Supplementary material for: Mijin, N. D., Milošević, J., Filipović, N. R., Mitić, D., Anđelković, K., Polović, N. Đ., & Todorović, T. R. (2022). The effect of non-specific binding of Pd(II) complexes with N-heteroaromatic hydrazone ligands on the protein structure. Journal of the Serbian Chemical Society, 87(10), 1143. https://doi.org/10.2298/JSC220518050M

Abstract

Previously, the cytotoxic actions of five Pd(II) complexes with bidentate N-heteroaromatic chelators (complexes 1–5) on a palette of several cancercell lines were investigated. However, the results of the cytotoxic activity didnot correlate with the hydrophobic character of the complexes. To gain furtherinsight into the structure–activity relationship, essential for the design of novelpotential drugs, other factors, such as non-specific interactions with cellularproteins, have to be taken into account. To explore the potential non-specificinfluence of the complexes on protein structures, ovalbumin (OVA) waschosen as a model system to mimic cellular non-specific crowding environments with high protein concentrations. A Fourier-transform infrared spectroscopy study implied that the binding of 3 and 4 led to only moderate alternations in the secondary structures of the protein, without the possibility to penetrate into hydrophobic core of the protein and disruption of protein native fold.Contrary, the effect of complex 5 on OVA secondary structures was concentration-dependent. While the lower concentration of complex 5 had no effecton OVA structure, a doubled concentration of complex 5 led to complete disruption of the content native-like secondary structures. The concentration-dependent effect of complex 5 on the changes in secondary structures and considerable increase in the exposure of OVA hydrophobic surfaces to water maybe related to a potential crosslinking that leads to OVA aggregation.