Development of Synthetic Copper(I) Transmembrane Transporters and their Biological Applications

The development of synthetic molecules able to transport ions through lipid bilayer membranes is of growing interest in the field of supramolecular chemistry. The balance of anions and cations has an important role in the biology of all living organisms. This thesis will focus on the development of copper(I) transporters, the methodologies developed to study them, and their biological applications. The first part of this thesis is focused on the development of copper(I) transmembrane transporters and the methodology required for their study. These transporters were developed for a potential therapeutic application, with the idea that synthetic copper(I) transporters could replace dysfunctional copper(I) transport proteins, which are responsible for distributing copper(I) within cells. Dysfunction of these proteins is the cause of Wilson and Menkes diseases.Calix4arene functionalised with two imidazole groups can strongly bind copper(I) through a linear coordination motif. This ability and their high lipophilicity made them good candidates to transport copper(I) through bilayer membranes. For that, a new assay was developed using liposomes as model systems for membranes, in which a phenanthroline based copper(I) sensitive dye is encapsulated. The changes in fluorescence as monitored by spectroscopy allowed for the observation of copper(I) transport. Most of these results are reported in the publication: “Transmembrane transport of copper(I) by imidazole-functionalised calix[4]arenes” N. Renier, O. Reinaud, I. Jabin, and H. Valkenier. Chem. Commun. 2020, 56, 8206-8209. The improvement and limitations of the transport assay are also described. In the second part, the development of a deliverable copper(I) transporter is described along with the biological effects of the compound on various biological systems. A new transporter was synthesised and shown to be able to reach liposomes membrane when added from an organic solution or from other liposomes, which was not th
Doctorat en Sciences de l'ingénieur et technologie
info:eu-repo/semantics/nonPublished