This 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. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/8227 |
| Date | 05 June 2017 |
| Creators | Zeng, Binqui |
| Contributors | Fyles, Thomas M. |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | Available to the World Wide Web |
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