Organic compounds that engage with specific biological targets while exhibiting distinct photophysical properties can serve as molecular tools to visualize and potentially influence disease-related processes within living organisms. Luminescent Conjugated Oligothiophenes (LCOs) are a class of organic compounds composed of a defined number of repeating thiophene units, forming a conjugated structure with alternating single and double bonds. These molecules exhibit strong luminescent properties due to their extended π-conjugated system, enabling efficient absorption and emission of light. The conjugation leads to unique optical and electronic properties, making LCOs highly useful in various scientific applications, for example as reporters of disease-related biological events.

In this thesis, thiophene-based ligands have been functionalized with amino acids to investigate their affinity towards various protein aggregates associated with neurodegenerative diseases, such as Alzheimer’s disease, as well as to explore their optical and supramolecular properties and potential as chiroptical materials. The amino acid functionalized thiophene-based ligands, denoted proteophenes, have specific amino acid side chain functionalities with various characteristics introduced at different positions in the molecular structure. Novel synthetic pathways have been developed to achieve pentameric LCOs, donor-acceptor-donor LCOs and thiophene-vinylene-based ligands, all functionalized with amino acids. The proteophenes’ affinity for disease-related protein aggregates has been evaluated and shown to be highly dependent on the chemical nature and positioning of the amino acid side chain moieties in the ligand structure. Moreover, the introduction of chiral amino acids to the structure influenced the optical behaviour of some of the molecules, resulting in induced circular dichroism and, under certain conditions, the formation of supramolecular assemblies.

Overall, this thesis demonstrates how organic synthesis can be employed to generate a library of ligands with different molecular motifs and thereby different photophysical and optical properties. We foresee that the proteophenes will provide valuable insights to how minor changes in the chemical structure of the ligands can affect their ability to be used as amyloid specific ligands, or as chiroptical materials, as well as expand the toolbox of fluorescent ligands for the study of neurodegenerative diseases.