Synthesis and Supramolecular Applications of Receptors for Molecular Recognition

Abstract

Molecular recognition is an important front in supramolecular chemistry for many years. Even though many synthetic receptors for anions/ cations have been investigated, further works are still necessary in order to design well selective synthetic receptors for specific anions/ cations because anion binding is a key process in many chemical and biological processes. In this study, we synthesize naphthalene-, anthracene-imidazolium, acridine-imidazolium and pyrene based receptors for specific anion/ cation recognition. In chapter 2, DNA intercalation has been very useful for engineering DNA-based functional materials. It is generally expected that the intercalation phenomenon in RNA would be similar to that in DNA. Here we note that the neighbor-exclusion principle is violated in RNA by naphthalene-based cationic probes, in contrast to the fact that it is usually valid in DNA. All the intercalation structures are responsible for the fluorescence, where small naphthalene moieties are intercalated in between bases via π-π interactions. The structure is aided by hydrogen bond between cationic moieties and ribose-phosphate backbone, which results in specific selectivity for RNA over DNA. This experimentally observed mechanism is supported by computationally reproducing the fluorescence and CD data. MD simulations confirm the unfolding of RNA due to intercalation of probes. Elucidation of the mechanism of selective sensing for RNA over DNA would be highly beneficial for dynamical observation of RNA which is essential for studying its biological roles. In chapter 3, Pyrene-based turn-on ratiometric fluorescent probe 1 demonstrates high sensitivity and exceptional selectivity toward Cr3+ in the presence of other metals including Fe3+ in aqueous media. Interaction of Cr3+ with probe 1 brings pyrene moieties close enough to have better aligned π-π stacking, thus enhancing the excimer peak many folds. On the other hand, the interaction of Fe3+ with probe 1 brings forth negligible difference in stacking, resulting in an insignificant change in fluorescence intensity. Exceptional selectivity of Probe 1 with Cr3+ over Fe3+ and other metals has been confirmed by theoretical studies in addition to experimental results. Imaging of HeLa cells observed by confocal fluorescence microscopy reveals that probe 1 can be used to monitor Cr3+ in live cells to map its subcellular distribution. In chapter 4, Cationic cyclophanes with bridging and spacer groups possess well-organized semirigid cavities and are able to encapsulate and stabilize anionic species through diverse molecular interactions. We highlight the precise tuning of functionalized cyclophanes toward selective recognition of AMP, GTP, and pyrophosphate (PPi) using fluorescence, NMR spectroscopy, and density functional theory (DFT). In chapter 5, Anion detection through ionic hydrogen bonding is a challenging task in aqueous solution due to potential interference from the solvent. In the case of GTP and Iodide, it is particularly more so due to the sugar moiety and heavy atom effect, respectively. This work shows that GTP and Iodide can exhibit characteristic responses upon binding to fluorescent receptors, which make selective detection possible. A water-soluble fluorescent chemosensors function as GTP and Iodide sensors selectively through chelation-enhanced fluorescence quenching over other biologically relevant anions in aqueous solution of physiological pH 7.4. These affinities can be attributed to the strong ionic H-bonding along with additional interactions of fluorophore moieties with the nucleic base of GTP and Iˉ.