14 research outputs found
Studies on the double alkylation of 2,2-disubstituted-1,3-dithiacycloalkane-S-oxides: synthesis of tertiary thiol derivatives
Di-alkylation of 2,2-dimethyl-1,3-dithiacycloalkane-S-oxides has been achieved allowing the synthesis of
two tertiary thiol centres. The diastereoisomers of the mono-alkylated products have been shown to
react at different rates. The X-ray crystal structures of three substituted dithiane-S-oxides have been
determined, and the conversion of the dialkylated products into cyclic disulfide derivatives of tertiary
thiols (1,2-dithiolanes) has been achieved by treatment with acid
Synthesis of fluorinated fused benzofurans and benzothiophenes: smiles-type rearrangement and cyclisation of perfluoro(het)aryl ethers and sulfides
Lithiumâbromine exchange in 2-bromophenyl perfluoroaryl ethers or sulfides affords fused fluorinated benzofurans or benzothiophenes respectively by SNAr substitution of the adjacent fluorine in the perfluoroaryl substituent. The structures of the new compounds were confirmed by NMR spectroscopy and single crystal X-ray diffraction analysis. In the case of 2-bromophenyl tetrafluoropyrid-4-yl ether, lithiation promoted a Smiles-type rearrangement which led to formation of 4-(2-hydroxyphenyl)tetrafluoropyridine, for which the structure was confirmed by X-ray crystallography
Determinations of the peroxidative susceptibilities of cod liver oils by a newly-developed 1H NMR-based method: resistance of an antioxidant-fortified product isolated from pre-fermented sources
Objective: To explore the molecular composition and antioxidant status of four natural (unrefined) cod liver oil (CLO)
products, three of which (Products 1â3) were non-fermented, whilst one (Product 4) was isolated from pre-fermented
cod livers, and hence was naturally antioxidant-fortified. Potential antioxidants and aldehyde-scavenging agents were
determined by recommended and/or 1H NMR methods; peroxyl radical-specific oxygen radical absorbance capacity
(ORAC) values were measured fluorimetrically. The activities of such antioxidants were also investigated by assessing
the susceptibilities/resistivities of these CLOs to thermo-oxidation by 1H NMR analysis, which monitored the timedependent evolution of aldehydic lipid oxidation products at 180 °C.
Results: Product 4 displayed much higher, albeit variable ORAC values (mean ± SEM 91.4 ± 19.5 mmol. trolox equivalents/kg) than those of Products 1â3, an observation arising from significant levels of peroxidation-blocking and/
or aldehyde-consuming collagenous polypeptides/peptides, flavonones, biogenic amines, total phenolics, tannins,
and ammoniacal agents therein. All of these agents were undetectable in Products 1â3. Quantitative considerations
indicated that collagenous gel agents (present at ca. 1.5% (w/w)) were the most powerful Product 4 antioxidants.
Significantly lower levels of aldehydes were generated in this product when exposed to thermal-stressing episodes.
Results confirmed the enhanced peroxidative resistivity of a pre-fermented, antioxidant-rich natural CLO over those of
corresponding non-fermented products. Product 4: Green Pasture Blue Iceâą fermented cod liver oil
Design, synthesis and antitrypanosomal activities of 2,6-disubstituted-4,5,7-Trifluorobenzothiophenes
Current treatments for Human African Trypanosomiasis (HAT) are limited in their application, have undesirable dosing regimens and unsatisfactory toxicities highlighting the need for the development of a safer drug pipeline. Our medicinal chemistry programme in developing rapidly accessible and modifiable heterocyclic scaffolds led to the design and synthesis of novel substituted benzothiophenes, with 6-benzimidazol-1-ylbenzothiophene derivatives demonstrating significant antitrypanosomal activities (IC50 <1 ÎŒM) against Trypanosoma brucei rhodesiense and no toxicity towards mammalian cells
Progress in low-field benchtop NMR spectroscopy in chemical and biochemical analysis
The employment of spectroscopically-resolved NMR techniques as analytical probes have previously been both prohibitively expensive and logistically challenging in view of the large sizes of high-field facilities. However, with recent advances in the miniaturisation of magnetic resonance technology, low-field, cryogen-free âbenchtopâ NMR instruments are seeing wider use. Indeed, these miniaturised spectrometers are utilised in areas ranging from food and agricultural analyses, through to human biofluid assays and disease monitoring. Therefore, it is both intrinsically timely and important to highlight current applications of this analytical strategy, and also provide an outlook for the future, where this approach may be applied to a wider range of analytical problems, both qualitatively and quantitatively
Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro
A small library of twelve, structurally diverse, fluoroaryl benzimidazoles was prepared using a simple synthetic strategy employing SNAr reactions. This allowed rapid assembly of heterocyclic structures containing linked and tethered fluoroaryl benzimidazoles. X-ray crystal structures of seven compounds were obtained including those of two macrocyclic compounds containing 21- and 24-membered rings. Three tethered fluoroaryl benzimidazole derivatives demonstrated micromolar inhibition against K-562 and MCF-7 cell lines. These compounds, in addition to 1-tetrafluoropyrid-4-yl-2-tetrafluoropyrid-4-ylsulfanyl-1H-benzimidazole, also demonstrated micromolar inhibition against G361 and HOS cell lines. Two of the compounds were found to activate caspases leading to apoptosis
The effect of particle size on the dehydration/rehydration behaviour of lactose
The effect of particle size on the dehydration/rehydration behaviour of lactos
NMR spectral analysis of strongly second-order 6-, 8-, 9- and 10- spin-systems (1 H-19 F, 19 F-19 F and 13 C-19 F) in perfluorotoluyl- and tetrafluoro-pyridyl- aromatics using the line-shape method ANATOLIA
A simple to use nuclear magnetic resonance analysis method has been tested on complex 1H, 19F, and 13C multiplets. This openâsource lineâshape analysis method analysis of total lineshape (ANATOLIA)1 provides some significant advantages over traditional assignâiterate methods of NMR spectral analysis by avoiding false minima and progressing optimisation to the global minimum. The target molecules are 1âperfluorotolâ4âylâ2âperfluorotolâ4âylâoxymethylâ1Hâbenzimidazole (moleculeâI) and 1âtetrafluoropyridâ4âylâ2âtetrafluoropyridâ4âylâthioâ1Hâbenzimidazole (moleculeâII) which were produced as part of a family of fluorinated drug scaffolds prepared for anticancer and antiparasitic screening. Spectra display significant secondâorder effects with 1H ÎÎŽ = 3.68 and 4.67 Hz for the aromatic hydrogen âtripletsâ, with 19F 4JAAâ, 4JBBâ, 4JXXâ, and 4JYYâ coupling constants range from +4.8 to â14.0 Hz and for 13Câisotopomers 19F ÎÎŽ of up to 111.56 Hz. A spinâsystem of six coupling nuclei (HaHbHcHd FYFYâ) was analysed in 12 s, a spinâsystem of nine coupling fluorine nuclei (AAâBBâCCCâYYâ) was analysed within 2 min, and 10 coupling nuclei (XXâYYâZZZâBBââHd) was optimised in 6 min using a laptop computer. ANATOLIA was also robust enough to be able to yield accurate spectral values from inaccurate input values. In both compounds, a fluorineâfluorine coupling constant was identified between the two fluoroâaromatic rings (FBBâ and FYYâ) of +4.05 and +4.67 Hz and attributed to a throughâspace interaction. Ab initio structure optimisations and coupling constant calculations provided useful input data for spectral analysis. A modern 19F nuclear magnetic resonance spectrum of perfluorotoluene (octafluorotoluene) and analysis from 1975 was used as a test data set to assess ANATOLIA
Low-field benchtop NMR spectroscopy as a potential non-stationary tool for point-of-care urinary metabolite tracking in diabetic conditions
We describe the advantages and diagnostic/prognostic significance of low-field, near-portable benchtop NMR spectrometers for the multicomponent metabolomics analysis of targeted and untargeted urinary biomarkers (â„15) in type 2 diabetes patients. Implementation of these facilities at âpoint-of-careâ clinical sites may yield valuable advantages for the sequential monitoring of diabetic and prediabetic individuals
A novel trisprotonated beta-dialdiminate cryptand
A novel trisprotonated beta-dialdiminate cryptan