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] = 0.067 (two complexes/duplex). Similarly, a shift in the melting temperature of +14 degrees C 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 DeltaT(m) 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.
Fu
Patty K L
PK
Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA.
Bradley
Patricia M
PM
Turro
Claudia
C
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013950:Thymus Gland; D014158:Transcription, Genetic / Q000187:drug effects
D007097:Imines; D008024:Ligands; D009841:Oligonucleotides; D009942:Organometallic Compounds; D011809:Quinones; D012333:RNA, Messenger; D012428:Ruthenium; D004247:DNA; D012238:Rhodium