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1
Rai, Prabin. "Design and synthesis of fluorescent probes." Thesis, Kent State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3618852.
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The fundamental objective of this project is to design, synthesize, and characterize fluorescent dyes, which may be utilized in super resolution imaging techniques. In Chapters 1, 2 and 3, we concentrated on photoswitchable rhodamine dyes. We synthesized several rhodamine dyes and increased their water solubility, installed a bioconjugation unit and, more importantly, we optimized the absorption properties (close to 400 nm) of the rhodamine spirolactams in their closed state and studied their basic photophysical properties as well. In Chapter 4, we synthesized azido-DCDHF fluorogens that can be converted to the bright state after a 1,3-dipolar cycloaddition reaction between an azide-Ph-DCDHF and a strained alkene. We synthesized some strained alkenes, which may speed up the kinetics in 1,3-dipolar cycloaddition. This chemical method of turning the dyes from dark to bright state is a new dimension in the bioconjugation arena. In Chapter 5, we synthesized Nile red derivatives which can switch to a bright state from a dark state by collision on the cell surface utilizing PAINT methodology. We expected that the design of new Nile red derivatives may have better properties than the parent Nile red. Besides the PAINT technique, we worked on some active control of emission by enzymatic cleavage of fluorescent dyes in a dark state to the bright state, which can be utilized in super resolution imaging. Related to the 1,3-dipolar cycloaddition reaction between azido-DCDHF and norbornene, we have examined recently popularized tetrazine chemistry. We linked pyridyl tetrazines to DCDHF with short spacer. In Chapter 6, we describe the preparation of co-crystals between perfluorophenazine and several polynuclear aromatic compounds/polynuclear heteroaromatic compounds. In Chapter 7 we describe the preparation of some partially fluorinated heteropolynuclear aromatic compounds such phenzaine and acridine class of compounds for possible use in organic semiconductors.
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Rai, Prabin. "Design and Synthesis of Fluorescent Probes." Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1375091914.
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Davenport, Eric Parker. "Fluorescent Probes to Investigate Homologous Recombination Dynamics." DigitalCommons@USU, 2016. https://digitalcommons.usu.edu/etd/5007.
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There are multiple mechanisms by which DNA can become damaged. Such damage must be repaired for the cell to avoid ill-health consequences. Homologous recombination (HR) is a means of repairing one specific type of damage, a double-strand break (DSB). This complex pathway includes the Rad51-DNA nucleoprotein filament as its primary machinery. Current methodology for studying HR proteins includes the use of fluorescently labeled DNA to probe for HR dynamics. This technique limits the number of proteins that can be involved in experimentation, and often only works as an end reporter. The work here aims at improving upon standard techniques by creating two fluorescent protein probes. The first probe was developed by directly attaching a fluorophore to Saccharomyces cerevisiae Rad51 with the use of click chemistry and the incorporation of unnatural amino acids. This probe could function as a primary reporter on the formation and dissociation of the Rad51-DNA filament in the presence of pro- and anti- HR mediator proteins. The second probe was created by labeling the exterior cysteine residues of Plasmodium falciparum single strand DNA binding protein (SSB) with a fluorophore via maleimide chemistry. This probe acts as a secondary reporter for HR dynamics by signaling for when free single stranded DNA (ssDNA) is available.
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Sánchez, Cid Antonio Alberto. "Organophosphorus compounds as fluorescent probes for cell imaging." Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/4043.
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Small molecules containing fluorescent moieties can be used as a means of studying cell structure and function, as a result of the high sensitivity of fluorescence microscopy. This technique allows one to obtain specific information about the cell and has recently attracted considerable interest by many research groups. This work presents three projects in which the main aim was to develop multi-modal imaging agents. They will possess a fluorescent group and also another moiety which provides predictable biological properties. Our interest is centred on two types of fluorophore: Polycyclic Aromatic Hydrocarbons (PAHs) and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY). The first project describes the synthesis of the phosphorus analogues of the biologically-active indazole core which remain rare in the literature. The synthesis presented here shows the versatility of our approach and allows for substitution on the phenyl ring of the newly formed phosphindole core simply by changing the nitrile used. Position 3 of the phosphindoles was also varied to bear different aromatic groups; the chosen aromatic systems were phenyl, naphthyl and anthracyl. These were chosen in order to prepare a fluorescent and biologically-active core. In practice, the phosphindoles showed near zero quantum yields. Photoinduced Electron Transfer and Dexter Energy Transfer seem to be the plausible responsible phenomena behind this lack of fluorescence. Temperature was found to be a key variable in the synthesis of phosphindoles since a temperature below 110 °C in the last step led to the formation of two chlorothiophosphonates. One of these unexpected chlorothiophosphonates showed strong activity against Bacillus subtilis and Streptococcus pyogenes. The second project describes the synthesis of the pyrene-based ligand 109, which is significant as it was based on an air-stable alkyl primary phosphine. This remarkable stability is provided by the electronic properties that both the pyrene and the butyl linker ii confer on the corresponding primary phosphine. The tridentate ligand 109 was obtained following a double hydrophosphination reaction of the primary phosphine, and 109 was subsequently used to create complexes with the transition metals from groups 9 and 10. These demonstrated demonstrated weak fluorescence despite the presence of a metallic core. The presence of the DNA intercalating pyrene unit and the presence of the square-planar Pt centre in complex 116 required an assessment of the cytotoxicity of the complex. In assays, 116 was shown to exert similar cytotoxicity towards bone osteosarcoma (U2OS) and transformed mammary cancer (HMLER) cell lines as the anticancer drug Cisplatin. The advantage of complex 116 is that it contains an intercalating function, a potential cytotoxic platinum centre and moderate/mild loss of fluorescence for cell imaging by optical microscopy. The final project discussed in this thesis is the synthesis of a phosphonium salt containing BODIPY as fluorophore, bound to a macrocycle which is able to undergo complexation reactions with d-block metals. This is another example of a molecule capable of multi-modal functionality, since phosphonium salts have been shown to target mitochondria. Positively charged compounds freely diffuse across the negatively charged mitochondrial membrane and the BODIPY moiety allows for imaging of the compound’s fate by optical microscopy. Finally, the tetraamine macrocycle of the molecule allowed ligand 154 to be reacted with [Cu(OAc)2] which gave the fluorescent Cu(II) complex 155. This complex is interesting because it proves that coorduination to Cu is possible. The next step in this research would be to prepare the 64Cu analogue, which would be a candidate for Positron Emission Tomography (PET) imaging. In this manner, 64Cu-154 would be a fluorescent organelle-specific PET imaging agent.
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Valente, John Vic. "Synthetic studies towards potential lead(II) specific fluorescent probes /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phv154.pdf.
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Rami, H. "A study of potential fluorescent probes for hypoxic cells." Thesis, Brunel University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377946.
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Dempsey, Graham Thomas. "Photoswitchable Fluorescent Probes for Localization-Based Super-Resolution Imaging." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10376.
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In recent years, localization-based super-resolution imaging has been developed to overcome the diffraction limit of far-field fluorescence microscopy. Photoswitchable probes are a hallmark of this technique. Their fluorescence can be modulated between an emissive and dark state whereby the sequential, nanoscale measurement of individual fluorophore positions can be used to reconstruct an image at higher spatial resolution. Despite the importance of photoswitchable probes for localization-based super-resolution imaging, both a mechanistic and quantitative understanding of the essential photoswitching properties is lacking for most fluorophores. In this thesis, we begin to address this need. Furthermore, we demonstrate the development of new probes and methodologies for both multicolor and live-cell super-resolution imaging. Chapter 2 describes our mechanistic insights into the photoswitching of a common class of dyes called carbocyanines. Red carbocyanines, such as Cy5, enter a long-lived dark state upon illumination with red light in the presence of a primary thiol. We show that the dark state is a covalent conjugate between the thiol and dye and that this dark state recovers by illumination with ultraviolet light. We also speculate on possible reactivation mechanisms. Our mechanistic studies may ultimately lead to the creation of new probes with improved photoswitching properties. Chapter 3 details our quantitative characterization of the photoswitching properties of 26 organic dyes, including carbocyanines and several other structural classes. We define the essential properties of photoswitchable probes, including photons per switching event, on/off duty cycle, photostability, and number of switching cycles, and demonstrate how these properties dictate super-resolution image quality. This rigorous evaluation will enable more effective use of probes. In Chapters 4 and 5, we focus on expanding the super-resolution toolbox with novel strategies for multicolor and live-cell imaging. Chapter 4 discusses two approaches we have developed for multicolor super-resolution imaging, which distinguish probes based on either the color of activation or emission light. These tools allow multiple cellular targets to be resolved with high spatial resolution. Lastly, Chapter 5 introduces a method for targeted cellular labeling with photoswitchable probes using a small peptide tag, as well as a new sulfonate-protection strategy for intracellular delivery of high performing photoswitchable dyes.
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Lister, Francis George Alexander. "Fluorescent probes of conformational signal relay in membrane environments." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/fluorescent-probes-of-conformational-signal-relay-in-membrane-environments(baa2cddd-94a1-4505-bf45-13403e0a6548).html.
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G-Protein Coupled Receptors (GPCRs) are a class of membrane-bound receptor proteins capable of relaying a biological signal across a cell membrane through a solely conformational change in their transmembrane domain. Previous work has shown that helical foldamers composed of achiral monomeric units can be used in an analogous manner to relay stereochemical information on the nano-scale through the conformational control of screw-sense preference. While this work has produced some highly successful examples of signal relay, mimicking the function of GPCRs, its reliance on screw-sense responsive NMR probes has restricted further development into membrane environments. This thesis describes the successful development of a pyrene based screw-sense responsive fluorescence probe and its subsequent use in the development of a series of membrane-based GPCR mimics. This thesis has also details the preliminary steps towards the development of light-responsive controllers of screw-sense preference for nano-scale signal relay devices.
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Hester, Jeffrey D. "Nitroxide-labeled oligonucleotides as hybridization probes a comparative study between nitroxide- and fluorescent-labeled probes /." Cincinnati, Ohio : University of Cincinnati, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=ucin.
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Hester, Jeffery Dean. "Nitroxide-Labeled Oligonucleotides as Hybridization Probes: A Comparative Study Between Nitroxide- and Fluorescent-Labeled Probes." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1069433831.
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Ghorbanian, Shohreh. "Studies of potentially useful thiol-reactive fluorescent probes and novel ion-responsive fluorescent quinoxalinone derivatives." Thesis, Brunel University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360815.
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Exton, S. P. "Synthesis and characterisation of novel luminescent probes." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368774.
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Goolamali, Zia. "The design, synthesis, and spectral properties fluorescent probes for potassium." Thesis, Brunel University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357110.
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Rice, Jason. "The detection and identification of nanoflagellates using fluorescent oligonucleotide probes." Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295749.
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Lindberg, Max. "Fluorescent fusion proteins as probes to characterize tau fibril polymorphism." Thesis, Linköpings universitet, Kemi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-158263.
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Alzheimer's disease (AD) is a large and growing problem and while we today lack a full understanding of this disease, we know that the protein tau and the amyloid fibrils it forms play a central role in its development. We also know that these fibrils can have different morphologies in different diseases and that fibrils produced in vitro not necessarily adopt any of the morphologies found in patients. This means there is a need for more pathologically relevant fibrils in vitro to be able to understand this disease better. One approach to satisfy this need is to use fibrils found in patients as seeds and thus transfer their morphology to recombinantly purified protein. To facilitate this process this study has attempted to develop a way to differentiate between different fibril morphologies using a FRET based system. This involves fluorescent fusion proteins (tau-EXFPs) and fluorescent amyloid probes as well as seeding experiments with pseudo wild type tau (PWT) and tau with the P301L mutation. Greater differences in terms of fibrillation rates and ThT fluorescence between PWT and P301L was shown than previously reported between WT and P301L. They were also shown to differ in fibril morphology in TEM. The ThT fluorescence intensity was to a certain degree transferable from PWT to P301L by seeding. Furthermore, this study confirms that the tau-EXFP fusion protein can be incorporated into amyloid fibrils and strongly suggests that a FRET effect between EXFP and BTD14 (as well as X34 and ThT) can be achieved. It also demonstrates differences in FRET efficiency between PWT and P301L fibrils using FLIM. These results indicate that a FRET based approach could be a useful method to discern different fibril morphologies from each other, but further measurements and optimization are needed before this method could be reliably applied. The fusion proteins could also be used to investigate tau spreading in vivo, e.g. in D. melanogaster. To find suitable FRET partners to the fusion proteins, a ligand screen was conducted. This could be used as an alternative to the FRET method. With the right selection of fluorescent amyloid probes, a unique fingerprint for each fibril morphology could maybe be generated and fulfill the same intended function as the FRET method.
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Lim, Mi Hee. "Metal-based turn-on fluorescent probes for nitric oxide sensing." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/36267.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006.Vita.
Includes bibliographical references.
Chapter 1. Metal-Based Turn-On Fluorescent Probes for Sensing Nitric Oxide. Nitric oxide, a reactive free radical, regulates a variety of biological processes. The absence of tools to detect NO directly, rapidly, specifically and selectively motivated us to develop metal-based fluorescent probes to visualize the presence of NO. We have prepared and investigated Co(II), Fe(II), Ru(II), Rh(II), and Cu(II) complexes as turn-on fluorescent NO sensors. Our exploration has provided insight into how the interaction of transition metal centers with nitric oxide can be utilized for NO sensing. Chapter 2. Fluorescence-Based Nitric Oxide Detection by Ruthenium Porphyrin Fluorophore Complexes. The ruthenium(II) porphyrin fluorophore complexes [Ru(TPP)(CO)(Ds-R)] (TPP = tetraphenylporphinato dianion; Ds = dansyl; R = imidazole (im), 1, or thiomorpholine (tm), 2) were synthesized and investigated for their ability to detect nitric oxide (NO) based on fluorescence. The X-ray crystal structures of 1 and 2 were determined. The Ds-im or Ds-tm ligand coordinates to an axial site of the ruthenium(II) center through a nitrogen or sulfur atom, respectively. Both exhibit quenched fluorescence when excited at 368 or 345 nm.
(cont.) Displacement of the metal-coordinated fluorophore by NO restores fluorescence within minutes. These observations demonstrate fluorescence-based NO detection using ruthenium porphyrin fluorophore conjugates. Chapter 3. Nitric Oxide-Induced Fluorescence Enhancement by Displacement of Dansylated Ligands from Cobalt. The cobalt complexes, [Co(Ds-AMP)2] (1) and [Co(Ds-AQ)2] (2), where Ds-AMP and Ds-AQ are the conjugate bases of dansyl aminomethylpyridine, Ds-HAMP, and dansyl aminoquinoline, Ds-HAQ, respectively, were synthesized in two steps as fluorescence-based nitric oxide (NO) sensors and characterized by X-ray crystallography. The fluorescence of both complexes was significantly quenched in CH3CN or CH3OH compared to that of the free Ds-HAMP or Ds-HAQ ligands. Addition of NO to a CH3CN solution of 1 or 2 enhanced the integrated fluorescence emission by factors of 2.1(_-+0.3) or 3.6(+0.4) within 35 or 20 min, respectively. Introduction of NO to methanolic solutions similarly increased the fluorescence by 1.4(±0.1) for 1 or 6.5(±1.4) for 2 within 1 h.
(cont.) These studies demonstrate that 1 and 2 can monitor the presence of NO with turn-on emission, and that their fluorescence responses are more rapid than those of previously reported cobalt systems in coordinating solvents such as CH3CN and CH3OH. H NMR and IR spectroscopic data revealed the formation of a {Co(NO)2'0 cobalt dinitrosyl adduct with concomitant dissociation of one ligand from the cobalt center as the metal-containing product of the NO reactions, indicating NO-induced ligand release to be the cause of the fluorescence Chapter 4. Fluorescent Nitric Oxide Detection by Copper Complexes Bearing Anthracenyl and Dansyl Fluorophore Ligands. Anthrancenyl and dansyl fluorophore ligands (AnCH2pipCS2K (1), Ds-Hen (2), Ds-HAMP (3), Ds-HAQ (4), and Ds-HAPP (5)) were prepared for copper(II). Five copper complexes, [Cu(AnCH2pipCS2)2] (6), [Cu(Ds-en)2] (7), [Cu(Ds-AMP)2] (8), [Cu(Ds-AQ)2] (9), and [Cu(Ds-APP)(OTf)] (10), were synthesized for fluorescent nitric oxide (NO) detection and were characterized by X-ray crystallography. A decrease in fluorescence of free ligands (1- 5) coordinated to the Cu(II) center was observed in all Cu(II) complexes (6-10).
(cont.) The fluorescence of fluorophore ligands in Cu(II) complexes was restored in the presence of NO in a CH3OH/CH2C12 solvent. Furthermore, compounds 7, 8, and 10, exhibited fluorescence response to NO in aqueous pH 7.0 or 9.0 buffered solutions. Fluorescence enhancement of these Cu(II) complexes occurs by NO-induced reduction from Cu(II) to Cu(I), as demonstrated spectroscopically. The present work suggest that a copper(II) complex would be effective as a fluorescent probe for sensing NO in both organic and aqueous settings. Chapter 5. Direct Nitric Oxide Detection In Aqueous Solution by Copper(II) Fluorescein Complexes. Fluorescein-based ligands (FL., n = 1 - 5) for Cu(II) were synthesized and their photophysical properties were determined. Introduction of nitric oxide (NO) to a pH 7.0 buffered solution of Cu(FLn) (1 M CuCl2 and 1 uM F Ln) induces an increase in fluorescence at 37 °C. The fluorescence response of Cu(FL.) is direct and specific, which is a significant improvement of commercially available small molecule-based probes that are capable only of indirect NO detection. NO-triggered fluorescence increase of Cu(FLn) occurs by reduction of Cu(II) to Cu(I) with concomitant dissociation of the N-nitrosated fluorophore ligand from copper.
(cont.) Spectroscopic and product analyses of the reaction of the copper fluorescein complex with NO suggest that the N-nitrosated fluorescein ligand (FLn-NO) is the species for fluorescence turn-on. Density functional theory (DFT) calculations of FL5 versus FL-NO reveal how N-nitrosation of the fluorophore ligand causes the fluorescence increase. The investigation of copper-based probes described in the present work is the basis for developing a metal complex for fluorescent NO detection. Chapter 6. Visualization of Nitric Oxide in Living Cells by a Copper-Based Fluorescent Probe. Nitric oxide (NO) is a highly reactive gaseous free radical that serves as a messenger for cellular signaling. To visualize NO in living cells, a turn-on fluorescent probe was designed and synthesized for use in combination with microscopy. Unlike existing fluorescent sensors, the construct, a Cu(II) complex of a fluorescein modified with an appended metal-chelating ligand (FL), directly and immediately images NO rather than a derivative reactive nitrogen species (RNS). Nitric oxide produced by both constitutive (cNOS) and inducible (iNOS) NO synthases in live neurons and macrophages is detected by the Cu(II)-based imaging agent in a concentration- and time-dependent manner.
(cont.) The sensitivity to nM levels of NO and the spatiotemporal information provided by this complex demonstrate its value for numerous biological applications. Appendix. Fluorescent Detection of Nitric Oxide by a Rhodium Fluorophore Embedded in a Silastic Polymer Using Two-Photon Microscopy. A Silastic membrane embedded with a dirhodium fluorophore conjugate, [Rh2(M-O2CPr)4(Ds-pip)] (Ds-pip = dansyl-piperzine), was prepared. Nitric oxide (NO) in aqueous media replaces the Ds-pip bound to the dirhodium core in the solid state, inducing the fluorescence increase observed by two-photon spectroscopy. This observation is the first effort for NO detection using two-photon microscopy and represents an initial step toward fiber-optic-based NO sensing in aqueous media using this dirhodium-containing polymer.
by Mi Hee Lim.
Ph.D.
17
McQuade, Lindsey Elizabeth 1981. "Turn-on fluorescent probes for detecting nitric oxide in biology." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/57895.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010.Cataloged from PDF version of thesis.
Includes bibliographical references.
Chapter 1. Investigating the Biological Roles of Nitric Oxide and Other Reactive Nitrogen Species Using Fluorescent Probes: This chapter presents an overview of recent progress in the field of reactive nitrogen species (RNS) sensing. Reactive nitrogen species, such as nitric oxide (NO) and its higher oxides, play important roles in cell signaling during many physiological and pathological events. Elucidation of the exact functions of these important biomolecules has been hampered by the inability to detect RNS reliably under biological conditions. A surge of research into RNS chemistry has resulted in the design of a new generation of fluorescent probes that are specific and sensitive for their respective RNS analytes. Progress in the field of nitric oxide, peroxynitrite, and nitroxyl sensing promises to advance our knowledge of important signaling events involving these species and should lead to a better understanding of oxidative biochemistry crucial to health and disease. Chapter 2. Mechanism of Nitric Oxide Reactivity and Fluorescence Enhancement of the NO-Specific Probe, CuFu1: The mechanism of the reaction of CuFu1 (FL1 = 2-{2-chloro-6-hydroxy-5-[(2- methylquinolin-8-ylamino)-methyl]-3-oxo-3H-xanthen-9-yl}benzoic acid) with NO to form FL1-NO in aqueous, buffered solutions was investigated. The reaction is first order in concentration of CuFL1, NO, and hydroxide ion. Rate saturation at high base concentrations is consistent with the fact that the protonation state of the secondary amine of the complex is crucial for reactivity. Based on this information, faster-reacting probes can be obtained by lowering the pKa of the secondary amine. The activation parameters for the reaction indicate that the mechanism is associative (ASI = -29 ± 3 cal/K-mol) and occurs with a modest thermal barrier (AHI = 9.7 ± 0.5 kcal/mol; Ea = 10.3 ± 0.5 kcal/mol). Variable pH EPR experiments indicate that as the secondary amine of CuFu1 is deprotonated, the electron density shifts yielding new spin-active species that has electron density localized on the deprotonated nitrogen atom. This result suggests that FL1-NO formation occurs when NO attacks the deprotonated secondary amine of the coordinated ligand, causing inner-sphere electron transfer to Cu(II) to form Cu(I) and subsequent FL 1-NO release from the metal. Chapter 3. Fluorescence-Based Nitric Oxide Sensing by Cu(II) Complexes that Can Be Trapped in Living Cells: A series of symmetrical, fluorescein-derived ligands appended with two derivatized 2- methyl-8-aminoquinolines were prepared and spectroscopically characterized. The ligands 2-{6-hydroxy-4,5-bis[(2-methylquinolin-8-ylamino)methyl]-3-oxo-3H-xanthen5 9-yl}benzoic acid (FL2), 2-{4,5-bis[(6-(2-ethoxy-2-oxoethoxy)-2-methylquinolin-8- ylamino)methyl]-6-hydroxy-3-oxo-3H-xanthen-9-yl}benzoic acid (FL2E), and 2,2'-{8,8'- [9-(2-Carboxyphenyl)-6-hydroxy-3-oxo-3H-xanthene-4,5-diyl]bis(methylene)bis(azanediyl) bis(2-methylquinolin-8,6-diyl)}bis(oxy)diacetic acid (FL2A) were designed to improve the dynamic range of previously described asymmetric systems, and the copper complex Cu2FL2E was constructed as a trappable NO probe that is hydrolyzed intracellularly to form Cu2FL2A. The ligands themselves are only weakly emissive and completely quenched in their Cu(II) complexes, which were generated in situ by combining each ligand with two equivalents of CuCl2 . The resulting complexes were investigated as fluorescent probes for nitric oxide. Upon introduction of excess NO under anaerobic conditions to buffered solutions of Cu2(FL2), Cu 2(FL2E), and Cu2(FL2A), the fluorescence increased by factors of 23 ± 3, 17 ± 2, and 27 ± 3, respectively. The corresponding rate constants for fluorescence turn-on were determined to be 0.006 ± 0.003 s-, 0.0058 ± 0.0009 s-4 and 0.010 ± 0.002 s4. The probes are highly specific for NO over other biologically relevant reactive oxygen and nitrogen species, as well as Zn(II), the metal ion for which structurally similar probes were designed to detect. Chapter 4. Visualization of Nitric Oxide Production in the Mouse Main Olfactory Bulb by a Cell-Trappable Copper(II) Fluorescent Probe: The visualization of NO production using fluorescence in tissue slices of the mouse main olfactory bulb is reported. This discovery was possible through the use of a novel, celltrappable probe for intracellular nitric oxide detection based on a symmetric scaffold with two NO-reactive sites. Ester moieties installed onto the fluorescent probe are cleaved by intracellular esterases to yield the corresponding negatively charged, cell-impermeable acids. The trappable ester probe Cu2(FL2E) and the membrane-impermeable acid derivative Cu2(FL2A) respond rapidly and selectively to NO in buffers that simulate biological conditions. Application of Cu2(FL2E) leads to detection of endogenously produced NO in cell cultures and olfactory bulb brain slices. Chapter 5. Dextran-Based Cell-Trappable Fluorescent Probes for Nitric Oxide Visualization in Living Cells: Two new cell-trappable fluorescent probes for nitric oxide are reported based on either incorporation of hydrolyzable esters or conjugation to aminodextran polymers. Both probes are highly selective for NO over other reactive oxygen and nitrogen species (RONS). The ability of these probes to image nitric oxide produced endogenously in Raw 264.7 cells by fluorescence is demonstrated. Chapter 6. A Cell-Trappable Fluorescent Probe for Detecting Biological Zinc: The synthesis and spectroscopic characterization of a new, cell-trappable fluorescent probe for Zn(II) is presented. This probe, 2-(4,5-bis((6-(2-ethoxy-2-oxoethoxy)quinolin- 8-yl)amino)methyl)-6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid (QZ2E) is poorly emissive in the off-state, but exhibits a dramatic, 120 ± 10-fold increase in fluorescence upon Zn(II) binding. This binding is selective for Zn(II) over other biologically relevant metal cations, toxic heavy metals, and most first-row transition metals, and is of appropriate affinity (Kdl = 150 ± 100 [tM, Kd2 = 3.5 ± 0.1 mM) to bind Zn(II) at physiological levels reversibly. In live cells, QZ2E localizes to the Gogli apparatus where it can detect Zn(II). It is cell membrane permeable until cleavage of its ester groups by intracellular esterases produces QZ2A, a negatively-charged acid that cannot cross the cell membrane. Appendix 1. Screening for bNOS Inhibitors in Bacillus anthracis: The incidence of anthrax infection by the Gram-positive bacterium Bacillus anthracis and the challenges of its treatment are presented. B. anthracis pathogenesis is critically dependent on NO production by the enzyme bacterial nitric oxide synthase (bNOS), a variant of the eukaryotic NOSes that does not contain a reductase domain required for catalysis. Using non-committed reductases in the cell, B. anthracis produced NO to neutralize the oxidative environment produced in macrophages as a host defense system. The fact that NO production is crucial for bacterial survival suggests that a selective bNOS inhibitor would make a good antibacterial agent against Bacillus anthracis and related pathogens. A high-throughput screen of a small-molecule library to identify potential bNOS inhibitors by fluorescence of an NO-specific probe is proposed. Optimization of fluorescence imaging in 384-well plates is presented as a first step toward this goal. Future directions to improve the screening protocol and steps for ensuring bNOS selectivity and efficacy in mice are discussed. Appendix 2. NMR Spectra.
by Lindsey Elizabeth McQuade.
Ph.D.
18
Pearson, Thomas D. Z. "Fluorescent probes for the labelling of cardiomyocyte and mitochondrial proteins." Thesis, Nottingham Trent University, 2017. http://irep.ntu.ac.uk/id/eprint/34377/.
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Organophosphates are a known danger to human health with an array of biochemical targets and complex toxic effects. Phenyl saligenin phosphate (PSP) is an organophosphate and related phenoxy substituted organophosphates irreversibly bind to a variety of important enzymes causing the condition known as organophosphate induced delayed neuropathy (OPIDN). These compounds also potentially cause cardiac muscle damage but little is known about how this class of compounds effect cardiomyocytes. The identification of proteins targeted by these toxins is of interest. This study investigates the synthesis and application of novel fluorescently labelled organophosphates to investigate organophosphate interaction with H9c2 cardiomyoblasts. The synthesis of probes with BODIPY, pyrene and rhodamine fluorescent component is explored with success in preparation of pyrene and rhodamine probes. The fluorescent behaviour of three rhodamine labelled phenyl saligenin phosphates probes with alkyl and PEG linkers is examined and the cytotoxicity of the probes assessed by monitoring MTT reduction, and LDH release from exposed H9c2 cardiomyoblasts. All three analogues showed cytotoxicity (4 h exposure; 100 μM). These probes were found to bind to proteins within mitochondria and spots from 2D-gel electrophoresis experiments, visualised at 532 nm, which are undergoing MS analysis. This project also describes progress towards a photoreactive-fluorescent probe to identify the site of action of the potassium channel opener, diazoxide, which activates cardioprotective pathways. The drug is believed to target mitochondrial KATP channels, but the protein structure of these channels has yet to be elucidated. The fluorescence labelling of whole cardiac cells with a dansyl fluorescent -benzophnone-photoreactoive diazoxide probe has been demonstrated and the progress toward a rhodamine fluorescent analogue is presented.
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Marginean, Denisse, and Ebba Hellstrand. "Fluorescent molecules as probes for characterization of amyloid β fibrils." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-178005.
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Alzheimer’s Disease (AD) is the leading cause of dementia in the world and the World Health Organization has recognized AD as a global public health priority. One of the pathological hallmarks of AD is amyloid plaques formed from amyloid β (Aβ) fibrils. Aβ is formed when amyloid precursor protein is cleaved by secretase enzymes. Cleavage by different secretases causes Aβ to occur in different forms, mainly as 40 and 42 residue long proteins, called Aβ1-40 and Aβ1-42, where Aβ1-42 is more likely to form amyloid fibrils and is therefore considered more harmful. Fluorescent probes are currently used to stain Aβ fibrils for their detection and characterization. We performed a literature study analysing which fluorescent probes are used for imaging of amyloid fibrils and present both the most commonly used probes but also newer probes that have been recently synthesized. Fluorescence spectra of a selection of probes were analysed in order to suggest some new combinations of probes for double-staining with the aim to be able to distinguish between Aβ1-40 and Aβ1-42. Microscopy images of the probe combinations were obtained in order to analyse the double staining results and the fluorescence intensities of the probes were plotted in different ways. All selected combinations were able to distinguish between Aβ1-40 and Aβ1-42, because of differently stained fibrils, and also displayed differences in fluorescence intensity at peak emission wavelength. The obtained results show that double-staining of amyloid fibrils with fluorescent probes can give additional information compared to staining fibrils with only one probe.
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Egleton, James Edward. "Small molecule colorimetric and fluorescent probes for specific protein detection." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:0a1a1c80-8055-491a-920a-3e17f7919e93.
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This thesis describes the design, synthesis, analysis, mechanistic evaluation and optimisation of small molecule probes for the specific detection of proteins, focusing on the target protein human arylamine N-acetyltransferase type 1 (HUMAN(NAT1)) and its murine homologue, mouse arylamine N-acetyltransferase type 2 (MOUSE(NAT2)). The HUMAN(NAT1) gene is reported to be one of the most highly overexpressed genes in estrogen-receptor-positive (ER+) breast tumours, leading to its potential use as both a novel diagnostic biomarker and a novel therapeutic target for this disease. Chapter 1 reviews the literature on optical methods for the specific detection of a protein target, exploring strategies both based on biosensors and on chemical probes, before introducing the arylamine N-acetyltransferases as a family of enzymes. In Chapter 2, a family of naphthoquinone inhibitors of HUMAN(NAT1) are introduced, which undergo a colour change from red to blue upon binding specifically to the enzyme. The mechanism of this colour change, a proton transfer-mediated process, is discussed via the synthesis, pharmacological and colorimetric evaluation of close analogues of the hit compound lacking a key acidic sulfonamide-NH proton. During these studies, it was found that direct O-methylation of a sulfonamide is possible under certain conditions; such a reaction has not previously been reported. Furthermore, upon heating in polar solvents the O-methylated sulfonamide was observed to undergo rearrangement, and the mechanism of this process is investigated via NMR and kinetic studies. In Chapter 3, the design, synthesis and evaluation of HUMAN(NAT1) inhibitors with improved pharmacological and colorimetric profiles over the initial hit are described. From this optimisation, structure-activity relationships and an in silico model of interactions between the inhibitors and enzyme are evaluated. Testing of these compounds in cellular environments, however, exposes some limitations of this approach, notably the lack of sensitivity of the probes when dosed at low concentrations in cellular samples. In order to overcome this limitation, in Chapter 4 fluorescent analogues of the hit compound are designed and synthesised. Initial compounds developed in this series possess promising properties, but each compound generated suffers from either a low fluorescent intensity, lack of a pH-dependent switch in fluorescence or a low fluorescence excitation wavelength, which overlaps with those of tryptophan or tyrosine residues in proteins. Insights into the mechanism of molecular fluorescence and application of some simple quantum mechanical principles, however, lead to the design of a species which possesses all the required properties. The fluorescent emission intensity of this probe correlates linearly with [MOUSE(NAT2)] in E. coli cell extracts, and can quantify as little as 0.64% MOUSE(NAT2) in the samples; furthermore, the probe is capable of unambiguously detecting HUMAN(NAT1) within a cell extract from the ER+ breast cancer cell line ZR-75-1; future work on this probe may therefore enable its clinical use in improved early diagnosis of breast tumours. This study also represents, to the best of our knowledge, the first ever example of a small molecule, non-covalent probe capable of quantifying the concentration of a target protein in cellular extracts. In Chapter 5, the series of naphthoquinone probes is further optimised in order to study the roles of HUMAN(NAT1) in a cellular environment. Firstly, structure-activity relationships are utilised to design inhibitors with improved physical properties such as aqueous solubility and cell membrane permeability, in order to test the effect of HUMAN(NAT1) inhibitors in tumour cell models, which could have implications for the future use of a HUMAN(NAT1) inhibitor as a therapeutic agent in oncology. Secondly, the effect of the cofactor folic acid on the function and activity of HUMAN(NAT1) is explored. Finally, in Chapter 6, the conclusions of this study are outlined and a hypothesis as to how the concepts developed in this thesis might be applied to alternative, more ubiquitous biological targets is discussed, paving the way for future investigations.
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Castello, Beltran Carlos. "Fluorescent probes for selective detection of ozone in plasma applications." Thesis, Loughborough University, 2015. https://dspace.lboro.ac.uk/2134/19716.
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This thesis presents an overview of the research activities undertaken during my PhD under the supervision of Dr. F. Iza from the School of Electronic, Electrical and Systems Engineering and Dr. B. Buckley from the Chemistry Department at Loughborough University. The thesis is divided as follows. The first chapter of the thesis presents an introduction to plasma and chemical probes as well as the motivation for developing fluorescent probes for plasma characterisation. Analytical techniques used during this work to analyse chemical substances are described in the second chapter. Results and discussions from the experiments are discussed in chapters 3 to 7. Conclusions and future work are presented in chapter 8. In chapter 9, experimental data is presented. In the last century, plasma has attracted the attention of numerous researchers. Due to the wide-range of applications of this ionised gas, people from different fields have focused their effort on studying plasma. Low-temperature plasmas have received growing attention in the last 50 years when the development in cold plasma devices made them more controllable. Plasma played (and continues to play) a critical role in the fabrication process of integrated circuits and recent advances in the generation of low-temperature atmospheric-pressure plasmas have resulted in the emergence of new applications including treatment of temperature sensitive surfaces and biological targets. During the first months at Loughborough I worked on the ozonolysis of various alkenes with air plasmas. This allowed me to familiarised myself with plasma as this was new to me and get a feeling of some of the challenges lying ahead. Nonetheless, the data I obtained was encouraging and I presented the results of batch and flow plasma-based ozonolysis of alkenes at the Technological Plasma Workshop held in Manchester in January 2012. Once I had familiarised myself with the plasma system, I worked on synthesising fluorescent probes to detect ozone, one of the many reactive species that are typically generated in oxygen containing plasmas. Details of the experiments conducted to date and most significant findings are discussed in this thesis.
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Lai, Yau-tsz, and 黎佑芷. "Lighting-up metalloproteins in living cells : seeing is believing." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/206989.
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One third of proteins in nature have been revealed as metalloproteins, whereas most of them remain uncharacterized, probably due to the lack of robust methods especially for tracking metalloproteins within the living context. Fluorescent labeling is capable to detect biomolecules with molecular resolution in living cells. Tracking metal-binding proteins in living cells by fluorescence could provide invaluable information in understanding their localization and potential functions in the native environment.
A synthetic molecular probe NTA-AC was designed and synthesized to track metal-associated proteins in living cells upon chelation with metal ions. The fluorescent probe consists of a small molecular fluorophores, a metal-chelating moiety to direct the metal-chelated probe to the protein targets, and a photo-active crosslinker. Metal being chelated could help further explore potential binding targets and direct the fluorescent agent to the appropriate region, then subsequently covalent linkage to targets could be generated through photo-activation. NTA-AC was therefore chelated with different metals to examine its binding preference to different proteins.
The Ni2+-chelating probe was applied to track Ni2+-binding proteins as an example to validate its applicability. Ni2+-NTA-AC preferentially binds to histidine-rich peptides and proteins thus verified its binding specificity. The Ni2+-chelated probe was further exploited to light up over-expressed histidine-rich proteins in Escherichia coli cells to validate its membrane permeability and binding specificity. In addition, the probe was applied to label His-tagged proteins expressed in tobacco plant cells to further evaluate its applicability in detecting and localizing the protein targets in eukaryotic cells. Afterwards, Ni2+-NTA-AC was exploited to track Ni2+-binding proteins in living Helicobacter pylori cells and incorporated with gel electrophoresis and mass spectrometry for protein identification. Many proteins identified are correlated to Ni2+-association and thus validating the applicability of the probe.
Bi3+-chelated NTA-AC was therefore used to mine potential targets in H. pylori. Intense fluorescence was observed within H. pylori cells thus indicating the effectiveness of the fluorescent labeling. Protein separation and identification was therefore initiated to trace potential targets, while finding that some of the Bi
3+-coordinated proteins participate in various functioning pathways of the pathogens. The effects of colloidal bismuth subcitrate (CBS) on pH buffering and redox defense systems were therefore determined and verified, confirming that respective proteins could be potential therapeutic targets of the drug.
Cr3+-NTA-AC was further applied to human Hep G2 cell line to determine Cr3+-binding targets in mammalian cells. Their localization on mitochondria was revealed, implying the potential effects of Cr3+ on mitochondria. Further confirmation of protein targets was performed through protein separation and identification. Proteins identified could be positively correlated to mitochondrial functions and thus revealing that Cr3+ might exert its effect at mitochondria. Addition of Cr3+ to Hep G2 could prevent mitochondrial fragmentation induced by hyperglycemia, which thus suggests the possible therapeutic function of Cr3+.
The extensive application of NTA-AC in tracking Ni2+-, Bi3+- and Cr3+-associated proteins has validated the effectiveness of such strategy in detecting and localizing metalloproteins within the living context and thus could be extended to investigate other metalloproteomes.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
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Carson, Travis D. "Development of a DNA probe and anisotropic films with an emphasis on self-assembly and fluorescence /." abstract and full text PDF (free order & download UNR users only), 2005. http://0-wwwlib.umi.com.innopac.library.unr.edu/dissertations/fullcit/3198195.
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Thesis (Ph. D.)--University of Nevada, Reno, 2005."May, 2005." Includes bibliographical references. Online version available on the World Wide Web. Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2005]. 1 microfilm reel ; 35 mm.
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Katchan, Ljudmila [Verfasser]. "Illuminating the function of AMPA receptors with fluorescent probes / Ljudmila Katchan." Berlin : Freie Universität Berlin, 2016. http://d-nb.info/112211110X/34.
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Chen, Yingche, and 陈映澈. "Studies on FRET-based fluorescent probes for the detection of peroxynitrite." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46924334.
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Garton, Natalie Jane. "Investigation of mycobacterial lipid domains by use of fluorescent lipid probes." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244396.
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Rowe, Brad A. "Characterization of bicelle model membranes using multidimensional spectroscopy of fluorescent probes." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 309 p, 2005. http://proquest.umi.com/pqdweb?did=954032061&sid=11&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Mackay, Martha. "The development of fluorescent probes targeting Caspase-3 for detecting apoptosis." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17972.
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The design and development of fluorescent reporters focussed on highly sensitive, specific, and selective imaging of cancer targets is described. These novel optical molecular probes were synthesised with the aim of creating bio-imaging breakthroughs that will aid the clinical analysis of cancer. A specific target of the project was to develop fluorescent reporters for Caspases; intracellular endopeptidases that play an essential role in apoptosis. Lack of activation of the ‘Caspase Cascade’ causes uncontrolled proliferation of cells and has been deemed a ‘Hallmark of Cancer’. In particular, low Caspases-3/7 activities have been associated with a range of cancers, thus molecular detection of Caspases-3/7 activities could therefore lead to advances in oncology. A 14-member FRET library, based upon Caspases-3/7 specific peptide sequences, was initially developed. The cleavage rates and KM values were evaluated for Caspases-3/7, along with the cleavage rates for Cathepsin B, to determine the peptide with the greatest affinity and specificity for Caspase-3. Also developed was a set of internally quenched activity based molecular reporters constructed by attaching fluorophores to a tribranched dendron through the Caspase specific peptide, developed from the FRET Library. The KM values of the dendron probes with Caspase-3 were also evaluated. Furthermore, the dendron reporters were attached to cell penetrating peptides to enable delivery to intracellular Caspase and allow in situ detection of activated Caspase-3 within live cells. In addition, a new labelling moiety was developed enabling dual detection of reporters through fluorescence and MRI imaging. To achieve this, a perfluoro tag (C8F17) was tethered to a Cy5 dye to enable dual detection. The dual 19F-MRI/Cy5 dye was conjugated onto to a cell penetrating peptide to enable in vivo detection of the probe by 19F-MRI and fluorescent imaging.
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Kucherak, Oleksandr. "Development of new fluorescent membrane probes for apoptosis and raft domains." Strasbourg, 2011. http://www.theses.fr/2011STRA6056.
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La première sonde ratiométrique capable de détecter l’apoptose (F2N12S) a récemment été développée au laboratoire. Le but du présent travail est de développer des sondes fluorescentes pour l’apoptose présentant des caractéristiques améliorées permettant de palier certains défauts de F2N12S. Nous avons découvert que l’apoptose induit non seulement une modification de la charge surfacique du feuillet externe, mais également de son hydratation et de son état de phase, expliquant ainsi la réponse de la sonde. Ensuite, nous avons synthétisé une vingtaine de nouvelles sondes membranaires, qui ont été classées en trois catégories en fonction de leur réponse obtenue sur membranes modèles. Une première catégorie montre une sensibilité presque nulle vis-à-vis de l’état de phase, mais nettement améliorée vis-à-vis de la charge surfacique (>3 fois), comparée à F2N12S. Une seconde catégorie montre une meilleure sensibilité à l’état de phase comme à la charge surfacique. Une troisième catégorie, dérivée du Rouge Nil, est sensible seulement à l’état de phase. En se basant sur ces résultats, nous avons proposé des principes généraux pour la conception de sondes membranaires fluorescentes. Enfin, nous avons décrit deux nouvelles classes de fluorophores sensibles à l’environnement basés sur les résidus fluoréne et 3-methoxychromone afin d’élaborer de nouvelles sondes membranaires. Ces nouveaux fluorophores ont montré des propriétés spectroscopiques intéressantes, telles qu’une forte luminosité, une excellente photostabilité et un solvatochromisme exceptionnel. Les premières tentatives pour convertir ces fluorophores en sondes membranaires ont été décritesFluorescent dyes are of great importance for investigation of biological processes. Recently, the first ratiometric fluorescent probe for apoptosis detection (F2N12S) was developed in our laboratory. The aim of the present work was to develop improved fluorescent apoptosis probes that will overcome the drawbacks of F2N12S. Primarily, we performed systematic studies of F2N12S in model membranes and cells to better understand the mechanism of its response to apoptosis. We found that in addition to surface charge, the membrane hydration and phase state are changed on apoptosis, thus explaining the spectroscopic response of the probe. On the second step, we have synthesized about 20 new membrane probes, which were classified into three types according to the experiments in model membranes. The first type of dyes showed nearly no sensitivity to the phase state while their sensitivity to surface charge was much higher (>3-fold) as compared to F2N12S. The second type showed improved sensitivity both to the surface charge and to the phase state of the lipid bilayers. The third type, which was based on Nile Red, was sensitive only to the phase state. Basing on these results we proposed general principles for the design of fluorescent membrane probes. Finally we described two new classes of environment-sensitive fluorophores on the base of fluorene and 3- methoxychromone units for further construction of new advanced membrane probes. These new fluorophores showed attractive spectroscopic properties, such as high brightness and photostability as well as an exceptional fluorescence solvatochromism. The first attempts to convert these fluorophores into membrane probes were described
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Zhou, Xiaobo. "Design, synthesis and sensing properties of chiral amine-based fluorescent probes." HKBU Institutional Repository, 2012. https://repository.hkbu.edu.hk/etd_ra/1442.
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Wang, Hao. "Development of fluorescent chemosensors : mercury sensing and biological molecules sensing probes." HKBU Institutional Repository, 2008. http://repository.hkbu.edu.hk/etd_ra/890.
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Zhu, Jianfa. "Fluorescent chemosensor development based on multifunctional spirobenzopyrans." HKBU Institutional Repository, 2011. https://repository.hkbu.edu.hk/etd_ra/1299.
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Wu, Yonggang. "Design, Synthesis and Characterization of Zinc(II)-Selective Ratiometric Fluorescent Sensors." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19735.
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Zinc is an important micronutrient but the biological function of its labile form is poorly understood. Zinc selective fluorescence sensors, recognized as the major tool to gain information about the role of zinc in living systems, have been attracting more and more interest.
The most promising solution currently being studied comes in the form of ratiometric sensors. Unlike sensors based on the switch-on mechanism, ratiometric sensors determine the free metal concentration directly from the ratio of the emission intensities at two wavelengths. The major restriction on the design of this type of sensor is from the necessity for a spectral-shift upon binding metal ions. To develop novel ratiometric sensors, we have developed designs based on excited-state intramolecular proton transfer (ESIPT).
In the absence of ZnII at neutral pH, the 2-(2 -sulfonamidophenyl)benzimidazole family undergoes ESIPT to yield a highly Stokes-shifted emission from the proton-transfer tautomer. Coordination of ZnII inhibits the ESIPT process and yields a significant hypsochromic shift of the fluorescence emission maximum. By implementing structural modifications, we were able to gauge free ZnII concentrations in the millimolar to picomolar range.
To tune the peak excitation towards lower energy, a property that is of particular importance in the light of biological applications, we modified the platform molecule with extended pi-conjugation and by substituent engineering. The position of the modification and the nature of the substituents strongly influenced the photophysical properties of the investigated derivatives. Several fluorophores revealed emission ratiometric properties with a large dynamic range combined with a peak absorption beyond 350 nm, rendering these probes promising candidates for applications.
To further understand the origin of the substituent effect, we studied five derivatives for the solvatochromic shift analysis and quantum chemical studies. The results showed that the negative solvatochromic shift behavior was most pronounced in protic solvents presumably due to specific hydrogen-bonding interactions. The extrapolated gas-phase emission energies correlated qualitatively with the trends in Stokes shifts, suggesting that solute-solvent interactions do not play a significant role in explaining the divergent emission energy shifts. Detailed quantum chemical calculations not only confirmed the moderately polarized nature of the ESIPT tautomers but also provided a rationale for the observed emission shifts based on the differential change in the HOMO and LUMO energies.
This study revealed the great potential of 2-(2 -arylsulfonamidophenyl)- benzimidazoles, such as tunable peak absorption and emission, a very wide dynamic range regarding to zinc binding, very little solvent polarity dependence, and especially, the emission ratiometric property. All these properties make this system a unique candidate to tackle the problems in the research of zinc biology.
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Caiazza, Daniela. "Crown ethers as potential lead (II) specific probes : a thesis submitted for the degree of Doctor of Philosophy /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phc1328.pdf.
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Peng, Tao, and 彭濤. "Rhodol fluorophores and fluorescent probes for the detection and imaging of reactive oxygen species." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B41757920.
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Peng, Tao. "Rhodol fluorophores and fluorescent probes for the detection and imaging of reactive oxygen species." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B41757920.
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Pan, Yilan, and 潘怡兰. "Studies on fluorescent probes for the detection of peroxynitrite and hypochlorous acid." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45515335.
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Magnusson, Karin. "Poly-and oligothiophenes : Optical probes for multimodal fluorescent assessment of biological processes." Doctoral thesis, Linköpings universitet, Kemi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-121815.
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One interesting class of molecules in the research field of imaging biological processes is luminescent conjugated polythiophenes, LCPs. These fluorescent probes have a flexible backbone consisting of repetitive thiophene units. Due to this backbone, the probes possess unique abilities to give rise to different spectral signatures depending on their target and environment. LCPs are a polydispersed material meaning there is an uneven distribution of lengths of the probe. Recently, monodispersed chemically well-defined material denoted luminescent conjugated oligothiophenes, LCOs, with an exact number of repetitive units and distinct sidechain functionalities along the backbone has been developed. LCOs have the advantages of being smaller which leads to higher ability to cross the blood brain barrier. The synthesis of minor chemical alterations is also more simplified due to the well-defined materials. During my doctoral studies I have used both LCPs and LCOs to study biological processes such as conformational variation of protein aggregates in prion diseases and cellular uptake in normal cells and cancer cells. The research has generally been based on the probes capability to emit light upon irradiation and the interaction with their targets has mainly been assessed through variations in fluorescence intensity, emission-and excitation profiles and fluorescence lifetime decay. These studies verified the utility of LCPs and LCOs for staining and discrimination of both prion strains and cell phenotypes. The results also demonstrated the pronounced influence minor chemical modifications have on the LCO´s staining capacity.
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Lamb, J. C. "Fluorescent derivatives of tubulin as probes for the analysis of microtubule dynamics." Thesis, University of East Anglia, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372350.
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Kujala, Naresh Gandhi Yu Ping. "Frequency domain fluorescent molecular tomography and molecular probes for small animal imaging." Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/7021.
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Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 26, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Ping Yu. Vita. Includes bibliographical references.
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Mabire, Anne B. "Fluorescent probes for stimuli-responsive polymers : to fluoresce, or not to fluoresce?" Thesis, University of Warwick, 2017. http://wrap.warwick.ac.uk/98100/.
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This thesis explores the use of aminobromomaleimide and dithiomaleimide functionalities to probe their environment. These fluorescent functionalities were incorporated into responsive polymeric nanostructures allowing their behaviour to be read-out upon external stimuli. Chapter 1 gives a brief introduction on nanoparticles formation and the polymerisation techniques used throughout the thesis. The properties of bromo- and thio-maleimides and their use in protein and polymer chemistry were also introduced. Chapter 2 describes a morphology transition simultaneously with a fluorescence on-to-off switch as a result of the modification of the dithiomaleimide substituent. Chapter 3 presents the synthesis of a library of aminomaleimides and explores their fluorescent properties. In Chapter 4, the fluorescent properties of aminobromomaleimide were incorporated into CO2-responsive polymeric nanoparticles for a built-in read-out of the CO2-response. Chapter 5 explores the possibility of using the fluorescent properties of aminobromomaleimide to read-out the behaviour of glutathione-responsive particles.
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Liu, Daniel S. (Daniel Shao-Chen). "Extending the utility of enzymes for site-specific targeting of fluorescent probes." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/87470.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, February 2014.Cataloged from PDF version of thesis. "February 2014."
Includes bibliographical references.
Genetically encodable fluorescence reporters such as the green fluorescent protein (GFP) are useful for studying protein expression, localization, and dynamics in a variety of biological systems. GFP and its related variants, however, suffer from several drawbacks. Compared to chemical fluorophores, they are large, dim, and limited in other reporting capabilities. Super-bright chemical fluorophores such as the Alexa Fluor dyes and quantum dots, on the other hand, are not genetically encodable and so their cellular targeting is challenging. To address this challenge, the Ting Lab engineered E. coli lipoic acid ligase (LpIA) to site-specifically attach reporters onto a 13-amino acid ligase recognition peptide, conferring comparable targeting specificity to genetic encoding. This thesis is an extension of this work, to expand the repertoire of chemical fluorophores that can be targeted to cellular proteins by this technology. We describe the computational redesign of LpIA into a red fluorophore ligase, and the validation of this design by X-ray protein crystallography. We used this new technology for live-cell fluorescence imaging and super-resolution imaging. For the attachment of other fluorophores than cannot be directly bound by the enzyme we engineered LplA to incorporate functional handles that can be chemoselectively derivatized with fluorophores in a second step. In one example, LplA targeted a strained alkene to cellular proteins, which can subsequently react with dienophiles with exceptional kinetics. In another example, we show that LplA-targeted haloalkanes can efficiently recruit a modified haloalkane dehalogenase. These methods were used to label cells with diverse fluorophores, including quantum dots, and allowed tracking of single membrane proteins to study their lateral diffusion.
by Daniel S. Liu.
Ph. D.
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Mastrodonato, Cristiano Matteo. "Elaboration of fluorescent molecular probes and molecular-based nanoparticles for bioimaging purposes." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0652/document.
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Les techniques de fluorescence sont des outils de choix pour l’étude et la compréhension fine des processus biologiques. Ceci requiert toutefois l’utilisation de sondes fluorescentes parfaitement adaptées au but visé et répondant aux différentes exigences requises pour l’application visée. Dans ce cadre, nous nous sommes plus particulièrement intéressés à l’élaboration de sondes biphotoniques de pH adaptées à une mesure très sensible de faibles variations de pH autour du pH neutre. Les variations et gradients de pH sont en effet impliqués dans un certain nombre de processus biologiques importants et peuvent être associées à des dysfonctionnements liés à certaines maladies. Dans ce cadre, nous avons développé de nouvelles sondes fluorescentes de pH fluorescentes présentant à la fois un comportement ratiométrique, une forte sensibilité autour du pH neutre et facilement excitables dans le proche IR par absorption à deux photons. Ces sondes de structure quadrupolaire et bolamamphiphile permettent ainsi la détection ratiométrique du pH dans des environnements biologiques au moyen d'une excitation biphotonique dans le proche IR. En parallèle, nous nous sommes intéressés à l’élaboration de nanoparticules hyperbrillantes dédiées à l’imagerie biologique par microscopie de fluorescence induite par excitation à deux photons. Nous nous sommes plus particulièrement attachées au design de nanoparticules organiques fluorescentes constituées de molécules organiques de bas poids moléculaire (FONs). Cette approche offre en effet une grande flexibilité et la possibilité d’accéder à des nanosondes ayant des brillances comparables aux très populaires quantum dots mais moins toxiques et plus facilement dégradables. L’ingénierie moléculaire des fluorophores utilisés pour la préparation des FON est cruciale puisqu’elle influence fortement à la fois les propriétés photophysiques (brillance, couleur…) et leur propriétés physico-chimiques (stabilité chimique et structurale, stabilité colloïdale). Dans ce contexte, une librairie de nouveaux chromophores dipolaires a été synthétisée et utilisées pour la préparation de FON par la méthode de nano-précipitation. Leurs propriétés ont été étudiées afin de déterminer la relation entre la structure du chromophore et les propriétés globales des nanoparticules constituées de ces colorants. Ce travail a permis d’identifier les paramètres structuraux permettant d’accéder à des nanoparticules présentant à la fois une brillance exceptionnelle, une émission modulable du vert au rouge et proche IR et une remarquable stabilité colloïdale. Ces nanoparticules présentent des potentialités majeures pour l’imagerie in vivo par excitation et détection dans le proche IRFluorescence-based techniques are popular tools for the study and understanding of biological processes. This has prompted continuous research aimed at the development of a wide range of fluorescent probes specifically designed for specific applications. Among them, fluorescent pH probes are of much interest as pH variations or gradients are involved in many biological events and anomalous alterations are often related to the onset of dysfunctions and diseases. In this framework we have developed a series of promising two-photon pH fluorescent molecular probes. These quadrupolar bolaamphiphilic probes are of great interest, as they combine a steep pH dependence of their optical properties close to neutral pH, ratiometric behavior and large response to two-photon (2P) excitation in the NIR region. As such they offer much promise for ratiometric detection of the pH in biological environments and in situ monitoring of acidification. In parallel, we have been interest in the design of ultrabright nanoparticles for bioimaging purpose (in particular highly sensitive optical imaging). We chose to focus on Fluorescent Organic Nanoparticles made of organic molecules with low molecular weight (FONs) as they offer a flexible route and promising alternatives to toxic quantum dots. In this case the design of the dye used as building blocks of the FONs is of crucial importance and strongly influence the chemical and physical properties of the nanoparticles generated, such as their one and two-photon brightness and both their structural and colloidal stability. In that context a library of novel dipolar chromophores have been synthesized and used to prepare FONs using the nanoprecipitation method. Their properties were thoroughly investigated in order to determine the relationship between the molecular design of the isolated dye and the overall properties of the nanoparticles made of these dyes. As a result, Hyperbright FONs emitting in the green to NIR region and combining giant brightness and remarkable stability have been achieved. They offer major promise for bioimaging based on both excitation and detection in the NIR region
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Matsumoto, Katsuhiko. "Development of fluorescent probes for sequence-specific detection of DNA and RNA." Kyoto University, 2012. http://hdl.handle.net/2433/157395.
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McQueen, Adonis. "Synthesis, in vitro Characterization and Applications of Novel 8-Aminoquinoline Fluorescent Probes." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7062.
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Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has seen minimal resistance development. 8-AQs have been shown to be effective against erythrocytic and exo-erythrocytic forms of plasmodium, and are often given in combination with a blood schizonticide such as chloroquine or artemisinin. These combinations clear all forms of plasmodium infection. With 8-AQs unique set of anti-malarial properties and the advent of increased drug resistance to other drugs, much research is being done to understand 8-AQs mechanism of action and toxicity. 8-AQ use is limited due to inducing extreme hemolytic anemia in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Primaquine is the only 8-AQ molecule available on the market with tafenoquine, an analog primaquine, currently in phase III clinical trials. It is believed that if the mechanism of action and toxicity of the 8-AQs are understood, then we can create new generation anti-malarials that will maintain the unique action of 8-AQs while reducing their toxicity. Studies have shown that 8-AQ mechanism of action has been attributed to the generation of unstable metabolites that induce ROS production in the parasite, as well as mitochondrial swelling. While there is some evidence suggesting molecular targets of 8-AQs, the actual target is still unknown. When 8-AQs is given in combination with chloroquine, a synergistic effect is observed. While chloroquine has no activity against liver stages, it still somehow potentiates primaquine’s activity in those stages. This mechanism of synergy in liver stages is not well understood, and its understanding can give us increased understanding of basic plasmodium biology in the liver. Additionally, more information about the mechanisms of action of both chloroquine and primaquine could be elucidated. Tagging drugs with fluorescent probes is a technique that can give much information about the drug’s pharmacological activity in vitro, and sometimes in vivo as well. Such an approach has been used for various disease states such as HIV and cancer. Malaria is no exception; fluorescent probes of artemisinin and chloroquine have been used to examine resistance mechanisms to both molecules. In addition to 8-AQs, there are other older antimalarials that have received attention recently due to increases in resistance. Menoctone, a hydroxynapthoquinone that subsequently lead to the discovery of atovaquone, has recently gained increased attention because of its similarities to atovaquone. Research surrounding menoctone was abandoned due to the discovery of more efficacious compounds. Similar to 8-AQs, understanding the mechanisms of action and resistance to menoctone could give us much more information about plasmodium responses to this class of compounds. This understanding could potentially lead to the discovery of novel therapeutics. To understand mechanisms of action and synergy of 8-AQs, we report the creation of novel fluorescent probes of the 8-AQ molecules primaquine and tafenoquine. The organic synthesis was designed and characterization was confirmed by NMR and high resolution mass spectra, and the fluorescent properties were examined using absorbance and steady-state emission experiments. We found that the anti-malarial, anti-leishmaniasis, and cytotoxic properties of these novel probes were similar to the parent compounds. These probes localized in the cytoplasm of infected parasites in vitro. We also attempted to view their localization in liver stage infection, and investigated the synergistic combination of 8-AQs with chloroquine and quinine. Menoctone resistance was induced in vivo to determine mechanisms of resistance. Cross resistance to atovaquone was observed, and the mutation responsible for resistance was also found.
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Wang, Lei. "Molecular Probes for Pancreatic Cancer Imaging." PDXScholar, 2016. http://pdxscholar.library.pdx.edu/open_access_etds/3108.
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Pancreatic ductal adenocarcinoma (PDAC) has the poorest five-year survival rate of any cancer. Currently, there are no effective diagnostics or chemotherapeutics. Surgical resection is the only curative therapy. However, most patients experience recurrence due largely to challenges in assessing tumor margin status in the operating room. Molecular probes that selectively highlight pancreatic cancer tissue, having the potential to improve PDAC margin assessment intraoperatively, are urgently needed. In this work, a series of red and near-infrared fluorescent probes is reported. Two were found to distribute to normal pancreas following systemic administration. One selectively accumulates in genetically modified mouse models of PDAC, providing cancer-specific fluorescence. In contrast to the small molecule probes reported previously, it possesses inherent affinity for PDAC cells and tissue, and thus does not require conjugation to targeting agents. Moreover, the probe exhibits intracellular accumulation and enables visualization of four levels of structure including the whole organ, tissue, individual cells and subcellular organelles. It can thus promote new strategies for precision image-guided surgery, pancreatic cancer detection, the monitoring of therapeutic outcomes and basic research.
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You, Qihua. "Development of fluorescent chemosensors based on different signal transduction mechanisms." HKBU Institutional Repository, 2014. https://repository.hkbu.edu.hk/etd_oa/95.
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A series of fluorescent probes based on different signal transduction mechanisms for the detection of Fe3+, Zn2+, histidine and pH was designed and synthesized. Their photophysical properties, binding abilities and the further application in cell imaging were fully evaluated. Building on the groundwork of our previous study, molecular scaffold 19 has been appended to spirobenzopyran fluorophore to furnish a highly selective and sensitive Zn2+ sensor. To broaden the application scope of this trifunctional receptive molecule, 19 was incorporated onto rhodamine, antipyrine and coumarin moieties to give 20, 21 and 23, respectively. Probe 20 operative on a chelation-enhanced fluorescence mechanism exhibited highly selective response to Fe3+ with 2:1 stoichiometry of 20-Fe3+ complex. However, a possible tendency of probe 20 to hydrolyze induced by Fe3+ and the unsuccessful attempt of cell imaging would limit its application scope. Probe 21 with O-N-N-N-N-ligand showed a highly selective and sensitive detection of Zn2+. The probe displayed suppressed response to Cd2+ which is the most common interference ion in zinc metal detection. The binding of Zn2+ to probe 21 inhibited the photoinduced electron transfer process originating from the lone pair of the nitrogen atom in the antipyrine moiety to quinoline fluorophore. Therefore, a turn-on fluorescent probe was developed. A moderate binding constant with 1:1 stoichiometry of 21-Zn2+ complex was established by fluorescence titration. The binding mechanism was fully explained by 1H NMR titration. To our delight, probe 21 was successfully applied for recognizing Zn2+ in living cells. The preparation of probe 23 was achieved by appendage of 19 to coumarin derived fluorophore and the probe exhibited a good selectivity and fluorescent turn-off property to Cu2+. The 1:1 stoichiometry of 23-Cu2+ ensemble can serve as an efficient probe for the detection of histidine and biothiols. In the presence of NEM, the influence of biothiols could be eliminated. Furthermore, this sensing ensemble was also used in the detection of histidine in hard-to-transfect U87MG cells with very low cytotoxicity. Based on our group’s previous work on the spiropyran platform, a novel ratiometric near-infrared pH probe 27 operating on an excited-state intramolecular electron transfer mechanism was developed. The pKa was calculated to be 5.9 and the ring-opening/ring-closing mechanism triggered by protons was reasonably explained by 1H NMR titration. However, this spiropyran-based probe was found to be unsuitable for cell imaging. To continue the innovation of pH sensing and extend its application in bioimaging, a series of ratiometric pH probes 32 and 38 characterized by their high quantum yield working in the NIR range was developed. The appendage of N,O-disubstituted hemiaminal ether moiety onto coumarin fluorophore with C=C double bond conferred the sensory material with the ability to display a pH-dependent ratiometric output operating on the ring-opening/ring-closing mechanism. The pKa of 32 and 38 were 6.9 and 5.8 – 6.0, respectively, which rendered them suitable for pH measurement in near-neutral and acidic media. A preliminary work of intracellular pH measurement was also conducted and promising results were obtained
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Sun, Zhenning. "Studies on fluorescent probes for the specific detection of reactive oxygen species and reactive nitrogen species in living cells." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36845395.
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Oleynik, Paul. "Design, synthesis, and characterization of new fluorescent probes for in vivo redox visualization." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18789.
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We have initiated a research program intended to prepare lipid soluble free radical sensitive fluorescent probes which can readily report the antioxidant activity within the lipid bilayers. This work provides a substantial amount of information useful in the rational design of pyrromethane dye-based off-on fluorescent probes/switches for redox visualization. In this thesis we report the photophysical properties of a newly prepared Trolox®-PM605 dye (B-TOH) which exhibits a marked off-on fluorescence behaviour in the presence of radicals in homogeneous and microheterogeneous solutions. The absorption and fluorescence spectra, fluorescence quantum yields, and fluorescence lifetimes for this probe when dissolved in organic solvents, as well as in dimirystoyl phosphatidylcholine (DMPC) lipid vesicle suspensions in water are reported herein. The analogous photophysical properties were measured for PM605, the precursor fluorophore used in B-TOH synthesis, its deacylated derivative PM-OH, and a control probe 3,5-Di-tert-butyl-4-hydroxybenzoic acid-PM605 (PM-BHB, which is expected to have a lower reactivity towards radicals) adduct whose synthesis is further described herein. We also report the emission time profile of B-TOH, PM-BHB, and PM-OH following their prolonged exposure to peroxyl radicals in organic solvents and liposome water suspensions. Via careful electrochemical analysis and HPLC oxidation product studies, the observed emission growth of B-TOH is shown to occur via the deactivation of a Photoinduced Electron Transfer (PET) process, operative only in reduced B-TOH. Following exposure of B-TOH to free radicals and subsequent oxidation, PET is surpressed. In summary, we report a novel hydrophobic fluorescent antioxidant indicator with optimum off/on ratio properties for homogeneous solution studies. Antioxidant depletion and the onset of radical mediated oxidation can be directly monitored following emission enhancement over time, thus dramatically facilitatiNous avons initié un programme de recherche qui a pour but de développer des sondes fluorescentes, sensibles aux radicaux libres, qui soient solubles dans les solutions lipidiques. Ces sondes devront pouvoir rapporter les activités anti-oxidantes des bi-couches lipidiques. Ce travail fournit des informations importantes pour la conception rationnelle de colorants dérivés du pyrrométhane qui pourront servir d'indicateurs fluorescents "on-off" de la visualisation des réactions redox. Dans cette thèse, nous rapportons les propriétés du nouvel indicateur Trolox-PM605 (B-TOH) qui montre un comportement fluorescent "on-off" marqué en présence de radicaux en solutions homogènes et micro-homogènes. Les spectres d'absorption et de fluorescence, les taux de fluorescence quantique, et la durée de vie de la fluorescence pour cette sonde quand dissoute dans des solvants organiques ainsi que dans des vésicules lipidiques de dimirystoyl de phoshatidylcholine (DMPC) en suspensions dans l'eau sont également rapportées. Les propriétés analogues photophysiques du PM605 (le précurseur fluorophore utilisé pour la synthèse du B-TOH) et du PM-OH (son dérivé acétyle) ainsi que celles d'une sonde contrôle, le 3,5-Di-tert-butyl-4-hydroxybenzoic acid-PM605 (PM-BHB, dont il est attendu d'observer une plus faible réactivité envers les radicaux libres) ont ainsi été mesurées. Nous rapportons également le profil temporel d'émission du B-TOH, du PM-BHB ainsi que du PM-OH, à la suite de leur exposition prolongée aux radicaux peroxydes en solution dans des solvants organiques ou des suspensions aqueuses de liposomes. De précises analyses électrochimiques et des études des produits d'oxidation HPLC ont permis l'observation de la croissance de l'émission du B-TOH, qui se déroule via la désactivation d'un processus de Transfert d'Electron Photo-induit (TEP), ce processus ne s'opérant que dans le contexte du B-TOH réduit. A la suite de l'exposition du B-T
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White, Brittany. "The Synthesis of Functionalized Cycloparaphenylenes as Novel Biocompatible Fluorescent Probes and Organic Materials." Thesis, University of Oregon, 2019. http://hdl.handle.net/1794/24521.
Full textAbstract:
Conjugated macrocycles have emerged as novel structural motifs that modulate the electronic properties of organic molecules because of their strained and contorted structures. Cycloparaphenylenes, known as nanohoops, are a particularly attractive scaffold for the design of new types of carbon nanomaterials because of their size-selective synthesis, radially oriented π-systems and tunable electronic properties. The development of modular syntheses of nanohoops over the past decade should enable the preparation of substituted derivatives that can be tuned for applications in biology and materials science.
Chapter I provides a brief overview of conjugated macrocycles recently reported in the literature with a discussion of the structural effects that are responsible for the remarkable properties of this class of molecules. Chapter II highlights a scalable and mild synthetic approach developed in our lab to prepare nanohoop conjugated macrocycles and expands the generality of this methodology with the formal synthesis of natural product Acerogenin E. Chapter III describes the synthesis of cycloparaphenylenes with versatile functional handles and uncovers the reactivity of the strain nanohoop backbone under reaction conditions that promote the formation of radical cations. Chapter IV takes advantage of the functional groups described in chapter III to develop the first example of nanohoops as a new class of biocompatible fluorophores. Chapter V details a novel synthetic approach that enables the incorporation of the linear acene pentacene into the nanohoop backbone and reports our findings on the impact that the macrocyclic structure has on the properties of this organic semiconductor. In summary, the findings discussed in this dissertation provide synthetic strategies for the selective functionalization of nanohoops and highlight this class of molecules as a novel scaffold for the design of new types of carbon nanomaterials.
This dissertation includes previously published and unpublished co-authored material.