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 degreesC relative to free 15-mer duplex (T-m == 55 degreesC) at [complex]/[DNA bases] = 0.067 (two complexes/duplex). Similarly, a shift in the melting temperature of +14 degreesC was measured for [Rh(bqdi)(2)phen](3+) (bqdi = 1,2-benzoquinone diimine), which possesses the nonintercalating bqdi ligand. In contrast, [Ru(phen)(2)phi](2+) and [Rh(phen)(2)L](3+) (L = phi, bqdi), which possess a single quinone diimine ligand, the parent [Ru(phen)(3)](2+) and [Rh(phen)(3)](3+) complexes, and ethidium bromide result in small shifts in the melting temperature of the duplex oligonucleotide. A distinct correlation between ATm and the relative concentration of each complex required to inhibit 50% of the transcription (R-inh(50)) was observed, independent of the presence of an intercalative ligand. The duplex stabilization by bis(quinone diimine) complexes results in inhibition of transcription in vitro at significantly lower complex concentrations than for the corresponding [Ru(phen)(2)phi](2+) and [Rh(phen)(2)L](3+) (L = phi, bqdi) complexes. Possible explanations for these observations are discussed.