A ferrocene-based reagent for the conjugation and quantification of reactive metabolites

In the present study, a method for the analysis of reactive metabolites via liquid chromatography (LC) with inductively coupled plasma–mass spectrometry (MS) was developed. A ferrocenyl-modified glutathione (GSH) reagent, consisting of GSH and succinimidyl-3-ferrocenylpropionate, was synthesized. Derivatization of the tripeptide was performed at the N-terminus, leaving the nucleophilic thiol group vacant for the attack of electrophilic compounds. The potential of ferrocenylpropionate (FP)-GSH as a trapping agent for reactive metabolites was investigated using an electrochemical flow-through cell for metabolism simulation coupled online to a LC system with electrospray ionization mass spectrometric detection. The pharmaceuticals amodiaquine, an antimalarial agent, and clozapine, an antipsychotic compound, served as model substances. By proving the successful adduct formation between the reactive metabolite and ferrocene-labeled GSH, it could be shown that FP-GSH is an effective trapping agent which eases routine reversed-phase LC analyses. In contrast to GSH, which is usually used for the conjugation of reactive metabolites and where the resulting adducts often show no or only very little retention, FP-GSH facilitates the detection of the corresponding metabolite adducts due to higher retention times.     

Comparison of polydimethyl siloxane stationary phases with 5% and 50% phenyl substitution for the separation of organophosphorus and organonitrogen pesticides under optimized gas chromatographic conditions

The CGC analysis of 25 organophosphorus and organonitrogen pesticides was optimized on two different stationary phases, namely a 5% diphenyl dimethyl silicone (SE-54 type) and a 50% diphenyl dimethyl silicone (OV-17 type) by selecting the best temperature program conditions, using computer simulation.     

Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and purine moieties: synthesis and evaluation of their cytostatic activity

We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside analogues 14-18. Structures of novel compounds 3-18 were deduced from their ¹H- and ¹³C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC₅₀ = 35 μM), whereas compound 10 showed moderate activity against the HeLa (IC₅₀ = 33 μM), HepG2 (IC₅₀ = 25 μM) and SW620 (IC₅₀ = 35 μM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.     

Synthesis, isolation, and spectroscopic characterization of holmium-based mixed-metal nitride clusterfullerenes: HoxSc3-xN@C80 (x=1, 2)

The synthesis, isolation and spectroscopic characterization of holmium-based mixed metal nitride clusterfullerenes Ho(x) Sc(3-x) N@C(80) (x=1, 2) are reported. Two isomers of Ho(x) Sc(3-x) N@C(80) (x=1, 2) were synthesized by the reactive gas atmosphere method and isolated by multistep recycling HPLC. The isomeric structures of Ho(x) Sc(3-x) N@C(80) (x=1, 2) were characterized by laser-desorption time-of-flight (LD-TOF) mass spectrometry and UV/Vis/NIR, FTIR and Raman spectroscopy. A comparative study of M(x) Sc(3-x) N@C(80) (M=Gd, Dy, Lu, Ho) demonstrates the dependence of their electronic and vibrational properties on the encaged metal. Despite the distinct perturbation induced by 4f(10) electrons, we report the first paramagnetic (13) C?NMR study on Ho(x) Sc(3-x) N@C(80) (I; x=1, 2) and confirm I(h) -symmetric cage structure. A (45) Sc NMR study on HoSc(2) N@C(80) (I, II) revealed a temperature-dependent chemical shift in the temperature range of 268-308?K.     

Preparation and Characterization of Niobium Oxide Coated Cellulose Fiber

The Nb₂O₅/cellulose composite was prepared by reacting α-cellulose with NbCl_5-n(OC₂H₅)_n, in nonaqueous solvent, under nitrogen atmosphere and submitting the obtained material to hydrolysis. An increase in the crystallinity degree is observed in the composite material because the precursor reagent reacts with the amorphous phase of the cellulose fibers. Loadings between 4.5 and 16.0% of the oxide were achieved and in every case the oxide particles uniformly cover the fiber surface. Lewis and Brønsted acid sites were determined by using pyridine as the basic molecular probe.     

Instrumental Dependent Dissociations of n-Propyl/Isopropyl Phosphonate Isomers: Evaluation of Resonant and Non-Resonant Vibrational Activations

Structural elucidation and distinction of isomeric neurotoxic agents remain a challenge. Tandem mass spectrometry can be used for this purpose in particular if a “diagnostic” product ion is observed. Different vibrational activation methods were investigated to enhance formation of diagnostic ions through consecutive processes from O,O-dialkyl alkylphosphonates. Resonant and non-resonant collisional activation and infrared multiphoton dissociation (IRMPD) were used with different mass spectrometers: a hybrid quadrupole Fourier transform ion cyclotron resonance (Qh-FTICR) and a hybrid linear ion trap-Orbitrap (LTQ/Orbitrap). Double resonance (DR) experiments, in ion cyclotron resonance (ICR) cell, were used for unambiguous determination of direct intermediate yielding diagnostic ions. From protonated n-propyl and isopropyl O-O-dialkyl-phosphonates, a diagnostic m/z 83 ion characterizes the isopropyl isomer. This ion is produced through consecutive dissociation processes. Conditions to favor its formation and observation using different activation methods were investigated. It was shown that with the LTQ, consecutive experimental steps of isolation/activation with modified trapping conditions limiting the low mass cut off (LMCO) effect were required, whereas with FT-ICR by CID and IRMPD the diagnostic ion detection was provided only by one activation step. Among the different investigated activation methods it was shown that by using low-pressure conditions or using non-resonant methods, efficient and fast differentiation of isomeric neurotoxic agents was obtained. This work constitutes a unique comparison of different activation modes for distinction of isomers showing the instrumental dependence characteristic of the consecutive processes. New insights in the dissociation pathways were obtained based on double-resonance IRMPD experiments using a FT-ICR instrument with limitation at low mass values.

Do halogen and methyl substituents have electronic effects on the structures of simple disilanes? An experimental and theoretical study of the molecular structures of the series X3SiSiMe3 (X = H, F, Cl and Br)

The gas-phase molecular structures of a series of halogen-substituted disilanes [X₃SiSiMe₃ (X = H, F, Cl and Br)], 1,1,1-trimethyldisilane (H₃SiSiMe₃), 1,1,1-trifluoro-2,2,2-trimethyldisilane (F₃SiSiMe₃), 1,1,1-trichloro-2,2,2-trimethyldisilane (Cl₃SiSiMe₃) and 1,1,1-tribromo-2,2,2-trimethyldisilane (Br₃SiSiMe₃), have been determined in the gas phase by electron diffraction. Ab initio calculations at the HF and MP2 level were used to support the experimental investigation using the SARACEN method. All of the investigated structures were determined to adopt a staggered structure with C _3v symmetry. The effect of substitution on the Si–Si bond and the Si–Si–X bond angle was investigated and these results were compared to results obtained from a recent study of halogen-substituted disilanes [X₃SiSiXMe₂ (X = F, Cl, Br and I)] to consider the effect of the methyl groups on the substituted disilanes.     

OH-terminated cyanopropyl silicones

Due to their high polarity and unique selectivity, cyanopropyl silicones are basic stationary phases for high resolution capillary gas chromatography. Different OH-terminated cyanopropyl silicones, containing a high cyanopropyl content, were synthesized and chromatographically evaluated. Special attention was paid to the degree of immobilization of the phases in FSOT columns. Depending on the problem at hand, a choice has to be made between immobilization and maximum selectivity.     

Chip-based nLC-TOF-MS is a highly stable technology for large-scale high-throughput analyses

Many studies focused on the discovery of novel biomarkers for the diagnosis and treatment of disease states are facilitated by mass spectrometry-based technology. HPLC coupled to mass spectrometry is widely used; miniaturization of this technique using nano-liquid chromatography (LC)-mass spectrometry (MS) usually results in better sensitivity, but is associated with limited repeatability. The recent introduction of chip-based technology has significantly improved the stability of nano-LC-MS, but no substantial studies to verify this have been performed. To evaluate the temporal repeatability of chip-based nano-LC-MS analyses, N-glycans released from a serum sample were repeatedly analyzed using nLC-PGC-chip-TOF-MS on three non-consecutive days. With an average inter-day coefficient of variation of 4 %, determined on log₁₀-transformed integrals, the repeatability of the system is very high. Overall, chip-based nano-LC-MS appears to be a highly stable technology, which is suitable for the profiling of large numbers of clinical samples for biomarker discovery.