Zeng, Binqui2017-06-052017-06-0519972017-06-05http://hdl.handle.net/1828/8227This thesis comprises three parts united by a single theme: development of flexible ditopic receptors. In part 1, two bis(crown ether)s were synthesized and their binding selectivities with alkali, alkaline earth and α,ω-primaryalkylidenediammonium cations were studied by electrospray ionization mass spectrometry (ESI-MS). First, we confirmed that the ion intensities of complexes in the gas phase are linearly related to the concentrations of complexes in solution for single crown ether dicarboxylic acid. Binding selectivities of complex bis(crown ether)s with mixtures of alkali cations and with mixtures of alkaline earth cations were then determined directly from ESI-MS spectra. The results from ESIMS are consistent with literature data if ions of like charge and similar type are compared (e. g., among the alkali metals). The stoichiometries of complexes in solution were also probed. Complexes with up to two K⁺ per crown ether were detected by ESI-MS. The research shows that ESI-MS provides an effective tool to study complexation by structurally complex molecules in solution. From the ESI-MS results, bis(crown ether) bolaamphiphiles were designed and synthesized as cation-recognition based membrane-disruption agents. Three bis(crown ether)s were obtained by capping an 18-crown-6 dicarboxylate anhydride with different lengthes of α,ω-alkanedicarboxylic acids extended as the 3-amino-1-propyl esters. Their membrane disrupting activities were explored using vesicle encapsulated 5(6)- carboxyfluorescein (CF) by a fluorescence self-quenching (FSQ) method. The membrane disrupting activity is significantly and specifically enhanced specifically by the addition Sr²⁺ or Ba²⁺ in solution. The membrane-disrupting activity is also enhanced with a increased aliphatic loop length of the starting α,ω-alkanedicarboxylic acid. Based on the mechanism studies of Regen and work conducted in this thesis, we propose that the active form for membrane-disruption is created by a U-shaped sandwich complex between Ba²⁺ and the bis(crown ether) bolaamphiphiles which interacts only with the outer leaflet of the vesicle bilayer. In part 3, a photoswitchable bis(crown ether) based on thioindigo was designed and synthesized as a cation- and photo-regulated membrane-disruption agent. The bis(crown ether) was prepared by capping an 18-crown-6 dicarboxylate anhydride with 7,7’-thioindigo dicarboxylic acid extended as the 8-amino-1-octanyl esters. There is significant difference in the membrane-disrupting activities of the cis- (U-shape) and trans- (S-shape) isomers using the vesicle entrapped CF (FSQ) method. Alkaline earth cations suppress the cis-to-trans thermal isomerization and stabilize the cis-isomers of the 7,7’- thioindigo bis(crown ether) in organic solvent. The results confirm the mechanism proposed, namely, that a U-shaped conformation is required for membrane disruption, that the bis(crown ether)s form sandwich complexes with alkaline earth metal ions.enAvailable to the World Wide WebIon channelsDrug receptorsThesis