Search

The work described in this thesis concerns the photochemistry of substituted aromatic compounds. In a previous study by the present author of the photonucleophilic substitution of monosubstituted benzenes the scope of the photo-substitution was investigated, but the mechanism was unclear. This work has been continued and the mechanism established. A radical process is excluded, and it is found that the reaction proceeds by attack of a nucleophile on the excited state of the aromatic compound, probably to give a sigma bonded intermediate (i), which decomposes to the substituted product. A series of kinetic experiments established that the nucleophile participates in the rate determining step, but for alkoxide ions the order of the reaction in alkoxide ion is not unity. This is interpreted as being doe to association of the ions to ion pairs and greater aggregates In the non-polar alcoholic solvent. A correlation was noted between the photochemical lability of substituents (where these are leaving groups in the context of nucleophilic substitution) and the development of a partial positive charge on the carbon atom bearing the substituent in the π, π* excited state of the aromatic compound, as calculated using an H. M. 0. approximation. An attempt was made to apply the same considerations to photonucleophilic substitution in the disubstituted benzene series. Although calculations indicated which compounds might be expected to be photochemically reactive, experimented difficulties precluded the formulation of substitution rules. In the monosubstituted naphthalene series the fluoronaphthalenes underwent photonucleophilic substitution readily, but the methoxynaphthalenes gave complex mixtures of unstable substances. In the case of 1-fluoronaphthalene a novel photochemical transformation product of the starting material, 3, 4-benz-2-fluro-tricyclo- (3, 1, O, 02, 6)-hex-3-ene (ii), was isolated. This is the first example of a benz-benzvalene. Irradiation of nitrobenzene with diethylamine was found to give, not the substituted product, N, N-diethylaniline, but reduction products, mainly aniline. A study of the reaction was made, and it was found that photo-reduction of aromatic nitrocompounds is a general phenomenon, in solvents bearing hydrogen atoms capable of abstraction. Interposition of a Pyrex glass filter between the lamp and the photolyte causes coupled species, initially the azoxycompound, to be formed as major products, when a basic solvent is used. However, the azoxycompound is not usually isolated, for it is transformed photochemically both to the o-hydroxyazocompound and, by photosensitization by the starting material, to the azocompound. Mechanistic studies on the photo-reduction of nitrobenzene indicate that reduction occurs by hydrogen abstraction processes, rather than by oxygen atom transfer or electron transfer. Although nitrosobenzene and phenylhydroxylamine have not been isolated from the reaction mixtures, their presence has been inferred, and it is suggested that they are removed from the solution, before they attain isolable concentrations, by reduction by the first formed intermediate C6H5NO2H. This intermediate is seen as arising by hydrogen abstraction from the solvent by excited nitrobenzene in a triplet π, π* state. Although hydrogen abstraction is not a reaction generally associated with π, π* states, H. M. O. calculations on nitrobenzene indicate that in this state an electron-deficiency develops on the oxygen atoms of the nitro group, giving them something of the character of an alkoxy radical. Photochemical studies on azoxycompounds shew that the well- known rearrangement to give the o-hydroxyazocompound (iii - iv) proceeds faster in polar solvents, perhaps suggesting an ionic process rather than a hydrogen atom abstraction/radical recombination. Sensitization encourages photo-reduction to the azocompound; this indicates that rearrangement is probably a reaction of the singlet state, whereas photo-redaction involves the triplet. The situation therefore parallels that found for nitrocompounds, where photo- reduction proceeds via the triplet state and the rearrangement of o-methynitrobenzenes to o-nitrosobenzyl alcohols (v - vi) is a function of the singlet state. Furthermore, just as the normal photo-reaction of o-nitrobenzyl compounds (reduction) is faster than the oxygen transfer rearrangement, so in the azoxycompounds, oxygen transfer to a phenyl ring is a process much preferred to oxygen atom transfer to an ortho methyl group (vii - viii).

BACKGROUND: There is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease. OBJECTIVE: We characterised Brugada syndrome (BrS) patients using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). METHODS: BrS was diagnosed according to international guidelines. 26% BrS patients carried SCN5A mutations. CMR data from 78 BrS patients were compared with 78 healthy controls (44±15 vs 42±14 years; p=0.434 and 64% vs 64% male; p=1.000). RESULTS: Right ventricular (RV) ejection fraction was slightly lower (61±8% vs 64±5%; p=0.004) and RV end-systolic volume slightly greater (31±10mL/m(2) vs 28±6mL/m(2); p=0.038) in BrS compared with controls. These values remained within the normal range. LGE was demonstrated in 8% BrS patients (left ventricular (LV) midwall LGE in 5%) but not in controls (p=0.028). In BrS patients with midwall LGE there were no other features of cardiomyopathy at the time of CMR but genetic testing and follow-up has revealed a desmoplakin mutation in one patient and evolution of T-wave inversion throughout all precordial ECG leads in another. Neither patient fulfils diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Some BrS patients have LV midwall LGE consistent with an underlying cardiomyopathic process. Even cases without LGE show greater RV volumes and reduced RV function. These findings lend further support to the presence of subtle structural abnormalities in BrS. The BrS pattern with LGE may serve as early markers for evolution of a cardiomyopathic phenotype over time. CMR is a potentially useful adjunct investigation in the clinical evaluation of BrS.

OBJECTIVES: The complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are met. Patient-specific computational fluid dynamics (CFD) were used to assess the effect of different aortic valve morphologies on velocity profiles, flow patterns, helicity, wall shear stress (WSS), and oscillatory shear index (OSI) in the thoracic aorta. METHODS: A total of 45 subjects were divided into 5 groups: volunteers, aortic regurgitation-tricuspid aortic valve (AR-TAV), aortic stenosis-tricuspid aortic valve (AS-TAV), aortic stenosis-bicuspid aortic valve right-left cusp fusion (BAV[RL]), and aortic stenosis-right-non cusp fusion (AS-BAV[RN]). Subjects underwent magnetic resonance angiography, with phase-contrast magnetic resonance imaging at the sino-tubular junction to define patient-specific inflow velocity profiles. Hemodynamic recordings were used alongside magnetic resonance imaging angiographic data to run patient-specific CFD. RESULTS: The BAV groups had larger mid-ascending aorta diameters (P