The objectives of this research proposal involve the application of supramolecular organic chemistry in the design of fluorogenic sensors for carbohydrates in aqueous solution. The saccharide receptors feature a cleft-like structure phenylboronic acid groups appended to a fluorescent indicator. It is anticipated that these rigid receptors will lead to a practical method for selectively monitoring saccharides at very low concentrations. Chemosensors that bind carbohydrates with a signal transduction are of particular interest since blood glucose levels are closely regulated to about 4.5 mM. Insights gained from the binding affinities of these receptors may provide new routes to discoveries into drug transport, and separation technologies for racemic sugars. Research design and methods involve modeling studies that provide calculated geometries of binding sites and host-guest interactions. Short and inexpensive synthetic schemes are based on condensation of amino phenylboronic acids with naphthalene anhydrides. Molecular modeling indicates that steric hindrance about the phenyl-imide bond results in atropisomerism of the rigid clefts. Torsional rotation is predicted to have an energy barrier of around 28 kcal/mol. The fixed U-shaped clefts provide fewer possible binding modes and should lead to greater saccharide selectivity. Naphthalene di- and tetra-carboxylic imides act as the fluorophore and have been incorporated by a modular synthetic strategy. These compounds were chosen because of their photostability and high quantum yield (phi = 99 percent). Measurements of binding affinity constants between saccharides and sensors will be obtained from proton NMR titration curves using a least squares analysis program Systat. Fluorescence intensity measurement differences between bound and unbound saccharide will be used to determine Photoinduced Electron Transfer (PET) mechanisms. Recognition events are expected to proceed via chelation enhanced fluorescence (CHEF) pathways, based on dative pi-donation between the imide nitrogen and electron deficient borate anion. Such interactions should result in lowering the working pH of the boronic acid saccharide receptor.
| Paudel, Sangita; Nandhikonda, Premchendar; Heagy, Michael D (2009) A comparative study into two dual fluorescent mechanisms via positional isomers of N-hydroxyarene-1,8-naphthalimides. J Fluoresc 19:681-91 |
| Cao, Zhi; Nandhikonda, Premchendar; Heagy, Michael D (2009) Highly water-soluble monoboronic acid probes that show optical sensitivity to glucose based on 4-sulfo-1,8-naphthalic anhydride. J Org Chem 74:3544-6 |
| Cao, Haishi; McGill, Tom; Heagy, Michael D (2004) Substituent effects on monoboronic acid sensors for saccharides based on N-phenyl-1,8-naphthalenedicarboximides. J Org Chem 69:2959-66 |
