Ru III prodrugs

Significant differences exist between the chemistry of ammlne Ru(II) and Ru(IIl) Ions (11,25) which can be taken to advantage In the design of anticancer pharmaceuticals. 

While both (NHo)5Ru(II and III) have comparable affinities for Imidazole (K 2 X 10°), Ru(III) has a five-fold higher affinity for ammonia and the stability constant of Ru(II) for pyridine Is A X 10 greater than that of Ru(III) (28). 

The relative chemical properties of Ru(II) versus Ru(III) suggest that animlneruthenlum(III) Ions should be far less active toward binding biochemical ligands than analogous RuCIi) complexes. In the case of most nitrogen ligands a wealth of chemical evidence exists In support of this (11). 

Recent studies on tumor metabolism Indicate very low levels of O2 to be available, even at very short distances from blood capillaries (31-33). This appears to be due to a 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

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A high percentage of the compounds tested, which would be expected to function as Ru(III)-prodrugs, have exhibited antitumor activity In rats. An exception to this are those complexes containing blpyrldyl or o-phenanthrollne ligands which strongly stabilize the lower valent state and which... 

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