Solution studies of the antitumor complex dichloro 1,2-propylendiaminetetraacetate ruthenium (III) and of its interactions with proteins.
A mixed complex of ruthenium (III) with 1,2-propylendiaminetetraacetate (PDTA) and chloride--RAP hereafter--has been found to exhibit favorable anticancer properties in vivo. To get some insight into the possible mechanism of action of this ruthenium (III) complex, its solution behavior and reactivity with proteins were investigated through absorption, circular dichroism and 1H NMR spectroscopies. Under physiological conditions RAP slowly looses the two coordinated chlorine atoms to produce a number of ruthenium (III) reactive species; a description of the distribution of these species on the dependence of pH has been obtained through 1H NMR studies of the hyperfine shifted signals. Remarkably, through the different solution conditions employed in this study, the ruthenium ion always remains in the 3+ oxidation state and the PDTA ligand is always bound to the metal. Upon reaction with albumin, apotransferrin or diferric transferrin, at a 1:1 ratio, RAP rapidly binds to these proteins to produce substantially equivalent and relatively stable adducts. This behavior is tentatively interpreted in terms of a tight interaction between RAP and surface residues of these proteins. The implications of these findings for the biological action of this novel ruthenium (III) compound are discussed.