Browsing by Subject "Porphyrins"
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Item Combining recognition motifs for improved sensing and biological activity of phosphorylated molecules(2010-08) Hargrove, Amanda E.; Sessler, Jonathan L.; Anslyn, Eric V., 1960-; Ellington, Andrew D.; Peppas, Nicholas A.; Brodbelt, JenniferPhosphorylated molecules play vastly important roles in the environment and biological systems. The main focus of this work sought to expand the current collection of synthetic phosphate receptors to include the binding of oligosaccharide phosphates. To this end, the synthesis of a boronic acid - appended porphyrin whose selectivity could be tuned through nucleic acid selection was pursued through a number of synthetic routes. Though difficulties were encountered with synthetic reactivities and product solubility, these efforts culminated in the development of a bis-boronic acid-substituted porphyrin soluble in DMSO/water mixtures that displays fluorescence quenching upon the addition of specific saccharide derivatives. In efforts to ease the synthetic burden, the creation of a DNA-based self-assembled receptor system was also investigated. Further, this work included the synthesis of phosphorylated derivatives of gemcitabine, a nucleoside chemotherapeutic drug, with the goal of developing targeted delivery systems for the improved treatment of cancer. Progress in each of these areas is discussed.Item Electron transport in single-molecule transistors(2006) Chae, Dong-hun; Yao, Zhen, Ph. D.Item Expanded porphyrins as experimental anticancer agents and MRI contrast agents(2012-12) Preihs, Christian; Sessler, Jonathan L.Texaphyrins represent the vanguard of experimental anticancer drugs and also symbolize a well-known example of expanded porphyrins, a class of oligopyrrolic macrocycles with tumor localization properties and powerful metal chelating properties. Chapter 1 of this thesis describes the unique structural characteristics of this complex synthetic molecule along with the biological relevance and scientific justifications for studying its anticancer properties and powerful MRI contrast ability. This Chapter also serves to underscore the need to improve further and refine the efficacy of texaphyrins as compounds that may be applied in the struggle against cancer. Chapter 2 details the synthesis of bismuth(III) and lead(II)-texaphyrin complexes that could potentially find use as [alpha]-core emitters for radiotherapy. In principle, porphyrins would ostensibly appear to be ideal ligands for use in radiotherapy due to their tumor-localizing ability. However, Bi(III)- and Pb(II)-porphyrin complexes are extremely rare, most reflecting the vastly challenging synthesis of these compounds as well as their general lack of stability. These limitations provided an incentive for us to use texaphyrins as more versatile ligands to prepare and fully characterize stable bismuth(III) and lead(II) complexes. To be of interest in future medical applications, we needed to prepare these complexes quickly as compared to the relevant time scales set by the half-lives of the isotopes targeted for use in radiotherapy. This goal was successfully realized. As mentioned above, texaphyrin is able to form stable complexes with a large variety of metals particularly in the lanthanide series. Gadolinium(III) complexes of texaphyrin have been studied in considerable detail. Chapter 3 details the synthesis and conjugation methods used to develop a texaphyrin conjugated dual mode nanoparticle contrast agent. This project has been done in collaboration with the group of Prof. Jinwoo Cheon (Yonsei University, Seoul, Korea), who demonstrated fascinating results with the texaphyrin functionalized nanoparticles. Not only do these conjugates act as improved magnetic resonance contrast agents displaying enhanced signals in both the T1 and T2 MRI modes, but also serve to sensitize apoptotic hyperthermia. It is this latter, double effector feature, that has been most extensively studied to date. Chapter 4 of this dissertation describes work done in close collaboration with Dr. Natalie Barkey and Dr. David Morse (Moffitt Cancer Center, Tampa, FL) where a gadolinium texaphyrin complex was developed that is able to target the melanocortin 1 receptor (MC1R) when encapsulated in a micellar system. As detailed in this Chapter, these collaborateurs demonstrated that these gadolinium-texaphyrin micelles are able to target MC1R-expressing xenograft tumors in vivo. This work relied on the supply of a new set of texaphyrin derivatives that were prepared and characterized as part of this dissertation work Chapter 5 of this disseration introduces sapphyrins, another class of expanded porphyrins with tumor selectivity. This project is based on the hypothesis that a direct linkage of sapphyrin with an anticancer agent based on ruthenium(II) could improve the efficacy of both compounds. Since sapphyrins exhibit limited ability to form stable complexes with transition metals, an appended 1,10-phenanthroline unit was chosen as an efficient N-donor aromatic ligand for ruthenium(II). Therefore, extensive synthetic efforts were made to form this sapphyrin-1,10-phenanthroline construct in an effort to stabilize a mixed sapphyrin-metallo-phenanthroline complex. Finally, Chapter 6 of this dissertation demonstrates the author's efforts to synthesize a planar rosarin species. Non-aromatic and non-planar rosarins have been known for over two decades. Through structural modification of the compound, namely through linking of both [Beta] positions on the bipyrrole unit, a new planar rosarin species has been synthesized exhibiting Hückel antiaromaticity.Item Porphyrin profile and chelator techniques in the assessment of mercury exposure and effects(Texas Tech University, 2000-05) Rummel, Kevin ToddHeavy metal contamination is wide spread globally as a result of mining and other industrial processes. Health effects end points, or biomarkers, combined with accurate estimates of target tissue metal burdens, are necessary to more precisely determine the risk posed to wildlife and humans. An optimal assessment tool would be one that non-lethally assesses both heavy metal health effects and metal burdens at target site soft tissues, allowing researchers to sample a given animal multiple times in a given year, use more animals than would otherwise be permitted (increasing the statistical power to the local population level), and study animals for which access is generally restricted, such as threatened or endangered species. A technique was developed using porphyrin profile alterations as a marker of biochemical effects, and the water-soluble chelator DMPS to approximate soft tissue mercury burdens through urinary depuration. A collection of urine is taken, DMPS is administered, and a subsequent urine sample is collected. The pre-chelation urinary porphyrin concentrations are indicative of existing health status, while the post-chelation urinary mercury residues approximate the soft tissue mercury burden. Preliminary studies with the prairie vole {Microtus ochrogastor) and deer mice {Peromyscus maniculatus) indicated the vole was the preferred test species based on responsiveness and urine volume generated. Methyl-mercury in drinking water (5 ppm) led to significant, 2-3 fold increases in urinary 5- and 4-CP. In voles exposed to methylmercury in their drinking water sub-chronically, renal residues increased in a dose dependent manner, with a plateau in concentration before, or during, the first three weeks of exposure. Urinary and renal porphyrins were analyzed and were highly variable. A field trial was performed on the Carson River mercury site near Virginia City, Nevada. Deer mice {Peromyscus maniculatus) and mountain voles {Microtus montanus) captured on this site had elevated mercury and porphyrin concentration when compared to reference site animals from the east fork of the Carson River. In deer mice, renal 4- carboxylporphyrin was significantly correlated to renal mercury resides (r = 0.4294, p = 0.0001, n = 38), while vole urinary pre-chelation 5-carboxylporphyrin was significantly related to urinary post-chelation organic mercury concentrations (r = 0.5870, p = 0.0001, n = 32). These findings support the continued study and application of the combined porphyrin profile/DMPS challenge technique to wildlife inhabiting metal contaminated sites. With further experimentation, this tool offers the capability to better assess heavy metal contamination and effects non-lethally in wildlife species under a variety of exposure scenarios.Item Sapphyrins : aggregation and anion binding behavior in polar, protic media(2001-12) Davis, Julian Murray; Sessler, Jonathan L.Sapphyrin was the first expanded porphyrin to be reported in the literature and remains among the most extensively studied of all expanded porphyrins. Much of the interest in this macrocycle reflects its ability to bind anions, a phenomenon that has been examined in solution and in the solid state by a wide range of experimental techniques. The first chapter of this dissertation provides a history of the anion binding chemistry of the sapphyrins, as well as a review of the synthetic methodologies employed to make them. The second chapter builds upon this work by examining the interactions of several water soluble sapphyrins with phosphate and chloride anions in aqueous media. The binding of phosphate and chloride anions in this milieu was found to be closely related to the aggregation state of sapphyrin, the study of which by optical spectroscopic techniques is also discussed in Chapter 2. In order to study the aggregation behavior of sapphyrins further, several 10,15-diaryl sapphyrins were prepared. The preparation and characterization of these systems is discussed in Chapter 3. The dimerization constants of these systems were measured in methanol, and a preliminary study of their anion binding behavior in organic solvents was performed. Finally, in Chapter 4, the synthesis of a new bipyrrole is laid out and several sapphyrin systems that could be prepared from this precursor are proposed. Future directions for the work described in this dissertation are also presented in this chapter. Experimental methods and characterization data for compounds synthesized by the author are presented in Chapter 5.Item Synthesis and anion binding studies of pyrazole and biimidazole-containing receptors(2005-08) Rubin, Bobbi Linden; Sessler, Jonathan L.This dissertation covers two different topics within the area of diaza-containing aromatic five-membered rings: biimidazoles and pyrazoles. With the exception that both these subject matters are explored in the context of developing new anion binding agents, the background and research associated with these two topics are vastly different and will be treated as such. Chapter two, dealing with biimidazoles, focuses solely on expanded porphyrins, while chapter three discusses pyrazoles as potential macrocyclic building blocks and as diamidic-functionalized anion binders. The first chapter covers several different topics in order to put into perspective the diverse subject matter presented in this dissertation. It begins with an overview of some well-known expanded porphyrins. The synthesis, classical applications, and newer studies of the biimidazole synthetic efforts are then described. The third part of the introductory chapter covers the synthesis and applications of pyrazoles. The use of heterocycles with more than one heteroatom in the construction of expanded porphyrins is just beginning to be explored, and is the focus of chapter two. The synthesis of a novel expanded porphyrin is described and its applications are investigated. More specifically, chapter two covers the synthesis of several biimidazole dialdehydes and their condensation with three 3,3',4,4'-functionalized bis-[alpha]-free bipyrroles to form a series of novel macrocycles. The characterization of these new compounds has been investigated and is discussed in detail. Also presented are preliminary studies of their anion binding properties. Pyrazoles, the subject of chapter three, are another overlooked class of potential building blocks in the area of expanded porphyrins and molecular recognition chemistry. Pyrazoles have rarely been reported in the literature as being part of a larger molecular framework. Until this work, their anion binding potential had remained unexplored. Thus, the attempted incorporation of a pyrazole fragment into an expanded porphyrin framework is described. Second, and more significantly, the design, synthesis, and anion binding properties of a new series of diamidic pyrazoles are reported.Item Synthesis, characterization and potential applications of porphyrin analogues: secochlorin and hydrazinophyrin(2004) Callaway, Wyeth Baillie; Sessler, Jonathan L.Expanded porphyrins and porphyrin analogs have attracted much attention in the literature as of late. They have proposed applications in many areas such as photodynamic therapy (PDT), X-ray radiation therapy, anion binding, enzyme models, and catalysis. Therefore, new porphyrin analogs which possess the unique physical or electronic properties appropriate for these applications are desired. Chapter 1 of this dissertation provides a discussion of natural porphyrin and porphyrin derivatives, as well as a more in depth description of advances in porphyrin synthesis and syntheses of porphyrins with extended π-systems. From this introduction, the attempted synthesis of novel π-extended porphyrins is described. During this process a heterofore unavailable pigment, the free-base secochlorin was discovered. Its characterization and preparation are outlined. Functionalization and potential applications of this chlorin isomer are discussed. Chapter 2 departs from the traditional porphyrin field, and presents an introduction to the growing field of Schiff-base expanded porphryins. Experimental work in this chapter describes the synthesis and full characterization of octamethoxy hydrazinophyrin and a water-soluble analog, octaPEGhydrazinophyrin. Chapter 3 begins with an introduction to liquid crystals, then moves to discotic porphyrin liquid crystals and ends with a review of known liquid crystal sensors. The main focus of the chapter is the synthesis and characterization of the first expanded porphyrin liquid crystals and first discotic uranium containing liquid crystals. The end of each chapter contains a discussion of future directions for research and an Experimental section describing the synthesis and characterization data of all novel compounds. Lastly, the Appendix outlines the synthesis of a dipropiol pyrrole that was not incorporated into any of the previous chapters but may be of use in creating functionalized porphyrins and expanded porphyrins.Item Transition metal complexes of expanded porphyrins(2007) Tomat, Elisa; Sessler, Jonathan L.Item Transition metal complexes of expanded porphyrins(2007-05) Tomat, Elisa, 1977-; Sessler, Jonathan L.Over the last three decades, the rapid development of efficient synthetic routes for the preparation of expanded porphyrin macrocycles has allowed the exploration of a new frontier involving “porphyrin-like” coordination chemistry. This doctoral dissertation describes the author’s exploratory journey into the area of transition metal cation complexation using oligopyrrolic macrocycles. The reported synthetic findings were used to gain new insights into the factors affecting the observed coordination modes and to probe the emerging roles of counter-anion effects, tautomeric equilibria and hydrogenbonding interactions in regulating the metalation chemistry of expanded porphyrins. The first chapter provides an updated overview of this relatively young coordination chemistry subfield and introduces the idea of expanded porphyrins as a diverse family of ligands for metalation studies. Chapter 2 details the synthesis of a series of binuclear complexes and illustrates the importance of metal oxidation state, macrocycle protonation and counter-anion effects in terms of defining the final structure of the observed metal complexes. The binding study reported in Chapter 3 demonstrates a strong positive allosteric effect for the coordination of silver(I) cations in a Schiff base expanded porphyrin. Chapter 4 introduces the use of oligopyrrolic macrocycles for the stabilization of early transition metal cations. Specifically, the preparation of a series of vanadium complexes illustrates the bimodal (i.e., covalent and noncovalent) recognition of the non-spherical dioxovanadium(V) species within the macrocyclic cavities. Experimental procedures and characterization data are reported in Chapter 5.