Browsing by Subject "Endoperoxide"

Now showing 1 - 6 of 6

Open Access
Chemical modulation of singlet oxygen generation rates in thermal endoperoxide decomposition & novel fluorescent sensors for hyperphosporylated tau proteins
(2016-05) Kaya, Cansu
Chemical control over singlet oxygen generation is an open to improvement because of the importance of this reactive species in biological systems. In the first project, we aimed to synthesize a silylated 1,4-dimethylnaphthalene endoperoxide derivative which is expected to release singlet oxygen on thermolysis at a relatively slow rate at room temperature. Upon the deprotection of the silyl units with fluorine ions, it is expected it to release singlet oxygen at a much higher rate, giving rise to a control over the release of the product. The absorption and the fluorescence measurement with a trap molecule which consumes the generated singlet oxygen reveals promising results for the future work for the control of singlet oxygen generation rates. In the second part of this thesis, we focused on the synthesis of a novel fluorescent sensor of a BODIPY derivative which is capable of sensing Zinc cations. The zinc complex is also expected to have a further usage for the sensing of hyperphosphorylated tau proteins, which are commonly produced in the brains of people with Alzheimer’s disease. With this, it has a potential usage in the field of early detection of Alzheimer’s disease.
Open Access
Iron oxide/silica core-shell nanoparticles as rechargeable sources of singlet oxygen for synthetic applications
(2017-04) Yıldız, Deniz
In the rapidly developing world ofsynthetic chemistry, there is aconstant need for high-efficient catalyst. Besides this, reusable and easily removable catalysts are highly desired to reduce costs for environmentally friendly synthesis for both synthetic and manufacturing requirements. Magnetic nano particles (MNPs) are promising candidates for effortlessly removable structures due to their ability of being removed by magnetic field. Iron oxide nano particles have a well distin- guished place among MNPs since they have unique properties and they can be prepared and functionalized easily. Combination of photo sensitizers with MNPs is a new approach forsynthetic applications due to the fact that singlet oxygen is a reactive specie for various types of reactions. Herein, BODIPY with2-pyridone moiety on silica coated iron oxide nanoparticle is designed as a magnetically remov able nanostructure that cangenerate, store and release singlet oxygen. The efficiency is studied by the oxidation of organic sulfides to sulfoxides since they are at the core of many biological processes. Furthermore, thisdesign can produce recyclable and reusable catalysts for additional transformations with high efficieny.
Open Access
Pyramidalized double bonds containing endoperoxide linkages: photooxygenation of dimethyl cis-3,8-dihydroheptalene-3,8, dicarboxylate
(American Chemical Society, 1999) Saraçoǧlu, N.; Menzek, A.; Sayan, Ş.; Salzner, U.; Balci, M.
Diels-Alder cycloaddition utilizing singlet oxygen as the dienophile with dimethyl cis-3,8-dihydroheptalene-3,8-dicarboxylate (5) has been investigated, and monoaddition product 7 has been isolated. The addition of a second singlet oxygen to the cycloheptatriene unit in 7 gave syn- bis(norcaradiene) bis(endoperoxide) 4. 1H NMR spectral studies and theoretical calculations indicate the increased pyramidalization in syn-4 compared with carbon analogue. The increased pyramidalization results from hyperconjugation between the central π-bond and the four adjacent C-O bonds and by rehybridization at C3, C4, C5, and C6. Furthermore, the increased reactivity for syn-4, which is probably arising from further folding of the central double bond, is also in agreement with theoretical calculations.
Open Access
Targeted photosensitizers and controlled singlet oxygen generation for therapeutic applications
(2018-12) Uçar, Esma
Photodynamic therapy of cancer plays a pivotal role due to its many superior features and potential. Considering the pathways for improving the practice of PDT of cancer is gradually increasing, enhancing the selectivity of photodynamic action is an obvious choice. Being the source of reactive oxygen species in the body, mitochondrion is one of the most proper organelles to target. There is plethora of findings suggesting that triphenlyphosphonium cation is a very favorable mitochondria targeting agent. Another aspect of PDT requires creation of smart molecules which respond to either the increased temperature or ion concentrations in order to release 1O2. Cyclic endoperoxides of naphthalene and anthracene could help in achieving the desired objective of storing 1O2 and regenerating it again when appropriate conditions meet. The half-life cycloreversion of 1,4-Dimethylnaphthalene could be changed at least 100-fold when 2-position of the naphthalene is sterically hindered. Taking advantage of the fact that fluoride ions’ silicophile nature, a novel perspective for drug design can be proposed. In the final project, a certain level magnetic hyperthermia, large enough to cause endoperoxide cycloreversion, but not large enough to cause necrotic death, is being sought after. Controlled generation singlet oxygen by the application of tissue penetrating alternating magnetic fields is the ultimate goal for that project.
Open Access
Towards mechanochemical generation of singlet oxygen
(2018-12) Aydonat, Simay
Singlet oxygen is a short-lived reactive species which is involved a number of biochemical processes and implicated as the primary photo-generated cytotoxic agent in photodynamic therapy (PDT) of cancer. Precise chemical control of singlet oxygen generation and or storage is therefore of immense interest. In this particular study, the possibility of mechanochemical release of singlet oxygen in cross-linked polymers carrying anthracene 9,10-endoperoxides was explored. 9,10-Diphenylanthracenes are stable at room temperature but undergo thermal cycloreversion when heated to produce singlet oxygen. Thus, a cross-linked polyacrylate was synthesized, incorporating anthracene-endoperoxide modules with chain extensions at the 9,10-positions. Previously in our lab, thermal lability of the anthracene endoperoxides were shown when attached to gold nanorods. In this work, it was demonstrated that on mechanical agitation in a cryogenic ball mill, fluorescence emission due to anthracene units in the polymer is enhanced, with a concomitant generation of singlet oxygen as proved by detection with a selective probe, SOSG. Also, a cross-linked polyacrylate and a PDMS elastomer incorporating anthracene-endoperoxide modules with chain extensions at the 9,10-positions were synthesized as the polymeric matrix for a better manifestation of mechanochemical process.
Open Access
Towards therapeutic automata and hypoxia activated singlet oxygen generators
(2019-08) Ayan, Seylan
Photodynamic therapy (PDT) is a treatment modality depends on the efficient generation of singlet oxygen (1O2) through excitation of a particular chromophore (sensitizer) followed by an energy transfer to the dissolved oxygen in tumor tissues. Cytotoxic singlet oxygen and other secondary products (reactive oxygen species, ROS) are responsible for the apoptotic and necrotic deaths of the tumor cells. We present a molecular 1:2 demultiplexer (DEMUX) which acts as a "terminator" automaton: once powered up by photoexcitation, the agent releases singlet oxygen to kill cancer cells. Once the cancer cells start apoptosis, the agent interacts with the exposed phosphatidylserines on the external leaflet, and autonomously switches to the signaling mode, turning on a bright emission signal, and turning off singlet oxygen generation. So, the output can switch between singlet oxygen and a confirmatory fluorescence emission for apoptosis, which are mutually exclusive in this design. The automaton that we present here, is based on logic gate considerations and a sound photophysical understanding of the system, and should be a very convincing case of molecular logic with a clear path of progress towards practicality. In another project, we are very much interested in transforming PDT into a more manageable and broadly applicable therapeutic protocol. Our approach to achieve that is to separate photosensitization event from the delivery of singlet oxygen, which is the primary cytotoxic agent of PDT. Thus, a storage compound (endoperoxide) for singlet oxygen has to be designed, which can react with molecular oxygen under typical photosensitization conditions, and then the metastable compound has to be transferred to the tumor site which would release its cargo in response to a chemical or enzymatic cue. This approach assumes that singlet oxygen produced stoichiometrically (as opposed to catalytically through photosensitization) by the chemical transformation of the carrier molecule, would be enough to trigger apoptotic response in cancer cells.