Exploiting soft and hard X-ray absorption spectroscopy to characterize metallodrug/protein interactions: the binding of [trans-RuCl4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) to bovine serum albumin.
The reaction of bovine serum albumin (BSA) with [ trans-RuCl 4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) (NAMI-A), an experimental ruthenium(III) anticancer drug, and the formation of the respective NAMI-A/BSA adduct were investigated by X-ray absorption spectroscopy (XAS) at the sulfur and chlorine K-edges and at the ruthenium K- and L 3-edges. Ruthenium K and L 3-edge spectra proved unambiguously that the ruthenium center remains in the oxidation state +3 after protein binding. Comparative analysis of the chlorine K-edge XAS spectra of NAMI-A and NAMI-A/BSA, revealed that the chlorine environment is greatly perturbed upon protein binding. Only modest changes were observed in the sulfur K-edge spectra that are dominated by several protein sulfur groups. Overall, valuable information on the nature of this metallodrug/protein adduct and on the mechanism of its formation was gained; XAS spectroscopy turns out to be a very suitable method for the characterization of this kind of systems.
Ascone
Isabella
I
Synchrotron-Soleil L'Orme des Merisiers Saint Aubin - BP 48 91192 Gif sur Yvette CEDEX, France. isabella.ascone@synchrotron-soleil.fr
Messori
Luigi
L
Casini
Angela
A
Gabbiani
Chiara
C
Balerna
Antonella
A
Dell'Unto
Francesca
F
Castellano
Agostina Congiu
AC
D000042:Absorption; D000818:Animals; D002417:Cattle; D002713:Chlorine / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D012428:Ruthenium / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013455:Sulfur / Q000737:chemistry; D014965:X-Rays
D009942:Organometallic Compounds; D004364:Pharmaceutical Preparations; C533067:trans-RuCl4(imidazole)(dimethylsulfoxide)(imidazole H); D012710:Serum Albumin, Bovine; D002713:Chlorine; D013455:Sulfur; D012428:Ruthenium