Selective binding and reverse transcription inhibition of single-strand poly(A) RNA by metal TMPyP complexes.

Ni-, Cu-, and Zn-TMPyP are capable of binding to single-strand poly(A) RNA with high preference and affinity and inhibiting the reverse transcription of RNA by both M-MuLV and HIV-1 reverse transcriptase. With 10 nM azidothymidine, the IC50 value of M-TMPyP could be lowered to 10(-1) µM order.

Structure-activity relationship of polypyridyl ruthenium(II) complexes as DNA intercalators, DNA photocleavage reagents, and DNA topoisomerase and RNA polymerase inhibitors.

To investigate the relationship between the molecular structure and biological activity of polypyridyl Ru(II) complexes, such as DNA binding, photocleavage ability, and DNA topoisomerase and RNA polymerase inhibition, six new [Ru(bpy)(2)(dppz)](2+) (bpy=2,2'-bipyridine; dppz=dipyrido[3,2-a:2,',3'-c]phenazine) analogs have been synthesized and characterized by means of (1)H-NMR spectroscopy, mass spectrometry, and elemental analysis. Interestingly, the biological properties of these complexes have been identified to be quite different via a series of experimental methods, such as spectral titration, DNA thermal denaturation, viscosity, and gel electrophoresis. To explain the experimental regularity and reveal the underlying mechanism of biological activity, the properties of energy levels and population of frontier molecular orbitals and excited-state transitions of these complexes have been studied by density-functional theory (DFT) and time-depended DFT (TDDFT) calculations. The results suggest that DNA intercalative ligands with better planarity, greater hydrophobicity, and less steric hindrance are beneficial to the DNA intercalation and enzymatic inhibition of their complexes.

Effect of ancillary ligands on the topoisomerases II and transcription inhibition activity of polypyridyl ruthenium(II) complexes.

To explore the structure-activity relationship of polypyridyl ruthenium(II) complexes as topoisomerase II and T7 RNA polymerase inhibitors, four new complexes, [Ru(4dmb)(2)(ppd)](2+) (4dmb=4,4'-dimethyl-2,2'-bipyridine, ppd=pteridino[6,7-f][1,10] phenanthroline-1,13(10H,12H)-dione), [Ru(5dmb)(2)(ppd)](2+) (5dmb=5,5'-dimethyl-2,2'-bipyridine), [Ru(dip)(2)(ppd)](2+) (dip=4,7-diphenyl-1,10-phenanthroline), and [Ru(ip)(2)(ppd)](2+) (ip=imidazole[4,5-f][1,10]phenanthroline) have been synthesized and characterized in detail by (1)H NMR spectroscopy, mass spectrometry and elemental analysis. Their interaction with calf thymus DNA and the inhibitory activity towards topoisomerase II and T7 RNA polymerase were investigated. The results suggest that although all of these four Ru(II) complexes are potent DNA intercalators, topoisomerase II inhibitors and DNA transcription inhibitors, their DNA binding strength and inhibitory activities are quite different. The activity of ip- and dip-complexes are significantly higher than the dmb-complexes. To explain the experimental regularity and reveal the underlying quantum chemistry mechanism of the biological activity, the properties of energy levels and population of frontier molecular orbitals and excited state transitions of these complexes have been studied by density functional theory (DFT) and time-depended DFT (TDDFT) calculations. The results suggest that ancillary ligands bearing lower energy of the lowest unoccupied molecular orbitals (LUMOs), better hydrophobicity and less steric hindrance of are beneficial to the DNA intercalation and topoisomerase II and DNA transcription inhibition of their complexes.