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The nitrogen analogues of haematoporphyrin and its derivativesForbes, Ethel January 1995 (has links)
No description available.
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Synthesis and investigation of novel material and medicinal phthalocyanine compoundsBarthelemy, Dean January 2001 (has links)
Becauseo f the importance of phthalocyaninesa s functional materials and in medicine their synthesis and applications have been well documented in the literature. In the introductory chapter (chapter 1) a brief account of preparative methods and applications is outlined. Photodynamic therapy (PDT) is becoming a widely investigated area of research. Phthalocyanine drug candidates for PDT have received a great deal of interest. Novel aromatic, heteroaromatic and functionalised aromatic asymmetric 3: 1 phthalocyaninesw ere synthesisede, xploiting the Suzuki cross-coupling reaction. Systematic investigation into their possible use as PDT candidates was explored in chapter 2. As a result of unexpected interactions between pyridyl functionalised 3: 1 zinc phthalocyanines, further investigation into complexes of `edge-to-face' assembliesw as undertaken.T he synthesiso f these assembliesth rough Lewis acid/base interactions between the nitrogen lone pair and a metal centre has been investigatedb y 'H NMR spectroscopy.A pplication to both phthalocyaninea nd phthalonitrile compounds produced some interesting `supramolecular' assemblies. Finally, to further exploit these interactions a photoswitchable, selfassembledm onolayer wasp repared.T he monolayerw as designedt o isomerise under irradiation with light, to facilitate an `on-off type switch, that could bind a metal centred phthalocyanine.
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Synthesis and applications of novel phthalocyanines and porphyrinsAl-Raga, Shaya Y. January 2002 (has links)
No description available.
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Fluorescence of PDT Photosensitizers for Quantitative Cancer Diagnosis and Treatment MonitoringYeh, Shu-Chi 06 February 2015 (has links)
Photodynamic therapy (PDT) has been considered a favorable approach in
certain oncology applications for its little invasiveness and better targeting
specificity compared to conventional therapies. In PDT, localized photosensitizers
can be activated by light to produce cytotoxic oxygen species. However, the
prescribed drug and light doses do not provide satisfying outcomes as the PDT
efficacy relies strongly on the interplay between localized dose factors. Therefore,
the fluorescence emission from active photosensitizers has been investigated
extensively for real-time PDT dosimetry.
This dissertation focuses on characterizing fluorescence properties of two
photosensitizers, Photofrin® and PpIX, in cellular models and discusses about their
potential clinical applications. First, we introduc time-resolve fluorescence (TRF)
of photosensitizers as a potential tool in PDT dosimetry. TRF acquires fluorescence
decay profiles and it is sensitive to drug-microenvironment interactions that occur
frequently in PDT. Therefore, it provides complementary information in addition to
fluorescence spectra that could be subject to intensity artifacts. In this dissertation,
we review TRF studies on PDT photosensitizers, and quantify TRF parameters of
Photofrin® at various subcellular locations. Moreover, analytical solutions are
developed to correct distorted TRF measurements from commonly used
time-domain data acquisition.
Second, we report a new concept – integrated detection and treatment of
Barrett’s Esophagus (BE). BE is a pre-cancerous lesion considered as a major risk
factor in developing esophageal cancers. However, early intervention of BE has
remained a challenging issue as tissue biopsy introduces significant sampling errors
and the separate procedures between diagnosis and treatment add relocation errors.
We proposed to use PpIX fluorescence to highlight morphological features at the
cellular level for quantitative classification, followed by well-characterized
treatment. Current proof-of-concept studies were performed separately, whilst the
detection and treatment can be integrated using confocal endomicroscopy
technology. Overall, these studies examine the potential benefits provided by
fluorescence of photosensitizers for cancer diagnosis and treatment monitoring. / Thesis / Doctor of Philosophy (PhD)
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Targeted Killing of Bacteria by Conjugation of a Soluble Photosensitizer to an Antimicrobial Peptide: Priniciples and MechanismsJohnson, Gregory Andrew 16 December 2013 (has links)
Antimicrobial peptides (AMPs) and photosensitizers (PS) have gained attention as potential alternatives to traditional antibiotics for the treatment of microbial infection due to the decreased likelihood for acquired resistance. However, many AMPs and PS suffer from insufficient activity, specificity, or a combination thereof. AMPs can require high concentrations for effective activity, leading to non-specific side effects and increased costs. PS, on the other hand, are quite active, but are typically hydrophobic and suffer from non-specific binding and damage to host tissues. To solve these problems, we report a novel PS-AMP construct of the soluble PS eosin Y conjugated to the selective AMP (KLAKLAK)_(2). Eosin Y has a high singlet oxygen quantum yield, which is suitable for photodynamic activity, although the solubility of eosin Y results in poor binding and activity toward membranes on its own. On the other hand, the specificity of (KLAKLAK)_(2) is high for an AMP, but could still benefit from enhanced activity at lower concentrations. The killing activity and binding specificity of eosin-(KLAKLAK)_(2) toward both bacteria and mammalian cells was assessed using microbiology, biochemistry, and fluorescence microscopy techniques. Additionally, the mechanism of eosin-(KLAKLAK)_(2) activity was investigated using liposome models to determine factors involved in binding and membrane disruption. Furthermore, novel applications of transmission electron microscopy (TEM) methods were employed to observe the photodynamic effects of eosin-(KLAKLAK)_(2) against bacteria.
The PS-AMP conjugate eosin-(KLAKLAK)_(2) displays synergistic activity between PS and AMP in model liposome systems, and is capable of killing several clinically relevant bacteria, including the multi-drug resistant Acinetobacter baumannii AYE strain. Furthermore, bacterial killing is achieved in the presence of red blood cells (RBCs) and other mammalian cell lines without significant toxicity. Liposome models reveal that the lipid composition of bacteria is a potential factor responsible for the observed binding specificity and corresponding activity. Additionally, TEM methods show that eosin-(KLAKLAK)_(2) causes extensive membrane damage to both Gram positive Staph aureus and Gram negative Escherichia coli, indicating a primary cause of cell death. A model is proposed where the activities of the PS and AMP, respectively, facilitate the activity of one another, leading to enhanced membrane disruption, and effective antibacterial activity while maintaining cell selectivity.
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Endogenous photosensitisation of pancreatic cancer cellsMesenhöller, Maike January 1999 (has links)
No description available.
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Two-photon chromophores as switches and sensitizersBoreham, Elizabeth January 2016 (has links)
Two-photon photo-activated functional molecules play key roles in a growing number of technological and biological applications as the availability of high powered, tuneable lasers increases. The development of new, strongly two-photon absorbing functional chromophores is key to the advancement of these technologies. A series of photoresponsive compounds including organic chromophores and transition metal coordination complexes were designed, synthesised and characterised by NMR, mass spectrometry, elemental analysis and X-ray crystallography. Photophysical characterisation of the compounds including electronic absorption spectroscopy, luminescence spectroscopy, luminescence lifetime studies and two-photon absorption (2PA) experiments were performed. Density functional theory (DFT) calculations were performed and supporting data are presented. Of particular interest is the use of photochromic materials to address the increasing demand for high-density data storage employing two-photon absorption for 3-dimensional control of excitation. Towards this, a series of four photochromic "push-pull" azobenzenes of donor-pie-acceptor structure containing a para-ethoxy donor substituent have been synthesized with varying strength of the acceptor group (para-NO2, CN, CO2Et, F). Kinetic studies of their one-photon photoisomerisation and thermal cis-trans isomerisation were performed in solution and in polymer films, and their non-linear two-photon trans-cis photoisomerisation was demonstrated. Luminescent metal centres offer the possibility of a fluorescent read-out mechanism for optical data storage, modulated by a photochromic ligand, which may quench fluorescence in one isomer and not the other. Two photochromic pyridyl azobenzene ligands were designed and synthesised and coordinated to Re(I), Pt(II) and Ru(II) polypridyl metal centres. The trans-cis photochromism of the ligands and complexes was investigated by one- and two-photon absorption. Luminescence modulation was demonstrated via photochromism of the coordinated ligand L2 for the Re(I) tricarbonyl bipyridyl complex ReL2 which displayed enhanced emission intensity in the cis form.2PA is also of interest for biological applications due to the longer, less damaging wavelengths used at which biological tissue is more transparent. Photodynamic therapy (PDT) is a non-invasive clinical treatment for cancers where a photosensitizer is optically excited to generate cytotoxic singlet oxygen, which kills cells in the area under irradiation. Platinum group transition metal complexes have been investigated for this purpose due to their strong 2PA properties and accessible low-lying triplet states, which make them efficient triplet-triplet energy transfer agents. A new cyclometallated Ir(III) complex bearing a fluorenyl phenanthroline ligand and a related bimetallic Ir(III)-Ru(II) complex were synthesised and assessed as two-photon singlet oxygen sensitizers. The monometallic Ir(III) complex was also shown to demonstrate PDT action by altering the morphology of C6 Glioma cells under 740 nm two-photon excitation.
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Ru(ii) Diimine Complexes Chromophores For Applications In Photodynamic Therapy: Singlet Oxygen Sensitizers And Substitutionally Photolabile ComplexesJanuary 2015 (has links)
1 / Tingting Feng
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Structural Effects of Photodynamic Therapy and Bisphosphonates on Healthy and Metastatically Involved Vertebral BoneWon, Emily 03 January 2011 (has links)
The vertebral column is the most common site of skeletal metastatic development secondary to breast cancer. Multiple clinical treatments are available for spinal metastasis, including systemic bisphosphonates and radiation therapy, however the success of current treatment approaches varies considerably. Alternative treatment strategies for spinal metastatic destruction must be aimed at both reducing tumor burden and restoring mechanical stability. Photodynamic therapy (PDT) has been shown to be successful at destroying osteolytic lesions in preclinical models of breast cancer spinal metastasis. However, the clinical feasibility of PDT for spinal metastasis is dependent on its potential effects on the structural integrity of vertebral bone. This thesis aims to determine the effects of PDT alone and in combination with bisphosphonate therapy on the structural architecture and mechanical properties of healthy and metastatically involved vertebrae. PDT was shown to have a positive effect on vertebral bone structure, alone and in combination with previous bisphosphonate therapy.
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Structural Effects of Photodynamic Therapy and Bisphosphonates on Healthy and Metastatically Involved Vertebral BoneWon, Emily 03 January 2011 (has links)
The vertebral column is the most common site of skeletal metastatic development secondary to breast cancer. Multiple clinical treatments are available for spinal metastasis, including systemic bisphosphonates and radiation therapy, however the success of current treatment approaches varies considerably. Alternative treatment strategies for spinal metastatic destruction must be aimed at both reducing tumor burden and restoring mechanical stability. Photodynamic therapy (PDT) has been shown to be successful at destroying osteolytic lesions in preclinical models of breast cancer spinal metastasis. However, the clinical feasibility of PDT for spinal metastasis is dependent on its potential effects on the structural integrity of vertebral bone. This thesis aims to determine the effects of PDT alone and in combination with bisphosphonate therapy on the structural architecture and mechanical properties of healthy and metastatically involved vertebrae. PDT was shown to have a positive effect on vertebral bone structure, alone and in combination with previous bisphosphonate therapy.
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