Based on preliminary reports, an extended series of bolamphiphilic oligoester compounds with structural symmetry were synthesized and then tested using a planar bilayer experiment with the voltage-clamp technique. The main structures of these compounds are identical, consisting of a mono or tri-aromatic core, two octamethylene chains and two benzoyl headgroups which are all connected through ester linkages. The structural variance was provided by the four differently functionalized benzoyl headgroups. The synthetic methods of three to five steps were mainly adapted from the previously reported method.1 The methods successfully produced eight compounds with overall yields of 20 to 30%. The voltage-clamp data suggested voltage-dependent behaviors occur at low concentrations while Ohmic behaviors require at high concentrations. The activity at low potentials showed relatively erratic behavior but the channels frequently switched between opening and closing states. The activity at high potential lasted longer as the channel maintained a longer state of opening. The exponential voltage-dependent behaviors were observed at higher potential while the voltage-independent Ohmic behaviors occur at low potential. These channel behaviors are highly time-dependent as there is no control over the stability and the aggregation level for the compounds forming active channels in the membrane. In some cases the current-voltage responses appear to be asymmetrical between the positive and the negative potentials. Mechanisms consistent with the observations are proposed. / Graduate / 0485 / 0490 / yzong@uvic.ca

Based on preliminary reports, an extended series of bolamphiphilic oligoester compounds with structural symmetry were synthesized and then tested using a planar bilayer experiment with the voltage-clamp technique. The main structures of these compounds are identical, consisting of a mono or tri-aromatic core, two octamethylene chains and two benzoyl headgroups which are all connected through ester linkages. The structural variance was provided by the four differently functionalized benzoyl headgroups. The synthetic methods of three to five steps were mainly adapted from the previously reported method.1 The methods successfully produced eight compounds with overall yields of 20 to 30%. The voltage-clamp data suggested voltage-dependent behaviors occur at low concentrations while Ohmic behaviors require at high concentrations. The activity at low potentials showed relatively erratic behavior but the channels frequently switched between opening and closing states. The activity at high potential lasted longer as the channel maintained a longer state of opening. The exponential voltage-dependent behaviors were observed at higher potential while the voltage-independent Ohmic behaviors occur at low potential. These channel behaviors are highly time-dependent as there is no control over the stability and the aggregation level for the compounds forming active channels in the membrane. In some cases the current-voltage responses appear to be asymmetrical between the positive and the negative potentials. Mechanisms consistent with the observations are proposed. / Graduate / 0485 / 0490 / yzong@uvic.ca

Les travaux présentés dans ce manuscrit de thèse s’articulent autour de la synthèse de nouvelles architectures moléculaires tridimensionnelles et de l’évaluation de ces architectures en tant que canaux ioniques synthétiques capables de promouvoir le transport transmembranaire d’ions. La première partie concerne la mise au point d’une voie d’accès à ces édifices ayant comme plateforme centrale une brique naphtothiophène, aromatique ou partiellement hydrogénée, ainsi que l’étude prospective de la conversion de ces architectures en plateforme hélicoïdale. Les propriétés de ces édifices sont étudiées à l’état solide et par voie de calculs théoriques, permettant de mettre en avant des informations quant à la topologie globale adoptée ainsi que la compréhension de certaines réactivités observées. Une seconde partie est dédiée à la fonctionnalisation de ces édifices en molécules présentant des propriétés amphiphiles puis à l’étude de la capacité de ces dernières à s’insérer dans une bicouche lipidiques modèle afin de promouvoir le transport d’ions à travers la membrane via la formation de canaux ioniques dits synthétiques. En outre, des études alliant des analyses de spectrométrie de masse et des calculs théoriques sont présentés afin de comprendre les interactions intervenant dans le processus de transport d’ions à travers la membrane lipidique. / The work presented in this manuscript is dealing with the synthesis of new three-dimensional molecular architectures and their evaluation as synthetic ion channels capable of promoting ion transmembrane transport. The first part aims at developing a straightforward approach to the synthesis of novel architectures based on a naphthothiophene platform, aromatic or partially hydrogenated, as well as the development of a strategy the convert 9-arylnaphthothiophene architectures into helical platforms. The properties of these molecules were studied in the solid state and were completed by theoretical calculations to highlight global topologies adopted. Theoretical calculations allowed us to understanding some reactivities observed. A second part is dedicated firstly to the functionalisation of these molecular architectures into amphiphilic molecules and secondly to study their abilities to insert themselves into a model bilayer lipid membrane by forming channels. Besides, in order to gain a better understanding of the interactions in play in the process, mass spectrometry analysis combined to theoretical calculations were set up.