Determination of selected neurotransmitter metabolites using monolithic column chromatography coupled with chemiluminescence detection

The oxidation of selected clinically important neurotransmitter metabolites with acidic potassium permanganate in the presence of polyphosphates evokes chemiluminescence of sufficient intensity to enable the sensitive determination of these species. Limits of detection for 5-hydroxyindole-3-acetic acid (5-HIAA), vanilmandelic acid (VMA; α,4-dihydroxy-3-methoxybenzeneacetic acid), 4-hydroxy-3-methoxyphenylglycol (MHPG), homovanillic acid (HVA, 4-hydroxy-3-methoxyphenylacetic acid) and 3,4-dihydroxyphenylacetic acid (DOPAC) were between 5 × 10⁻⁹ and 4 × 10⁻⁸ M, using flow-injection analysis methodology. In addition, we demonstrate the rapid determination of homovanillic acid and 5-hydroxyindole-3-acetic acid in human urine - without the need for extraction procedures - using monolithic column chromatography with chemiluminescence detection.     

Zappa–Szép product groupoids and $$C^*$$-blends

We study the external and internal Zappa–Szép product of topological groupoids. We show that under natural continuity assumptions the Zappa–Szép product groupoid is étale if and only if the individual groupoids are étale. In our main result we show that the \(C^*\)-algebra of a locally compact Hausdorff étale Zappa–Szép product groupoid is a \(C^*\)-blend, in the sense of Exel, of the individual groupoid \(C^*\)-algebras. We finish with some examples, including groupoids built from \(*\)-commuting endomorphisms, and skew product groupoids.     

The importance of chain length for the polyphosphate enhancement of acidic potassium permanganate chemiluminescence

Sodium polyphosphate is commonly used to enhance chemiluminescence reactions with acidic potassium permanganate through a dual enhancement mechanism, but commercially available polyphosphates vary greatly in composition. We have examined the influence of polyphosphate composition and concentration on both the dual enhancement mechanism of chemiluminescence intensity and the stability of the reagent under analytically useful conditions. The average chain length (n) provides a convenient characterisation, but materials with similar values can exhibit markedly different distributions of phosphate oligomers. There is a minimum polyphosphate chain length (∼6) required for a large enhancement of the emission intensity, but no further advantage was obtained using polyphosphate materials with much longer average chain lengths. Providing there is a sufficient average chain length, the optimum concentration of polyphosphate is dependent on the analyte and in some cases, may be lower than the quantities previously used in routine detection. However, the concentration of polyphosphate should not be lowered in permanganate reagents that have been partially reduced to form high concentrations of the key manganese(III) co-reactant, as this intermediate needs to be stabilised to prevent formation of insoluble manganese(IV).     

Factors from trees

We construct factors of type for , from group actions on homogeneous trees and their boundaries. Our result is a discrete analogue of a result of R.J Spatzier, where the hyperfinite factor of type is constructed from a group action on the boundary of the universal cover of a manifold.

     

A screening test for heroin based on sequential injection analysis with dual-reagent chemiluminescence detection

A sequential injection analysis procedure with dual-reagent chemiluminescence detection was applied to the screening of street drug seizure samples for the presence of heroin. The chemiluminescence reagents (acidic potassium permanganate and tris(2,2'-bipyridine)ruthenium(III)) were aspirated from either side of a sample aliquot that was sufficiently large to prevent interdispersion of the reagent zones, and therefore two different chemical reactions could be performed simultaneously at either end of the sample zone. The presence of heroin in seizure samples was indicated by a strong response with the tris(2,2'-bipyridine)ruthenium(III) reagent and confirmed by a significant increase in the response with the permanganate reagent when the sample was treated with sodium hydroxide to hydrolyse the heroin to morphine. Nicomorphine (a morphine-derived pharmaceutical) was synthesised and tested under the same conditions. The responses with the permanganate reagent were similar to those for heroin, which supports the proposed chemical basis for the test. However, the responses with tris(2,2'-bipyridine)ruthenium(III) were far lower for nicomorphine than heroin (approximately 5-fold for the samples that had not been hydrolysed).     

Mechanistically inspired design of Fe(III)-TAML peroxide-activating catalysts

Recent broad-ranging mechanistic studies of FeIII-TAML peroxide activators enable a strategy for designing catalysts with improved (i) hydrolytic and (ii) operational stabilities, (iii) faster activation of H2O2 and other peroxides, and (iv) a pH of highest activity closer to 7. Combining all items of insight leads to [Fe{1-NO2C6H3-3,4-(NCOCMe2NCO)2CF2}(OH2)]- (1a) which exhibits the most desirable technical performance in its class.     

Acidic potassium permanganate as a chemiluminescence reagent--a review

A critical and comprehensive review of acidic potassium permanganate chemiluminescence is presented. This includes discussion on reaction conditions, the influence of enhancers such as polyphosphates, formaldehyde and sulfite, the relationship between analyte structure and chemiluminescence intensity, and the application of this chemistry to determine a wide variety of compounds, such as pharmaceuticals, biomolecules, antioxidants, illicit drugs, pesticides and pollutants. Previous proposals for the nature of the emitting species are re-evaluated in light of recent evidence.     

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor

The bromodomain‐containing proteins BRD9 and BRD7 are part of the human SWI/SNF chromatin‐remodeling complexes BAF and PBAF. To date, no selective inhibitor for BRD7/9 has been reported despite its potential value as a biological tool or as a lead for future therapeutics. The quinolone‐fused lactam LP99 is now reported as the first potent and selective inhibitor of the BRD7 and BRD9 bromodomains. Development of LP99 from a fragment hit was expedited through balancing structure‐based inhibitor design and biophysical characterization against tractable chemical synthesis: Complexity‐building nitro‐Mannich/lactamization cascade processes allowed for early structure–activity relationship studies whereas an enantioselective organocatalytic nitro‐Mannich reaction enabled the synthesis of the lead scaffold in enantioenriched form and on scale. This epigenetic probe was shown to inhibit the association of BRD7 and BRD9 to acetylated histones in vitro and in cells. Moreover, LP99 was used to demonstrate that BRD7/9 plays a role in regulating pro‐inflammatory cytokine secretion.     

Effects of variation in modulator temperature during cryogenic modulation in comprehensive two‐dimensional gas chromatography

Many modulation systems in comprehensive 2D GC (GC×GC) are based on cryogenic methods. High trapping temperatures in these systems can result in ineffective trapping of the more volatile compounds, whilst temperatures that are too low can prevent efficient remobilisation of some compounds. To better understand the trapping and release of compounds over a wide range of volatilities, we have investigated a number of different constant temperature modulator settings, and have also examined a constant temperature differential between the cryo‐trap and the chromatographic oven. These investigations have led us to modify the temperature regulation capabilities of the longitudinally modulated cryogenic system (LMCS). In contrast to the current system, where the user sets a constant temperature for the cooling chamber, the user now sets the temperature difference between the cryo‐trap and the chromatographic oven. In this configuration, the cooling chamber temperature increases during the chromatographic run, tracking the oven temperature ramp. This produces more efficient, volatility‐dependent modulation, and increases the range of volatile compounds that can be analysed under optimal trap‐and‐release conditions within a single analytical run. This system also reduces cryogenic fluid consumption.     

Determination of Citrus aurantium protoalkaloids using HPLC with acidic potassium permanganate chemiluminescence detection

Acidic potassium permanganate chemiluminescence was explored as a sensitive and selective mode of detection for phenolic phenethylamines (adrenergic amines) in consumer products containing Citrus aurantium extracts. Nine commercially available weight-loss products were analysed using rapid reversed-phase chromatography with a monolithic column (separation time of 4 min). The results were in good agreement with package labelling, with some notable exceptions. The products contained a wide concentration range of synephrine and total adrenergic amines, and the difference in consumer intake was even greater when the manufacturers’ recommended daily consumption was considered. The quantity of the extract, often specified on the packaging as equivalent grams of dry C. aurantium fruit, was a poor indicator of the concentration of the active ingredients. Methionine, a thioether amino acid contained in some weight-loss products, was identified as a potential interferent for this mode of detection.