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Luminescent Pt(II) tag for monitoring peptide (mis)folding and aggregation processes

Subject Area Inorganic Molecular Chemistry - Synthesis and Characterisation
Biochemistry
Organic Molecular Chemistry - Synthesis and Characterisation
Term from 2017 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 393103351
 
Final Report Year 2020

Final Report Abstract

The research objective of this proposal was to design a luminescent tag for monitoring the aggregation processes of amyloid-like peptides. As luminescent tag, a highly luminescent square planar Pt(II) complex based on bis-1,2,4-triazolyl-2,6-pyridine pincer ligand was chosen. Those complexes are known to exhibit visible emission, large Stokes shifts, high quantum yields, long excited state lifetimes, and high stability. Moreover the aforementioned complexes are able to self-assemble into supramolecular structures, leading to a change of the emission properties. A Pt(II) complex bearing an aggregating dipeptide moiety AG (alanine-glycine) was therefore synthesised, purified, and characterised. It was found that the complex does aggregate in acetonitrile to form straight, micrometer-long, nanoribbons, but assembles into twisted fibres upon aggregation in 1,1,2,2-tetrachloroethane. Both photophysical and morphological properties of the different aggregates were investigated, as well as the role of the media and the concentration. The two identified structures were chiral according to CD spectroscopy, however only the twisted fibres show morphological chirality. The aggregation processes were investigated using temperature- and concentration-dependent absorption and emission spectroscopy, leading to the discovery that the straight nanoribbons follow a cooperative mechanism (seedingelongation), whereas the twisted fibres seem to follow an isodesmic process. The interconversion between twisted fibres and nanoribbons was realised and followed via measurement of the photoluminescence quantum yield, but could also be monitored in real time using a confocal microscope. Finally, atomistic and coarse-grained simulations, providing results consistent with the experimental observations, allows to obtain a molecular-level insight into the interesting solvent-responsive behaviour of this system. Such findings could be used to further elucidate the selfassembly properties of biologically relevant proteins such as amyloid-β, or create relevant models. Finally, the synthesis of a Pt(II) complex bearing a large, aggregating peptide [KIGAKI]3 was tried. However the three different synthesis strategies put in place did not afford the wished compound in satisfactory yield or purity due to unforeseeable issues at different synthesis levels.

 
 

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