Research Projects

Neurodegenerative diseases (NDs), such as Alzheimer’s, Parkinson’s, and prion disorders, are marked by abnormal protein aggregation, which leads to progressive neuronal dysfunction. The buildup of misfolded proteins, including amyloid-β (Aβ), tau, and α-synuclein, results in the formation of toxic oligomers and fibrils that disrupt cellular homeostasis and cause extensive damage. Despite progress in understanding these mechanisms, early detection and treatment remain significant clinical challenges. Transition metal complexes have become important chemical tools because of their unique redox properties, adjustable coordination chemistry, and ability to interact with protein aggregation. Noble metal complexes like Ru, Ir, Pt, and Re show promise as aggregation inhibitors and fluorescence imaging agents; however, their toxicity, cost, and limited biocompatibility hinder clinical use. Most existing systems mainly target mature fibrils, overlooking the harmful oligomeric intermediates, and often struggle with blood–brain barrier (BBB) permeability and biological selectivity. This study aims to fill this gap by the design and synthesis of novel 3d transition metal complexes using benzothiazole, benzimidazole, and Schiff base ligands. These molecular structures exhibit advantageous coordination chemistry and have the ability for hydrogen bonding, π–π stacking, and metal–ligand charge transfer—attributes essential for targeted interaction with amyloidogenic peptides. Moreover, structural alterations, such as the incorporation of lipophilic chains and excited-state intra proton transfer ESIPT-active groups, will be implemented to enhance cellular uptake and fluorescence signaling. The central hypothesis asserts that these synthetically tunable 3d metal complexes can serve dual functions: (i) selectively engaging with and modulating the aggregation pathways of deleterious peptides, and (ii) functioning as fluorescent indicators for the early detection of amyloids via aggregation-induced emission or ESIPT-based switching. The scientific objectives include the synthesis and structural characterisation of ligand frameworks and their associated metal complexes. The evaluation of binding affinity and selectivity for Aβ, PrP106–126, and analogous peptides with assessment of inhibition and disaggregation capability of complexes via different spectroscopic and microscopic techniques. The examination of photophysical parameters to assess ESIPT/PET fluorescence behavior concerning aggregation and the investigation of biocompatibility and the in vitro detection capabilities in model cellular systems. This project will substantially advance the field by creating a novel class of 3d metal-based theranostic agents with potential uses in the early diagnosis and treatment of neurodegenerative diseases. It links synthetic inorganic chemistry to biomedical relevance and facilitates cost-efficient, metal-coordination-based methodologies in amyloid research. The results will yield a deeper fundamental understanding of metal–protein interactions concerning pathological aggregation and redox-associated neurotoxicity.