Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2002. / On t.p. "[beta]" appears as the beta symbol. Includes bibliographical references (leaves 286-308). Also available in electronic version. Access restricted to campus users.

Μελέτες έχουν δείξει ότι το νευροστεροειδές διυδροεπιανδροστερόνη (DHEA) προστατεύουν τους νευρώνες από ανοξία και απόπτωση. Έχει επίσης αποδειχθεί ότι το DHEA ενισχύει την κινητική δραστηριότητα πιθήκων με τη νόσο του Parkinson, ενώ επίσης σε συνδυασμό με την αλλοπρεγνανολόνη προκαλεί δημιουργία νευρώνων σε αρκετά πειραματικά μοντέλα. Τα λιποσώματα είναι σφαιρικά σωματίδια αποτελούμενα από ενυδατωμένες διπλοστοιβάδες φωσφολιπιδίων οι οποίες σχηματίζονται αυθόρμητα κατά τη διασπορά λιπιδίων στο νερό, εγκλωβίζοντας υδατικό διάλυμα στο εσωτερικό τους. Οι κυκλοδεξτρίνες είναι ολιγοσακχαρίτες με ειδική δομή κώνου, που έχουν υδρόφιλη πολική επιφάνεια και μη πολική εσωτερική κοιλότητα, έχουν τη δυνατότητα να ενσωματώνουν λιπόφιλα φάρμακα στην εσωτερική τους κοιλότητα (με τη δημιουργία συμπλόκων) και να αυξάνουν την υδατική διαλυτότητά τους. Στην παρούσα μελέτη χρησιμοποιήθηκαν τρία παράγωγα του νευροστεροειδούς DHEA, που έχουν τροποποιηθεί στις θέσεις C3 και C17 με σκοπό να βελτιώσουν την αντιαποπτωτική και νευροπροστατευτική δράση τους, καθώς και την αναστολή της μετατροπής τους σε ανδρογόνα και οιστρογόνα. Τα παράγωγα αυτά είναι εξαιρετικά λιπόφιλα και έχουν μικρό μοριακό βάρος και πολύ χαμηλή διαλυτότητα, γεγονός που καθιστά αδύνατη την χορήγησή τους. Για να αντιμετωπιστεί το πρόβλημα της χαμηλής διαλυτότητας, δοκιμάστηκαν δύο μέθοδοι: (1) H παρασκευή σύμπλοκων με υδροξυ-προπυλ-β-κυκλοδεξτρίνη (HP-beta-CD), και (2) Η ενσωμάτωσν των νευροστεροειδών στη λιπιδική μεμβράνη μικρών μονοστoιβαδιακών λιποσωμάτων (SUV) διαφόρων λιπιδικών συστάσεων. Μετά από τροποποίηση μιας ειδικής τεχνικής μέτρησης των στεροειδών, υπολογίστηκαν οι συγκετρώσεις που ενσωματώθηκαν στα λιποσώματα, καθώς και στα σύμπλοκα με τη κυκλοδεξτρίνη. Οι λιποσωμικές μορφές των παραγώγων δεν είχαν την αναμενόμενη ικανότητα ενσωμάτωσης τους, με αποτέλεσμα η συγκέντρωση των λιποσωμικών διαπορών να μην είναι αρκετά υψηλή για in vivo χορήγηση. Αντίθετα η HP-β-CD έδωσε σύμπλοκα που αύξησαν την υδατική διαλυτότητα των παραγώγων θεαματικά.Τα σύμπλοκα χαρακτηρίστηκαν με διάφορες τεχνικές, για να πιστωποιηθεί ο σχηματισμός τους. Με σκοπό να παρασκευαστούν μορφές με δυνατότητα ελεγχόμενης αποδέσμευσης των στεροειδών, μελετήθηκε στο επόμενο στάδιο της διατριβής, η ανάπτυξη υβριδικών μορφών που περιλαμβάνουν τον συνδυασμό συμπλόκων κυκλοδεξτρίνης και λιποσωμάτων, δηλαδή: λιποσώματα που στην εσωτερική τους κοιλότητα εγκλωβίζουν τα υδατοδιαλυτά σύμπλοκα των παραγώγων με κυκλοδεξτρίνες. Τα υβριδικά αυτά συστήματα είχαν αυξημένη ενσωμάτωση των νευροστεροειδών σε σύγκριση με τα συμβατικά λιποσώματα και κατάλληλα χαρακτηριστικά για in vivo χορήγηση. / Studies have shown that the neuroactive steroid dehydroepiandrosterone (DHEA) protects neurons from anoxia and apoptosis. It has also been demonstrated that DHEA is able to potentiate locomotor activity of hemi – Parkinsonian monkeys, and in conjunction with allopregnanolone can induce neurogenesis in various experimental models. Liposomes are spherical particles composed of hydrated bilayers of phospholipids which are formed spontaneously during the dispersion of lipids in water, entrapping aqueous solution inside. Cyclodextrins are oligosaccharides with specific cone structure that have the ability to incorporate lipophilic drugs and increase their aqueous solubility. In the present study, three DHEA analogues were used, which have been modified at positions C3 and C17 in order to improve the antiapoptotic and neuroprotective activity, and to inhibit of their conversion into androgens and estrogens. These derivatives are highly lipophilic and have small molecular weight. In order to find a solution for their very low aqueous solubility which is a problem for their in vivo administration, two methodologies were investigated: (1) The formation of soluble complexes with hydroxy-propyl-beta-cyclodextrin (HP-β-CD), and (2) the incorporation of the steroids in the lipid bilayer of small unilamellar liposomes (SUV) of various lipid compositions. After adjusting a special measurement technique for the neurosteroids, we calculated the concentration of the neurosteroids incorporated into liposomes, as well as in complexes with the cyclodextrin.The liposomal forms of the derivatives did not have the expected integration ability, resulting in a concentration of liposomal dispersion which is not high enough for in vivo administration. On the other hand, the HP-β-CD complexes increased the aqueous solubility of the derivatives to a significant extent. The complexes were characterized by various techniques, in order to verify their existence. With the aim of preparing formulations with the ability of controlled release of steroids, we investigated in the last part of this thesis, the possibility to develop hybrid systems that consist of liposomes which entrap the highly soluble steroid-cyclodextrin complexes in their internal cavity. These hybrid systems had better integration capacity compared to conventional liposomes and were suitable for in vivo administration (for both intravenous and intravitreal administration). These hybrid systems can also ensure controlled release of the steroid analogues.

M.Sc. / The removal of organic pollutants from industrial and municipal water is a great challenge to water providers worldwide. Some of these pollutants are very toxic and pose serious health risks to both humans and animals. Additionally, the presence of organic pollutants in the water often leads to the corrosion of turbines used for power generation at power stations. This obviously makes the power generation process less efficient and thus has cost implications, especially for the end user. Besides the corrosion of turbines, organic water pollutants impact on the cost of generating clean water. To this end, municipalities and industries sourcing water from Rand Water’s treatment plants and Eskom’s power stations (coal-fired power station) may be plagued by high water costs. Geosmin and 2-MIB are detectable by the human nose at concentration levels as low as 10 ng/L. These common water pollutants and are renowned for causing bad taste and odour in drinking water. Although geosmin and 2-MIB do not pose any serious health risks to humans, they impact on the aesthetic and consumer acceptability of drinking water. Currently available technologies such as activated carbon are unable to remove these pollutants to low levels (i.e. ppb levels). In our laboratories, we have found cyclodextrin-based polyurethanes to be effective in the removal of a range of organic pollutants from water to the desired ppb levels. However, these investigations were confined to water samples deliberately spiked with specific pollutants and have not been proven with "real" water samples. We sought to integrate data accumulated in the laboratory by testing and applying these polymers on a larger scale and on real systems. Cyclodextrin (CD) polymers were employed in the removal of 2-MIB, geosmin and other organic pollutants from water. The water was sampled from a coal-fired power station and Zuikerbosch Water Treatment Plant (Rand Water). After using Solid Phase Microextraction (SPME) for the extraction of organic pollutants from the water samples the organic pollutants were identified and quantified using Gas chromatography-mass spectrometry (GC-MS). The new cyclodextrin polymer technology was compared with treatment methods currently applied at both the power station and treatment plant. To determine the environmental friendliness of this technology, polymer degradation studies were also carried out. These entailed performing soil burial tests prior to the characterization of the polymers. Thermogravimetric analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM) and Braunner Emmet Tellet (BET) analysis were used for the characterization of the polymers. The techniques were also used to determine if any degradation modifications occurred on the polymeric material. The findings of the study are summarized below: • SPME extraction and GC-MS analyses of geosmin, 2-MIB and other pollutants were successfully accomplished. • The cyclodextrin polymers were effective in the removal of geosmin and 2-MIB (up to 90%) from water sampled at Zuikerbosch water treatment plant. The polymers remained effective (90%) in the absorption of geosmin and 2-MIB even when the water samples were spiked with a competing pollutant (i.e. humic acid). Activated carbon has been noted to have reduced adsorption capacity when humic acid is present in water. • The polymers demonstrated the ability to remove as much as 90% of organic pollutants from raw water compared to the 50% removed by the polyelectrolyte and optimum minimal polyaluminium chloride employed at the coal-fired power station. Analyses of the samples using TOC before and after treatment were accomplished. Reduction in the TOC was noted at the different sampling points after Eskom’s water treatment regime. • Results from the study indicated that the β-CD TDI polymers underwent a greater weight-loss during soil burial when first digested in sulphuric acid (ca. 50% maximum mass loss). On the other hand, β-CD HMDI polymers appeared to be unaffected by predigestion and experienced the same amount mass loss for the digested and undigested polymers (ca. 30% maximum mass loss). SEM studies revealed changes in the surface morphology of the polymers. Moreover, thermogravimetric analysis (TGA) gave an indication of polymer degradation under all soil burial conditions the polymer was subjected to.

Lau, Ting Fong Janet. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references. / Abstracts in English and Chinese. / Abstract --- p.iii / Abstract (in Chinese) --- p.v / Acknowledgment --- p.vii / Table of Contents --- p.ix / List of Figures --- p.xiii / List of Tables --- p.xix / List of Schemes --- p.xxi / Abbreviations --- p.xxiii / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- General --- p.1 / Chapter 1.1.1 --- History of Phthalocyanines --- p.1 / Chapter 1.1.2 --- General Synthesis --- p.2 / Chapter 1.1.3 --- Properties and Usage of Phthalocyanines --- p.8 / Chapter 1.2 --- Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy --- p.9 / Chapter 1.2.1 --- Photophysical and Biological Mechanisms of Photodynamic Therapy --- p.10 / Chapter 1.2.2 --- Photosensitizers in Photodynamic Therapy --- p.13 / Chapter 1.2.2.1 --- First-Generation Photosensitizers --- p.13 / Chapter 1.2.2.2 --- Second-Generation Photosensitizers --- p.16 / Chapter 1.2.2.3 --- Phthalocyanine-Based Photosensitizers --- p.20 / Chapter 1.3 --- An Introduction on Supramolecular Chemistry --- p.27 / Chapter 1.3.1 --- Phthalocyanine-Based Supramolecular Systems --- p.28 / Chapter 1.3.2 --- Mixed Porphyrin-Phthalocyanine Supramolecular Assemblies --- p.31 / Chapter 1.4 --- Cyclodextrins as Building Blocks for Supramolecular Structures --- p.38 / Chapter 1.4.1 --- Background of Cyclodextrins --- p.38 / Chapter 1.4.2 --- Phthalocyanine-Cyclodextrin Supramolecular Systems --- p.41 / Chapter 1.5 --- Objectives of This Study --- p.47 / Chapter 1.6 --- References --- p.47 / Chapter Chapter 2 --- Permethylated β-Cyclodextrin Disubstituted Silicon(IV) Phthalocyanines / Chapter 2.1 --- Introduction --- p.55 / Chapter 2.2 --- Results and Discussion --- p.57 / Chapter 2.2.1 --- Preparation and Characterization --- p.57 / Chapter 2.2.2 --- Electronic Absorption and Photophysical Properties --- p.62 / Chapter 2.2.3 --- In vitro Photodynamic Activities --- p.66 / Chapter 2.3 --- Conclusion --- p.73 / Chapter 2.4 --- Experimental Section --- p.73 / Chapter 2.4.1 --- General --- p.73 / Chapter 2.4.2 --- Photophysical Measurements --- p.74 / Chapter 2.4.3 --- Synthesis --- p.75 / Chapter 2.4.4 --- Cell Lines and Culture Conditions --- p.83 / Chapter 2.4.5 --- Photocytotoxicity Assay --- p.83 / Chapter 2.4.6 --- ROS Measurements --- p.84 / Chapter 2.4.7 --- Microscopic Studies --- p.85 / Chapter 2.4.8 --- Subcellular Localization Studies --- p.85 / Chapter 2.5 --- References --- p.86 / Chapter Chapter 3 --- Unsymmetrically Substituted β-Cyclodextrin-Appended Silicon(IV) Phthalocyanines / Chapter 3.1 --- Introduction --- p.89 / Chapter 3.2 --- Results and Discussion --- p.90 / Chapter 3.2.1 --- Preparation and Characterization --- p.90 / Chapter 3.2.2 --- Electronic Absorption and Photophysical Properties --- p.94 / Chapter 3.2.3 --- In vitro Photodynamic Activities --- p.98 / Chapter 3.3 --- Conclusion --- p.107 / Chapter 3.4 --- Future Work --- p.108 / Chapter 3.5 --- Experimental Section --- p.108 / Chapter 3.5.1 --- General --- p.108 / Chapter 3.5.2 --- Synthesis --- p.109 / Chapter 3.6 --- References --- p.114 / Chapter Chapter 4 --- Construction of Mixed Phthalocyanine-Porphyrin Systems through Host-Guest Interactions in Aqueous Media / Chapter 4.1 --- Introduction --- p.117 / Chapter 4.2 --- Results and Discussion --- p.119 / Chapter 4.3 --- Conclusion --- p.132 / Chapter 4.4 --- Experimental Section --- p.132 / Chapter 4.5 --- References --- p.133 / Appendix A Determination of Binding Constants --- p.135 / Appendix B 1H and 13C{1H} NMR Spectra --- p.137 / Appendix C Mass Spectra --- p.151

Thesis submitted to the Division of Veterinary and Biomedical Sciences. Bibliography: leaves 237-283.

Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. Since it is believed that OxC blocks the removal of normal cholesterol from cells in the artery wall, it is possible that selective removal of OxC in the vessel wall in-vivo may prevent or reverse atherosclerosis.As a prelude to major studies, this research project was designed to answer two critical questions; 1/. What is the best route for delivery of CD. 2/. How do animals (apoE-/- mice) tolerate it. Pilot studies were established and results noted. These studies have provided valuable information in the apoE-/- mouse for subsequent studies to prevent or reverse atherosclerosis in this animal model. / Master of Science (Hons)

No description available.

A series of novel [2]rotaxanes of general formula 1 has been synthesised, exploiting the hydrophobic effect to cause binding inside α- or β-cyclodextrin cavities, and making use of Suzuki coupling to stopper the rotaxane. The size complementarity of the dumbbell and cyclodextrin units was investigated. The rotaxanes were characterised by use of 2D NMR techniques and, in one case, by X-ray crystallography. The reactivity of one such rotaxane (α-cyclodextrin, stilbene core and carboxylic acid stoppered) was investigated by comparison with the corresponding dumbbell. The presence of the cyclodextrin was shown to have a protective influence towards some reactants. The absorption and emission properties of these rotaxanes were compared. We have demonstrated an increase in the fluorescence quantum yield by up to a factor of three. The photo-induced isomerisation of all the stilbene-based rotaxanes and dumbbells synthesised was surveyed; in one case it was found that encapsulation had completely prevented this isomerisation. A quantitative investigation of the proportions and extinction coefficients of the trans and cis isomers of one rotaxane in the photostationary state was undertaken, and the quantum yields of switching deduced. The rate of photodegradation and the ultimate products of this were investigated. The major photoproduct in both cases arose through photo-induced hydration of the stilbene double bond. The final chapter is concerned with attempts to synthesise rotaxanes by reaction of a 1,3,5-triazine with an azo dye (2). Related rotaxanes have been successfully prepared in the past^1-3 , however in this instance the attempts did not result in significant amounts of rotaxane formation. This was rationalised by the shorter length of the dye. The thesis as a whole illustrates the stabilisation of chromophores that is possible through the formation of rotaxanes.

Copy of author's previously published article inserted. / Includes bibliographies / vi, 230 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis studies the B-cyclodextrins which are modified at the primary rim to incorporate an additional coordination or hydrophobic recognition site. The natural organic host, cyclodextrin and its chemically modified derivatives, are utilised as hosts for the inclusion of a range of guests. The study contributes to understanding the fundamental factors influencing selectivity of binding and the stability of the complexes formed when a guest is bound essentially at two recognition sites. / Thesis (Ph.D.)--University of Adelaide, Dept. of Chemistry, 1996

Thesis (Ph. D.)--University of Adelaide, Dept. of Physical and Inorganic Chemistry, 1985. / Offprints of two author's journal articles inserted at end of the v. Includes bibliographical references (leaves 10-12).