We report the synthesis and characterization of Ru-diimine complexes designed to bind to cytochrome P450cam (CYP101). The sensitizer core has the structure [Ru(L-2)L'](2+), where L' is a perfluorinated biphenyl bridge (F(8)bp) connecting 4,4'-dimethylbipyridine to an enzyme substrate (adamantane, F(8)bp-Ad), a heme ligand (imidazole, F(8)bp-Im), or F (F(9)bp). The electron-transfer (ET) driving force (-DeltaGdegrees) is varied by replacing the ancillary 2,2'-bipyridine ligands with 4,4',5,5'-tetramethylbipyridine (tmRu). The four complexes all bind P450cam tightly: Ru-F(8)bp-Ad (1, K-d = 0.077 muM); Ru-F(8)bp-Im (2, K-d = 3.7 muM); tmRu-F(9)bp (3, K-d = 2.1 muM); and tmRu-F(8)bp-Im (4, K-d = 0.48 muM). Binding is predominantly driven by hydrophobic interactions between the Ru-diimine wires and the substrate access channel. With Ru-F(8)bp wires, redox reactions can be triggered on the nanosecond time scale. Ru-wire 2, which ligates the heme iron, shows a small amount of transient heme photoreduction (ca. 30%), whereas the transient photoreduction yield for 4 is 76%. Forward ET with 4 occurs in roughly 40 ns (k(f) = 2.8 x 10(7) s(-1)), and back ET (Fe-II --> Ru-III, k(b) approximate to 1.7 x 10(8) s(-1)) is near the coupling-limited rate (k(max)). Direct photoreduction was not observed for 1 or 3. The large variation in ET rates among the Ru-diimine:P450 conjugates strongly supports a through-bond model of Ru-heme electronic coupling.