The interaction of two ruthenium(III) complexes exhibiting high anticancer activity - namely trans-Indazolium(bisindazole) tetrachlororuthenate(III), Hlnd[RuInd2Cl4], and trans-Imidazolium (bisimidazole)
tetrachlororuthenate(III), Hlm[RuIm2Cl4], - with human serum apotransferrin has been
investigated through spectroscopic and chromatographic techniques with the ultimate goal of
preparing adducts with good selectivity for cancer cells due to the fact that tumour cells express
high amounts of transferrin receptors on their cell surface.
Whereas the binding of Hlm[RuIm2Cl4] to human serum apotransferrin takes several hours,
Hlnd[RuInd2Cl4], the less toxic complex, gives rise to a well defined 2:1 complex within a few
minutes. Hlnd[RuInd2Cl4] will react with apotransferrin only in the presence of bicarbonate, this
anion dictating the kinetic and mechanistic characteristics of protein-binding.
Circular dichroism studies had previously indicated that binding of both Ru(III) complexes occurs
around the unoccupied iron(III) binding sites; this result is now confirmed by preliminary X-ray
data of Hlnd[RuInd2Cl4] and Hlm[RuIm2Cl4] bound to apolactoferrin, a related iron protein. The
crystallograhic data reveals that binding of both complexes takes place at histidine residues, and
that the ligand (indazole) remains bound in the case of Hlnd[RuInd2Cl4].
