipocytes.

Intracellular AGEs accumulation increases RAGE and GLP1R and reduces glucose uptake in adipocytes.

Long-term effect of pioglitazone vs glimepiride on lipoprotein oxidation in patients with type 2 diabetes: a prospective randomized study.

AIMS: Type 2 diabetes (DM2) is associated to oxidative modifications of high-density lipoproteins (HDL), which can interfere with their function. Pioglitazone has proved effective in raising HDL cholesterol (HDL-C) and lowering small dense low-density lipoprotein (LDL), but no clinical studies have examined its effect on lipoprotein oxidation in patients with DM2. METHODS: We assessed the effect of pioglitazone vs glimepiride after 1 year on HDL oxidation, expressed as relative abundance of peptides containing Met112O in ApoA-I (oxApoA-I) estimated by mass spectrometry (MALDI/TOF/TOF), in 95 patients with DM2. The oxLDL and AGE were quantified by ELISA. RESULTS: Patients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (Δ = 7.2 ± 14.8 mg/dL, p < 0.02) and a reduction in oxApoA-I (Δ = - 1.0 ± 2.6%, p < 0.02); this reduction was not significantly different from glimepiride. oxLDL showed a slight, but not significant increase in both treatment groups. Regression analysis showed a correlation between ΔoxApoA-I and ΔAGE (r = 0.30; p = 0.007) in all patients, while both of these parameters were unrelated to changes in HbA1c, HDL-C, duration of illness, or use of statins. CONCLUSIONS: Long-term treatment with pioglitazone was effective in reducing the oxidation of HDL, but not LDL in patients with DM2, while glimepiride didn't. This finding seems to be associated to the change of glyco-oxidation status, not to any improvement in glycemic control or lipid profile. TRIAL REGISTRATION: NCT00700856, ClinicalTrials.gov Registered June 18, 2008.

[99mTc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of αvß3 Integrin: Synthesis, Structure-Activity and Pharmacokinetic Studies.

New integrin-selective molecules suitable for therapeutic or imaging purposes are currently of interest in development of effective personalized medical platforms. RGDechi is a bifunctional peptide selective for integrin αvß3. Herein, RGDechi and three truncated derivatives functionalized with a cysteine (1-4) were synthesized and labeled with the [99mTc][Tc(N)PNP43]-synthon ([PNP43 = (CH3)2P(CH2)2N(C2H4OCH3)(CH2)2P(CH3)2]) (99mTc1-4) as a basis for selective integrin recognition. The pharmacological parameters of all radiolabeled peptides were assessed along with the pharmacokinetic profiles of the most promising 99mTc1 and 99mTc2 compounds both on healthy and melanoma-bearing mice. Their metabolism and metabolite identification are also reported. 99mTc1-2 are able to discriminate between endogenously expressed integrins αvß3 and αvß5 and possess favorable pharmacokinetics characterized by low liver uptake and rapid elimination from nontarget tissues resulting in positive target-to-nontarget ratios. Results are encouraging; the presented construct can be considered the starting point for the development of agents for the selective detection of αvß3 expression by SPECT.

Electrospray ionization study of tricarbonyl fac-[Re(CO)3 (PO)(X)]-type complexes: influence of ancillary co-ligands in the release of carbon monoxide.

RATIONALE: fac-[Re(CO)3 (PO)(X)]-type complexes (PO = chelated bidentate tertiary phosphine (1-), X = various neutral, mono-dentate ligands) represent a class of compounds that meets the synthetic criteria for the preparation of potential carbon monoxide (CO) release molecules (CORMs) for medicinal application. The aim of our investigation was to achieve qualitative information whether the nature of the ancillary X ligand might influence the release of CO. METHODS: The release of CO has been investigated by means of product ion spectrometry of electrospray ionization (ESI)-generated [M + H]+ species, produced by multiple collisional experiments, using an ion trap mass spectrometer. RESULTS: Tandem mass spectrometry applied to the protonated species [Re(CO)3 (PO)(X) + H]+ of seven complexes (those including X = OH2 (1), isonitrile (2, 3), imidazole (4), pyridine (5) and phosphine (6, 7)) shows initial loss of coordinated water (1) or pyridine (5), whereas the majority of investigated entries display initial, sequential release of CO groups. The energetics of CO release have been investigated by breakdown curves for selected collisionally activated decomposition processes involving CO, and compared with those involving X groups. CONCLUSIONS: The nature of the co-ligand X drives the primary loss in the MSn processes of [Re(CO)3 (PO)(X) + H]+ compounds. When X = solvent, the energetics of these decompositions follow the trend H2 O < MeOH < CO. In each case, loss of CO is a favored fragmentation route with associated energies following the trend: N-py ≤ P-phosphine < C-isonitrile. Overall, MSn pathways indicate that [Re(PO)] (Re with chelated PO phosphine) constitutes the residual moiety. This behavior indicates that the presence of a functionalized phosphine is essential for a sequential, controlled release of CO.

Molecular Engineering of MnII Diamine Diketonate Precursors for the Vapor Deposition of Manganese Oxide Nanostructures.

Molecular engineering of manganese(II) diamine diketonate precursors is a key issue for their use in the vapor deposition of manganese oxide materials. Herein, two closely related ß-diketonate diamine MnII adducts with different fluorine contents in the diketonate ligands are examined. The target compounds were synthesized by a simple procedure and, for the first time, thoroughly characterized by a joint experimental-theoretical approach, to understand the influence of the ligand on their structures, electronic properties, thermal behavior, and reactivity. The target compounds are monomeric and exhibit a pseudo-octahedral coordination of the MnII centers, with differences in their structure and fragmentation processes related to the ligand nature. Both complexes can be readily vaporized without premature side decompositions, a favorable feature for their use as precursors for chemical vapor deposition (CVD) or atomic layer deposition applications. Preliminary CVD experiments at moderate growth temperatures enabled the fabrication of high-purity, single-phase Mn3 O4 nanosystems with tailored morphology, which hold great promise for various technological applications.

Phthalates and heavy metals as endocrine disruptors in food: A study on pre-packed coffee products.

Phthalate plasticizers and heavy metals are widely recognized to be pollutants that interfere with key developmental processes such as masculinization. We investigated the release of phthalates and heavy metals in coffee brewed from coffee packed in single-serve coffee containers made from different types of materials: metal, biodegradable and plastics. We detected with GC-MS small amounts phthalates, below the tolerated daily risks levels, in all the coffees prepared from the different types of capsules. Specifically, Di (2-ethyl-hexyl)-phthalate and DiBP: Diisobuthyl-pthalate were ubiquitously present despite the high variability among the samples (respective range 0.16-1.87 µg/mL and 0.01-0.36 µg/mL). Whereas, diethyl-phthalate (range 0.20-0.26 µg/mL) and di-n-buthyl-phthalate (range 0.02-0.14 µg/mL) were detected respectively in one and three out of the four types of capsule tested. In contrast, we detected by atomic mass spectrometry on mineralized samples heavy metals lead (Pb) and nickel (Ni), in all coffee tested. PB levels (respective range 0.32-211.57 µg/dose) accounted for 42-79%, whereas Ni levels (respective range 166.25-1950.26 µg/dose) accounted for >100% of the tolerable daily intake. These results add to the already present concerns related to the multiple pathways of human exposure and the ubiquitous presence of these pollutants in consumer products and their long-term effect on human health.

Synthesis and characterization of rhenium(iii) complexes with (Ph2PCH2CH2)2NR diphosphinoamine ligands.

The synthesis and characterization of a new series of neutral, six-coordinated compounds [ReIIIX3(PNPR)], where X is Cl or Br and PNPR is a diphosphinoamine having the general formula (Ph2PCH2CH2)2NR (R = H, CH3, CH2CH3, CH2CH2CH3, CH2CH2CH2CH3 and CH2CH2OCH3) are reported. Stable [ReIIIX3(PNPR)] complexes were synthesized, in variable yields, starting from precursors where the metal was in different oxidation states (iii and v), by ligand-exchange and/or redox-substitution reactions. The compounds were characterized by elemental analysis, proton NMR spectroscopy, cyclic voltammetry, UV/vis spectroscopy, positive-ion electrospray ionization mass spectrometry (ESI(+)-MS) and X-ray diffraction analysis. Although the formulation of the complexes allows either meridional or facial isomers, the latter arrangement was prevalent both in the solid and solution states. Only [ReCl3(PNPH)] showed a meridional configuration both in solution and in the crystalline state. [ReBr3(PNPme)] prefers the meridional configuration in the crystalline state and the facial one in solution. While ESI(+)-MS and voltammetric data seem to indicate some dependency from the nature of the alkyl substituent at the nitrogen, the available structural data of the complexes show only slight differences both for angles and bond lengths upon change of the alkyl chain tethered to the nitrogen.

The Role of Ligand Topology in the Decomplexation of Luminescent Lanthanide Complexes by Dipicolinic Acid.

In this study, we present the aqueous solution behavior of two luminescent lanthanide antenna complexes (Eu3+ ⊂1, Dy3+ ⊂9) with different ligand topologies in the presence of dipicolinic acid (DPA, pyridine-2,6-dicarboxylic acid). Macrocyclic (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, DO3A, 9) and acyclic (1,4,7-triazaheptane-1,1,7,7-tetraacetic acid, DTTA, 1) ligands have been selected to form a ratiometric pair in which Dy3+ ⊂9 acts as a reference and Eu3+ ⊂1 acts as a probe for the recognition of DPA. The pair of luminescent complexes in water reveals the capability to work as a DPA luminescent sensor. The change of emission intensity of Eu3+ indicates the occurrence of a new sensitization path for the lanthanide cation through excitation of DPA. NMR evidence implies the presence of free 1 and mass spectrometry shows the formation of emitting [EuDPA2 ]- as a result of a ligand exchange reaction.

A preliminary study on human placental tissue impaired by gestational diabetes: a comparison of gel-based versus gel-free proteomics approaches.

Gestational diabetes (GDM) is the most common complication of pregnancy and it is associated with maternal and fetal short- and long-term consequences. GDM modifies placental structure and function, but many of the underlying mechanisms are still unclear. The aim of this study is to develop and compare two different methods, based respectively on gel-based and gel-free proteomics, in order to investigate the placental proteome in the absence or in the presence of GDM and to identify, through a comparative approach, possible changes in protein expression due to the GDM condition. Placenta homogenates obtained by pooling six control samples and six samples from GDM pregnant women were analyzed by two-dimensional (2D) electrophoresis coupled with mass spectrometry [nano-liquid chromatography (nano-LC) tandem mass spectrometry (MS/MS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)] and by a label-free mass spectrometry method based on LC-MS(E). The gel-based approach highlights 13 over-expressed proteins and 16 under-expressed proteins, while the label-free method shows the over- expression of 10 proteins and the under-expression of nine proteins. As regards 2D gel electrophoresis, a comparison between two different protein identification methods, based respectively on nLC-electrospray ionization-MS/MS and MALDI-MS/MS, was performed taking into consideration the sequence coverage, the MASCOT score and the exponentially modified protein abundance index. The analysis of the complex proteome through an integrated strategy revealed that the quantitative gel-free and label-free MS approach might be suitable to identify candidate markers of GDM.

Folic acid-conjugated europium complexes as luminescent probes for selective targeting of cancer cells.

We report the synthesis of three optical probes (Eu(3+)⊂1, Eu(3+)⊂2, and Eu(3+)⊂3) having a luminescent Eu complex (signaling unit) bonded in different positions to folic acid (FA), the folate receptor (FR) targeting unit. The structures of the two regioisomers Eu(3+)⊂1 and Eu(3+)⊂2 were assigned by mass spectrometric experiments. The optical properties and stability of these probes were assessed in phosphate-buffered saline, cell culture medium, rat serum, and cellular lysate, and results indicated that they are chemically and photophysically stable. Cytotoxicity was studied with ovarian cancer cells having high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells, was in the order Eu(3+)⊂2 > Eu(3+)⊂1 > Eu(3+)⊂3. No internalization was observed for A2780 cells. Such results, together with those obtained in competition experiments of FA versus Eu(3+)⊂2 and FA or Eu(3+)⊂2 versus (3)H-FA, indicate that internalization is receptor-mediated and that Eu(3+)⊂2 shows high selectivity and specificity for FR.

A preliminary fastview of mitochondrial protein profile from healthy and type 2 diabetic subjects.

Type 2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Mitochondrial dysfunctions are thought to be the major contributor to the development of various pathologies, including type 1 and type 2 diabetes mellitus. Mitochondrial oxidative stress has been reported in models of both type 1 and type 2 diabetes mellitus and may play a central role in mitochondrial dysfunction. In the present study, we investigated the occurrence of protein alterations, due to the presence of type 2 diabetes, in mitochondria isolated from human peripheral blood mononuclear cells (PBMCs] by matrix-assisted laser desorp- tion/ionization mass spectrometry (MALDI-MS]. PBMCs may be suitable for this investigation because they have insulin receptors that quickly respond to changes in insulin concentration, and in the presence of insulin rapidly increase their rates of glucose utiliza- tion. In the presence of insulin-resistance conditions, such as type 2 diabetes mellitus, this mechanism is altered and the glycation of cytoplasmic as well as mitochondrial proteins may plausibly appear. Therefore, PBMCs may be useful tools to verify modifications or altered expression of mitochondrial proteins. Human mitochondria were obtained from 32 subjects, 16 healthy controls and 16 type 2 diabetic patients. Two different methods for mitochondria isolation and purification were employed and compared. Some proteins have been found to be differently expressed in the two groups of subjects under investigation and can be classified into two sets: i.e. proteins related to ATP synthase [e.g. 6.8kDa mitochondrial proteolipid [MLQ]; ATP-CF6 [m/z 12,597)] and proteins related to cell proliferation and apoptosis [e.g. TIMM9 [m/z 10,378); Bcl-2-like protein 2 (m/z20,742)].

Study of isobaric grape seed proanthocyanidins by MALDI-TOF MS.

Positive matrix-assisted laser desorption ionization (MALDI) spectra of grape seed raw extracts show the signals of putative proanthocyanidin (PA) oligomers, including those of several sodium and potassium adducts with the same nominal molecular weight. As a result, the MALDI time-of-flight profiles are characterized by several isobaric signals from different PAs. The presence of isobaric PA adducts was studied by sodium and potassium exchange experiments on the seed extracts of six grape varieties. This approach was effective in differentiating PAs with isobaric signals, and 15 different PAs were identified in the MALDI spectra of all samples.

Triacylglycerol profile in cocoa liquors using MALDI-TOF and LC-ESI tandem mass spectrometry.

Triacylglycerols are responsible for chocolate's peculiar melting behavior: the type and position of fatty acids on the glycerol molecule strongly affect the melting range of cocoa butter. For this reason, the characterization of triglyceride composition in cocoa products is particularly important. In this work, triacylglycerols extracted from cocoa liquor samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight (TOF) and electrospray ionization tandem mass spectrometry (MS/MS) coupled to liquid chromatography. Extracted samples were initially analyzed by direct injection in MS to obtain information on triglyceride molecular weights; relevant MS parameters were optimized, and the possible formation of the adducts [M + Na](+) and [M + NH(4)](+) was studied. Tandem mass experiments (both with triple quadrupole and TOF/TOF) were performed to study the fragmentation pathways (in particular, the loss of palmitic, stearic and oleic acid) and identify the triacylglycerols in cocoa liquors. Some signals of the spectra obtained with both MS techniques could indicate the presence of diacylglycerols in the cocoa extract, but different experimental evidences demonstrated that they were generated by the in-source fragmentation of triglycerides. A nonaqueous reversed-phase chromatographic separation was also developed and used to support the identification of the analytes; nine triacylglycerols were recognized in the cocoa liquor extracts. The three different batches of Ecuador cocoa liquor did not show significant differences in the triacylglycerol profile.