Bronsted acidic ionic liquids derived from alkylamines as catalysts and mediums for Fischer esterification : study of structure–activity relationship

Esterification of acetic acid with 1-octanol was studied using a series of alkylammonium salts as Brønsted acidic ionic liquids. The following
ionic liquids were prepared and used as catalysts and mediums in the esterification reaction; [Et₃NH][HSO₄], [Et₃NH][H₂PO₄], [Et₃NH][BF₄],
[Et₃NH][p-CH₃C₆H₄SO₃], [Et₂(PhCH₂)NH][HSO₄], [n-Bu₃NH][HSO₄], [n-Oct₃NH][HSO₄], [Et₂NH₂][HSO₄], [Et₂NH₂][H₂PO₄], [Et₂NH₂]
[BF₄], [i-Pr₂NH₂][HSO₄], [EtNH₃][HSO₄], [EtNH₃][H₂PO₄], and [EtNH₃][BF₄]. Higher acidity of the anion in the ionic liquid resulted in high yield of the ester. Yield of the ester decreased with increase in the size of the cation. There was no phase separation in the reactions where size of anion and/or cation was bigger

Transport and phase dynamics of poly(vinyl pyrrolidone) doped plastically crystalline N-methyl-N-propylpyrrolidinium tetrafluoroborate

The plastic crystal phase forming N-methyl-N-propylpyrrolidinium tetrafluoroborate organic salt (P₁₃BF₄) was combined with 2, 5 and 10 wt.% poly(vinyl pyrrolidone) (PVP). The ternary 2 wt.% PVP/2 wt.% LiBF₄/P₁₃BF₄ was also investigated. Thermal analysis, conductivity, optical thermomicroscopy, and Nuclear Magnetic Resonance (¹¹B, ¹⁹F, ¹H, ⁷Li) were used to probe the fundamental transport processes. Both the onset of phase I and the final melting temperature were reduced with increasing additions of PVP. Conductivity in phase I was 2.6 × 10^{− 4} S cm^{− 1} 5.2 × 10^{− 4} S cm^{− 1} 1.1 × 10^{− 4} S cm^{− 1} and 3.9 × 10− 5 S cm− 1 for 0, 2, 5 and 10 wt.%PVP/P₁₃BF₄, respectively. Doping with 2 wt.% LiBF₄ increased the conductivity by up to an order of magnitude in phase II. Further additions of 2 wt.% PVP slightly reduced the conductivity, although it remained higher than for pure P₁₃BF₄.

High-pressure phase transition in cyclo-octane

Structural behaviour of cyclo-octane under high pressure is studied by using a synchrotron x-ray source in a diamond anvil cell (DAC) up to 40.2 GPa at room temperature. The cyclo-octane firstly solidifies to the triclinic phase at 0.87GPa. With the increasing pressure, the phase of cyclo-octane changes to the tetragonal phase at about 6.0 GPa and then transforms to amorphous phase above 18.2 GPa, which is kept till to 40.2 GPa. All the phase transitions of cyclo-octane are irreversible.

Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape)

AIM: To test the hypothesis that a 'basal plus' regimenadding once-daily main-meal fast-acting insulin to basal insulin once dailywould be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction. METHODS: This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose <7 mmol/l but HbA1c >7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms. RESULTS: For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c <7%, 20.6 vs 27.9%; p = 0.12), weight gain (2.06 vs 2.50 kg; p = 0.2), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life average weighted impact (AWI) score) and generic health status (five-dimension European Quality of Life questionnaire). Overall hypoglycaemia rates were similar between groups (15.3 vs 18.2 events/patient-year; p = 0.22); nocturnal hypoglycaemia was higher with the basal plus regimen (5.7 vs 3.6 events/patient-year; p = 0.02). CONCLUSION: In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

An investigation of solubility of aliquat 336 in different extracted solutions

A major concern in solvent extraction processes is the loss of extractant into the aqueous phase due to its slight solubility in the aqueous phase. Similarly, in membrane extraction processes, extractant loss through extractant leakage from the membrane into the aqueous phase is also a concern. Several published membrane extraction studies using Aliquat 336 as the extractant, have expressed this concern, but none has studied extractant leakage quantitatively. It is the authors’ opinion that the extractant leakage should be considered as a technical parameter of a membrane. In our laboratory active progress has been made in using Aliquat 336 ‘entangled’ into the polymer membranes to remove heavy metal ions from wastewater samples. In this work, we studied the loss of Aliquat 336 from the point of view of its solubility in aqueous solutions. The results showed that the solubilities of Aliquat 336 in an aqueous phase acidified with 2 M HCl is about 0.1 g/100 m/ of the solution. This figure provides a useful guideline for evaluating the leakage of the Aliquat 336 extractant from the membranes.

Quality-of-life measurement in patients undergoing radiation therapy for head and neck cancer: a Hong Kong experience

The aims of this study are (1) to establish a reliable and valid quality-of-life (QOL) questionnaire for Chinese patients with head and neck (H&N) cancer who are treated with radiation therapy and (2) to evaluate the impact of the immediate side effects of treatment on the QOL of these patients. The 39-item "Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module" (QOL-RTI/H&N) was translated into Chinese. In the reliability evaluation phase (study module 1), the questionnaire was administered twice to 56 H&N cancer patients, 7 days apart, during the second and third week of radiation therapy. In the validity evaluation phase (study module 2), 138 patients completed the QOL-RTI/H&N before starting and at the end of radiation therapy. Sixty-nine of these 138 patients also completed the QOL-RTI/H&N during the second week of their radiation therapy, at the same time as completing the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire. Cronbach alpha coefficients were 0.88 for the general-tool QOL-RTI and 0.90 for the H&N subscale. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.89 for the general-tool QOL-RTI and 0.75 for the H&N subscale. The instrument can discriminate between patients with stage I or II disease and those with stage III or IV disease (P < .05). Concurrent validity was established by the good agreement with the FACT-H&N (r = 0.86, P < .001). A highly significant deterioration was in the QOL from the baseline to the end of treatment (mean difference for general tool = 1.95, P < .001; mean difference for H&N subscale = 4.85, P < .001). The Chinese QOL-RTI/H&N is a reliable and valid tool for determining the QOL in H&N cancer patients receiving radiation therapy. The immediate side effects of treatment had a significantly negative impact on the patients' QOL. The impact was relatively large for the functional and treatment-site aspects.

Mechanochemical synthesis of nanocrystalline SnO2-ZnO photocatalysts

Mechanochemical processing of anhydrous chloride precursors with Na₂CO₃ has been investigated as a means of manufacturing nanocrystalline SnO₂ doped ZnO photocatalysts. High-energy milling and heat-treatment of a 0.1SnCl₂+0.9ZnCl₂+Na₂CO₃+4NaCl reactant mixture was found to result in the formation of a composite powder consisting of oxide grains embedded within a matrix of NaCl. Subsequent washing with deionized water resulted in removal of the NaCl matrix phase and partial hydration of the oxide reaction product with the consequent formation of ZnSn(OH)₆. The extent of this hydration reaction was found to decrease in a linear fashion with the temperature of the post-milling heat-treatment over the range of 400–700 °C. For a heat-treatment temperature of 700 °C, the SnO₂ doped ZnO powder was found to exhibit significantly higher photocatalytic activity than either single-phase SnO₂ or ZnO powders that were synthesized using similar processing conditions. The heightened photocatalytic activity of the SnO₂ doped ZnO was attributed to its higher specific surface area and the enhanced charge separation arising from the coupling of ZnO with SnO₂.

A comparative study of secondary Ion emission from water ice under Ion bombardment by Au+, Au3+, and C60+

Secondary ion emission from water ice has been studied using Au⁺, Au₃⁺, and C₆₀⁺ primary ions. In contrast to the gas phase in which the spectra are dominated by the (H₂O)_nH⁺ series of ions, the spectra from ice using all three primary ions are principally composed of two series of cluster ions (H₂O)_nH⁺ and (H₂O)_n⁺. Dependent on the conditions, the unprotonated series can dominate the spectra. Since in the gas phase (H₂O)_n⁺ is unstable with respect to the formation of the protonated ion series, the presence of the solid must provide a means to stabilize their formation. The cluster ion yields under Au⁺ bombardment are very low and can be understood in terms of sputtering on the borderline between linear cascade and thermal spike behavior. There is a 10⁴ increase in yield across the whole spectrum compared to Au⁺ when Au₃⁺ and C₆₀⁺ species are used as primary ions. The character of the spectra differed between these two primary ions, but insights into the mechanism of secondary ion emission for both is discussed within an energy deposition framework provided by the fluid flow-based mesoscale energy deposition footprint (MEDF) model that predicts a cone-shaped zone of activation and emission. C₆₀⁺ differs from Au^₃+ in that it delivers its energy closer to the surface, and it is argued this has consequences for the cluster ion distribution and yield. Increasing the ion dose by sputtering suppresses the yield of (H₂O)_n⁺ and increases the yield of the protonated ions in the small cluster region, whereas the yield in the large cluster regime is suppressed significantly. The three primary ions show rather different behavior, and this is discussed in the light of the sputtering models. Finally, negative ion spectra including cluster ions have been observed for the first time. C₆₀⁺ delivers the highest yields, but these are less than 10 times the positive ion yields, probably because the O and OH fragment ions on which the clusters are based are easily neutralized by protons.

A novel approach to needs assessment in curriculum development: going beyond consensus methods

BACKGROUND: Needs assessment should be the starting point for curriculum development. In medical education, expert opinion and consensus methods are commonly employed. AIM: This paper showcases a more practice-grounded needs assessment approach. METHODS: A mixed-methods approach, incorporating a national survey, practice audit, and expert consensus, was developed and piloted in thrombosis medicine; Phase 1: National survey of practicing consultants, Phase 2: Practice audit of consult service at a large academic centre and Phase 3: Focus group and modified Delphi techniques vetting Phase 1 and 2 findings. RESULTS: Phase 1 provided information on active curricula, training and practice patterns of consultants, and volume and variety of thrombosis consults. Phase 2's practice audit provided empirical data on the characteristics of thrombosis consults and their associated learning issues. Phase 3 generated consensus on a final curricular topic list and explored issues regarding curriculum delivery and accreditation. CONCLUSIONS: This approach offered a means of validating expert and consensus derived curricular content by incorporating a novel practice audit. By using this approach we were able to identify gaps in training programs and barriers to curriculum development. This approach to curriculum development can be applied to other postgraduate programs.

Prevalence of the thioamide {···H-N-C=S}2 synthon-solid-state (X-ray crystallography), solution (NMR) and gas-phase (theoretical) structures of O-methyl-N-aryl-thiocarbamides

Structural investigations, i.e. solid-state (X-ray), solution (¹H NMR) and gas-phase (theoretical), on molecules with the general formula MeOC(S)N(H)C₆H₄-4-Y: Y = H (1), NO₂ (2), C(O)Me (3), Cl (4) have shown a general preference for the adoption of an E-conformation about the central C–N bond. Such a conformation allows for the formation of a dimeric hydrogen-bonded {H–N–C=S}₂ synthon as the building block. In the cases of 1–3, additional C–H^...O interactions give rise to the formation of tapes of varying topology. A theoretical analysis shows that the preference for the E-conformation is about the same as the crystal packing stabilisation energy and consistent with this, the compound with Y = C(O)OMe, (5), adopts a Z-conformation in the solid-state that facilitates the formation of N–H^...O, C–H^...O and C–H^...S interactions, leading to a layer structure. Global crystal packing considerations are shown to be imperative in dictating the conformational form of molecules 1–5.

Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis,  apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining  coordinated gene expression profiles but are also highly effective for molecularly “fingerprinting” diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious  disease pathogenesis.

Characterisation of nickel(II) extraction by 2-hydroxy-5-nonylacetophenone oxime (LIX 84) in a micellar phase

The properties of the nickel(II)/2-hydroxy-5-nonylacetophenone oxime (HNAPO), an active ingredient in LIX 84, extraction system were characterised in a micellar system. The extinction coefficient, λ_max of HNAPO (316 nm) and the Ni²⁺ complex (387 nm) in a neutral micellar system, poly dispersed octa-ethyleneglycol mono-n-dodecyl ether (G₁₂A₈) were determined as 3100 and 3500 M⁻¹ cm⁻¹, respectively. HNAPO was found to have a neutral micellar phase and bulk aqueous phase pK_a of 11.5 and 12.5, respectively. The extraction equilibrium constant, K_ex, was determined to be 10^−8.0, and the deviation from theory observed at high pH can be accounted for by consideration of the competition for nickel(II) ions by hydroxide ions and HNAPO. A micellar phase of octa-ethyleneglycol mono-n-dodecyl ether (C₁₂E₈) was determined to be an appropriate model of the free oil/water interface from the solubilised location of HNAPO. Utilising the interfacial probe, 4-heptadecyl-7-hydroxy coumarin (HHC) allowed the determination of the electrostatic surface potential of mixed micelles of G₁₂A₈ and sodium dodecyl sulphate (SDS) or dodecyl trimethyl ammonium chloride (DTAC). The electrostatic surface potential was a linear function of the number of additional surfactant monomers within the G₁₂A₈ micelle, for the concentration range studied. For G₁₂A₈/DTAC mixed micelles, the surface potential was given by +1.1 mV per DTAC molecule per micelle, and for G₁₂A₈/SDS mixed micelles the relationship was −1.4 mV per SDS molecule per micelle.

Investigations into the analytical applications and fundamental chemistry of the chemiluminescent reactions of Tris(2,2'-bipyridyl)ruthenium(III) with certain Papaver Somniferum alkaloids and other related compounds

The reaction of tris(2,2’-bipyridyl)ruthenium(III) (Ru(bipy) ₃³⁺) with various analytes to generate chemiluminescence has been well documented. This investigation sought to undertake a chemiluminometic study of the reactions of Ru(bipy) ₃³⁺ with selected Papaver Somniferum alkaloids and specifically synthesised phenethylamines. The investigation, based on a kinetic study, primarily addressed the effect of varying reaction conditions (pH) on Ru(bipy) ₃³⁺ chemiluminescence production. To monitor these reactions, a batch chemiluminometer was specifically designed, fabricated and automated to conduct an extensive study on the selected compounds of interest. The instrumentation incorporated a custom built reaction cell and comprised an ‘on-line’ sample preparation system with which calibration standards could be automatically prepared. The instrumentation provided both time-independent (peak area) and time-dependent (kinetic profile) information. A novel approach to the stabilisation of Ru(bipy) ₃³⁺ as a chemiluminescencent reagent was also investigated and a recirculating system was employed with the batch chemiluminometer to provide a stable supply of Ru(bipy) ₃³⁺. Codeine, thebaine and 6-methoxy-codeine were the Papaver Somniferum alkaloids selected for this study and several N-methylated and N,N-dimethylated phenethylamines and methoxy-substituted phenetheylamines were also synthesised to investigate the affect of pH on the chemiluminescence emission efficiency. The versatility of the batch chemiluminometer facilitated the kinetic study of numerous analytes over a broad pH range. The exemplary performance of the chemiluminometer as an analytical instrument, was demonstrated by the calibration functions, based on peak area data, which exhibited excellent linearity and sensitivity. The estimated detection limits (3s) for the selected alkaloids were in the range 2 x 10^-9 M to 7 x 10^-9 at pH 5.0 and above, which compared favourably to detection limits for the same compounds determined using FIA. Relative standard deviations (n=5) for peak areas ranged between 1% to 5% with a mean of 3.1% for all calibration standards above 2.5 x 10^-8 M. Correlation between concentration and peak area, irrespective of pH and analyte was excellent, with all but two calibration functions having r-squared values greater than 0.990. The analytical figures of merit exemplified the precision and robustness of the reagent delivery and ‘on-line’ sample preparation, as well as the sensitivity of the system. The employment of the chemiluminometer for the measurement of total chemiluminescence emission (peak area) was in itself a feasible analytical technique, which generated highly reproducible and consistent data. Excellent analytical figures of merit, based on peak area, were similarly achieved for the phenethylamines. The effects of analyte structure on chemiluminescence activity was also investigated for the alkaloids and the phenethylamines. Subtle structural variations between the three alkaloids resulted in either a moderately reduced or enhanced total emission that was two or three fold difference only. A significant difference in reaction kinetics was observed between thebaine and codeine/6-methoxy-codeine, which was dependent upon pH. The time-dependent data, namely the observed rate constants for the initial rise in intensity and for the subsequent decay rate, were obtained by fitting a mathematical function (based on the postulated reaction mechanism) to the raw data. The determination of these rate constants for chemiluminescence reactions highlighted the feasibility for utilising such measurements for quantitative analytical applications. The kinetic data were used to discriminate between analyte responses in order to determine the concentrations of individual analytes in a binary mixture. A preliminary, multi-component investigation performed on a binary mixture of codeine and 6-methoxy-codeine (1:1) successfully determined the concentrations of these individual components using such rate constant measurements. Consequently, variations in kinetics resulted in a significant difference between the relative chemiluminescence response based on peak area measurements and the relative response base on peak height measurements obtained using FIA. With regards to the observed reactivity of secondary amines and tertiary amines, chemiluminescence peak area determinations confirmed the vital role of pH on reaction efficiency, which was governed by structural features and kinetics. The tertiary amines investigated generally produced a greater emission under acidic conditions than the corresponding secondary amines. However, the measured chemiluminescence responses were highly dependent upon pH, with similar peak areas obtained for both amine groups under slightly alkaline conditions.

Chemistry, spectroscopy and analytical applications of certain chemiluminescent reactions

Chemiluminescence, the production of light from a chemical reaction, has found widespread use in analytical chemistry. Both tris (2, 2’-bipyridyl) ruthenium (II) and acidic potassium permanganate are chemiluminescence reagents that have been employed for the determination of a diverse range of analytes. This thesis encompasses some fundamental investigations into the chemistry and spectroscopy of these chemiluminescence reactions as well as extending the scope of their analytical applications. Specifically, a simple and robust capillary electrophoresis chemiluminescence detection system for the determination of codeine, O6-methylcodeine and thebaine is described, based upon the reaction of these analytes with chemically generated tris(2,2'-bipyridyl)ruthenium(III) prepared in sulfuric acid (0.05 M). The reagent solution was contained in a glass detection cell, which also held both the capillary and the cathode. The resultant chemiluminescence was monitored directly using a photomultiplier tube mounted flush against the base of the detection cell. The methodology, which incorporated a field amplification sample introduction procedure, realised detection limits (3a baseline noise) of 5 x 10~8 M for both codeine and O6-methylcodeine and 1 x 10~7 M for thebaine. The relative standard deviations of the migration times and the peak areas for the three analytes ranged from 2.2 % up to 2.5 % and 1.9 % up to 4.6 % respectively. Following minor instrumental modifications, morphine, oripavine and pseudomorphine were determined based upon their reaction with acidic potassium permanganate in the presence of sodium polyphosphate. To ensure no migration of the permanganate anion occurred, the anode was placed at the detector end whilst the electroosmotic flow was reversed by the addition of hexadimethrine bromide (0.001% m/v) to the electrolyte. The three analytes were separated counter to the electroosmotic flow via their interaction with a-cyclodextrin. The methodology realised detection limits (3 x S/N) of 2.5 x 10~7 M for both morphine and oripavine and 5 x 10~7 M for pseudomorphine. The relative standard deviations of the migration times and the peak heights for the three analytes ranged from 0.6 % up to 0.8 % and 1.5% up to 2.1 % respectively. Further improvements were made by incorporating a co-axial sheath flow detection cell. The methodology was validated by comparing the results realised using this technique with those obtained by high performance liquid chromatography (HPLC), for the determination of both morphine and oripavine in seven industrial process liquors. A complimentary capillary electrophoresis procedure with UV-absorption detection was also developed and applied to the determination of morphine, codeine, oripavine and thebaine in nine process liquors. The results were compared with those achieved using a standard HPLC method. Although over eighty papers have appeared in the literature on the analytical applications of acidic potassium permanganate chemiluminescence, little effort has been directed towards identifying the origin of the luminescence. It was found that chemiluminescence was generated during the manganese(III), manganese(IV) and manganese(VII) oxidations of sodium borohydride, sodium dithionite, sodium sulfite and hydrazine sulfate in acidic aqueous solution. From the corrected chemiluminescence spectra, the wavelengths of maximum emission were 689 ± 5 nm and 734 ± 5 nm when the reactions were performed in sodium hexametaphosphate and sodium dihydrogenorthophosphate or orthophosphoric acid environments respectively. The corrected phosphorescence spectrum of manganese(II) sulfate in a solution of sodium hexametaphosphate at 77 K, exhibited two peaks with maxima at 688 nm and 730 nm. The chemical and spectroscopic evidence presented strongly supported the postulation that the emission was an example of solution phase chemically induced phosphorescence of manganese(II). Thereby confirming earlier predictions that the chemiluminescence from acidic potassium permanganate reactions originated from an excited manganese(II) species. Additionally, these findings have had direct analytical application in that manganese(IV) was evaluated as a new reagent for chemiluminescence detection. The oxidations of twenty five organic and inorganic species, with solublised manganese(IV), were found to elicit analytically useful chemiluminescence with detection limits (3 x S/N) for Mn(II), Fe(II), morphine and codeine of 5 x 10-8 M, 2.5 x 10-7 M, 7.5 x 10-8 M and 5 x 10-8M, respectively. The corrected emission spectra from four different analytes gave wavelengths of maximum emission in the range from 733 nm up to 740 nm indicating that these chemiluminescence reactions also shared a common emitting species, excited manganese(II). Whilst several analytical problems were addressed in this thesis and answers to certain questions regarding the fundamentals of acidic potassium permanganate chemiluminescence were proposed, there are several areas that would benefit from further research. These are outlined in the final chapter of this thesis.