Development of Luminescent Inorganic and Organometallic Transition Metal Complexes as a Novel Class of PEGylation Reagents: From Fundamentals to Applications

The aim of this project is to develop luminescent inorganic and organometallic transition metal complexes as a novel class of PEGylation reagents. PEGylation is the covalent modification of proteins, peptides, antibody fragments and drug molecules with poly(ethylene glycol) (PEG). This derivatization procedure favourably alters properties of the molecules without sacrificing their specific biological or therapeutic characteristics: most notably the toxicity of the molecules is significantly reduced. PEGylated molecules are less immunogenic, more biocompatible and soluble in aqueous solution, and display reduced nonspecific interactions with surfaces and other biological entities. For these reasons, a number of PEGylation reagents have been developed.Although fluorescent organic dyes are commonly used as probes for biological molecules and cellular components, luminescent transition metal complexes are considered to be excellent alternative choices because they offer such advantages as high photostability, large Stokes’ shifts, long emission lifetimes and high structural variation that leads to rich emission characteristics. These complexes also exhibit environment-sensitive emission, which reflects the local environments of the probes. Hence, there is an emerging interest in using these complexes as covalent biological labels.Whilst PEGylation reagents and transition metal PEG complexes have been well documented, there has been no report about the development of PEGylation reagents derived from luminescent inorganic and organometallic transition metal complexes. In this project, we will design novel PEGylation reagents using inorganic and organometallic transition metal complexes with interesting luminescence properties. These reagents will be used to PEGylate a wide range of targets including small model molecules, proteins and macromolecules. The photophysical behaviour and biological properties, including the cellular uptake efficiency and cytotoxicity, of the PEGylated conjugates will be investigated using various approaches. The favourable photophysical properties of luminescent inorganic and organometallic transition metal complexes, together with the non-cytotoxic and hydrophilic nature of PEG, will render the proposed luminescent PEGylation reagents a novel generation of biological tools with extremely high application potential.