Reactivity and Transformation of Antimetastatic and Cytotoxic Rhodium(III)–Dimethyl Sulfoxide Complexes in Biological Fluids: An XAS Speciation Study

Abstract

Rhodium­(III) anticancer drugs can exert preferential antimetastatic or cytotoxic activities, which are dependent on subtle structural changes. In order to delineate factors affecting the biotransformations and speciation, mer,cis-[RhCl3(S-dmso)2(O-dmso)] (A1) and mer,cis-[RhCl3(S-dmso)2(2N-indazole)] (A2) have been studied by X-ray absorption spectroscopy (XAS). Interactions of these complexes with saline buffer, cell culture media, serum proteins (albumin and apo-transferrin), native and chemically degraded collagen gels, and A549 cells have been studied using linear combination fitting (LCF) and 3D scatter plots of XAS data. Following initial aquation and hydrolysis reactions involving stepwise displacement of Cl– and S-/O-dmso ligands, the Rh­(III) complexes underwent further ligand substitution reactions with biological nucleophiles (e.g., amino acid residues of serum proteins). The reaction of A1 with chemically degraded collagen gel was postulated to be a key reason for its antimetastatic activity. Analyses of the XAS of Rh-treated bulk cells were consistent with structure–reactivity relationships in which the more reactive A1 was predominantly antimetastatic and the less reactive A2 was predominantly cytotoxic, showing relationships parallel to typical Ru­(III) anticancer agents, i.e., NAMI-A ([ImH] trans-[RuCl4(S-dmso)­(N-imidazole)2], ImH = imidazolium cation) and KP1019/NKP1339 (KP1019, [IndH] trans-[RuCl4(N-indazole)2], IndH = indazolium cation; NKP1339, sodium trans-[RuCl4(2N-indazole)2]), respectively.

From poison to promotor –unique Rh4 structural motifs in supported rhodium sulphides as hydroformylation catalysts

“…This corresponds to an oxidation state of Rh δ+ based on the partial charge transfer from Rh to S, in agreement with XPS and DRIFTS analyses. The characteristic broad white line around 23240 eV observed in the XANES data was already reported for diverse RhxSy species 36,37 . The corresponding Fourier transform extended X-ray absorption fine structure (FT-EXAFS) spectra are plotted in Figure 3e and prove the existence of rhodium sulphides phases.…”

From poison to promoter: investigation of supported rhodium sulphides as heterogeneous hydroformylation catalysts

“…This basically corresponds to an oxidation state of Rh δ+ based on the partial charge transfer from Rh to S in rhodium sulphide samples, as already concluded before from XPS and DRIFTS analyses. The characteristic broad white line around 23240 eV observed in the XANES data was already reported for diverse RhXSY species [46][47][48] . The corresponding Fourier transformed extended X-ray absorption fine structure (FT-EXAFS) spectra are plotted in Figure 3e and prove the existence of rhodium sulphides phases.…”

Fluorescent, phosphorescent, magnetic resonance contrast and radioactive tracer labelling of extracellular vesicles

“…258,509 In studies by Wardhani et al, the stability of these Ru(II) phosphophores under biologically relevant conditions was validated through XAS (X-ray absorption spectroscopy) at the Ru K-edge, as each element in biological matrix occurs at different energies. 509,[526][527][528][529][530][531][532][533][534][535] XAS of Rubb 7 -TNL in biological media (human serum and cell culture medium) closely resembled that of the free complex and did not change after 24 hr of incubation at 310 K. 509 XAS analysis of the coordination environment of metal complexes in complex biological matrices is a very powerful technique, 509,526,528,533,535 and XAS results indicated that Rubb 7 -TNL maintained its original ligands, and is highly stable to substitution reactions with targets in biological environments. Slight differences were observed in the cell culture medium compared to PBS due to the presence of proteins and the potential binding of Rubb 7 -TNL in specific protein pockets, which resulted in minor outersphere effects.…”