DNA Binding, Photocleavage, and Topoisomerase Inhibition of Functionalized Ruthenium(II)‐Polypyridine Complexes

Abstract

The interaction of ruthenium(II)-polypyridyl complexes with DNA has attracted considerable interests during the past two decades. This paper presents some recent progresses in our laboratory on the interaction of Ru(II)-polypyridyl complexes with DNA. The first part describes the effect of modulating the intercalative ligand on the DNA-binding behaviors of the complexes, such as DNA-binding affinity, DNA-binding enantioselectivity, DNA molecular 'light switch' effect, and DNA sequence selectivity. The second part focuses on the DNA photocleavage by the complexes and its mechanism. In the final part, we discuss the topoisomerase inhibition and its mechanism, as well as the antitumor activity of the Ru(II)-polypyridyl complexes.

Synthesis, and characterization of ruthenium(II) polypyridyl complexes containing α-amino acids and its DNA binding behavior

“…The conformational changes in the structure of DNA from B-Z form is evidenced by observed change in the ratio A 295 /A 260 . An increase in the ratio of A 295 /A 260 from 0.18 (for free DNA) to 0.77(3), 0.66(6), 0.78(7) and 0.56 (13) suggested destabilization of the DNA helix. Further, condensation of calf thymus CT DNA induced by the complexes was monitored spectrophotometrically by UV-absorption ratio of A 320 /A 260 .…”

“…All the complexes were found to cause condensation of DNA at 20 lg concentration. The condensation of DNA was monitored by measuring increase in the value of absorption at 320 nm [0.075 for free DNA to 0.38(4), 0.28(6), 0.45 (10), and 0.53 (13)]. …”

“…Many of the complexes bind DNA through a combination of binding modes that is dependent on the structural characteristics of compounds. An understanding of how the metal complexes bind DNA will not only pave the way to understand fundamentals of these interactions but also, about the variety of potential applications [13][14][15][16].…”

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

“…Polypyridyl ruthenium(II) complexes have attracted considerable attentions of late due to their stable octahedral coordinate structure, various of photophysical and photochemical properties, diverse binding modes of nucleic acids and promising DNA cleavage activity [15][16][17][18][19]. Recently, a series of polypyridyl ruthenium(II) complexes have been found to exhibit high topoisomerase II and transcription inhibition activity and moderate antitumor activity by us [20][21][22][23].…”

Trinuclear Ru(II) polypyridyl complexes as human telomeric quadruplex DNA stabilizers

“…Some of them have been investigated as nucleic acid probes, DNA mediated electron transfer, anticancer drugs, and DNA footprinting and sequence-specific cleaving agents [12]. However, study involving the interaction between telomeric DNA and Ru(II) complexes is rare.…”