A fast atom bombardment mass spectrometry study of tris (3, 6-dioxaheptyl) amine-alkali metal halide complexes and hydrogen bonded complexes

The objective of this thesis was to demonstrate the potential of fast atom bombardment mass spectrometry (FABMS) as a probe of condensed phase systems and its possible uses for the study of hydrogen bonding. FABMS was used to study three different systems. The first study was aimed at investigating the selectivity of the ligand tris(3,6-dioxaheptyl) amine (tdoha) for the alkali metal cations. FABMS results correlated well with infrared and nmr data. Systems where a crown ether competed with tdoha for a given alkali metal cation were also investigated by fast atom bombardment. The results were found to correlate with the cation affinity of tdoha and the ability of the crown ether to bind the cation. In the second and third studies, H-bonded systems were investigated. The imidazole-electron donor complexes were investigated and FABMS results showed the expected H-bond strength of the respective complexes. The effects of concentration, liquid matrix, water content, deuterium exchange, and pre-ionization of the complex were also investigated. In the third system investigated, the abundance of the diphenyl sulfone-ammonium salt complexes (presumably H-bonded) in the FABMS spectrum were found to correlate with qualitative considerations such as steric hindrance and strength of ion pairs.

Cell-selective modulation of the neuromuscular system in Drosophila

The capacity for all living cells to sense and interact with their environment is a necessity for life. In highly evolved, eukaryotic species, like humans, signalling mechanisms are necessary to regulate the function and survival of all cells in the organism. Synchronizing systemic signalling systems at the cellular, organ and whole-organism level is a formidable task, and for most species requires a large number of signalling molecules and their receptors. One of the major types of signalling molecules used throughout the animal kingdom are modulatory substances (e.x. hormones and peptides). Modulators can act as chemical transmitters, facilitating communication at chemical synapses. There are hundreds of circulating modulators within the mammalian system, but the reason for so many remains a mystery. Recent work with the fruit fly, Drosophila melanogaster demonstrated the capacity for peptides to modulate synaptic transmission in a neuron-specific manner, suggesting that peptides are not simply redundant, but rather may have highly specific roles. Thus, the diversity of peptides may reflect cell-specific functions. The main objective of my doctoral thesis was to examine the extent to which neuromodulator substances and their receptors modulate synaptic transmission at a cell-specific level using D. melanogaster. Using three different modulatory substances, i) octopamine - a biogenic amine released from motor neuron terminals, ii) DPKQDFMRFa - a neuropeptide secreted into circulation, and iii) Proctolin - a pentapeptide released both from motor neuron terminals and into circulation, I was able to investigate not only the capacity of these various substances to work in a cell-selective manner, but also examine the different mechanisms of action and how modulatory substances work in concert to execute systemic functionality . The results support the idea that modulatory substances act in a circuit-selective manner in the central nervous system and in the periphery in order to coordinate and synchronize physiologically and behaviourally relevant outputs. The findings contribute as to why the nervous system encodes so many modulatory substances.