The effect of non-specific binding of Pd(II) complexes with N-heteroaromatic hydrazone ligands on the protein structure

Previously, the cytotoxic actions of five Pd(II) complexes with biden-tate N-heteroaromatic chelators (complexes 1???5) on a palette of several cancer cell lines were investigated. However, the results of the cytotoxic activity did not correlate with the hydrophobic character of the complexes. To gain further insight into the structure???activity relationship, essential for the design of novel potential drugs, other factors, such as non-specific interactions with cellular proteins, have to be taken into account. To explore the potential non-specific influence of the complexes on protein structures, ovalbumin (OVA) was chosen as a model system to mimic cellular non-specific crowding environ-ments with high protein concentrations. A Fourier-transform infrared spectro-scopy study implied that the binding of 3 and 4 led to only moderate alternat-ions in the secondary structures of the protein, without the possibility to penet-rate into hydrophobic core of the protein and disruption of protein native fold. Contrary, the effect of complex 5 on OVA secondary structures was concen-tration-dependent. While the lower concentration of complex 5 had no effect on OVA structure, a doubled concentration of complex 5 led to complete dis-ruption of the content native-like secondary structures. The concentration-dep-endent effect of complex 5 on the changes in secondary structures and con-siderable increase in the exposure of OVA hydrophobic surfaces to water may be related to a potential crosslinking that leads to OVA aggregation.