Cellular effects of transferrin coordinated to [Cl(NH3)(5)Ru]Cl-2 and cis-[Cl-2(NH3)(4)Ru]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) sug gests that Ru-III, but not Ru-II complexes bind with a higher affinity to t he iron binding sites. Several other presumably histidyl imidazole sites bi nd with approximately the same affinity (K-eff = 10(2) to 10(3) M-1) to bot h Ru-II and Ru-III. Compared to HeLa cells, an order of magnitude higher le vel 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 5 0% of the cell growth in the Jurkat T-ag cell line. Against Jurkat T-ag cel ls, the toxicity of the pentaammineruthenium(III) group is enhanced by appr oximately two orders of magnitude upon binding primarily to the Fe-sites in apotransferrin. whereas the toxicity of the tetraammineruthenium(III) moie ty is only marginally increased. Binding to Fe2Tf does not increase the tox icity of either group. Significant dissociation over 24 h of the ammineruth enium(III) ions From apotransferrin requires reduction to Ru-II. (C) 2001 E lsevier Science B.V. All rights reserved.