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A redox-active diamine ligand, 4,4'-bis(di-p-anisylamino)-2,2'-bipyridine (NNbpy), has been prepared. Electrochemical and spectroscopic studies suggest that little electronic coupling is present between two amine groups in NNbpy. After chelation with Ru(bpy)2 (bpy is 2,2'-bipyridine), the resulting complex displays two N(•+/0) processes at +1.02 and +1.16 V versus Ag/AgCl. In the mixed-valent state, rich near-infrared absorptions have been observed, which are believed to consist of multiple metal-to-ligand charge transfer and intervalence charge transfer transitions in the low-energy region. These results suggest that the amine-amine electronic coupling has been enhanced by chelation with Ru(bpy)2. In contrast, no efficient electronic coupling can be realized by chelation with Ir(ppy)2 (ppy is 2'-phenylpyridine) or Re(CO)3Cl. A ruthenium ion-mediated electron transfer mechanism, instead of through-space coupling, has been proposed to explain this phenomenon. For the purpose of comparison, a monoamine-substituted bpy ligand and corresponding Ru(bpy)2 complex have been synthesized and studied. In addition, EPR, DFT, and TDDFT studies have been performed to complement the experimental results.

Organometallic ruthenium(II) complexes [(η(6)-arene)Ru(en)Cl](+) (arene = e.g., biphenyl (1), dihydrophenanthrene, tetrahydroanthracene) show promising anticancer activity both in vitro and in vivo and are cytotoxic to cisplatin-resistant cancer cells, implying that these monofunctional complexes have a different mechanism of action from that of bifunctional cisplatin. We demonstrate here that complex 1 binds selectively to the guanine base in the 15-mer single-stranded oligodeoxynucleotides (ODNs) 5'-CTCTCTX7G8Y9CTTCTC-3' [X = Y = T; X = C, Y = A; X = A, Y = T; X = T, Y = A] to form thermodynamically stable adducts, but thymine bases (T7/T11 or T6/T11) compete kinetically with guanine for binding to 1. The T-bound monoruthenated species eventually convert to diruthenated products via a second step of binding at G or/and to G-bound monoruthenated species through dissociation of the diruthenated adducts. Complex 1 was further shown to bind preferentially to the middle T in a sequence rather than to a T near the terminus and favor coordination to a 5'-T compared to a 3'-T. Interestingly, the T bases in the human telomeric G-quadruplex sequence (5'-AGGGTTAGGGTTAGGGTTAGGG-3') were found to be more competitive both kinetically and thermodynamically with G bases for binding to 1. These results suggest that thymine bases play a unique role in the pathways of ruthenation of DNA by organoruthenium anticancer complexes and illustrate that kinetic studies can provide new insight into the mechanism of action of metallodrugs in addition to study of the structures and functions of the thermodynamically stable end products.

A new bridging ligand 1,3,6,8-tetrakis(1-butyl-1H-1,2,3-triazol-4-yl)pyrene (ttapyr) was designed and synthesized by "click" chemistry. This ligand was used to construct a linear dimetallic biscyclometalated Ru(II) complex [(tpy)Ru(ttapyr)Ru(tpy)](2+) and a monometallic complex [(tpy)Ru(ttapyr)](+), where tpy is 2,2':6',2″-terpyridine. The electronic properties of these complexes were studied and compared by electrochemical and spectroscopic methods with the aid of DFT calculations. One-electron oxidation of [(tpy)Ru(ttapyr)Ru(tpy)](2+) with cerium ammonium nitrate produced a mixed-valent complex [(tpy)Ru(ttapyr)Ru(tpy)](3+). The intramolecular electronic coupling between individual metal centers was quantified by the intervalence charge transfer transition analysis. Mixed-valent complex [(tpy)Ru(ttapyr)Ru(tpy)](3+) exhibits a metal-centered rhombic EPR signal at 77 K with an average g factor of 2.203.