Fu Patty K L, Bradley Patricia M, Turro Claudia
Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA.
Inorg Chem. 2003 Feb 10;42(3):878-84. doi: 10.1021/ic020338p.
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 and Ru(phi)(2)phen (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 (bqdi = 1,2-benzoquinone diimine), which possesses the nonintercalating bqdi ligand. In contrast, Ru(phen)(2)phi and Rh(phen)(2)L (L = phi, bqdi), which possess a single quinone diimine ligand, the parent Ru(phen)(3) and Rh(phen)(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 and Rh(phen)(2)L (L = phi, bqdi) complexes. Possible explanations for these observations are discussed.
研究了具有醌二亚胺配体的八面体配合物通过稳定DNA双链结构来抑制转录的能力。发现其配位球中含有两个醌二亚胺配体的铑（III）和钌（II）配合物能显著提高15聚体双链DNA的解链温度（ΔT(m)）。Rh(phi)(2)phen和Ru(phi)(2)phen（phi = 9,10 - 菲醌二亚胺，phen = 1,10 - 菲咯啉）在[配合物]/[DNA碱基]=0.067（两个配合物/双链体）时，相对于游离的15聚体双链体（T(m)=55℃），其ΔT(m)值分别为+21℃和+15℃。同样，对于具有非嵌入性bqdi配体的Rh(bqdi)(2)phen，测得其解链温度变化为+14℃。相比之下，含有单个醌二亚胺配体的Ru(phen)(2)phi和Rh(phen)(2)L（L = phi，bqdi）、母体Ru(phen)(3)和Rh(phen)(3)配合物以及溴化乙锭，导致双链寡核苷酸的解链温度变化较小。观察到ΔT(m)与抑制50%转录所需的每种配合物的相对浓度（R(inh)(50)）之间存在明显的相关性，与嵌入性配体的存在无关。双（醌二亚胺）配合物对双链体的稳定作用导致在体外抑制转录时所需的配合物浓度显著低于相应的Ru(phen)(2)phi和Rh(phen)(2)L（L = phi，bqdi）配合物。讨论了对这些观察结果的可能解释。
