Table of Contents
Metal-Based Drugs
Volume 1, Issue 2-3, Pages 169-173

Protein-binding Properties of two Antitumour Ru(III) Complexes to Human Apotransferrin and Apolactoferrin

1Department of Inorganic Chemistry, University of Heidelberg, Im Neuenheimer Feld 270, Heidelberg W - 6900, Germany
2Massey University, Department of Chemistry and Biochemistry, Palmerston North, New Zealand

Received 2 September 1993

Copyright © 1994 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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].