Non-conventional photoactive transition metal complexes that mediated sensing and inhibition of amyloidogenic aggregates

Abstract Alzheimer’s disease (AD), a devastating neurodegenerative disease, is associated with the abnormal accumulation and aggregation of β-amyloid proteins (Aβ) along with the deposition of high levels of Cu, Fe and Zn ions in the brain, causing neuronal cell deaths to lead the cognitive disabilities and even death. As there is a direct relationship between AD and Aβ aggregation, an intense research activity has been made to develop drug materials that serve as probes and inhibitors for controlling the pathways of Aβ peptide aggregation. However, their relatively instability in aqueous medium, tedious sample treatment, multistep syntheses, or low detection ability limit their potential applications. Therefore, the development of photoactive metal complexes for the selective detection and inhibition effects of Aβ aggregation is a thrust area in biomedical research. In this review, the use of non-conventional photoactive metal complexes including Ru(II), Re(I), Ir(III) and Pt(II) has the potential advantages of probes for monitoring and inhibiting the fibrillation as well as the toxicity of Aβ over conventional dyes such as Thioflavin T (ThT). The geometry, multiple electronic/spin states and redox nature of metal centres have made them tunable properties. Upon binding to the Aβ peptide aggregates, they exhibit promising potential as anti-AD agents due to their fascinating photophysical properties include red emissions, large Stokes shifts, and long lifetimes, which differentiate the competitive binding of other short-lived fluorescent molecules via photoluminescence, and time-resolved measurements. In addition, metal complexes display their remarkable selectivity and superiority over ThT. Competition study between photoactive metal complexes and ThT on fibrillation process show their effective binding of metal complex with Aβ42 fibrils by hindering the ThT binding to give higher binding constants than that of ThT. Computational studies predicted a hydrophobic domain between amino acid binding sites and the functional group of photoactive metal complexes via different noncovalent interactions. Thus, attractive characteristics of photoactive metal complexes could influence remarkable evolutions in new dimensions, which in turn address current challenges in the clinical use of the detection and inhibition of Aβ fibrils.