Normal- and Reversed-Phase Behaviour of 16,17-Secoestrone Derivatives on Cyanopropyl-Bonded Silica Gel

The retention behaviour of a number of 16,17-secoestrone derivatives has been studied by LC and HPTLC on a polar cyanopropyl-bonded stationary phase using non-aqueous and aqueous-organic mobile phases. The retention behaviour has been discussed in terms of nature of the solute, eluent and stationary phase. The correlation between retention constants of 16,17-secoestrone derivatives obtained from reversed-phases and commercially available ACD log P software (Advanced Chemistry, Toronto, Canada) has also been examined.

     

Tritium in organic matter around Krško Nuclear Power Plant

The aim of the research was to obtain first results of tritium in the organic matter of environmental samples in the vicinity of Kr?ko NPP. The emphasis was on the layout of suitable sampling network of crops and fruits in nearby agricultural area. Method for determination of tritium in organic matter in the form of Tissue Free Water Tritium (TFWT) and Organically Bound Tritium (OBT) has been implemented. Capabilities of the methods were tested on real environmental samples and its findings were compared to modeled activities of tritium from atmospheric releases and literature based results of TFWT and OBT.     

Synthesis of a new hydrophilic poly(ethylene glycol)-ionic liquid and its application in peptide synthesis

The synthesis of a new hydrophilic ammonium-based poly(ethylene glycol)-ionic liquid (PEG-IL) is reported; the structure was assigned by NMR ((1)H, (13)C) and MALDI mass spectrometry. The viscosity and thermal stability were also studied, as well as its polarity. Its application as an alternative solvent in the synthesis of dipeptides under microwave irradiation is also described.     

Identification and quantification of phosphatidylcholines containing very-long-chain polyunsaturated fatty acid in bovine and human retina using liquid chromatography/tandem mass spectrometry

The retina is one of the vertebrate tissues with the highest content in polyunsaturated fatty acids (PUFA). A large proportion of retinal phospholipids, especially those found in photoreceptor membranes, are dipolyunsaturated molecular species. Among them, dipolyunsaturated phosphatidylcholine (PC) molecular species are known to contain very-long-chain polyunsaturated fatty acids (VLC-PUFA) from the n-3 and n-6 series having 24-36 carbon atoms (C24-C36) and four to six double bonds. Recent interest in the role played by VLC-PUFA arose from the findings that a protein called elongation of very-long-chain fatty acids 4 (ELOVL4) is involved in their biosynthesis and that mutations in the ELOVL4 gene are associated with Stargardt-like macular dystrophy (STD3), a dominantly inherited juvenile macular degeneration leading to vision loss. The aim of the present study was to develop an HPLC-ESI-MS/MS method for the structural characterisation and the quantification of dipolyunsaturated PC molecular species containing VLC-PUFA and validate this methodology on retinas from bovines and human donors. Successful separation of phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), PC, lyso-phosphatidylcholine (LPC) and sphingomyelin (SM) was achieved using a silica gel column and a gradient of hexane/isopropanol/water containing ammonium formate as a mobile phase. A complete structural characterisation of intact phosphatidylcholine species was obtained by collision-induced dissociation (CID) in the negative mode. Fatty acid composition and distribution can be clearly assigned based on the intensity of sn-2/sn-1 fragment ions. The PC species were characterised on bovine retina, 28 of which were dipolyunsaturated PC species containing one VLC-PUFA (C24-C36) with three to six double bonds. VLC-PUFA was always in the sn-1 position while PUFA at the sn-2 position was exclusively docosahexaenoic acid (DHA, C22:6n-3). Most of these VLC-PUFA-containing dipolyunsaturated PCs were detected and quantified in human retinas. The quantitative analysis of the different PC molecular species was performed in the positive mode using precursor ion scanning of m/z 184 and 14:0/14:0-PC and 24:0/24:0-PC as internal standards. The relationship between the MS peak intensities of different PC species and their carbon chain length was included for calibration. The main compounds represented were those having VLC-PUFA with 32 carbon atoms (C32:3, C32:4, C32:5 and C32:6) and 34 carbon atoms (C34:3, C34:4, C34:5 and C34:6). Dipolyunsaturated PCs with 36:5 and 36:6 were detected but in smaller quantities. In conclusion, this new HPLC-ESI-MS/MS method is sensitive and specific enough to structurally characterise and quantify all molecular PC species, including those esterified with VLC-PUFA. This technique is valuable for a precise characterisation of PC molecular species containing VLC-PUFA in retina and may be useful for a better understanding of the pathogenesis of STD3.     

A general dual-bolus approach for quantitative DCE-MRI

Purpose

To present a dual-bolus technique for quantitative dynamic contrast-enhanced MRI (DCE-MRI) and show that it can give an arterial input function (AIF) measurement equivalent to that from a single-bolus protocol.

Methods

Five rabbits were imaged using a dual-bolus technique applicable for high-resolution DCE-MRI, incorporating a time resolved imaging of contrast kinetics (TRICKS) sequence for rapid temporal sampling. AIFs were measured from both the low-dose prebolus and the high-dose main bolus in the abdominal aorta. In one animal, TRICKS and fast spoiled gradient echo (FSPGR) acquisitions were compared.

Results

The scaled prebolus AIF was shown to match the main bolus AIF, with 95% confidence intervals overlapping for fits of gamma-variate functions to the first pass and linear fits to the washout phase, with the exception of one case. The AIFs measured using TRICKS and FSPGR were shown to be equivalent in one animal.

Conclusion

The proposed technique can capture even the rapid circulation kinetics in the rabbit aorta, and the scaled prebolus AIF is equivalent to the AIF from a high-dose injection. This allows separate measurements of the AIF and tissue uptake curves, meaning that each curve can then be acquired using a protocol tailored to its specific requirements.     

Uncharged isocoumarin-based inhibitors of urokinase-type plasminogen activator

Background  

Urokinase-type plasminogen activator (uPA) plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis. Consequently, uPA is an attractive target for the development of small molecule active site inhibitors. Most of the recent drug development programs aimed at nonpeptidic inhibitors targeted at uPA have focused on arginino mimetics containing amidine or guanidine functional groups attached to aromatic or heterocyclic scaffolds. There is a general problem of limited bioavailability of these charged inhibitors. In the present study, uPA inhibitors were designed on an isocoumarin scaffold containing uncharged substituents.     

Extending the Family of V4+ S=${{ 1/2 }}$ Kagome Antiferromagnets

The ionothermal synthesis, structure, and magnetic susceptibility of a novel inorganic–organic hybrid material, imidazolium vanadium(III,IV) oxyfluoride [C₃H₅N₂][V₉O₆F₂₄(H₂O)₂] (ImVOF) are presented. The structure consists of inorganic vanadium oxyfluoride slabs with kagome layers of V⁴⁺ S=${{ 1/2 }}$ ions separated by a mixed valence layer. These inorganic slabs are intercalated with imidazolium cations. Quinuclidinium (Q) and pyrazinium (Pyz) cations can also be incorporated into the hybrid structure type to give QVOF and PyzVOF analogues, respectively. The highly frustrated topology of the inorganic slabs, along with the quantum nature of the magnetism associated with V⁴⁺, means that these materials are excellent candidates to host exotic magnetic ground states, such as the highly sought quantum spin liquid. Magnetic susceptibility measurements of all samples suggest an absence of conventional long‐range magnetic order down to 2 K despite considerable antiferromagnetic exchange.