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Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers
Kollár, Jan ; Zimčík, Petr (advisor) ; Mosinger, Jiří (referee) ; Zitko, Jan (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mgr. Jan Kollar Supervisor: prof. PharmDr. Petr Zimcik, Ph.D. Advisor: doc. PharmDr. Veronika Novakova, Ph.D. Doctoral Thesis: Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers Phthalocyanines (Pcs) and their aza-analogues (e.g. tetrapyrazinoporphyrazines, TPyzPzs) represent a promising group of organic dyes with interesting photophysical properties (strong absorption in area 650-750 nm, strong singlet oxygen production) highly suitable for the use in photodynamic therapy (PDT) of cancer. However, they have also some drawbacks lowering their potential use in PDT (low solubility in water, strong tendency to aggregate). The topic of my dissertation thesis closely follows the topic of my diploma thesis, during which TPyzPz with sixteen carboxylate groups in rigid arrangement was prepared and in which we have disclosed strong negative effect of low pH and serum proteins on photodynamic activity. In the first part of this thesis I prepared new zinc TPyzPz with eight sulfonate groups on periphery, which was characterised by good solubility in water. Sulfonates were chosen as stronger acids than carboxylic groups, so they were...
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Nanofiber membranes generating singlet oxygen with magnetic separation
Liška, Vojtěch ; Mosinger, Jiří (advisor) ; Kubíček, Vojtěch (referee)
This thesis focuses on the preparation and study of a new type of photoactive polyurethane nanofiber membrane with encapsulated 5,10,15,20-meso-tetraphenylporphyrin (TPP) photosensitizer and maghemite nanoparticles. The membrane was prepared by electrospinning and shows effective photogeneration of O2 (1 Δg) and photoantibacterial effect on the surface. The membrane can be easily separated by a magnetic field. The magnetic behaviour of the maghemite nanoparticles was studied using Mössbauer spectroscopy. Their size was estimated by DLS. The final nanofiber membrane was characterized by UV-VIS, emission spectroscopy, and by electronic microscopy (SEM). The kinetics of O2 (1 Δg) generation was studied by time-resolved spectroscopy and the relative efficiency of photooxidation was studied using external acceptor of O2 (1 Δg). Significant photoantibacterial properties against bacteria strain Escherichia coli were detected on the surface of the membrane functionalized with TPP photosensitizer.
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Polymer nanoparticles generating singlet oxygen
Berzédiová, Veronika ; Mosinger, Jiří (advisor) ; Tyrpekl, Václav (referee)
This theses focuses on preparation and characterisation and comparison of two types of polymer nanoparticles using photophysical methods. The first type was polystyrene nanoparticles prepared by modified nanoprecipitation method from polymeric sulfonated nanofiber membranes with diffrent content of sulfonated groups. The second type was polymer nanoparticles with diferent lenght of hydrophobic polycaprolactone (PCL) and hydrophilic poly(ethyleneglycol) (PEG) blocks. Both types of nanoparticles conteined encapsulated photosensitizer 5,10,15,20-meso-tetraphenylporphyrin with a high quantum singlet oxygen yield. In the prepared nanoparticles with a photosensitizer, the kinetics of singlet oxygen generation was studied using time resolved spectroscopy. The relative efficiency of photooxidation was studied using external akceptor of singlet oxygen. The effect of temperature, size and matrix (type of polymer) of nanoparticles on photooxidation efficiency was also studied. In the next part of this these was studied the influence of time on the size and stability of nanoparticles and also the effect of solution pH and ionic strength on prepared nanoparticles.
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Functionalized Polystyrene Nanomaterials for Biomedicinal Applications
Dolanský, Jiří ; Mosinger, Jiří (advisor) ; Dědic, Roman (referee) ; Zimčík, Petr (referee)
Nowadays, there is an increasing risk of bacterial infections from bacteria strains resistant towards antibiotics. Thus, it is of utmost importance to research novel therapies which can overcome this difficulty. The presented thesis focuses on the preparation, characterization and antibacterial evaluation of polystyrene polymer nanomaterials (nanofiber membranes and nanoparticles) modified with compounds that can efficiently inhibit bacterial growth either by their nature (polyethyleneimine) or by photoactivation upon visible light excitation (NO- photodonors, photosensitizers) and consequent production of highly reactive inorganic bactericidal species, nitric oxide (NO) and singlet oxygen (O2(1 g)). All materials were fully characterized by several independent methods. The concentrations of NO and O2(1 g) were measured by amperometric and time-resolved spectroscopic techniques and by variety of chemical analytic procedures. Due to the presence of bactericidal species and the efficient photogeneration of NO and O2(1 g) at physiological conditions, all materials exhibit strong antibacterial action tested on a Gram-negative bacterial strain Escherichia coli. Hence, these functionalized polymer nanomaterials may be intriguing systems for medical-, biological-, or environmental- application where a...
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Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Řezáčová, Martina (referee) ; Mosinger, Jiří (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of biochemical sciences Candidate Mgr. Miloslav Macháček Supervisor doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer. Photodynamic therapy (PDT) of cancer is non-invasive treatment modality for solid tumour treatment using three basic components - molecular oxygen, light and photosensitizer (PS). These elements are essentially non-toxic on their own, but in the combination they induce reactive oxygen species (ROS; singlet oxygen mainly) production, causing damage to cellular components and subsequent cell death. Type of cell demise is dependent mainly on the type of PS, length of irradiation and subcellular localization of the drug. Singlet oxygen is highly reactive and is capable of limited diffusion in biological environment. Apart from direct cytotoxic effect, vascular shutdown (oxygen and nutrition deprivation) and activation of immune system are involved in tumour eradication. Combination of effective compound with delivery system, conjugation with targeting substances or synthesis of highly effective non-aggregating water soluble compounds are the main pathways in design of modern PSs. In our...
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Complexes of aminoalkylphosphineoxides
Mészáros, Bence ; Kubíček, Vojtěch (advisor) ; Mosinger, Jiří (referee)
Title: Comlpexes of aminoalkylphosphineoxides Author: Bence Mészáros Department: Department of Inorganic Chemistry, Faculty of Science UK Supervisor: doc. RNDr. Vojt ch Kubí ek, Ph.D. Supervisor's e-mail address: kubicek@natur.cuni.cz Three selected aminoalkylphosphine oxides were synthesized: Aminomethyl(diphenyl)phosphine oxide, N-piperidylmethyl(diphenyl)phosphine oxide, N,N-diethylaminomethylbis(hydroxomethyl)phosphine oxide. All prepared substances were characterized by NMR spectroscopy and mass spectrometry. The aminomethyl(diphenyl)phosphine oxide and N-piperidylmethyl(diphenyl)phosphine oxide were obtained in the solid state as single crystals and their structure was determined by X-ray analysis. Acid-base and complexing properties of the studied compounds were studied by potentiometric titration and NMR titration. Protonation constants of all three compounds were obtained, stability constants were not determined because of the low solubility of the complexes in water or low stability of the complexes. The structure of the aminomethyl(diphenyl)phosphine oxide complex with Cu2+ was determined by X-ray analysis. Keywords: complexes, organophosphorus synthesis, phosphine oxides, acid-base and complexation properties
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Polystyrene photoactive nanomaterials producing singlet oxygen
Henke, Petr ; Mosinger, Jiří (advisor) ; Dědic, Roman (referee) ; Kolářová, Hana (referee)
The increasing number of multidrug-resistant strains of bacteria call for alternatives to antibiotic therapy and, more generally, for the antimicrobial material as a component of prevention. Of particular interest is the photodynamic inactivation of bacteria and other pathogens caused by photogenerated singlet oxygen. This work is focused on the field of photoactive polymer nanofiber membranes and nanoparticles, generating singlet oxygen, suitable for medical applications. We prepared different types of photoactive modified polystyrene nanofiber membranes with encapsulated or externally bound porphyrin photosensitizers. These materials efficiently produce highly reactive and cytotoxic singlet oxygen capable of restricted diffusion into to the external environment. Our results demonstrate the crucial role of wettability for materials of this type with a short diffusion length of generated singlet oxygen, illustrate the effect of temperature and indicate their potential use as multifunctional materials. Due to their antimicrobial properties, these materials are suitable alternative to antibiotics and local antiseptics. With good breathability and short diffusion length of singlet oxygen good results can be expect in in vivo tests. From these nanofiber materials we also prepared photoactive extremely...
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Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Řezáčová, Martina (referee) ; Mosinger, Jiří (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of biochemical sciences Candidate Mgr. Miloslav Macháček Supervisor doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer. Photodynamic therapy (PDT) of cancer is non-invasive treatment modality for solid tumour treatment using three basic components - molecular oxygen, light and photosensitizer (PS). These elements are essentially non-toxic on their own, but in the combination they induce reactive oxygen species (ROS; singlet oxygen mainly) production, causing damage to cellular components and subsequent cell death. Type of cell demise is dependent mainly on the type of PS, length of irradiation and subcellular localization of the drug. Singlet oxygen is highly reactive and is capable of limited diffusion in biological environment. Apart from direct cytotoxic effect, vascular shutdown (oxygen and nutrition deprivation) and activation of immune system are involved in tumour eradication. Combination of effective compound with delivery system, conjugation with targeting substances or synthesis of highly effective non-aggregating water soluble compounds are the main pathways in design of modern PSs. In our...
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