A. Chouai

Reactions of 3,6-bis(2'-pyridyl)-1,2,4,5-tetrazine (bptz) and 3,6-bis(2'-pyridyl)-1,2-pyridazine (bppn) with the AgX salts (X = [PF6]-, [AsF6]-, [SbF6]-, and [BF4]-) afford complexes of different structural motifs depending on the pi-acidity of the ligand central ring and the outer-sphere anion. The bptz reactions lead to the polymeric [[Ag(bptz)][PF6]]infinity (1) and the dinuclear compounds [Ag2(bptz)2(CH3CN)2][PF6]2 (2) and [Ag2(bptz)2(CH3CN)2][AsF6]2 (3), as well as the propeller-type species [Ag2(bptz)3][AsF6]2 (4) and [Ag2(bptz)3][SbF6]2 (5a and 5b). Reactions of bppn with AgX produce the grid-type structures [Ag4(bppn)4][X]4 (6-9), regardless of the anion present. In 6-9, pi-pi stacking interactions are maximized, whereas multiple and shorter (therefore stronger) anion-pi interactions between the anions and the tetrazine rings are established in 1-5b. These differences reflect the more electron-rich character of the bppn pyridazine ring as compared to the bptz tetrazine ring. The evidence gleaned from the solid-state structures was corroborated by density functional theory calculations. In the electrostatic potential maps of the free ligands, a higher positive charge is present in the bptz as compared to the bppn central ring. Furthermore, the electrostatic potential maps of 3, 4, and 5b indicate an electron density transfer from the anions to the pi-acidic rings. Conversely, upon addition of the [AsF6]- ions to the cation of 7, there is negligible change in the electron density of the central pyridazine ring, which supports the presence of weaker anion-pi interactions in the bppn as compared to the bptz complexes. From the systems studied herein, it is concluded that anion-pi interactions play an important role in the outcome of self-assembly reactions.

Members of a family of Ru(II)-appended pyrenylethynylene dyads were synthesized, characterized according to their photophysical and photobiological properties, and evaluated for their collective potential as photosensitizers for metal-organic photodynamic therapy. The dyads in this series possess lowest-lying (3)IL-based excited states with lifetimes that can be tuned from 22 to 270 μs in fluid solution and from 44 to 3440 μs in glass at 77 K. To our knowledge, these excited-state lifetimes are the longest reported for Ru(II)-based dyads containing only one organic chromophore and lacking terminal diimine groups. These excited states proved to be extremely sensitive to trace amounts of oxygen, owing to their long lifetimes and very low radiative rates. Herein, we demonstrate that (3)IL states of this nature are potent photodynamic agents, exhibiting the largest photocytotoxicity indices reported to date with nanomolar light cytotoxicities at very short drug-to-light intervals. Importantly, these new agents are robust enough to maintain submicromolar PDT in pigmented metastatic melanoma cells, where the presence of melanin in combination with low oxygen tension is known to compromise PDT. This activity underscores the potential of metal-organic PDT as an alternate treatment strategy for challenging environments such as malignant melanoma.

Four complexes of the ligand 1,12-diazaperylene (DAP) have been prepared, [Ru(bpy)n(DAP)(3-n)]2+ where n = 0-2 and [Ru(DAP)3]2+. The [Ru(DAP)3]2+ complex was characterized by X-ray analysis and was found to exhibit the expected propeller-like structure with significant intermolecular pi-stacking interactions. The three Ru(II) complexes showed self-consistent optoelectronic properties with similar ligand-centered pi-pi* absorptions in the range of 333-468 nm and MLCT bands associated with the DAP which increased in intensity and decreased in energy as the number of DAP ligands varied from 1 to 3. Hypochromicity and viscosity changes were observed that were consistent with DAP intercalation into DNA, and binding constants were measured in the range of 1.4-1.6 x 10(6) M(-1) for the mixed ligand complexes. Furthermore, the complex [Ru(bpy)2(DAP)]2+ was found to photocleave plasmid DNA upon irradiation with visible light.

The emission of the DNA light-switch complex [Ru(bpy)2(tpphz)]2+ (bpy = 2,2'-bipyridine, tpphz = tetrapyrido[3,2-a:2',3'-c:3' ',2' '-h:2' '',3' ''-j]phenazine) can be reversibly turned ON and OFF over several cycles. The tpphz and taptp (taptp = 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene) ligands in [Ru(bpy)2(tpphz)]2+ and [Ru(bpy)2(taptp)]2+, respectively, intercalate between the DNA bases, and a 50-fold increase in emission intensity of [Ru(bpy)2(tpphz)]2+ is observed upon DNA intercalation. The [Ru(bpy)2(tpphz)]2+ DNA light switch can be turned OFF statically in the presence of Co2+, Ni2+, and Zn2+, and the emission can be fully restored by the addition of EDTA. Cycling of the DNA light switch OFF and ON can be accomplished through the successive introduction of Co2+ and EDTA, respectively, to solutions of DNA-bound [Ru(bpy)2(tpphz)]2+. Owing to the absence of additional coordination sites, the emission of DNA-intercalated [Ru(bpy)2(taptp)]2+ is not quenched by transition metal ions in solution. To our knowledge, this work presents the first example of a reversible DNA light switch.

In the series Rh2(O2CR)4 (R=CH3, 1; R=CF3, 2), [Rh2(O2CR)2(phen)2]2+ (R=CH3, 3; R=CF3, 4), and [Rh2(O2CR)2(dppz)2]2+ (R=CH3, 5; R=CF3, 6), 2, 4, and 6 are twice as cytotoxic as 1, 3, and 5, respectively. The substitution reactions of 2 with 9-ethylguanine at various temperatures take place at faster rates than those of 1, and the activation energy Ea(1)=69+/-4 kJ/mol is twice Ea(2)=35+/-2 kJ/mol. The higher cytotoxicities of [Rh2(micro-O2CCH3)2(eta1-O2CCH3)L(MeOH)]+ (L=dppz, 7; L=dppn, 8) relative to [Rh2(micro-O2CCH3)2(bpy)L]2+ (L=dppz, 10; L=dppn, 11) are attributed to the labile equatorial groups in 7 and 8 not present in 10 and 11. The toxicities of complexes 1-8 are not related to their charge or the ease by which they transverse the cellular membrane but to the lability of the ligands on the dirhodium core.