Novel mass spectral fragmentation of heptafluorobutyryl derivatives of acyl analogues of platelet-activating factor

Direct derivatization of the acyl analogue of platelet-activating factor (acyl-PAF) with heptafluorobutyric anhydride results in replacement of the phosphocholine moiety with a heptafluorobutyryl (HFB) group. Electron capture (EC) mass spectrometric analysis of this compound that makes use of negative ion detection along with subsequent accurate mass measurement and tandem mass spectrometry studies revealed that in addition to expected fragmentation due to losses of elements of HF, ketene, and/or acetic acid, there is a rearrangement reaction between the HFB group and the substituent on carbon-2 of the glycerol backbone. For 2-acetyl isomers, this fragmentation yields a characteristic ion at m/z 237; for 1-acetyl isomers, the analogous ion is observed at [M-135]⁻, along with a corresponding carboxylate anion. The use of the HFB derivative is invaluable for analysis of PAF homologues and analogues because it provides detailed structural information in combination with the high sensitivity of a gas chromatography combined with EC-mass spectrometry assay.     

Syntheses and conformations of some cyclic hydroxamates. X-Ray crystal structure of 2-(p-nitrobenzoyl)tetrahydro-2H-1,2-oxazine

Alkylation of potassium p-nitrobenzohydroxamate with 1,4-dibromobutane gave 2-(p-nitrobenzoyl)tetrahydro-2H-1,2-oxazine (3). The X-ray crystal structure of 3 has been determined. The crystals are monoclinic, space group P2₁/n with a = 6.749(1), b = 7.644(1), c = 21.557(2)Å, β = 98.89(1), V = 1098.8(2)ų and Z = 4. The structure, which was refined to R = 0.039 using 1340 observed reflections, shows the oxazine and carbonyl oxygen atoms trans to each other. Alkylation of potassium benzohydroxamate with 1,3-dibromobutane gave a mixture of 3-methyl-2-benzoyloxazolidine (4) and 5-methyl-2-benzoyloxazolidine (5). The ¹H and ¹³C nmr spectra of the mixture of 4 and 5 indicates that these cyclic hydroxamates exist predominantly in the s-trans conformation.     

CONFORMATIONAL CHANGES OF BOVINE LENS CRYSTALLINS IN A PHOTODYNAMIC SYSTEM

Abstract— Conformational changes of bovine lens crystallins in a photodynamic system generating singlet oxygen, have been investigated. The formation of intersubunit crosslinks was observed in all three classes (α-, β and γ-) of crystallins by irradiation in the presence of the photosensitizer methylene blue. Near-UV circular dichroism (CD) spectra of the crystallins were significantly altered by irradiation under these conditions, indicating changes in tertiary structure but the far-UV CD remained unchanged suggesting that the secondary structure ((β-sheet conformation) remains unchanged. Significant changes in the absorption and fluorescence spectra were also observed. Measurement of total sulfhydryl content showed a decrease of 27%, 50% and 37% for α-, β- and γ-crystallins respectively, after irradiation. Fluorescence lifetime measurements of N-iodoacetyl-N'-(5-sulfo-l-naphthyl)ethylenediamine-labeled crystallins showed a significant decrease of the lifetime of the major decay components of the label bound to sulfhydryl groups of α- and γ-crystallins, but showed no change in the microenvironment of the sulfhydryl groups of β-crystallin. The results are consistent with the microenvironments of the tryptophan and sulfhydryl groups predicted from sequence studies.     

A model for quantitatively describing linear velocity programming in capillary SFC

Summary Linear velocity in capillary SFC is commonly controlled by restricting capillaries. In this paper, a model is described that quantitatively predicts the linear velocity of a supercritical fluid in SFC using tapered or ceramic frittype restrictors. In this model, the flow from the restricting capillary is assumed to be an isentropic expansion. The variation of the linear velocity as a function of pressure, temperature and cross-sectional area of the restricting aperture was predicted by this model. This predictive capability is important to the use of gradient programming in capillary SFC. Finally, the ideal variable restrictor for gradient programming was found to be one that could reversibly increase or decrease the linear velocity independent of the pressure, temperature, and/or density conditions used to create the gradient.     

Nucleosides. Part LX. Synthesis and Characterization of Monomeric Cordycepin-Vitamin and Cordycepin-Lipid Conjugates Model Substances for Biodegradable Ester and Carbonate Linkages in Conjugates and Potential Inhibitors of HIV-1 Replication

Monomeric 3′-deoxyadenosine (cordycepin) was modified at the 2′-O- ( 13–18 ) and 5′-O-position ( 25–29 ) by the vitamins E, D₂, and A and by the two lipids 1,2-di-O-palmitoylglycerol and 1,2-di-O-hexadecylglycerol via succinate or carbonate linkages. The base-labile conjugates afforded protection groups like the 2-(4-nitro-phenyl)ethoxycarbonyl (npeoc) and monomethoxytrityl group (MeOTr) that are cleavable without harming the ester and carbonate bonds, respectively. Monomeric conjugates of cordycepin and vitamin E, vitamin D₂, 1,2-di-O-palmitoylglycerol, and 1,2-di-O-hexadecylglycerol (see 13, 14, 17, 18, 25, 26, 28 , and 29 ) inhibited HIV-1-induced syncytia formation 1.7 to 6.2 fold compared to 1.5-fold for cordycepin (see Table); IC₅₀ values for 25 and 28 were 257 and 267 m?M , respectively. In addition, the monomeric cordycepin-vitamin and -lipid conjugates inhibited HIV-1 RT activity 28–49% which compares with a 13% inhibition of HIV-1 RT observed for cordycepin. The minimal inhibition of HIV-1-induced syncytia formation and HIV-1 RT activity did not proceed by the activation of RNase L. The monomeric conjugates tested ( 13, 14 ) increased PKR expression.     

Efficient CO2 Removal for Ultra‐Pure CO Production by Two Hybrid Ultramicroporous Materials

Removal of CO₂ from CO gas mixtures is a necessary but challenging step during production of ultra‐pure CO as processed from either steam reforming of hydrocarbons or CO₂ reduction. Herein, two hybrid ultramicroporous materials (HUMs), SIFSIX‐3‐Ni and TIFSIX‐2‐Cu‐i , which are known to exhibit strong affinity for CO₂, were examined with respect to their performance for this separation. The single‐gas CO sorption isotherms of these HUMs were measured for the first time and are indicative of weak affinity for CO and benchmark CO₂/CO selectivity (>4000 for SIFSIX‐3‐Ni ). This prompted us to conduct dynamic breakthrough experiments and compare performance with other porous materials. Ultra‐pure CO (99.99 %) was thereby obtained from CO gas mixtures containing both trace (1 %) and bulk (50 %) levels of CO₂ in a one‐step physisorption‐based separation process.     

Physicochemical Investigations on the Interaction of Surfactants and Salts with Polyvinylpyrrolidone in Aqueous Medium

Microcalorimetric investigations have been carried out onthe interaction of the surfactants sodium cholate, sodium deoxycholate, tetradecyltrimethylammonium bromide, cetyl(hexadecyl)trimethylammonium bromide, and p-tert-octylphenoxy polyoxy-ethylene ether (Triton X-100) and the salts potassium iodide, sodium benzoate, sodium bromide, and sodium salicylate with the neutral polymer polyvinylpyrrolidone (PVP). The enthalpy of dilution of the surfactants has been measured in the absence and presence of the polymer and the results are compared to determine the effect of PVP on the micellization of the surfactants and the energetics of the process. As well, the micellization activity of the surfactants in the presence of the polymer has been studied by conductometric and fluorimetric methods. The enthalpy of dilution of the salts has been measured to provide an understanding of the nature and magnitude of their interaction with PVP. Copyright 2001 Academic Press.     

Novel Osmium‐based Coordination Complexes as Photosensitizers for Panchromatic Photodynamic Therapy

Cancer remains a major global malaise requiring the advent of new, efficient and low‐cost treatments. Photodynamic therapy, which combines a photosensitizer and photons to produce cytotoxic reactive oxygen species, has been established as an effective cancer treatment but has yet to become mainstream. One of the main limitations has been the paucity of photosensitizers that are effective over a wide range of wavelengths, can exert their cytotoxic effects in hypoxia, are easily synthesized and produce few if any side effects. To address these shortfalls, three new osmium‐based photosensitizers (TLD1822, TLD1824 and TLD1829) were synthesized and their photophysical and photobiological attributes determined. These photosensitizers are panchromatic (i.e. black absorbers), activatable from 200 to 900 nm and have strong resistance to photobleaching. In vitro studies show photodynamic therapy efficacy with both red and near‐infrared light in normoxic and hypoxic conditions, which translated to good in vivo efficacy of TLD1829 in a subcutaneous murine colon cancer model.     

Natural abundance 13C - 13C coupling constants observed via double quantum coherence. Structural elucidation by the one- and the two-dimensional NMR experiements of velloziolone,a new seco-diterpene.

With the help of Natural Abundance ¹³C - ¹³C Coupling Constants, observed via double quantum coherence, the structural determination of VELLOZIOLONE (1), a new diterpene, has been carried out.