Towards a new pseudo-quantitative approach to evaluate the ionization response of nitrogen compounds in complex matrices.

Ultra high-resolution mass spectrometry (FT-ICR MS) coupled to electrospray ionization (ESI) provides unprecedented molecular characterization of complex matrices such as petroleum products. However, ESI faces major ionization competition phenomena that prevent the absolute quantification of the compounds of interest. On the other hand, comprehensive two-dimensional gas chromatography (GC × GC) coupled to specific detectors (HRMS or NCD) is able to quantify the main families identified in these complex matrices. In this paper, this innovative dual approach has been used to evaluate the ionization response of nitrogen compounds in gas oils as a case study. To this extent, a large gas oil dataset has been analyzed by GC × GC/HRMS, GC × GC-NCD and ESI(+/-)-FT-ICR MS. Then, the concentrations obtained from GC × GC-NCD have been compared to those obtained from FT-ICR MS hence proving that strong ionization competitions are taking place and also depending on the origin of the sample. Finally, multilinear regressions (MLR) have been used to quantitatively predict nitrogen families from FT-ICR MS measurements as well as start rationalizing the ionization competition phenomena taking place between them in different types of gas oils.

Low-Level Fusion of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Data Sets for the Characterization of Nitrogen and Sulfur Compounds in Vacuum Gas Oils.

A total of 18 vacuum gas oils have been analyzed by Fourier transform ion cyclotron resonance mass spectrometry considering six replicates in three different ionization modes (electrospray ionization (ESI)(+), ESI(-), and atmospheric pressure photoionization (APPI)(+)) to characterize the nitrogen and sulfur compounds contained in these samples. Classical data analysis has been first performed on generated data sets using double bond equivalents (DBE) versus number of carbon atoms (#C) plots in order to observe similarities and differences within the nitrogen and sulfur-containing molecular classes from samples produced by different industrial processes. In a second step, three-way arrays have been generated for each ionization mode considering three dimensions: DBE related to aromaticity, number of carbon atoms related to alkylation, and sample. These three-way arrays have then be concatenated using low-level data fusion strategy to obtain a new tensor with three new modes: aromaticity, alkylation, and sample. The PARAFAC method has then been applied for the first time to this three-way data structure. A two components decomposition has allowed us to highlight unique samples with unexpected reactivity behaviors throughout hydrotreatment. The obtained loadings led to the identification of the variables responsible for this specific character. This original strategy has provided a fast visualization tool able to highlight simultaneously the impact of the three ionization modes in order to explain the differences between the samples and compare them.

Insights from Nitrogen Compounds in Gas Oils Highlighted by High-Resolution Fourier Transform Mass Spectrometry.

Twenty-three gas oil samples from different origins were analyzed in positive and negative ion modes by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(±)-FT-ICR MS). Sample ionization and ion transfer conditions were first optimized using Design of Experiment approach. Advanced characterization of basic and neutral nitrogen compounds in these samples was then performed through ESI(±)-FT-ICR MS analysis. A good repeatability was observed from the analysis of six replicates for each gas oil sample. Significant differences in molecular composition were spotted between the gas oils, either considering identified heteroatomic classes or within nitrogen families and were later correlated to samples macroscopic properties. The evolution of nitrogen relative intensities for one feed and two corresponding effluents has also been studied to monitor hydrotreatment reaction pathways toward aromaticity and alkylation levels evolutions.

Chemometric Exploration of APPI(+)-FT-ICR MS Data Sets for a Comprehensive Study of Aromatic Sulfur Compounds in Gas Oils.

Sulfur content in gas oils is strictly regulated by legal specifications for environmental reasons. Gas oils are composed of various aromatic sulfur compounds, and some of them are known to be very refractory for sulfur removal reactions. Thus, an accurate analysis of sulfur compounds is important to find the appropriate operating conditions of the gas oil hydrotreating processes. Aromatic sulfur compounds contained in 23 gas oils samples were analyzed using APPI(+)-FT-ICR MS considering six replicates. Significant differences were spotted within several processed gas oils. A comparison of one feed and its corresponding effluents also confirmed the well-known refractory character of sulfur compounds such as polyalkylated dibenzothiophenes. To go deeper in the molecular exploration, chemometric tools were applied on this spectral data set including principal component analysis (PCA) and hierarchical cluster analysis (HCA). A unique data rearrangement was performed directly inspired on DBE vs carbon number plots that are systematically used in petroleomics studies. Then, these chemometric tools provided a successful classification of each type of gas oils. The PCA model has also been validated on mixed blends allowing us to conclude that it could be applied to unknown samples in order to identify the process used to produce them. Moreover, the exploration of the generated loadings revealed key types of molecules driving the classification such as C3-DBT which is a dibenzothiophene core with three additional carbon atoms. Indeed, it is known to remain mainly in deeply hydrotreated samples, validating previous observations regarding its potential refractory character. The ability of chemometric tools to extract specific molecular information from ultra-high resolution MS spectra reveals its huge potential for an exhaustive study of highly complex mixtures such as crude oils.

Ultra-high performance supercritical fluid chromatography hyphenated to atmospheric pressure chemical ionization high resolution mass spectrometry for the characterization of fast pyrolysis bio-oils.

Extensive characterization of complex mixtures requires the combination of powerful analytical techniques. A Supercritical Fluid Chromatography (SFC) method was previously developed, for the specific case of fast pyrolysis bio oils, as an alternative to gas chromatography (GC and GC × GC) or liquid chromatography (LC and LC × LC), both separation methods being generally used prior to mass spectrometry (MS) for the characterization of such complex matrices. In this study we investigated the potential of SFC hyphenated to high resolution mass spectrometry (SFC-HRMS) for this characterization using Negative ion Atmospheric Pressure Chemical ionization ((-)APCI) for the ionization source. The interface between SFC and (-)APCI/HRMS was optimized from a mix of model compounds with the objective of maximizing the signal to noise ratio. The main studied parameters included both make-up flow-rate and make-up composition. A methodology for the treatment of APCI/HRMS data is proposed. This latter allowed for the identification of molecular formulae. Both SFC-APCI/HRMS method and data processing method were applied to a mixture of 36 model compounds, first analyzed alone and then spiked in a bio-oil. In both cases, 19 compounds could be detected. Among them 9 could be detected in a fast pyrolysis bio-oil by targeted analysis. The whole procedure was applied to the characterization of a bio-oil using helpful representations such as mass-plots, van Krevelen diagrams and heteroatom class distributions. Finally the results were compared with those obtained with a Fourier Transform ion-cyclotron resonance mass spectrometer (FT-ICR/MS).

Development of a supercritical fluid chromatography method with ultraviolet and mass spectrometry detection for the characterization of biomass fast pyrolysis bio oils.

The characterization of complex mixtures is a challenging issue for the development of innovative processes dedicated to biofuels and bio-products production. The huge number of compounds present in biomass fast pyrolysis oils combined with the large diversity of chemical functions represent a bottleneck as regards analytical technique development. For the extensive characterization of complex samples, supercritical fluid chromatography (SFC) can be alternative to usual separation techniques such as gas (GC) or liquid chromatography (LC). In this study, an approach is proposed to define the best conditions for the SFC separation of a fast pyrolysis bio-oil. This approach was based on SFC data obtained directly from the bio-oil itself instead of selecting model compounds as usually done. SFC conditions were optimized by using three specific, easy-to-use and quantitative criteria aiming at maximizing the separation power. Polar stationary phases (ethylpyridine bonded silica) associated to a mix of acetonitrile and water as polarity modifier provided the best results, with more than 120 peaks detected in SFC-UV.

Redox Self-Adaptation of a Nitrene Transfer Catalyst to the Substrate Needs.

The development of iron catalysts for carbon-heteroatom bond formation, which has attracted strong interest in the context of green chemistry and nitrene transfer, has emerged as the most promising way to versatile amine synthetic processes. A diiron system was previously developed that proved efficient in catalytic sulfimidations and aziridinations thanks to an FeIII FeIV active species. To deal with more demanding benzylic and aliphatic substrates, the catalyst was found to activate itself to a FeIII FeIV L. active species able to catalyze aliphatic amination. Extensive DFT calculations show that this activation event drastically enhances the electron affinity of the active species to match the substrates requirements. Overall this process consists in a redox self-adaptation of the catalyst to the substrate needs.

1,4,8,11,15,18,22,25-Alkylsulfanyl phthalocyanines: effect of macrocycle distortion on spectroscopic and packing properties.

The effect of phthalocyanine macrocycle distortion on its spectroscopic and packing properties is studied, by comparing two phthalocyanines octa-non-peripherally substituted by alkanethiols of different bulkiness (n-hexyl and tert-butyl). Their X-ray structures evidence their core shape, respectively planar and strongly distorted, inducing a 55 nm shift of their maximum absorption wavelength. Comparison of frontier orbital energies revealed that this distortion decreases the conjugation potency of the benzo rings to the central pyrrolic rings. Also the tert-butyl derivative presents a MOF-like porous crystalline assembly with 22.2% void.

Site-selective formation of an iron(iv)-oxo species at the more electron-rich iron atom of heteroleptic µ-nitrido diiron phthalocyanines.

Iron(iv)-oxo species have been identified as the active intermediates in key enzymatic processes, and their catalytic properties are strongly affected by the equatorial and axial ligands bound to the metal, but details of these effects are still unresolved. In our aim to create better and more efficient oxidants of H-atom abstraction reactions, we have investigated a unique heteroleptic diiron phthalocyanine complex. We propose a novel intramolecular approach to determine the structural features that govern the catalytic activity of iron(iv)-oxo sites. Heteroleptic µ-nitrido diiron phthalocyanine complexes having an unsubstituted phthalocyanine (Pc1) and a phthalocyanine ligand substituted with electron-withdrawing alkylsulfonyl groups (PcSO2R) were prepared and characterized. A reaction with terminal oxidants gives two isomeric iron(iv)-oxo and iron(iii)-hydroperoxo species with abundances dependent on the equatorial ligand. Cryospray ionization mass spectrometry (CSI-MS) characterized both hydroperoxo and diiron oxo species in the presence of H2O2. When m-CPBA was used as the oxidant, the formation of diiron oxo species (PcSO2R)FeNFe(Pc1)[double bond, length as m-dash]O was also evidenced. Sufficient amounts of these transient species were trapped in the quadrupole region of the mass-spectrometer and underwent a CID-MS/MS fragmentation. Analyses of fragmentation patterns indicated a preferential formation of hydroperoxo and oxo moieties at more electron-rich iron sites of both heteroleptic µ-nitrido complexes. DFT calculations show that both isomers are close in energy. However, the analysis of the iron(iii)-hydroperoxo bond strength reveals major differences for the (Pc1)FeN(PcSO2R)FeIIIOOH system as compared to (PcSO2R)FeN(Pc1)FeIIIOOH system, and, hence binding of a terminal oxidant will be preferentially on more electron-rich sides. Subsequent kinetics studies showed that these oxidants are able to even oxidize methane to formic acid efficiently.

Synthesis and characterization of µ-nitrido, µ-carbido and µ-oxo dimers of iron octapropylporphyrazine.

Three µ-X bridged diiron octapropylporphyrazine complexes having Fe(III)-O-Fe(III), Fe(+3.5)-N[double bond, length as m-dash]Fe(+3.5) and Fe(IV)[double bond, length as m-dash]C[double bond, length as m-dash]Fe(IV) structural units have been prepared and characterized by UV-vis, EPR, X-ray absorption spectroscopy and electrochemical methods. Single crystals of all the complexes were obtained from benzene-acetonitrile and their structures were determined by X-ray diffraction. In contrast to µ-oxo complex (), µ-nitrido () and µ-carbido () dimers crystallized with one benzene molecule per two binuclear complex molecules arranged cofacially to the porphyrazine planes at Fe-Cbenzene distances of 3.435-3.725 Å and 3.352-3.669 Å for and , respectively. The short distances suggest an interaction between the iron sites and the benzene π-system which is stronger in the case of the Fe(IV)[double bond, length as m-dash]C[double bond, length as m-dash]Fe(IV) unit with a higher Lewis acidity. The Fe-X-Fe angle increases in the sequence -- from 158.52° to 168.5° and 175.10°, respectively, in agreement with the Fe-X bond order. However, the lengths of the Fe-X bonds do not follow this trend: Fe-O = 1.75/1.76 Å > Fe-C = 1.67/1.67 Å > Fe-N = 1.65/1.66 Å indicating unexpectedly long Fe-C bonds. This observation can be explained by back π-donation from the µ-carbido ligand to the Fe-C antibonding orbital thus decreasing the bond order which is confirmed by DFT calculations.

A hydrophobic disordered peptide spontaneously anchors a covalently bound RNA hairpin to giant lipidic vesicles.

The attraction of nucleic acids to lipidic compartments is the first step for carriers of potentially inheritable information to self-organise in functionalised synthetic cells. Confocal fluorescence imaging shows that a synthetic amphiphilic peptidyl RNA molecule spontaneously accumulates at the outer bilayer membranes of phospho- and glycolipidic giant vesicles. Cooperatively attractive interactions of -3.4 to -4.0 kcal mol(-1) between a random coil hydrophobic peptide and lipid membranes can thus pilot lipophobic RNA to its compartmentation. The separation of mixed lipid phases in the membranes further enhances the local concentration of anchored RNA.

Expeditious selective access to functionalized platforms of A(7)B-type heteroleptic lanthanide double-decker complexes of phthalocyanine.

A one-step method to access to functionalized heteroleptic lanthanide double-decker complexes of phthalocyanine of A7B-type is reported. This optimized statistical method led to two hydroxylated model europium complexes, one of which was further converted into its mesylated and azido derivatives.

Synthesis, characterization and optical properties of an amino-functionalized gold thiolate cluster: Au10(SPh-pNH2)10.

Research interest in ultra small gold thiolate clusters has been rising in recent years for the challenges they offer to bring together properties of nanoscience and well-defined materials from molecular chemistry. Here, a new atomically well-defined Au10 gold nanocluster surrounded by ten 4-aminothiophenolate ligands is reported. Its synthesis followed the similar conditions reported for the elaboration of Au144(SR)60, but because the reactivity of thiophenol ligands is different from alkanethiol derivates, smaller Au10 clusters were formed. Different techniques, such as ESI-MS, elemental analysis, XRD, TGA, XPS and UV-vis-NIR experiments, have been carried out to determine the Au10(SPh-pNH2)10 formula. Photoemission experiment has been done and reveals that the Au10 clusters are weakly luminescent as opposed to the amino-based ultra-small gold clusters. This observation points out that the emission of gold thiolate clusters is highly dependent on both the structure of the gold core and the type of the ligands at the surface. In addition, ultra-small amino-functionalized clusters offer the opportunity for extended work on self-assembling networks or deposition on substrates for nanotechnologies or catalytic applications.

A diiron(III,IV) imido species very active in nitrene-transfer reactions.

Metal-catalyzed nitrene transfer reactions arouse intense interest as clean and efficient procedures for amine synthesis. Efficient Rh- and Ru-based catalysts exist but Fe alternatives are actively pursued. However, reactive iron imido species can be very short-lived and getting evidence of their occurrence in efficient nitrene-transfer reactions is an important challenge. We recently reported that a diiron(III,II) complex is a very efficient nitrene-transfer catalyst to various substrates. We describe herein how, by combining desorption electrospray ionization mass spectrometry, quantitative chemical quench experiments, and DFT calculations, we obtained conclusive evidence for the occurrence of an {Fe(III) Fe(IV) NTosyl} intermediate that is very active in H-abstraction and nitrene-transfer reactions. DFT calculations revealed a strong radical character of the tosyl nitrogen atom in very low-lying electronic configurations of the Fe(IV) ion which are likely to confer its high reactivity.

Monoglycoconjugated phthalocyanines: effect of sugar and linkage on photodynamic activity.

BACKGROUND: Click chemistry can be advantageously used to graft carbohydrates on phthalocyanines which are potent photosensitisers, but the effect of the presence of triazole moieties on photodynamic efficiency was not investigated systematically to date. The nature and linkage of the sugar were investigated in order to define structure-activity relationships. METHOD: Two sets of monoglycoconjugated water-soluble phthalocyanines have been designed and their photodynamic activity and uptake investigated in HT-29 human colon adenocarcinoma cells. Carbohydrates: galactose, mannose or lactose were grafted onto Zn(II) phthalocyanines either by glycosylation or by click reaction. RESULTS: The triazole linkage formed by click conjugation lowered the biological efficiency for mannose and galactose, compared to classical glycosylation grafting. The mannose conjugate formed by glycosylation was the most photodynamically active, without correlation with the photosensitiser cell uptake.

Assessing the dual activity of a chalcone-phthalocyanine conjugate: design, synthesis, and antivascular and photodynamic properties.

Photodynamic therapy (PDT) and vascular-disrupting agents (VDA) each have their advantages in the treatment of solid tumors, but also present drawbacks. In PDT, hypoxia at the center of the tumor limits conversion of molecular oxygen into singlet oxygen, while VDAs are deficient at affecting the rim of the tumor. A phthalocyanine-chalcone conjugate combining the VDA properties of chalcones with the PDT properties of phthalocyanines was designed to address these deficiencies. Its vascular targeting, photophysical, photochemical, photodynamic activities are reported herein.

Efficient epoxidation of olefins by H2O2 catalyzed by iron "helmet" phthalocyanines.

High yields of epoxides were obtained in the oxidation of a large range of olefins using 1.2-2 equiv. of H2O2 in the presence of iron helmet phthalocyanines. The involvement of high-valent iron oxo species was evidenced using cryospray mass spectrometry.

Incorporation of a 3-(2,2,2-trifluoroethyl)-γ-hydroxy-γ-lactam motif in the side chain of 4-aminoquinolines. Syntheses and antimalarial activities.

In this paper we report the synthesis and antimalarial properties of two series of fluoroalkylated γ-lactams derived from 4-aminoquinoline as potent chemotherapeutic agents for malaria treatment. These molecules obtained in several steps resulted in the identification of very potent structures with in vitro activity against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) in the range of 19-50 nM with resistance indices in the range of 1.0-2.5. In addition, selected molecules (50, 51, 58, 60, 63, 70, 72, 74, 78, 81, 84, and 87) that are representative of the two series of compounds did not show cytotoxicity in vitro when tested against human umbilical vein endothelial cells up to a concentration of 100 µM. The most promising compounds (82 and 84) showed significant IC50 values close to 26 and 19 nM against the chloroquino-sensitive strain 3D7 and 49 and 42 nM against the multi-drug-resistant strain W2. Furthermore, two model compounds (50 and 70) were found to be quite stable over 48 h at pH 7.4 and 5.2. Overall, our preliminary data indicate that this class of structures contains promising candidates for further study.

An N-bridged high-valent diiron-oxo species on a porphyrin platform that can oxidize methane.

High-valent oxo-metal complexes are involved in key biochemical processes of selective oxidation and removal of xenobiotics. The catalytic properties of cytochrome P-450 and soluble methane monooxygenase enzymes are associated with oxo species on mononuclear iron haem and diiron non-haem platforms, respectively. Bio-inspired chemical systems that can reproduce the fascinating ability of these enzymes to oxidize the strongest C-H bonds are the focus of intense scrutiny. In this context, the development of highly oxidizing diiron macrocyclic catalysts requires a structural determination of the elusive active species and elucidation of the reaction mechanism. Here we report the preparation of an Fe(IV)(µ-nitrido)Fe(IV) = O tetraphenylporphyrin cation radical species at -90 °C, characterized by ultraviolet-visible, electron paramagnetic resonance and Mössbauer spectroscopies and by electrospray ionization mass spectrometry. This species exhibits a very high activity for oxygen-atom transfer towards alkanes, including methane. These findings provide a foundation on which to develop efficient and clean oxidation processes, in particular transformations of the strongest C-H bonds.