Synthesis and spectroscopy of cyanotriacetylene (HC7N) in solid argon.

UV laser irradiations of cryogenic solid argon matrices doped with a mixture of acetylene and cyanodiacetylene (HC5N) resulted in the formation of a longer carbon-nitrogen chain, cyanotriacetylene (HC7N). The identification of this species was accomplished based on IR vibrational spectroscopy (including the study of isotopically labeled compounds), on electronic luminescence spectroscopy, and on theoretical predictions. Additionally, IR absorption bands recognized as due to HC7N were detected in photolysed Ar matrices doped with a cyanoacetylene/diacetylene mixture; this assignment was confirmed with the mass spectrometry of gases released upon the warm-up of the sample.

Hydroxypropylmethylcellulose lowers cholesterol in statin-treated men and women with primary hypercholesterolemia.

BACKGROUND/OBJECTIVES: Consumption of hydroxypropylmethylcellulose (HPMC), a viscous dietary fiber, lowers total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, HPMC had not previously been studied in individuals receiving lipid drug therapy. SUBJECTS/METHODS: This randomized, double-blind crossover trial examined the lipid effects of HPMC in subjects with hypercholesterolemia on statin therapy. Men (n=5) and women (n=8) with LDL-C> or =2.59 mmol/l after at least 4 weeks of stable-dose statin therapy, and a mean age of 58.6 years, were enrolled. Subjects received twice daily doses of either 2.5 g HPMC or control, delivered in a lemonade beverage for 4 weeks, then crossed over to receive the opposite treatment for an additional 4 weeks. RESULTS: Mean baseline concentrations of TC, non-high-density lipoprotein cholesterol (non-HDL-C), LDL-C, HDL-C, triglyceride (TG), TC/HDL-C ratio and apolipoprotein (Apo) B were 4.95, 3.63, 3.03, 1.33, 1.30 and 3.89 mmol/l and 1.00 g/l, respectively. HPMC consumption resulted in significantly larger reductions (P<0.01 vs control for all) in TC (-10.9 vs -3.5%), non-HDL-C (-12.8 vs -2.9%), LDL-C (-15.7 vs -5.1%), TC/HDL-C ratio (-5.3 vs +1.3%) and Apo B (-8.7 vs -3.9%). There were no differences between treatments for changes in HDL-C (-5.2 vs -4.3%) or TG (+3.9 vs +8.9%). CONCLUSIONS: These results support the view that HPMC is an effective adjunct to statin therapy for further lowering atherogenic lipids and lipoproteins in men and women with primary hypercholesterolemia.

Hydroxypropylmethylcellulose significantly lowers blood cholesterol in mildly hypercholesterolemic human subjects.

OBJECTIVE: To determine the cholesterol-lowering efficacy of hydroxypropylmethylcellulose (HPMC) in mildly hypercholesterolemic humans. SUBJECTS: Trial one: entry mean (range) total serum cholesterol values of eight female and four male subjects were 6.48 (5.57-7.51) mmol l(-1) (250 (215-290) mg dl(-1)) and 6.60 (5.57-7.64) mmol l(-1) (255 (215-295) mg dl(-1)), respectively. Trial two: corresponding values for 20 women and 20 men were 5.96 (5.43-6.48) mmol l(-1) 230 (210-250) mg dl(-1)) and 6.05 (5.46-6.63) mmol l(-1) 233 (211-256) mg dl(-1)), respectively. RESULTS: Trial one: HPMC decreased (P< or =0.05) total and LDL-cholesterol 9.3 and 15.3% (medium), 16.9 and 23.5% (high) and 13.8 and 19.4% (ultra-high), respectively, over placebo. Trial two: total and LDL-cholesterol decreased (P< or =0.05) throughout the 8 weeks, with mean (weeks 4-8) reductions of 7 and 8% at 5 g day(-1), and 12 and 15% at 15 g day(-1), respectively, over placebo. Adverse effects were minimal. Trial one: medium, high and ultra-high viscosity HPMC at 15 g day(-1) for 1 week each;1-week wash-out between treatments. Trial two: ultra-high viscosity HPMC at 5 or 15 g day(-1) for 8 weeks. CONCLUSIONS: HPMC soluble fiber, especially high-viscosity grades, significantly lowers cholesterol at well-tolerated doses, showing promise as a treatment of hypercholesterolemia.

External interface for trap-and-release membrane introduction mass spectrometry applied to the detection of inorganic chloramines and chlorobenzenes in water.

Construction and evaluation of an external configuration trap-and-release membrane introduction system for mass spectrometry is described. This novel interface allows independent control of the temperature of the membrane and eliminates the dependence of membrane heating efficiency on its position in the ion source. The external trap-and-release MIMS configuration is successfully applied to detection of inorganic chloramines and chlorobenzenes. The method is shown to give temporal resolution of volatile vs. semi-volatile compounds, which increases its sensitivity for semi-volatiles in the presence of volatiles and provides an additional selectivity parameter. Further selectivity is provided by tandem mass spectrometry.

Selectivity of stationary phases in reversed-phase liquid chromatography based on the dispersion interactions.

Selectivity of 15 stationary phases was examined, either commercially available or synthesized in-house. The highest selectivity factors were observed for solute molecules having different polarizability on the 3-(pentabromobenzyloxy)propyl phase (PBB), followed by the 2-(1-pyrenyl)ethyl phase (PYE). Selectivity of fluoroalkane 4,4-di(trifluoromethyl)-5,5,6,6,7,7,7-heptafluoroheptyl (F13C9) phase is lowest among all phases for all compounds except for fluorinated ones. Aliphatic octyl (C8) and octadecyl (C18) phases demonstrated considerable selectivity, especially for alkyl compounds. While PBB showed much greater preference for compounds with high polarizability containing heavy atoms than C18 phase, F13C9 phase showed the exactly opposite tendency. These three stationary phases can offer widely different selectivity that can be utilized when one stationary phase fails to provide separation for certain mixtures. The retention and selectivity of solutes in reversed-phase liquid chromatography is related to the mobile phase and the stationary phase effects. The mobile phase effect, related to the hydrophobic cavity formation around non-polar solutes, is assumed to have a dominant effect on retention upon aliphatic stationary phases such as C8, C18. In a common mobile phase significant stationary phase effect can be attributed to dispersion interaction. Highly dispersive stationary phases such as PBB and PYE retain solutes to a significant extent by (attractive) dispersion interaction with the stationary phase ligands, especially for highly dispersive solutes containing aromatic functionality and/or heavy atoms. The contribution of dispersion interaction is shown to be much less on C18 or C8 phases and was even disadvantageous on F13C9 phase. Structural properties of stationary phases are analyzed and confirmed by means of quantitative structure-chromatographic retention (QSRR) study.

Collagen immobilised on silica derivatives as a new stationary phase for HPLC.

Synthesis of new stationary phases containing covalently bound collagen has been described. Commercially available soluble collagen and the silica derivatives, aminopropylsilica (APS) and diol-silica, were used for the experiment. The products of synthesis were subjected to elemental analysis and to a 13C-NMR analysis to prove the presence of the covalently bound protein on the support's surface. The stationary phases were packed into the columns and introduced into an HPLC system. A series of diversified test compounds was analysed to elucidate the retention mechanism operating on the collagen column by means of the quantitative structure-retention relationship (QSRR) analysis. Chromatographic analysis of a series of selected compounds was performed for which human skin permeation data were available. Quantitative structure-activity relationship (QSAR) analysis was done to model the human skin permeation by employing of the chromatographic data determined on the collagen column. The newly obtained collagen phases were demonstrated to possess distinctive retention properties due to a combination of specific (polar) and hydrophobic solute-stationary phase interactions. The normal-phase retention mechanism seemed to prevail on the collagen phases. For the set of test solutes available the interactions with collagen appear to be of secondary importance for their ability to permeate human skin compared to their hydrophobicity and binding to keratin. None the less, the collagen columns may be of value to complete the chromatographic model of human skin permeation.

Keratin immobilized on silica as a new stationary phase for chromatographic modelling of skin permeation.

Skin permeability of organic compounds depends on their lipophilicity but can also be affected by compounds interactions with specific skin components. A good chromatographic model of percutaneous penetration determined solely by lipophilicity is provided by the immobilized artificial membrane (IAM) columns. To complete the model a new high-performance liquid chromatographic (HPLC) stationary phase was prepared by physical immobilization of keratin on silica support. The keratin immobilized on silica has properties typical for the reversed-phase materials but it retains specifically acidic solutes. The keratin column can be used to conveniently compare keratolytic properties of xenobiotics. It was demonstrated that retention parameters determined on a keratin column can be combined with the retention parameters determined on the IAM column to predict differences in skin permeability within a class of drugs. It has been postulated that HPLC can model skin permeation thus reducing research time and costs as well as the use of laboratory animals.

Quantitative structure-retention relationships in the examination of the topography of the binding site of antihistamine drugs on alpha 1-acid glycoprotein.

Quantitative relationships between the structure of antihistamine drugs (AHD) and their retention on an alpha 1-acid glycoprotein (AGP) HPLC column (QSRR) were studied in order to identify characteristic structural features of the binding site for AHD on AGP. The hydrophobicity of AHD was determined by HPLC on an immobilized artificial membrane (IAM) column. A highly significant QSRR equation was obtained which describes the retention of AHD on AGP in terms of the chromatographically determined hydrophobicity parameter, electron excess charge on the aliphatic nitrogen and a molecular size descriptor. The topography of the AHD-binding site on AGP was suggested to be a conical pocket with lipophilic regions at the mouth of the receptor and an anionic region close to the spike of the cone. Protonated aliphatic nitrogen is supposed to guide a drug molecule towards the anionic region of the binding site. Hydrophobic aryl moieties provide anchoring of the molecule in the lipophilic regions of the binding site. Steric hindrance prevents the molecule from plunging into the binding site.

Binding site for basic drugs on alpha 1-acid glycoprotein as revealed by chemometric analysis of biochromatographic data.

Interactions between alpha 1-acid glycoprotein (AGP) and 52 basic drugs were quantified by means of high-performance liquid chromatography (HPLC). The HPLC retention parameters were related quantitatively to the hydrophobicity and molecular modelling parameters, giving rise to the prediction of relative drug-AGP binding from the chemical structure of a drug. A structural model of one binding site on AGP, common for various classes of drugs, was defined which accounted for the observed and reported differences in binding to AGP. A combination of biochromatography and chemometrics has been presented as a promising new approach in biochemical/pharmacological studies.

Comparative studies of antiplatelet activity of nonsteroidal antiinflammatory drugs and new pyrazine CH- and NH-acids.

Nine known nonsteroidal antiinflammatory drugs (NSAID) and three new pyrazine derivatives possessing an active methylene moiety (pyrazine CH/NH-acids) were tested with regards to their in vitro and in vivo antiplatelet activity. Concentrations of the agents were determined which caused 25% and 50% inhibition of aggregation of human blood platelets induced by fixed concentrations of ADP, collagen and epinephrine. The in vivo test consisted in determination of percent protection of mice from pulmonary microembolism caused by injection of a mixture of collagen and epinephrine. The in vitro antiaggregatory activity of the agents studied was rather low, excepting the inhibition of the collagen-induced aggregation by ketoprofen. Several NSAID and two new pyrazine CH/NH-acids appeared highly potent antithrombotic agents in vivo. Activity of NSAID expressed as percent protection against lung thromboembolism in the mouse was demonstrated to depend quantitatively on acid properties of the agents. The new chemical class of pharmacologically active agents, pyrazine CH/NH-acids, offers an original pharmacophore which is distinctive from the carboxylic or enolic functionalities typical for the established NSAID, and as such, may be devoid of some disadvantages of known antiplatelet drugs.