[Ru((t)Bu(2)bpy)(2)(2-appt)](PF6)(2) [1 center dot(PF6)(2), (t)Bu(2)bpy = 4,4'-di-tert-butyl-2,2'-bipyridine, 2-appt = 2-amino-4-phenylamino-6-(2-pyridyl)-1,3,5-triazine] and [Re(CO)(3)(2-appt)Cl] (2) were prepared and characterized by X-ray crystal analysis. The binding of 1 center dot(PF6)(2) and 2 to calf thymus DNA (ct DNA) led to increases in the DNA melting temperature (Delta T-m = +12 degrees C), modest hypochromism (29% and 5% of the absorption bands at lambda(max) = 450 and 376 nm, respectively), and insignificant shifts in the absorption maxima. The binding constants of 1 center dot(PF6)(2) and 2 with ct DNA, as determined by absorption titration, are (8.9 +/- 0.5) x 10(4) and (3.6 +/- 0.1) x 10(4) dm(3) mol(-1), respectively. UV-vis absorption titration, DNA melting studies, and competition dialysis using synthetic oligonucleotides [poly(dA-dT)(2) and poly(dG-dC)(2)] revealed that 1 center dot(PF6)(2) and 2 exhibit a binding preference for AT sequences. A modeling study on the interaction between 1 or 2 and B-DNA revealed that the minor groove is the most favored binding site and an extensive hydrogen-bonding network is formed. As determined by MTT assays, 1 center dot(PF6)(2) and 2 exhibited moderate cytotoxicities toward several human cancer cell lines (KB-3-1, HepG2, and HeLa), as well as a multi-drug-resistant cancer cell line (KB-V-1). According to confocal microscopic and flow cytometric studies, 1 center dot(PF6)(2) and 2 induced apoptosis (50-60%) in cancer cells with <5% necrosis detected.