Herein, the effects of a novel half-sandwich Os(II) complex on the aggregation of an amyloid model system, derived from the C-terminal domain of the nucleophosmin 1 protein (NPM1264–277), were investigated. The thioflavin T (ThT) binding assay revealed that the complex [(η6-toluene)Os(NHCglu)Cl2] (where NHCglu is the N-heterocyclic carbene ligand 1-methyl-3-{2,3,4,6-tetra-O-acetyl-1-glucosyl}imidazol-2-ylidene), hence named Os-Tolu, was able to repress amyloid aggregation in a dose-dependent way. Conformational studies through circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies clearly indicated that this inhibitory effect occurred through the stabilization of α-helical structures of monomeric NPM1264–277, thus hampering self-recognition. Electrospray ionization mass spectrometry (ESI-MS) studies evidenced, through the formation of coordination adducts, direct interactions of the amyloid peptide with the Os-glucoconjugate complex that, in turn, promote chemical modifications of the sequence further disfavoring the self-assembly process. Noticeably, the presence of Os-Tolu completely repressed the formation of amyloid fibers in scanning electron microscopy (SEM) analysis and induced a slight rescue of cell viability, in contrast to its reduction caused by the amyloid model in human SH-SY5Y neuroblastoma cells. These data strongly support the hypothesis of expanding the use of osmium-based agents to neurodegenerative diseases, positioning them as potential neurodrugs.
