Browsing by Subject "Dendrimers"
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Item Dyes and indicators in molecular sensing ensembles : progress toward novel uses of dendrimers and reactands in optical sensing methods(2008-12) Rainwater, John Chance, 1979-; Anslyn, Eric V., 1960-Over the past two decades, the field of molecular sensing has developed into a mature offshoot of molecular recognition, and sensing protocols based on optical signal modulations have enjoyed particularly great success. Such sensing methods are the focus of this dissertation, in which efforts toward the integration of dendrimers and reactands into separate, optically-based sensing platforms are described. To this end, Chapter 1 provides a brief introduction to molecular sensing and its supramolecular underpinnings. The remainder of Chapter 1 is dedicated to dendrimers and their application to molecular recognition and sensing. A discussion of the physicochemical properties of dendrimers is also included to lend perspective on the structure, size, and shape of these macromolecules. The role of dyes and indicators in the elucidation of dendritic structure and function is given special consideration. Finally, selected reports of dendrimers in molecular recognition and optical sensing are summarized. Chapter 2 details original research directed toward the incorporation of dendrimers into molecular sensing ensembles. This use of dendrimers in molecular recognition and sensing is distinguished from those examples described in Chapter 1 by its modular nature. This modularity is achieved through the use of a non-covalent sensing motif based on indicator displacement. The identification and optimization of the appropriate components for use in such dendrimer-based sensing ensembles represents a contribution of the research described herein. An evaluation of indicator dyes for their incorporation into an enantioselective indicator displacement assay (eIDA) for common organic molecules is the subject of the research discussed in Chapter 3. The selected indicator dyes were assessed for use in a novel eIDA that relies on covalent bond formation for the enantioselective signaling of monofunctional organic analytes. A survey of colorimetric methods for the identification and discrimination of amines is included because these compounds served as an initial target in the proposed assay. Optical enantiosensing strategies are also reviewed in light of their relevance to the present work.Item Photophysics of perylene diimides in solutions and self-assembled films(2006) Tang, Tingji; Bout, David A. VandenItem Synthesis and biological evaluation of 2-(2'-hydroxyphenyl) benzoxazole analogs of UK-1 and G-quadruplex selectivity of perylene diimide compounds: /(2007-12) McKee, Mireya Loreley, 1978-; Kerwin, Sean M.A great number of pharmaceutical drugs target nucleic acids. However, drug-DNA interactions can be region non-specific and lead to undesired side effects. Understanding the mechanisms that regulate drug-DNA binding can help in the design of potent and selective therapeutic agents with fewer deleterious side effects. The present investigation explores the metal-mediated DNA binding of a group of 2-(2-hydroxyphenyl)benzoxazole (HPB) ligands and the aggregation dependant G-quadruplex selectivity of a series of perylene tetracarboxylic acid diimides (PTCDI) compounds. HPB ligands are simplified analogs of the bis-benzoxazole natural product UK-1. This compound is able to inhibit cell growth of various tumor cell lines, bind divalent cations, and interact with DNA in a metal dependant fashion. The HPB moiety present in UK-1 was identified as relevant for its metal ion binding and biological properties. For this work, novel HPB ligands were synthesized with different substitutions at the C4 or C7 position. Their ability to bind metal ions and DNA was evaluated and their cytotoxicity was assessed in multiple cancer cell lines. The ligands bound to Cu²⁺ with the highest affinity among metals studied. Consequently, Cu²⁺ promoted the most dramatic increase in DNA binding and affected the ligand's cellular cytotoxicity. The second project focused on targeting four-stranded structures called G-quadruplexes, which can form in G-rich nucleic acid sequences. Compounds that stabilize these structures may inhibit nucleic acid-processing enzymes such as telomerase and potentially act as anti-cancer agents. PIPER is a PTCDI that is particularly selective for G-quadruplex DNA versus duplex DNA under conditions in which it forms aggregates. This work investigated ligand aggregation in a series of PIPER analogs with different structural features under high and low salt buffers, changes in pH, metal binding and temperature changes. A negatively charged analog was determined to form metal-mediated aggregates while novel thermophilic mediated aggregation was discovered for an analog with methoxyethoxymethyl groups. The ability of these ligands to bind different DNA structures was evaluated under aggregating and non-aggregating conditions. This study supports the idea that ligand aggregation increases their quadruplex selectivity and decreases double-stranded DNA binding.