The role of stable nitroxyl radical precursors as antioxidants in polyolefins

Various 2,2,6,6-tetramethyl piperidines and their N-alkyl derivatives of stable nitroxyl radical precursors containing acrylic(s) and methacrylic(s) groups were reactively processed in the presence of a peroxide as bound-antioxidant masterbatches for polyolefin stabilisation. It was found that grafting of the antioxidant monomers onto the polymer backbone was inevitably in competition with homopolymerisation of the monomers as well as melt degradation of the polymer and other side reactions. As previously reported, binding efficiency of bisacrylic nitroxyl precursor was maximum due to formation of unextractable homopolymer of the antioxidant. On the other hand, the binding efficiency of monoacrylic derivatives was low and the homopolymers were found extractable, which suggests that the bound monoacrylic derivatives are entirely grafted onto the polyolefin backbone. Application of bis and tri-functional coagents gave improved binding efficiency of the monoacrylic monomers. This may be due to copolymerisation of the antioxidants with the coagents and grafting of the copolymers onto the polymer backbone. Comparison of photostabilising activity of the fully extracted bound antioxidants to those of the corresponding unbound analogous showed lower results for the former. However, thermal stabilising activity of the bound antioxidants was higher than that of the unbound analogous due to better substantivity. Analysis using physical techniques and GPC for molecular weight distribution of masterbatches containing the bound monoacrylic antioxidants showed formation of high molecular weight products. Model reaction of a secondary amine derivative in liquid hydrocarbon and analysis of the product using FTIR and NMR spectroscopy indicated a possibility of side reaction, i.e. involvement of the amine active group (>N-H) of the antioxidant in the binding process to form the high molecular weight product. Implementation of various N-alkylated derivatives did not inhibit the side reaction. The photostabilising activity of the bound-antioxidants can be improved when applied in conjunction with small amounts of a benzophenone uv-stabiliser. The synergistic stabilising activity, however, was diminished when the uv-stabiliser was removed from the system during the service time. Nitroxyl precursors containing methacrylic group(s) gave lower binding efficiency than the corresponding acrylic derivatives. Reversible deploymerisation of the grafted methacrylic antioxidants may be responsible for this. Bis and tris-acrylic coagents improved the binding efficiency, and the presence of methacrylic group improved stabilising activity of the antioxidants. N-methyl derivatives were found to exhibit better stabilising activity than their parent secondary amine derivatives.

Organometallic precursors for pillared clay synthesis

The synthetic hectorite, laponite has been used within the paper industry to produce mildly conducting paper for use in electrographic printing. The aim of this research was to modify laponite in order to improve the electrical conductivity. In a continuation of a previous investigation involving organotin intercalation of laponite, the organotin precursor (p-CH3,OC6H4)4Sn was synthesised and characterised using Mass Spectroscopy, Infrared Spectroscopy and elemental analysis. Results of intercalation with this compound and a range of organobismuth and organoantimony compounds suggested that a halide content within the precursor was necessary for improvement in conductivity to be observed. Organometallic intercalation of a range of organotellurium compounds with laponite provided evidence that a hydrolysis reaction on the clay surface followed by the release of hydrochloric acid was an important first step if a reaction was to occur with the clay. Atomic Absorption Spectroscopy studies have shown that the acid protons underwent exchange with the interlayer sodium ions in the clay to varying degrees. Gas-liquid Chromatography and Infrared Spectroscopy revealed that the carbon-tellurium bond remained intact. Powder X-ray diffraction revealed that there had been no increase in the basal spacing. The a.c. conductivity of the modified clays in the form of pressed discs was studied over a frequency range of 12Hz - 100kHz using two electrode systems, silver paste and stainless steel. The a.c. conductivity consists of two components, ionic and reactive. The conductivity of laponite was increased by intercalation with organometallic compounds. The most impressive increase was gained using the organotellurium precursor (p-CH3OC6H4)2TeCl2. Conductivity investigations using the stainless steel electrode where measurements are made under pressure showed that in the case of laponite, where poor particle-particle contact exists at ambient pressure, there is a two order of magnitude increase in the measured a.c. conductivity. This significant increase was not seen in modified laponites where the particle-particle contact had already been improved upon. Investigations of the clay surface using Scanning Electron Microscopy suggested that the improvement in particle-particle contact is the largest factor in the determination of the conductivity. The other important factor is the nature and the concentration of the interlayer cations. A range of clays were synthesised in order to increase the concentration of sodium interlayer cations. A sol-gel method was employed to carry out these syntheses. A conductivity evaluation showed that increasing the concentration of the sodium cations within the clay led to an increase in the conductivity.

The preparation of carbon fibres: a study of the physics and chemistry of the preparation of carbon fibres from acrylic precursors

High strength, high modulus carbon fibres are becoming increasingly important as high performance engineering materials. This thesis describes how they may be prepared by heat treatment from filaments spun from polyacrylonitrile and its copolymers. The chemistry of the first stages of heat treatment is very important in controlling the mechanical properties of the carbonised product. A cyclisation reaction has been found to be responsible for the relatively high thermal stability of pyrolysed polyacrylonitrile, but without oxidation the fibres degrade and fuse. An initial oxidation stage is, therefore, essential to the preparation of fibre of high orientation. The cyclised product of pyrolysis is probably a poly 1,4 dihydropiridine and oxidation converts this to aromatic structures, and cyclised structures containing carbonyl and other oxygenated groups. Oxidation is found to assist the carbon fibre preparation process, by producing a product which condenses at an earlier stage of heat treatment, before fusion can occur. Carbon fibre strength and modulus are dependent upon producing a highly oriented crystal structure. While oxidation of the polymer stabilises the fibre so as to prevent disorientation, further large increases in orientation, with a commensurate improvement in strength and modulus, can be obtained by stretching at temperatures above 1,700 °C. This process is analogous to the way fibre orientation is increased by the stretching of the precursor. A lamellar graphite structure can be created in high temperature fibre, by carefully controlling the degree of oxidation. This type of graphite can produce very high values of Young's modulus. More often, however, graphite fibre has a fibrillar fine structure, which is explicable in terms of continuous graphite ribbons. A ribbon model is the most satisfactory representation of the structure of carbon fibre, as it explains the mechanism of the development of long range order and the variation of Young's modulus with crystalline preferred orientation.

Polymerisable octahedral rhenium cluster complexes as precursors for photo/electroluminescent polymers

New polymerisable photoluminescent octahedral rhenium cluster complexes trans-[{Re6Q8}(TBP)4(VB)2] (Q = S or Se; TBP-p-tert-butylpyridine; VB-vinyl benzoate) have been synthesised, characterised and used to construct rhenium cluster-organic polymer hybrid materials. These novel polymer systems are solution-processable and the rhenium clusters retain their photoluminescent properties within the polymer environment. Notably, when the rhenium cluster complexes are incorporated into the matrix of the electroluminescent polymer poly(N-vinylcarbazole), the resultant cluster polymer hybrid combined properties of both components and was used successfully in the construction of a polymer light emitting diode (PLED). These prototype devices are the first PLEDs to incorporate octahedral rhenium clusters and provide the first direct evidence of the electroluminescent properties of rhenium clusters and indeed, to the best of our knowledge, of any member of the family of 24-electron hexanuclear cluster complexes of molybdenum, tungsten or rhenium.

Potential for Cell-Transplant Therapy with Human Neuronal Precursors to Treat Neuropathic Pain in Models of PNS and CNS Injury: Comparison of hNT2.17 and hNT2.19 Cell Lines

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate the potential of cell-based release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes-related injury) and CNS (spinal cord injury) damage in rat models. Both cell lines transplants potently and permanently reverse behavioral hypersensitivity without inducing tumors or other complications after grafting. Functioning as cellular minipumps for antinociception, human neuronal precursors, like these NT2-derived cell lines, would likely provide a useful adjuvant or replacement for current pharmacological treatments for neuropathic pain.

Estudio del efecto de la reducción del contenido de sales nitrificantes en la calidad microbiológica y aroma de los embutidos crudos curados

Entre las diferentes técnicas que se utilizan para la conservación de la carne se encuentra el curado, método tradicional basado en el empleo de cloruro sódico conjuntamente con sales nitrificantes (nitratos y/o nitritos). Estos compuestos ejercen un importante papel como antimicrobianos y antioxidantes, y participan en la formación del color y aroma típicos de los productos curados. A pesar de todos estos efectos beneficiosos, las sales nitrificantes pueden ser precursoras de la formación de nitrosaminas, compuestos con actividad carcinogénica, teratogénica y mutagénica demostrada. Por este motivo, en los últimos años se ha planteado la posibilidad de reducir la presencia de nitratos y nitritos o incluso evitar su utilización en los productos cárnicos. Para ello es necesario llevar a cabo estudios rigurosos sobre el impacto real de la concentración de nitrificantes en estos productos, a fin de evaluar la posibilidad de disminuir las cantidades permitidas, sin que ello afecte a su seguridad y calidad sensorial. Teniendo en cuenta estos antecedentes, esta Tesis Doctoral se planteó como objetivo evaluar el efecto de la reducción de la concentración de nitrato y nitrito (hasta en un 50% de la cantidad máxima permitida actualmente) en la evolución de la microbiota habitual de los embutidos crudos curados y en el control de los principales microorganismos patógenos asociados a su consumo, así como en el perfil de compuestos volátiles responsables de su aroma...

Organometallic derivatives of cyclotriphosphazene as precursors of nanostructured metallic materials: a new solid state method

The cyclic phosphazene trimers [N3P3(OC6H5)5OC5H4N·Ti(Cp)2Cl][PF6] (3), [N3P3(OC6H4CH2CN·Ti(Cp)2Cl)6][PF6]6 (4), [N3P3(OC6H4-But)5(OC6H4CH2CN·Ti(Cp)2Cl)][PF6] (5), [N3P3(OC6H5)5C6H4CH2CN·Ru(Cp)(PPh3)2][PF6] (6), [N3P3(OC6H5)5C6H4CH2CN·Fe(Cp)(dppe)][PF6] (7) and N3P3(OC6H5)5OC5H4N·W(CO)5 (8) were prepared and characterized. As a model, the simple compounds [HOC5H5N·Ti(Cp)2Cl]PF6 (1) and [HOC6H4CH2CN·Ti(Cp)2Cl]PF6 (2) were also prepared and characterized. Pyrolysis of the organometallic cyclic trimers in air yields metallic nanostructured materials, which according to transmission and scanning electron microscopy (TEM/SEM), energy-dispersive X-ray microanalysis (EDX), and IR data, can be formulated as either a metal oxide, metal pyrophosphate or a mixture in some cases, depending on the nature and quantity of the metal, characteristics of the organic spacer and the auxiliary substituent attached to the phosphorus cycle. Atomic force microscopy (AFM) data indicate the formation of small island and striate nanostructures. A plausible formation mechanism which involves the formation of a cyclomatrix is proposed, and the pyrolysis of the organometallic cyclic phosphazene polymer as a new and general method for obtaining metallic nanostructured materials is discussed.

Synthesis and characterization of cyclotriphosphazenes containing silicon as single solid-state precursors for the formation of silicon/phosphorus nanostructured materials

The synthesis and characterization of new organosilicon derivatives of N3P3Cl6, N3P3[NH(CH2)3Si(OEt)3]6 (1), N3P3[NH(CH2)3Si(OEt)3]3[NCH3(CH2)3CN]3 (2), and N3P3[NH(CH2)3Si(OEt)3]3[HOC6H4(CH2)CN]3 (3) are reported. Pyrolysis of 1, 2, and 3 in air and at several temperatures results in nanostructured materials whose composition and morphology depend on the temperature of pyrolysis and the substituents of the phosphazenes ring. The products stem from the reaction of SiO2 with P2O5, leading to either crystalline Si5(PO4)6O, SiP2O7 or an amorphous phase as the glass Si5(PO4)6O/3SiO2·2P2O5, depending on the temperature and nature of the trimer precursors. From 1 at 800 °C, core−shell microspheres of SiO2 coated with Si5(PO4)6O are obtained, while in other cases, mesoporous or dense structures are observed. Atomic force microscopy examination after deposition of the materials on monocrystalline silicon wafers evidences morphology strongly dependent on the precursors. Isolated islands of size ∼9 nm are observed from 1, whereas dense nanostructures with a mean height of 13 nm are formed from 3. Brunauer−Emmett−Teller measurements show mesoporous materials with low surface areas. The proposed growth mechanism involves the formation of cross-linking structures and of vacancies by carbonization of the organic matter, where the silicon compounds nucleate. Thus, for the first time, unique silicon nanostructured materials are obtained from cyclic phosphazenes containing silicon.

Impact of Genetic Testing and Family Health History Based Risk Counseling on Behavior Change and Cognitive Precursors for Type 2 Diabetes.

Family health history (FHH) in the context of risk assessment has been shown to positively impact risk perception and behavior change. The added value of genetic risk testing is less certain. The aim of this study was to determine the impact of Type 2 Diabetes (T2D) FHH and genetic risk counseling on behavior and its cognitive precursors. Subjects were non-diabetic patients randomized to counseling that included FHH +/- T2D genetic testing. Measurements included weight, BMI, fasting glucose at baseline and 12 months and behavioral and cognitive precursor (T2D risk perception and control over disease development) surveys at baseline, 3, and 12 months. 391 subjects enrolled of which 312 completed the study. Behavioral and clinical outcomes did not differ across FHH or genetic risk but cognitive precursors did. Higher FHH risk was associated with a stronger perceived T2D risk (pKendall < 0.001) and with a perception of "serious" risk (pKendall < 0.001). Genetic risk did not influence risk perception, but was correlated with an increase in perception of "serious" risk for moderate (pKendall = 0.04) and average FHH risk subjects (pKendall = 0.01), though not for the high FHH risk group. Perceived control over T2D risk was high and not affected by FHH or genetic risk. FHH appears to have a strong impact on cognitive precursors of behavior change, suggesting it could be leveraged to enhance risk counseling, particularly when lifestyle change is desirable. Genetic risk was able to alter perceptions about the seriousness of T2D risk in those with moderate and average FHH risk, suggesting that FHH could be used to selectively identify individuals who may benefit from genetic risk testing.

Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.

OBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.

Impurity profiling and synthesis of precursors to the hallucinogenic amphetamine DOB

DOB (4‐bromo‐2,5‐dimethoxyamphetamine) is a newly emerging hallucinogenic amphetamine that sparked serious health warnings in Ireland, following its first seizure back in 2003. Known more commonly as “snowball”, this drug is highly potent and may be used as a substitute to ecstasy (MDMA) and lysergic acid diethylamide (LSD). To date, the work carried out on the impurity profiling of DOB is limited in comparison to amphetamine, methamphetamine and MDMA. In this work, the impurity profile of 4‐bromo‐2,5‐dimethoxyphenyl‐2‐propanone (4‐Br‐2,5‐P2P) is explored. This ketone is a direct precursor to DOB. Its more versatile non‐bromo analogue, 2,5‐ dimethoxyphenyl‐2‐propanone (2,5‐P2P) is also examined, as in addition to DOB, it may be used in the synthesis of a range of several other hallucinogenic amphetamines. A number of different routes to both 2,5‐P2P and 4‐Br‐2,5‐P2P were investigated. For each of these routes, the impurities produced were carefully isolated. Following isolation, the impurities were fully characterised (by 1H‐NMR/13C‐NMR spectroscopy, IR, MS), in order to aid structure elucidation. Compounds not easily resolved by flash column chromatography were analysed by LC‐MS and/or independently synthesised for the purpose of attaining reference standards. Adaptation of the well‐known ‘phenylacetic acid route’ to synthesis of both 2,5‐P2P and 4‐Br‐2,5‐P2P, was found to provide low yields of the expected ketone products. Four impurities were isolated during the preparation of both ketones. The yield of one of these impurities (possessing a dibenzylketone core), was greatly influenced by the amount of acetic anhydride reagent used during the reaction. Having carried out the reaction with several different equivalents of acetic anhydride, it was found that formation of the ‘dibenzylketone’ could not be eliminated. This may increase its likelihood of being detected in the final drug product. The ‘Darzens route’, having very recently emerged as a synthetic route to amphetamine and MDMA precursors, was discovered to be a viable route for manufacture of 2,5‐P2P and 4‐Br‐2,5‐P2P. Despite execution of the reaction being more tedious, the route provides superior yields (≈50–60%) to those achieved using the ‘phenylacetic acid route’ (≈35–38%). Incorporation of a bromine atom (at the aromatic 4‐position) is required at some stage during synthesis of DOB. The bromination of many intermediates/starting materials was therefore also examined in detail. Bromination of the acid starting material 2,5‐dimethoxyphenylacetic acid (2,5‐PAA) was found to be clean and high yielding. This was in stark contrast to the bromination of the benzaldehyde starting material, the ketone precursor 2,5‐P2P and the dibenzylketone‐based impurity. Numerous brominated products were isolated from each of these reactions, many of which were novel compounds, and previously unreported as impurities in the literature. The unpredictable/nondescript nature of these brominations is likely to have a significant impact on the impurity profile of illicitly produced DOB.

THE DESIGN AND SYNTHESIS OF SILOXANE PRECURSORS FOR CHIRAL PERIODIC MESOPOROUS ORGANOSILICA MATERIALS

The development of cost-effective and reliable methods for the synthesis and separation of asymmetric compounds is paramount in helping to meet society’s ever-growing demand for chiral small molecules. Of these methods, chiral heterogeneous supports are particularly appealing as they allow for the reuse of the chiral source. One such support, based on the synergy between chiral organic units and structurally stable inorganic silicon scaffolds are periodic mesoporous organosilicas (PMOs). In the work described herein, I examine some of the factors governing the transmission of chirality between chiral dopants and prochiral bulk phases in chiral PMO materials. In particular, the exploration of 1,1’-binaphthalene-bridged chiral dopants with a focus on the point of attachment into the materials. Moreover, the effects of ordering in the materials are examined and reveal that chirality transfer is more facile in materials with molecular-scale order then those containing amorphous walls. Secondly, the issues surrounding the synthesis and purification of aryl-triethoxysilanes as siloxane precursors are addressed. Both the introduction of a two-carbon linker and the direct attachment of allyl and mixed allyldiethoxysilane species are explored. This work demonstrates that allyldiethoxysilanes are ideal, in that they are stable enough to permit facile synthesis, while still being able to hydrolyze completely to produce well-ordered materials. Lastly, the production of new bulk phases for chiral PMO materials is examined by introducing new prochiral nitrogen-containing siloxane precursors. Biphenyldiamine and bipyridine-bridged siloxane precursors are readily synthesized on reasonable scales. Their use as the bulk siloxane precursor in the production of PMO materials however, is precluded by insufficient gelation and additional siloxane precursors are necessary for the production of ordered materials. In addition to the research detailed above that forms the body of this thesis, two short works are appended. The first details the production of polythiophene assemblies mediated through coordination nanospaces, while the second explores the production of N-heterocyclic carbene functionalized gold nanoparticles through ligand exchange.

Effetto di composti d'aroma sulla risposta fisiologica di Listeria monocytgenes

La citofluorimetria è una tecnica applicata per misurare le caratteristiche fisiche, morfologiche e fisiologiche di cellule microbiche ed ha il pregio di generare un dato per ogni singola particella (cellula) analizzata. Poiché è noto che l’assenza di sviluppo in piastra non implica necessariamente l’assenza di forme microbiche vitali, questa tecnica ha un grande potenziale nello studio dei trattamenti termici che mirano alla stabilizzazione ed alla sicurezza igienico-sanitaria dei prodotti alimentari. Infatti, nel contesto industriale la tendenza è quella di ridurre l’entità di questi trattamenti (tempi/temperature). Ciò può avvenire anche grazie all’utilizzo di composti d’aroma, la cui attività antimicrobica è ben documentata, poiché il trattamento termico, incrementando la tensione di vapore di queste sostanze, ne potenzia l’attività antimicrobica. Questa tesi è incentrata su due aspetti: da una parte, l’effetto dell’esposizione di L. monocytogenes a diverse concentrazioni di timolo e carvacrolo (terpenoidi prevalenti in oli essenziali di Labiatae tra cui timo e origano), dall’altra la valutazione degli effetti di trattamenti termici subletali (45, 50, 55°C), anche in presenza di composti d’aroma, sulla disattivazione e sul successivo recupero di L. monocytogenes. I risultati hanno confermato la forte sinergia tra trattamento termico e presenza di sostanze terpeniche. È stato inoltre dimostrato che la presenza di tali composti incide drasticamente sulle potenzialità di recupero degli eventuali sopravvissuti dopo il trattamento termico. I risultati a volte discordanti tra l’analisi citofluorimetrica (focalizzata sull’integrità della membrana) e i conteggi in piastra hanno evidenziato come i due approcci debbano essere utilizzanti in modo complementare. L’utilizzo di altri coloranti legati ad altre funzioni biologiche e metaboliche permetterà l’ottenimento di informazioni aggiuntive circa la risposta fisiologica di questo microrganismo.