Novel luminescent lanthanide complexes as reporters of cellular oxidative stress

• Main Author: Vitiello, Bianca
• Published: Open University 2018
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.757659

A series of lanthanide complexes based on asymmetrically substituted cyclen ligands were designed and synthesised in this project in order to develop ROS-responsive luminescent molecular sensors. A synthetic strategy involving the synthesis of an intermediate ligand was applied to the asymmetrically functionalisation of the cyclen ring. The intermediate ligand was called “the generic ligand” since it possesses a generic chemical structure that could be modified in many ways in order to produce different types of ligands. The generic ligand was designed and synthesised by exploiting an orthogonal protection strategy. The synthetic strategy involving the synthesis of the intermediate generic ligand proved to be very versatile and successfully applicable to the synthesis of different asymmetrically substituted cyclen-based ligands. Seven types of ligands (L1-L7) were synthesised in this project exploiting the synthetic strategy mentioned above. The ligands were complexed with trivalent lanthanide ions giving arise to eleven lanthanide complexes EuL1-EuL7. The photophysical properties of the lanthanide complexes were measured using absorption and emission spectroscopy. The photophysical properties of two Eu(III) based complexes were measured in presence of ROS species generated in situ by H₂O₂ and Fe(II) perchlorate. The ROS response of these Eu(III)-based complexes was also measured in vitro by using a cellular ROS assay. In this assay H₂O₂ and tBHP were used to increase the ROS production within the cells. A mitochondrial stress test (MST) was performed on EuL1-TbL4 with the aim to identify compounds that exhibit a potential mitochondrial and/or cellular toxicity. A calcium loading capacity assay was performed on the same lanthanide complexes tested with the MST with the aim of investigating their effect on the mitochondrial capability to uptake and internalize Ca²⁺.