Browsing by Subject "Porphyrins--Synthesis"
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Item Cyclo[n]pyrroles and their applications(2006) Lee, Jeong Tae; Sessler, Jonathan L.; Whitman, Christian P.Item Development of new methodologies for the synthesis of expanded porphyrins and aspects of the conformational behavior of some previously unknown oligopyrrolic systems(2002) Seidel, Daniel; Sessler, Jonathan L.In spite of the considerable number of expanded porphyrin systems that are now known, methods for synthesizing these compounds remain quite limited. Aspects of this dissertation address this problem. For instance, in Chapter 2 a new methodology that allows, for the first time, the synthesis of quaterpyrrolecontaining expanded porphyrins is described. Specifically, using a Cr(VI)-based oxidative coupling approach, three previously unknown macrocycles were synthesized that were inaccessible using classic approaches. Likewise, in Chapter 4 the use of new Fe(III)-based oxidative couplings as a very effective way to produce previously unknown cyclo[8]pyrroles is detailed. The latter macrocycles, species of remarkable symmetry and potential utility, are prepared in high yields in a single synthetic step from readily available bipyrrolic precursors. Further, a modification of this strategy is presented that allows for the synthesis of linear quaterpyrrole, a species characterized structurally for the first time in the course of this work. The second major focus of this dissertation work was the study of conformational effects in oligopyrrolic macrocycles. A remarkable range of conformations is seen in many expanded porphyrins. This is not the result of rational design. Rather, it is an intrinsic feature of these systems, albeit an unexpected one. A desire to understand the origins of these effects has prompted the synthesis and study of four new expanded porphyrins. This work is presented in Chapter 3, wherein the use of simple symmetry considerations in the design and conformational analysis of previously unknown systems is described.Item Synthesis and studies of gadolinium texaphyrin conjugates and model platinum therapeutic agents(2008-08) Fountain, Mark Edward, 1960-; Sessler, Jonathan L.The experimental cancer therapeutic agent gadolinium texaphyrin (MGd) is a cationic paramagnetic expanded porphyrin currently being tested as an X-Ray sensitizing (XRS) agent, and is a compound with demonstrated tumor localization. Additionally MGd shows promise as a chemotherapeutic agent, both as a stand-alone agent, and showing activity in vitro with ascorbate via a novel ROS generating mechanism.3 This dissertation reports the synthesis, characterization, and cell studies of novel MGdfluorophore, and platinum therapeutic conjugates. Also discussed are cationic Pt agents having cytotoxic activity. In this research we set out to answer three questions: i) can fluorescent conjugates of MGd be synthesized, with observable subcellular localization, different from that of MGd, ii) can MGd-Pt conjugates with observable Pt release be synthesized?, and iii) can Pt compounds containing a cationic moiety be tuned to have efficacy comparable to traditional Pt therapeutic agents? Two MGd-xanthene fluorophore conjugates were synthesized with the goal of using them to probe sub-cellular distribution. The anionic (FITC), and cationic (Rhodamine), fluorophore conjugates demonstrated nuclear and mitochondrial localization, respectively. In an ongoing project designed to reduce non-specific agent toxicity, a platinumreleasing MGd therapeutic conjugate was synthesized. The MGd-amidopropylmalonato-Pt conjugate demonstrated efficacy equivalent to carboplatin, a classical “non-selective” agent as inferred from in-vitro studies with A549 lung cancer cells. Aqueous stability studies of this conjugate gave results in agreement with hydrolytic loss of Pt, reversible with added Pt-diaquo. Finally, Pt complexes of amino-1-benzylpyridinium salts were synthesized and found to demonstrate significant cytotoxicity in screening studies. This latter positive development led to the suggestion that complexes of this type could consititute a new class of lipophilic-quaternary-cation Pt therapeutic agents. It is hoped that this series of putative Pt anti-cancer agents will prove useful as both stand-alone therapeutic agents and as the basis for producing conjugate with biolocalizing properties.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.