Two anticancer gold(III) compounds, Au₂phen and Auoxo4, were encapsulated within a ferritin nanocage. The gold-compound loaded proteins were characterized by UV-Vis spectroscopy, inductively coupled plasma mass spectrometry and circular dichroism. X-ray crystallography shows that the compounds degrade upon encapsulation and gold(I) ions bind Ft within the cage, close to the side chains of Cys126. The gold-encapsulated nanocarriers are cytotoxic to human cancer cells. Au(I)-loaded Ft, obtained upon the encapsulation of Au₂phen within the cage, induces oxidative stress activation, which finally leads to apoptosis in MCF-7 cells.

The interactions between the cytotoxic paddlewheel dirhodium complex [Rh ₂ (μ-O ₂ CCH ₃ ) ₄ ] and the model protein bovine pancreatic ribonuclease (RNase A) were investigated by high-resolution mass spectrometry and X-ray crystallography.

Examples from the literature and experience in our own laboratory on the characterization of the interactions between biological macromolecules and metal-based drugs are provided.

New five-coordinate Pt(II) complexes containing a glycosylated carbene fragment were synthesized. A member of this class shows very high in vitro cytotoxicity and an exceptional selectivity toward malignant cells. The complex lacking the sugary portion fails in the recognition of cancer cells. The results support the use of glycosylation in the design of carbene Pt-based anticancer agents.

The NAMI A/HuHf adduct with selective binding of a Ru ion to His105 is described. This adduct is of potential pharmaceutical interest as a carrier of ruthenium ions.

The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2′-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties.