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.

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.

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.

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.

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.

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.

Alpha actinin is specifically recognized by Multiple Sclerosis autoantibodies isolated using an N-glucosylated peptide epitope.

Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MuS), e.g. neurofascin, contactin, CNPase, and other T-cell receptor membrane anchored proteins. These putative antigens, although differing from the conventional myelin derivatives, are conceptually based on an animal model of experimental autoimmune encephalomyelitis. In this report we describe the identification of putative antigens based on their recognition by autoantibodies isolated from MuS patient serum. In a previous work from this laboratory we have shown that a peptide probe, named CSF114(Glc), specifically identifies serum autoantibodies in a subset of MuS patients, representing ∼30% of the patient population. The autoantibodies, purified from MuS patients' sera (six), through CSF114(Glc) affinity chromatography, detected three immunoreactive protein bands present in the rat brain. Proteomic analysis of the immunoreactive bands, involving MALDI and MS/MS techniques, revealed the presence of four proteins distinguishable by their mass: alpha fodrin, alpha actinin 1, creatine kinase, and CNPase. The immunoreactive profile of these rat brain proteins was compared with that of commercially available standard proteins by challenging against either CSF114(Glc) purified MuS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by the following procedure: whereas monoclonal antibodies recognized all rat brain proteins, isolated MuS specific antibodies recognize only alpha actinin 1 as a putative antigen. In fact, alpha actinin 1 displayed a robust immunoreactive response against all MuS patients' sera examined, whereas the other three bands were not consistently detectable. Thus, alpha actinin 1, a cytoskeleton protein implicated in inflammatory/degenerative autoimmune diseases (lupus nephritis and autoimmune hepatitis) might be regarded as a novel MuS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.

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)].

Some preliminary matrix-assisted laser desorption/ionization imaging experiments on maternal and fetal sides of human placenta.

An investigation on placenta proteins has been carried out by matrix-assisted laser desorption/ionization (MALDI) ion imaging (II) experiments. This was performed by laser irradiation of the maternal and fetal sides of placenta tissue. To investigate the possible changes in protein profile due to the development of gestational diabetes mellitus (GDM), five placenta samples from GDM patients and five placenta samples from healthy pregnant women were analyzed. An extensive optimization of the tissue slice treatment and of the matrix deposition method was performed. As already observed in MALDI spectra of placenta homogenates, and also in the MALDI-II condition, the most abundant peaks are due to hemoglobin α chain, hemoglobin ß chain and hemoglobin γ chain. However, higher molecular weight protein species were detected in the m/z range 20,000-47,000. The species at m/z 30335, m/z 31235 and m/z 32000 show some differences in their abundance in the maternal and fetal sides of the tissue in both classes of subjects under investigation. Comparison with the literature data suggest that they can result from the presence of mitochondrial proteins at tissue level.

Chemical aspects of the primary ionization mechanisms in matrix-assisted laser desorption ionization.

It has been proposed that the primary ionization mechanism occurring in matrix-assisted laser desorption ionization (MALDI) experiments originates from the presence, in the solid-state matrix-analytes sample, of matrix dimers. These species are formed by the interaction of carboxylic groups present in the matrix molecules with the formation of strong hydrogen bonds. Theoretical calculations proved that the laser irradiation of these structures leads to one or two H-bridge cleavages, giving rise to an "open" dimer structure or to disproportionation with the formation of MH(+) and [M-H](-) species. The ions so formed can be considered highly effective in their reaction with analyte ions, leading to their protonation (or deprotonation). To achieve further evidence for these proposals, in the present study the energetics of the reactions of ions from different aromatic carboxylic acids with two amino acids (glycine and lysine) and three multipeptides (gly-gly, gly-gly-gly and gly-gly-gly-gly) was investigated. The lowest ∆G values were obtained for 2,5- dihydroxybenzoic acid, widely employed as the MALDI matrix. Also, for p-nitrobenzoic acid the reaction is slightly exothermic, while for the other aromatic carboxylic acids derivatives positives values of ∆G are present.

The relationship between electrospray ionization behavior and cytotoxic activity of [M(I)(P)4](+)-type complexes (M = Cu, Ag and Au; P = tertiary phosphine).

RATIONALE: To try to find a correlation between the antiproliferative activity of a series of [M(I)(P)4](+) complexes (M = Cu, Ag and Au; P = tertiary phosphine) and their stability at micromolar concentration under mass spectrometric conditions. METHODS: [M(I)(P)4](+) complexes were investigated by positive ion electrospray ionization mass spectrometry with multiple collisional experiments using an ion trap mass spectrometer. RESULTS: The displacement of P from native [M(I)(P)4](+), previously described for the copper derivative, is common for the triad complexes leading to the formation of [M(P)3](+) and [M(P)2](+) adducts. Further dissociation of [M(P)2](+) depends on the nature of the metal (Cu ~ Ag > Au). More labile [Cu(P)2](+) and [Ag(P)2](+) are more cytotoxic against HCT-15 human colon carcinoma cells compared to less labile [Au(P)2](+) species. CONCLUSIONS: The dissociation of P ligand(s) from the [M(I)(P)4](+) complexes is the driving force for the triggering of the antiproliferative activity. The more favored is the displacement of P from the [M(P)2](+) active form, the more favored is in turn the possibility for the metal to interact with biological substrates related to cancer proliferation.

Fucoxanthin from Undaria pinnatifida: photostability and coextractive effects.

Fucoxanthin is one of the most abundant carotenoids and possesses a number of beneficial medicinal qualities which include its anti-oxidant, anti-obesity and anti-cancer properties. In this study, the photostability of fucoxanthin in extracts with different chemical profiles was studied. The extracts were obtained from Undaria pinnatifida, a seaweed rich in this carotenoid, using conventional liquid solvent extraction procedures and the QuEChERS method. All the extracts contained all-trans-fucoxanthin as the major compound. Conventional procedures produced a fucoxanthin purity of lower than 50%, whereas after liquid-liquid partition, PSA cleanup, and PSA and GCB cleanup (QuEChERS method) fucoxanthin purity increased to 70%, 86%, and 94%, respectively. Although in the acetone extract the initial content of fucoxanthin was the highest, results demonstrate that coextractives play an important role in enhancing the rate of photodegradation. After light exposure, the conventional extracts lost around 90% of the initial fucoxanthin content. On the other hand, the extracts obtained by the QuEChERS method showed significantly higher light stability than the conventional extracts. These results suggest that the QuEChERS method could be used and further improved to obtain more purified and stable extracts for fucoxanthin from U. pinnatifida.

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.

A fast and selective method for anthocyanin profiling of red wines by direct-infusion pneumatic spray mass spectrometry.

RATIONALE: Anthocyanins confer the color to red wines. During wine aging, new anthocyanin derivatives with peculiar chromatic characteristics are formed. A fast and selective method for screening the anthocyanin composition of wine has been developed. METHODS: Direct-infusion electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of wine extracts has been performed by operating in positive ion mode with a low spray capillary voltage (0.5 kV) to detect only the species already present in ionic form. The method has been called direct-infusion pneumatic spray (DIPS) mass spectrometry. The anthocyanin profiles of thirteen red wines at different aging stages were studied. Using malvidin-3,5-diglucoside as internal standard, the indices of wine color and of wine color evolution were estimated. RESULTS: By decreasing the spray capillary voltage a dramatic increase in selectivity toward anthocyanins has been observed and the related peaks are the most abundant in the spectra. Several anthocyanins and anthocyanin derivatives (pyranoanthocyanins and derivatives formed by reaction with flavan-3-ols) have been identified in the wines. The younger wines showed higher total anthocyanin index. The aged wines showed color evolution index higher than 20% while it was lower in the younger samples. CONCLUSIONS: The anthocyanin fingerprint is effective for estimating the aging state of wine. The color evolution index can be correlated to barrel conditions during wine aging and used to distinguish between aged and younger wines. The study of pyranoanthocyanins and anthocyanin-flavanol derivatives can be useful to predict wine color stability.

Dinuclear Cu(II) complexes of isomeric bis-(3-acetylacetonate)benzene ligands: synthesis, structure, and magnetic properties.

Highly versatile coordinating ligands are designed and synthesized with two ß-diketonate groups linked at the carbon 3 through a phenyl ring. The rigid aromatic spacer is introduced in the molecules to orient the two acetylacetone units along different angles and coordination vectors. The resulting para, meta, and ortho bis-(3-acetylacetonate)benzene ligands show efficient chelating properties toward Cu(II) ions. In the presence of 2,2'-bipyridine, they promptly react and yield three dimers, 1, 2, and 3, with the bis-acetylacetonate unit in bridging position between two metal centers. X-ray single crystal diffraction shows that the compounds form supramolecular chains in the solid state because of intermolecular interactions. Each of the dinuclear complexes shows a magnetic behavior which is determined by the combination of structural parameters and spin polarization effects. Notably, the para derivative (1) displays a moderate antiferromagnetic coupling (J = -3.3 cm(-1)) along a remarkably long Cu···Cu distance (12.30 Å).

Investigation on the role of pneumatic aspects in electrospray, desorption electrospray surface ionization and surface activated chemical ionization.

This review reports the results of some studies carried out by us on the role of pneumatic aspects in electrospray and desorption electrospray surface ionization, with the aim to propose some relevant aspects of the mechanisms involved in these ionization methods. Electrospray ion sources, with the exception of the nano- electrospray source, operate with the concurrent action of a strong electrical field and a supplementary coaxial gas flow. The electrical field is responsible for electrospraying of the analyte solution but the use of a coaxial gas flow leads to a significant increase of the analyte signal and allows the use of higher solution flows. However, by employing capillary voltages much lower than those necessary to activate the electrospray phenomenon, analyte ions are still observed and this indicates that different mechanisms must be operative for ion production. Under these conditions, ion generation could take place from the neutral pneumatically sprayed droplet by field-induced droplet ionization. Also in the case of desorption electrospray ionization (DESI), and without any voltage on the spraying capillary as well as on the surface of interest, ions of analytes present on the surface become detectable and this shows that desorption/ionization of analytes occurs by neutral droplets impinging the surface. Consequently, the pneumatic effect of the impinging droplets plays a relevant role, and for these reasons the method has been called pneumatic assisted desorption (PAD). Some analogies existing between PAD and surface activated chemical ionization (SACI), based on the insertion of a metallic surface inside an atmospheric pressure chemical ionization source operating without corona discharge, are discussed.