Peptide Decorated Multinuclear Architectures for Dual Imaging and Delivery Applications

Abstract

Small lanthanide complexes, such as mononuclear and bimetallic triple stranded helicates (Ln2L3), have been observed within aqueous environments via luminescence detection. Waterproof lanthanide complexes with internal voids are highly desired as they can combine imaging, sensing and delivery applications. An array of species have been encapsulated within lanthanide organic polyhedra including small biomolecules, such as disaccharides and RNA-bases, aromatic molecules (nitroaromatics and polyaromatic hydrocarbons), and anions. Encapsulation of guest molecules can quench or enhance lanthanide luminescence allowing for 'turn-on' or 'turn-off' detection of guest release. Chapter one introduces a review of previously published lanthanide organic polyhedra and reports on commonly adopted features within LOP chemistry and potential applications of lanthanide organic polyhedra. Chapter two reports the synthesis and characterisation of an asymmetric ditopic ligand, utilising dipicolinic binding sites, along with its complexation products. Complexation products vary depending on the lanthanide ion (europium, ytterbium and lutetium) used suggesting ion-dependent formation of architectures, determined via mass spectral analysis. The role of anions in the formation of the architectures were also investigated. The radius of the hexanuclear complex was measured via DOSY NMR and ion mobility mass spectrometry, whilst luminescence studies suggested lanthanide coordination sphere was not satisfied by dipicolinic binding moieties. Chapter three explores the synthesis, characterisation and subsequent complexation of three ditopic ligands. Varying linker groups results in the formation of different LOP or LOP mixtures with mass spectrometry and NMR spectroscopy utilised as characterisation techniques. Photophysical studies investigate ion-ligand pairs to identify the most promising ligand backbone to take forward for peptide modification and subsequent self-assembly with lanthanide ions. Chapter four details ligand-peptide coupling experiments alongside peptide and vesicle synthesis. Initial experiments focused on dipicolinic acid as a ligand, and moved towards ditopic ligands identified in Chapter 3. Luminescence studies of mononuclear dipicolinic acid-based Sm(III) and Eu(III) complexes, in acetonitrile and methanol, indicated ligand-sensitised luminescence and lonf radiative lifetimes. Potential incubation of Ln(III) complexes within giant unilamellar vesicles was explored via photophysical studies, however these studies indicated solubility challenges with amino acid appended dipicolinic acid which we hope would not persist with the target complexes incorporating more amino acid moieties. Chapter five summarises the main achievements, such as the synthesis and complexation of multiple ditopic ligands, and elaborates on future work that may be undertaken on the project. The outlook for LOP and peptide decorated supramolecular complexes is explored with attention paid to potential applications including imaging via luminescence or magnetic resonance, drug delivery through variable host-guest interactions, as well as sensing capabilities due to the plethora of examples on 'turn on' and 'turn off' luminescence alterations reported.

Date of Award	31 Dec 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Imogen Riddell (Supervisor) & Louise Natrajan (Supervisor)