Sequence Dependent Binding Modes of the Delta Delta- and Lambda Lambda-binuclear Ru(II) Complexes to poly[d(G-C)(2)] and poly[d(A-T)(2)]

Abstract

The binding properties and sequence selectivities of Delta Delta- and Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) (bip = 4,4'-biphenylene (imidazo [4,4-f][1,10]phenanthroline) complexes with poly[d(A-T)(2)] and poly[d(G-C)(2)] were investigated using conventional spectroscopic methods. When bound to poly[d(A-T)(2)], a large positive circular dichroism (CD) spectrum was induced in absorption region of the bridging moiety for both the Delta Delta- and Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) complexes, which suggested that the bridging moiety sits in the minor groove of the polynucleotide. As luminescence intensity increased, decay times became longer and complexes were well-protected from the negatively charged iodide quencher compared to that in the absence of poly[d(A-T)(2)]. These luminescence measurements indicated that Ru(II) enantiomers were in a less polar environment compared to that in water and supported by minor groove binding. An angle of 45 degrees between the molecular plane of the bridging moiety of the Delta Delta-[mu-Ru-2(phen)(4)(bip)](4+) complex and the local DNA helix axis calculated from reduced linear dichroism (LDr) spectrum further supported the minor groove binding mode. In the case of Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) complex, this angle was 55 degrees, suggesting a tilt of DNA stem near the binding site and bridging moiety sit in the minor groove of the poly[d(A-T)(2)]. In contrast, neither Delta Delta- nor Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) complex produced significant CD or LDr. signal in the absorption region of the bridging moiety. Luminescence measurements revealed that both the Delta Delta- and Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) complexes were partially accessible to the I- quencher. Furthermore, decay times became shorter when bis-Ru(II) complexes bound to poly[d(G-C)(2)]. These observations suggest that both the Delta Delta- and Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) complexes bind at the surface of poly[d(G-C)(2)], probably electrostatically to phosphate group. The results indicate that Delta Delta- and Lambda Lambda-[mu-Ru-2(phen)(4)(bip)](4+) are able to discriminate between AT and GC base pairs.