Cellular effects of transferrin coordinated to [Cl(NH3)5Ru]Cl2 and cis-[Cl2(NH3)4Ru]Cl

Estimates of the net equilibrium binding constants for [(H2O)(NH3)(5)Ru-II](2+), [Cl(NH3)(5)Ru-III](2+), cis-[(H2O)(2)(NH3)(4)Ru-II](2+) and cis-[Cl-2(NH3)(4)Ru-III](+) with apotransferrin (TF) and holotransferrin (Fe2Tf) suggests that Ru-III, but not Ru-II complexes bind with a higher affinity to the iron binding sites. Several other presumably histidyl imidazole sites bind with approximately the same affinity (K-eff = 10(2) to 10(3) M-1) to both Ru-II and Ru-III. Compared to HeLa cells, an order of magnitude higher level of nuclear DNA binding ([Ru](DNA)/[P](DNA)) was required to achieve the same level of toxicity in Jurkat T-ag cells, which probably relates to the substantially higher levels of cis-[Cl-2(NH3)(4)Ru](-) needed to inhibit 50% of the cell growth in the Jurkat T-ag cell line. Against Jurkat T-ag cells, the toxicity of the pentaammineruthenium(III) group is enhanced by approximately two orders of magnitude upon binding primarily to the Fe-sites in apotransferrin. whereas the toxicity of the tetraammineruthenium(III) moiety is only marginally increased. Binding to Fe2Tf does not increase the toxicity of either group. Significant dissociation over 24 h of the ammineruthenium(III) ions From apotransferrin requires reduction to Ru-II. (C) 2001 Elsevier Science B.V. All rights reserved.