Self-Assembly Through Coordination And Hydrogen-Bonding; Application To The Synthesis Of Metalloreceptors And To RNA Detection
Self-assembly plays a crucial role in many natural and artificial systems. This manuscript illustrates the application of self-assembly principles to the design, synthesis and functions of molecular receptors and probes for biological targets. The objective of Chapter 2 was to synthesize macrocyclic metalloreceptors composed of two triazole-pyridine chelates connected via a xylyl spacer. In our design, the spacers provide interaction sites which define hydrophobic cavities for the binding of extrahelical nucleosides. To this end, three novel strand ligands with terminal hydroxyl, allyl, and amine groups were synthesized. Various metal ions were utilized to pre-organize the structure of the macrocycle through the self-assembly of 2:2 metal:ligand complexes. Following metal templation, macrocyclization would be achieved via Grubb’s metathesis, reductive amination or SN2 reaction. Coordination self-assembly studies with the hydroxyl- and allyl-ligands were hindered due to poor solubility. However, preliminary data analysis of the self-assembly of the more soluble amine-ligand with zinc(II) acetate2, as studied by 1H NMR spectroscopy, suggests that the desired metal templated complex has been formed. In Chapter 3, two ligands using the bis(pyrazole)pyridine chelate as the central platform connecting two aromatic moieties were synthesized. Upon metal coordination, the conformation of the ligands switches to adopt a shape similar to that of molecular tweezers. To explore the self-assembly of a novel molecular tweezer with two metal-binding sites, a third ligand was synthesized. This ligand is comprised of the tridentate (bis(pyrazole)pyridine) unit connected to two terminal bidentate (triazole-pyridine) chelating units via xylyl spacers. In the presence of coordinating anions, the self-assembly outcome of this ligand with proper metal ions would provide a metalloreceptor wherein the substrate binding event is controlled by the coordination chemistry of the terminal chelates. In Chapter 4, a technique known as RNA Fluorescence In Situ Hybridization (RNA-FISH) was used to visualize ribonucleic acids (RNA) in cells. In this method, the detection of RNA relies on the self-assembly of RNA with partially complementary oligonucleotide probes through weak non-covalent interactions. A number of such fluorescein and biotin labeled oligodeoxynucleotide probes were therefore synthesized and utilized for the selective detection of particular RNA molecules in archived formalin-fixed paraffin-embedded tissues.
URI for this recordhttp://hdl.handle.net/1974/15742
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