Synthesis, structure and reactions of organometallic compounds of Groups 1–3 containing bulky silicon-substituted alkyl groups

Complexes trans-[PtX(L)(PPh₃)₂]A [1: X = CF₃; A = BF₄; L = NCNH₂, NCNMe₂, NCNEt₂, or NCNC(NH₂)₂. 2: X = Cl; A = BPh₄; L = NCNMe₂ or NCNEt₂] and cis-[PtCl(L)(PPh₃)₂][BPh₄] [3: L = NCNH₂ or NCNC(NH₂)₂], which appear to be the first cyanamide or cyanoguanidine complexes of platinum to be reported, have been prepared by treatment of trans-[PtBr(CF₃)(PPh₃)₂] (in CH₂Cl₂/acetone and in the presence of Ag[BF₄]) or of cis-[PtCl₂(PPh₃)₂] (in THF and in the presence of Na[BPh₄]), respectively, with the appropriate substrate. In KBr pellets or in solution 1 (L = NCNMe₂ or NCNEt₂) undergoes ready replacement of the organocyanamide (under the trans influence of CF₃) by bromide to regenerate trans-(PtBr(CF₃)(PPh₃)₂]. The X-ray structure of 1 (X = CF₃, A = BF₄, L = NCNEt₂) is also reported, and shows the presence of two apical intramolecular contacts of the metal with two ortho-hydrogen atoms of the phosphines, whereas the amine N atom of the diethylcyanamide is trigonal planar in the linear NCN framework with a delocalized π system.     

Cytotoxic compounds from Polygala vulgaris

To search for antitumor agents from plants, we studied Polygala vulgaris since cytotoxic lignans are known to occur in some Polygala species. Preliminary data on plant petrol ether, chloroform, and methanol extracts from the roots and aerial parts, showed in vitro cytotoxic activity against the solid tumor LoVo cell line. Fractionation of the active extracts led to the isolation of three new compounds, a derivative of aucuparine and two xanthones, as well as a known methylsinapate. All compounds were tested for in vitro cytotoxic activity using two cell lines, LoVo and its strain, which express resistance to common antitumor agents.     

Determination of perfluorooctane sulfonate and perfluorooctanoic acid in human plasma by large volume injection capillary column switching liquid chromatography coupled to electrospray ionization mass spectrometry

Rapid, selective, and sensitive methodology for the quantification of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in human plasma using packed capillary liquid chromatography coupled to electrospray ionization ion-trap mass spectrometry has been developed. Plasma proteins were precipitated using acetonitrile and the resulting supernatant was diluted 1+1 with water containing 10 mM ammonium acetate (NH4Ac) prior to injection. Sample volumes of 250 microL were loaded onto a 30 mm x 0.32 mm ID 10 microm Kromasil C18 precolumn by a carrier solution consisting of 10 mM NH4Ac in ACN/H2O (5/95, v/v) at a flow rate of 100 microL/min, providing on-line analyte enrichment and sample clean-up. Backflushed elution onto a 100 mm x 0.32 mm ID 3.5 microm Kromasil C18 analytical column was conducted using an ACN/H2O solvent gradient containing 10 mM NH4Ac. In order to improve the robustness and performance of the method, perfluoroheptanoic acid (PFHA) was used as internal standard. Separation and detection of PFOA, PFHA, and PFOS were achieved within 10 minutes. Ionization was performed in the negative mode in the m/z range 250-550. The method was validated over the concentration range 1-200 ng/mL for PFOA and over the range 5-200 ng/mL untreated plasma for PFOS, yielding correlation coefficients of 0.997 (PFOA) and 0.996 (PFOS), respectively. The within-assay (n = 6) and between-assay (n = 6) precisions were in the range 2.1-9.2 and 5.6-12%, respectively. The concentration limits of detection (cLOD) of PFOA was 0.5 ng/mL while the cLOD of PFOS was estimated to be 0.2 ng/mL in untreated plasma.     

Detecting pM concentrations of prostaglandins in cell culture supernatants by capillary SCX-LC-MS/MS

A highly sensitive, improved online strong cation exchange (SCX)--RP capillary liquid chromatographic (cLC) method with IT mass spectrometric (IT-MS/MS) detection for the simultaneous determination of prostaglandin (PG)A(1), PGD(2), PGE(1), PGE(2), PGF(2alpha), 8-iso-(8i)PGF(2alpha), 6-keto-(6k)PGF(1alpha), and 15-Delta(12, 14)-deoxy-PGJ(2) (15dPGJ(2)) in cell culture supernatants was developed and validated. Pretreatment of the cell culture supernatants included only dilution and filtration, and the analysis time including all sample preparation steps was 60 min per sample. Peptides/proteins contained in the matrix were removed by the SCX column. LODs in the range of 8-44 pg/mL (25-120 pM) cell culture supernatant were obtained. Excellent linearity (R(2) > 0.99) and satisfactory recoveries and within- and between-day precisions were obtained. Human mesenchymal stem cells (hMSCs) were stimulated with tumor necrosis factor alpha (TNFalpha) or TNFalpha/IL-17, and PG production was analyzed using the developed method. The four PGs, 6kPGF(1a), PGF(1a), PGE(2), and PGE(1 )were detected both in nonstimulated and stimulated cells. The amount of PG produced by the cell increased when the cell was stimulated.     

Two-dimensional LC-MS/MS in detection of peptides in hypothalamus of the rat subjected to hypoxic stress

A capillary 2-D LC method coupled with IT MS has been used for separation and identification of peptides in rat hypothalamus. Animals of two different age groups (8 and 50 wk) were exposed to two different rates of CO(2 )in inhaled air to investigate the influence of different hypoxia/hypercapnia levels and their stress-related factor on the peptide excretion. Peptide compounds were fractionated (strong cation exchange chromatography), trapped, and separated (RP chromatography), and MS/MS mass spectra were used for identification. About 107 peptide compounds were identified and 88 of them were semiquantified. Among the characterized peptides, there were fragments from proteins such as proenkephalin A, proSAAS, prosomatostatin, prooxytocin, vasopressin, etc. Explorative principal component analysis (PCA) combined with hypothesis testing was applied to the obtained data to investigate the impact of age and hypoxic stress factors on the peptide pattern. Twenty-six peptides revealed significant differences in concentrations between the animal groups influenced by age and influx rate.     

Synthesis of terpene and steroid dimers and trimers having cyclobutadienyl-Co and aromatic tethers

The reaction of natural product derived propargylic alcohols with CpCo(CO)2 produces three new types of natural product hybrids having two or three terpene or steroid fragments. The tether joining the natural product subunits is built during the reaction. Type 1 hybrids have two terpene or steroid moieties joined by a CpCo-cyclobutadiene tether, with the two units disposed in a 1,2-arrangement (9, 14, 22). Type 2 hybrids have a Co-cyclopentadienone tether (10). Type 3 has three units of terpene or steroid joined to a benzene ring (11, 12, 15). An unusual Co-mediated beta-carbon elimination pathway of propargylic alcohols leading to ketones (an unknown process in this chemistry) has been observed.     

Discrimination of prostate cancer cells by reflection mode FTIR photoacoustic spectroscopy

In this communication reflection mode Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) is used to obtain IR spectra of four prostate and prostate cancer cell line types (CaP) allowing their differentiation by principal components analysis.     

Identification of neuropeptides in rat brain rhinencephalon

A capillary two-dimensional liquid chromatography method coupled with ion trap mass spectrometry has been used for separation and identification of neuropeptides in rat rhinencephalon. Animals of three different age groups were exposed to slow and quick CO2 influx. The neuropeptides were extracted by solid phase extraction and the purified extracts were analysed by 2-D HPLC. The compounds were fractionated (strong cation exchange column), trapped and separated, and MS/MS fragment mass spectra were used for identification. About thirty peptide compounds were identified. A significant difference between concentration levels of "stressed" (quick CO2 influx) and "non-stressed" (slow CO2 influx) rats was found for 25 of the identified peptides.     

An alternative multiple-trapping LC-SPE-NMR system

In this paper, we describe approaches that make RP LC-SPE-NMR simpler, and in our opinion, result in more reliable methods for trapping and subsequent transfer of separated trace-level compounds to the NMR. An SPE unit based on a commercially available, low dead-volume 10 port high-pressure column selector gives the possibility of trapping compounds on nine individual SPEs that have standard fittings. This allows the operator to employ specific stationary phases that are not available as SPEs in commercially available LC-SPE-NMR systems. Multiple trappings of small compounds like monuron, 1-(4-chlorophenyl)-3-methylurea, and 4-chlorophenylurea were easily performed employing a porous-carbon SPE material. The system was optimized to elute the SPE-trapped compounds to the NMR probes in as small a volume as possible using back-flushing. The proper match of NMR probe volume and SPE column inner diameter and elution volume was discussed, as well as the necessity of drying loaded SPEs prior to NMR transfer when using porous-carbon SPE material.     

Inside vs "Outside" photooxygenation reactions: singlet-oxygen-mediated surface passivation of polymer films

Films of poly(acrylonitrile- co-2,3-dimethyl-1,3-butadiene) were exposed to singlet oxygen. The extent of polymer oxygenation was monitored for singlet oxygen generated (1) within the polymer film and (2) at the polymer surface in an aqueous medium. When singlet oxygen is generated within the film, oxygenation of the polymer is pronounced and extensive. When singlet oxygen is generated at the polymer surface, oxygenation reactions are limited to the surface. The data suggest that the initial oxygenation reactions at the film surface passivate the polymer against further reaction with singlet oxygen and, hence, also minimize the progressively detrimental effects of secondary reactions. These results indicate that one should exercise restraint when implicating singlet oxygen as a reactive species in some processes of polymer oxygenation.