Selective coordination to zinc over other members of the first row transition metal series is important for the commercial application of lipophilic ligands for the hydrometallurgic recovery of the metal. In order to achieve selectivity for zinc(n) over other ions, particularly copper(II) and iron(III), ligands have to be designed which take advantage of zinc's preferred tetrahedral coordination geometry and the borderline donor atom preference of the metal. With such ligands in mind, three new classes of ligand system have been designed and synthesised based on the benzimidazole, quinoline and pyridine ring systems with appended phosphinic and thiophosphinic acid anionic donor groups. Benzimidazole ligands which bind zinc in a 2:1 manner in solution have been made and their complexation ability assessed by ESMS, (^31)p NMR, liquid-liquid extraction, fluorescence and UV absorption spectroscopic methods. A bisbenzimidazole ligand with a C(_3) spacer in the 2,2' position was synthesised and shown to bind zinc initially in a 2:1 manner, at low metal concentrations, and predominantiy as a 1:1 species at higher metal concentrations. The formation constant for the ML complex was shown to be logK(_ML)=5 by analysis of the NMR titration curve, which was in close agreement with the value obtained from liquid-liquid extraction studies. A directly linked 2,2'- bisbenziraidazole system was also synthesised as an extension to previous work, however isolation of the target ligand proved to be difficult due to the insolubility of the desired bis-acid.8-(Quinolinyl)phenylphosphinic acid and 8-(2-metiiylquinolinyl)phenylphosphinic acid were also synthesised and their solution complexation behaviour studied in detail. The unsubstituted ligand appeared to form 1:1 complexes with zinc at all the metal concentrations studied, and the absence of the methyl substituent does not inhibit coordination to the ferric ion. In contrast the metiiyl substituted ligand initially forms a 2:1 L:M complex, and 1:1 complexes at higher metal concentrations. The initial ML(_2) complex probably involves coordination of two of the phosphinic acid moieties. Three pyridyl derived ligand systems were also synthesised varying the bulk of the C-6 substituent and the effect of the phosphinic versus the thiophosphinic acid moiety towards zinc coordination was examined. Both of the methyl appended ligands were shown to bind zinc in a 2:1 manner, with the thiophosphinic acid exhibiting a greater avidity for zinc. In contrast, the unsubstituted ligand predominantly forms 1:1 complexes at all metal concentrations.

The utility of fluorophores for sensing applications in the current state of the art of biological imaging hardly needs to be stated. The use of fluorophores in exploring and determining the internal structure and active dynamics of cellular processes has been pivotal, allowing us to explore areas of study inaccessible through other means. A simple search of fluorophores in Scifinder© demonstrates their popularity, as the number of hits increases year after year, until the year of 2015 when there were 1400+ journal articles published with the phrase. Fluorophore applications range far and wide, from sensing applications related to environmental concerns, to public health, to clinical usage. Fluorophores have been developed to detect explosive residues, to monitor environmental pollutants, and even to detect illicit substances. In cellular applications, a fluorophore needs to be well suited to examining the relevant processes, including participating in the cellular milieu and actively signifying the phenomena that are desired. Chapter I examines the usage of alkynes in fluorescent sensing scaffolds and gives a survey of their applicability in the field. Chapter II demonstrates the utility of disulfide-based macrocyclic scaffolds in the design of supramolecular hosts for chloride anions and their use as solid-state sensors for these anions. Chapter III explores the synthesis and application of an alkyne-based scaffold in the reversible detection of dithiol/disulfide redox flux and a new mode of quantification of dithiol-disulfide redox couples, a classically difficult area of study. Chapter IV focuses on methods utilized to improve the disulfide-based redox sensing capabilities. Chapters V and VI explore the properties of a new fluorophore scaffold discovered during research into another sensing scaffold, demonstrating a new reaction which yields a heretofore underexplored heterocycle with novel photophysical and supramolecular behaviors. This dissertation contains both previously published and unpublished co-authored material.

Les phosphinosucres appelés aussi « phostines » sont des analogues phosphorés des sucres pyranoses et des C-arylglycosides. L'évaluation biologique de ses composés a révélé une activité anticancéreuse des phosphinosucres sur les cellules de glioblastome multiforme, un cancer particulièrement malin et invasif qui ne possède pas de solution thérapeutique. Dans le but de comprendre les mécanismes d'action des phosphinosucres et la stéréo-dépendance de leur activité biologique, la caractérisation des diastéréomères de « phostines » a été menée. Suite à cette détermination structurale, le développement de synthèses diastéréosélectives a permis d'obtenir un mélange fortement enrichi en diastéréomère le plus actif par une séquence réactionnelle qui a mis en jeu une réaction d'oxydation de phosphinosucres -hydroxylés en α-cétophosphinosucres, suivie d'une réduction diastéréosélective. Afin d'améliorer l'activité antiproliférative des phosphinosucres, une diversification chimique a été réalisée. Les variations du groupement aryle lié à l'atome de phosphore nous ont amené à développer une synthèse des aryl-hydrogénophosphinates qui a permis d'obtenir une large variété de ces composés. Par la suite, les aryl-hydrogénophosphinates obtenus ont été engagés dans la synthèse des « phostines ». De plus, des variations chimiques sur le carbone en position α de l'atome de phosphore ont été entreprises et ont permis l'élaboration de plusieurs composés (triflate, azido, amino, déoxy et triazolyles), puis finalement à l'analogue phosphinosucre du N-acétylglucosamine qui a présenté une importante activité anticancéreuse in vitro. / Phosphinosugars also called « phostines » are new cyclic phosphinates, analogs of carbohydrates and C-aryglycosides, with phosphorus atom mimicking the anomeric carbon. Biological screening tests of these compounds revealed an anticancer activity against glioblastoma multiform, a highly invasive and malignant tumor without curative therapy.With the aim of understanding the phosphinosugars mode of action and their stereo-dependent biological activity, characterization of four phosphinosugars diastereomers formed during the chemical process has been performed. After their structural determination, diastereoselective synthesis enabled us to obtain an enriched mixture of the most active diastereomer based on an oxidation of -hydroxyled phosphinosugars in corresponding -keto phosphinosugars followed by a diastereoselective reduction. Thereafter, antiproliferative activity of phoshinosugars was performed by chemical diversification. Modification of the aryl group linked to phosphorus atom led us to develop aryl-hydrogenophosphinate synthesis to create a broad variety of these structures. Then, the expected aryl-hydrogenophosphinates were used for phostines preparation. Furthermore, chemical modifications on the carbon in α position of phosphorus atom were led and furnished several new compounds (triflate, azido, amino, deoxy and triazolyl), as well as the phosphinosugar analog of N-acetylglucosamine which presented in vitro a high anticancer activity.