First ID14 results analyse potential anticancer complex

Osmium, a rare transition metal, has gained interest in anticancer research as a potential alternative to platinum-based chemotherapy drugs like cisplatin. Its compounds show promise due to their unique properties and ability to target cancer cells effectively.

Osmium complexes with osmium in different oxidation states (II, III, IV, VI) have exhibited antiproliferative activity in cancer cell lines. However, the mechanisms of action of Osmium-based anticancer drug candidates remain unclear and despite some preclinical studies, none of them has been approved for medical use. Among other reasons, this is due to a lack of metallodrug speciation data under physiologically relevant conditions.

Gabriel Büchel and Dimitrios Bessas (ESRF) on the beamline during the experiment.

Several experimental techniques may be used to study such compounds. Atomic Absorption Spectroscopy and Induced Coupled Plasma-Mass Spectrometry (ICP-MS) are destructive and provide only the total metal amount without information on metal speciation unless individual components are separated.

Scientists then turned to X-ray absorption spectroscopy (XAS), which is superior for having elemental specificity, being nondestructive to drugs, and having greater tolerance for biologically relevant matrices. All these advantages make XAS the currently preferred technique for the speciation of metallodrugs in biological systems. However, XAS often requires higher concentrations in the cell medium than those biologically relevant, which makes it difficult to extrapolate the results.

New approach to potential anticancer complex

Nuclear resonance scattering (a synchrotron radiation variant of conventional Mössbauer spectroscopy) has higher sensitivity than  XAS, because of its resonant nature, but requires the presence of specific isotopes (the so-called Mössbauer active isotopes). Nuclear resonance scattering has risen as a valuable tool for studying iron complexes, enabling researchers to elucidate their electronic and magnetic properties as well as to extract the isotope specific vibrations, which is crucial for understanding their chemical behavior and potential applications.

Now a team led by the University of Vienna (Austria), KU Leuven (Belgium) and Roosevelt University (USA) has shown that ¹⁸⁷Os nuclear resonance scattering is a reliable technique for the investigation of hyperfine interactions and osmium specific vibrations in osmium(VI) species. This means that the technique can be applied to osmium complexes of other oxidation states, including those with potential anticancer activity such as Os(III) and Os(IV).

Nuclear resonance scattering in combination with first-principles calculations, allowed the researchers to fully model the Os(VI) chemical compound under study from the perspective of both its electronic structure and its atomic vibrations.  Comparison with data obtained for another Os(IV) reference compound already showed the electronic differences between the two. Expansion of this database will allow correlation between these fundamental physical/chemical parameters extracted from synchrotron-based experiments and in vitro and eventually in vivo biomedical activity of osmium complexes.

Vladimir Arion, one of the co-corresponding authors of the publication, explains: “Even though conventional 189Os Mössbauer spectroscopy has been applied in the past for a series of osmium compounds in different oxidation states, the short half-life of the radioactive source, ¹⁸⁹Ir, is only 13.3 days. This makes such studies for a broader research community inconvenient from practical point of view. In the case of ¹⁸⁷Os, suitable radioactive sources are missing. The use of ID14 beamline facilities is an excellent option under such circumstances. I do not know other beamlines where investigation of ¹⁸⁷Os compounds can be performed”. 

In terms of the impact of this research, Gabriel Büchel, author of the study, explains: “It will hopefully show us the transformations of osmium-based prodrugs in ‘real world’ environments, namely cell culture media, the extracellular matrix, cellular cytoplasm and the cell nucleus”.

Reference: 

Stepanenko, I., et al, Science Advances, 7 Feb 2025, Vol 11, Issue 6.

Text by Montserrat Capellas Espuny

Top image: The sample on the beamline.