Fluorescent Chemosensors For Divalent Metal Ions

This thesis describes the rational design of fluorescent sensing systems for paramagnetic Mn2+. The reported fluorescent probes for Mn2+ display quenched fluorescence as a result of interaction between the fluorophore and unpaired electrons of Mn2+ ion. Two different approaches were developed that achieved "ON" fluorescence when sensing Mn2+.;A displacement assay originally designed for detecting paramagnetic Cu 2+ was found to be applicable to Mn2+ with decreased sensitivity. Excess Mn2+ did not compete effectively with Cd 2+ for chelation by Fz1, affording a significant advantage for this system with Mn2+ compared to Cu2+ where excess Cu2+ quenched green fluorescence. The method was applied successfully to the detection of Mn2+ in live A549 cells, one of the first applications of a supramolecular displacement assay in live cell imaging. Fluorescence imaging results correlated well with the behavior observed in vitro.;Some known calcium sensors show "ON" fluorescence when binding Mn 2+ but suffer from severe calcium interference. A series of BAPTA-based ligands were developed whose binding affinity to Mn2+ and Ca 2+ could be tuned by substituting carboxylate groups with pyridines. A new ligand 9 was identified that exhibited strong Mn 2+ selectivity over Ca2+. Fluorescent probes based on 9 were synthesized. Solution and in vitro cell studies showed "ON" fluorescence signal of these sensing molecules towards Mn2+ ion. To our knowledge, probes 20 and 23 are the first selective "ON" fluorescence Mn2+ probes reported.;Soluble derivatives of tris((6-phenyl-2-pyridyl)methyl)amine were found to exhibit pronounced red shift and fluorescence enhancement upon binding Zn2+ in CH3CN. The fluorescence properties of the Zn 2+ ion-coordinated ligands were consistent with charge-transfer character in the excited state, with possible contributions from a planarization of the pyridyl-trimethoxyphenyl groups, and from excitonic interactions.;Lastly, the configurational stability of potentially chiral tertiary amine ligands was measured. A tetradentate tripodal ligand containing a chiral center and three different coordinating arms was designed and synthesized. NMR experiments demonstrated the formation of two diastereomers, indicating the stabilization of the central tertiary amine configuration by metal coordination. The inversion of pyramidalization of the central tertiary amine of the ligand was found to be dependent upon metal ion, solvent, and temperature.