Exploration of Macrocyclic and Protein-Derived Luminescent Lanthanide Complexes Toward the Development of Discrete Molecular Probes

Abstract

Investigation of the photophysical properties of trivalent lanthanide ions (LnIII) constitutes a vast research area, stretching across multiple disciplines and a variety of technologies. Specifically, the development of discrete molecular probes for LnIII luminescence is an ongoing and challenging field as a result of the weak extinction coefficients and significant vibrational quenching of emissive 4f elements. This thesis contains three distinct approaches toward the design and synthesis of novel, emissive LnIII complexes. Chapter I presents an overview of the principles underpinning the observation of LnIII luminescence, in addition to a description of the unique electronic structure and transitions of 4f elements that give rise to their characteristic behaviour. This is followed by a literature basis for results Chapters II, III, and IV describing the rationale behind the design and execution of individual projects. Chapter II is a published article describing the synthesis, measurement and analysis of a series of bimetallic trinuclear [Ln2Ln'] (Ln = Yb, Eu; Ln' = Tb, Eu) complexes based on a bis-DO3A/DTPA scaffold. Extended photophysical analysis of these complexes under various excitation wavelengths, temperatures and physical states revealed phenyl-sensitised emission of all metal centres simultaneously. The potential for intermetallic energy transfer was also investigated, with observed evidence for a TbIII / EuIII interaction. Chapter III describes a manuscript on the effect of changing bound LnIII metals and covalent linker variety in a series of [Ln-R-780]+ cyanine dye antenna complexes (Ln = Yb, Er, Gd; R = Et, Ph). Here, the focus was shifted onto the spectrally diverse IR-780 dye molecule, which displayed a significant hypsochromic shift in ethyl-bridged LnIII complexes. Energy transfer from the dye antenna to each metal acceptor was also investigated, however only sensitised YbIII was observed. DFT calculations of singlet transitions for both linkers without the respective LnIII sites supported the observed changes in dye spectra. The final results section in Chapter IV is a departure from macrocyclic LnIII complexes and instead refers to the use of tryptophan-modified (Trp) peptide loops as ligands for mononuclear LnIII binding to facilitate protein-mediated sensitised emission. Molecular dynamics (MD) simulations were used to optimise Trp placement in an 'EF hand' peptide sequence (EF3) derived from the lanthanide-binding protein lanmodulin (LanM). Stepwise introduction of Trp at each available non-ligating site on EF3 highlights a difference in simulation stability and Trp-metal distances for each potential variant. Spectrophotometric titration of the prime Trp-EF3 candidate with EuIII and CaII showed the first reported example of Trp-sensitised EuIII emission in a protein-derived peptide sequence.

Date of Award	21 Feb 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Louise Natrajan (Main Supervisor), Sam Hay (Co Supervisor) & Patrick Parkinson (Co Supervisor)