Photophysical properties, DNA photocleavage, and photocytotoxicity of a series of dppn dirhodium(II,II) complexes.

A series of dirhodium(II,II) complexes of the type cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppn)(L)](2+), where dppn = benzo[i]dipyrido[3,2-a:2',3'-h]quinoxaline and L = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-f:2'3'-h]quinoxaline (dpq, 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4), and dppn (5), were synthesized and their photophysical properties investigated to probe their potential usefulness as photodynamic therapy agents. The ability of the complexes to bind and photocleave DNA was also probed, along with their toxicity toward human skin cells in the dark and when irradiated with visible light. Nanosecond time-resolved absorption measurements established that the lowest energy excited state in 1-5 is dppn-localized (3)pipi* with lifetimes of 2.

Dirhodium(II,II) complexes: molecular characteristics that affect in vitro activity.

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.

cis-[Rh2(mu-O2CCH3)2(CH3CN)6]2+ as a photoactivated cisplatin analog.

The complex cis-[Rh2(mu-O2CCH3)2(CH3CN)6]2+ (1) exchanges the two axial CH3CN ligands for solvent molecules in water to yield cis-[Rh2(mu-O2CCH3)2(CH3CN)4(H2O)2]2+ (2). Photolysis of 2 in H2O results in the photoaquation of two equatorial acetonitrile ligands to yield [Rh2(mu-O2CCH3)2(CH3CN)2(H2O)4]2+ (3), which is able to covalently bind to free 2,2'-bipyridine (bpy) and 9-ethylguanine in solution, as well as double-stranded DNA (lambdairr >/= 455 nm). Complex 2 exhibits 20-fold lower cytotoxicity towards human skin cells than hematoporphyrin in the dark, and its toxicity increases by a factor of 34 when irradiated with visible light (400-700 nm, 30 min).

Photocytotoxicity of a new Rh2(II,II) complex: increase in cytotoxicity upon irradiation similar to that of PDT agent hematoporphyrin.

A new type of heteroleptic dirhodium complex cis-[Rh(2)(mu-O2CCH3)2-(bpy)(dppz)]2+ (3) was synthesized and its potential as a photodynamic therapy (PDT) agent was investigated. Although 27% hypochromicity of the absorption of 3 in the near-UV and visible regions is observed in the presence of duplex DNA, relative viscosity measurements reveal that the complex does not intercalate between the DNA bases. The DNA photocleavage with visible light by 3 proceeds via both oxygen dependent and independent mechanisms, and it is more efficient than that of related complexes.

DNA binding and photocleavage in vitro by new dirhodium(II) dppz complexes: correlation to cytotoxicity and photocytotoxicity.

Two new dirhodium(II) complexes possessing the intercalating dppz ligand (dppz = dipyrido[3,2-a:2',3'-c]phenazine), cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppz)(eta(1)-O(2)CCH(3))(CH(3)OH)](+) (1) and cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppz)(2)](2+) (2), were synthesized and characterized as potential agents for photochemotherapy. Various techniques show that 1 binds to DNA through intercalation, although some aggregation of the complex on the DNA surface is also present. In contrast, 2 does not intercalate between the DNA bases; however, strong hypochromic behavior is observed in the presence of DNA, which can be attributed to intermolecular pi-stacking of 2 enhanced by the polyanion.

Photoinduced DNA cleavage and cellular damage in human dermal fibroblasts by 2,3-diaminophenazine.

Aromatic amines, such as o-phenylenediamine (OPD), have been used extensively in commercial hair dyes and in the synthesis of agricultural pesticides. Air oxidation of OPD results in the formation of 2,3-diaminophenazine (DAP). Although the mutagenic toxicity of DAP has been shown in both prokaryotic and eukaryotic systems, its phototoxicity remains largely unexplored.

Effect of equatorial ligands of dirhodium(II,II) complexes on the efficiency and mechanism of transcription inhibition in vitro.

The nature of the equatorial ligands spanning the dirhodium core was shown to affect the ability and mechanism of various lantern-type complexes to inhibit transcription in vitro. The inhibition of transcription by Rh(2)(mu-O(2)CCF(3))(4), Rh(2)(mu-HNCOCF(3))(4), and [Rh(2)(mu-O(2)CCH(3))(2)(CH(3)CN)(6)](2+) appears to proceed predominantly via binding of the complexes to T7-RNA polymerase (T7-RNAP) and is dependent on the concentration of enzyme and Mg(2+) ions in solution. The concentrations of the aforementioned complexes required to inhibit 50% of the transcription, C(inh)(50), are similar to that measured for activated cisplatin, whereas a significantly higher concentration of Rh(2)(mu-HNCOCH(3))(4) is required to effect similar inhibition; the inhibition induced by Rh(2)(mu-HNCOCH(3))(4) does not involve binding to T7-RNAP.

Inhibition of transcription in vitro by anticancer active dirhodium(II) complexes.

The DNA binding and inhibition of transcription in vitro by neutral Rh(2)(mu-O(2)CCH(3))(4) and cationic cis-[Rh(2)(mu-O(2)CCH(3))(2)(phen)(2)](2+) complexes were investigated. The binding constants of the two complexes to calf-thymus DNA were estimated from absorption titrations to be 4.6 x 10(2) M(-)(1) and 1.

Stabilization of duplex DNA structure and suppression of transcription in vitro by bis(quinone diimine) complexes of rhodium(III) and ruthenium(II).

The ability of octahedral complexes possessing quinone diimine ligands to inhibit transcription by stabilization of the DNA duplex structure was investigated. Rh(III) and Ru(II) complexes possessing two quinone diimine ligands in their coordination sphere were found to significantly increase the melting temperature (DeltaT(m)) of a 15-mer duplex DNA. [Rh(phi)(2)phen](3+) and [Ru(phi)(2)phen](2+) (phi = 9,10-phenanthrenequinone diimine, phen = 1,10-phenanthroline) exhibit DeltaT(m) values of +21 and +15 degrees C relative to free 15-mer duplex (T(m) = 55 degrees C) at [complex]/[DNA bases] = 0.

DNA photocleavage by a supramolecular Ru(II)-viologen complex.

A novel Ru(II) complex possessing two sequentially linked viologen units, Ru-V(1)-V(2)(6+), was synthesized and characterized. Upon excitation of the Ru(II) unit (lambda(exc) = 532 nm, fwhm approximately 10 ns), a long-lived charge-separated (CS) state is observed (tau = 1.7 micros) by transient absorption spectroscopy.