Structure-based biological investigations on ruthenium complexes containing 2,2'-bipyridine ligands and their applications in photodynamic therapy as a potential photosensitizer.

Ruthenium complexes have been investigated for various biological applications by virtue of their radical scavenging, DNA binding, receptor binding, and cytotoxic abilities; especially the possible potential application of these complexes in photodynamic therapy (PDT). This study focuses on the synthesis, structural characterization and biological application (pertaining to its cytotoxicity and radical generation) of ruthenium complexed with salicylaldehyde fumaryl-dihydrazone (slfhH4 ), salicylaldehyde glutaryl-di-hydrazone (slfgH4 ) and 2,2'-bipyridine (bpy). During the synthesis, the anticipated complex was precipitated out but as serendipity, Ruthenium(II) tris (2,2'-bipyridyl) monochloride nonahydrate {[Ru(bpy)3 ]2+ .Cl.9H2 O} (RBMN) and Ruthenium(II) tris (2,2'-bipyridyl) monochloride septahydrate {[Ru(bpy)3 ]2+ .Cl.7H2 O}(RBMS) were crystallized from the filtrate. The crystal structure of complexes RBMN and RBMS were determined by a single-crystal X-ray diffraction methods and it showed that chlorine anion lies at the crystallographic axis and forms a halogen hydrogen-bonded organic framework (XHOF) to provide the stability. In comparison with similar structures in Cambridge Crystallographic Data Center (CCDC) revealed that the nature of the XHOF framework and the layered packing are conserved. The compounds showed excellent cytotoxic ability (against L6 cells) and the nitro blue tetrazolium (NBT) assay upon irradiation to light revealed its ability to produce reactive oxygen species (ROS). The presence of partially occupied water molecules in the layered organization within the crystal packing mimics the release of ROS resulting in cytotoxicity. The structural results together with the biological data make these complexes interesting candidates for potential photosensitizers for PDT applications.

The models of proton assisted and the unassisted formation of CGC base triplets.

The triple helix is formed by combining a double and a single strand DNAs in low pH and dissociates in high pH. Under such conditions, protonation of cytosine in the single strand is necessary for triplex formation where cytosine-guanine-cytosine (CGC+) base triplet stabilizes the triple helix. The mechanism of CGC+ triplet formation from guanine-cytosine (GC) and a protonated cytosine (C+) shows the importance of N3 proton. Similarly in the case of CGC (unprotonated) triplet, the donor acceptor H-bond at N3 hydrogen of the cytosine analog (C) initiates the interaction with GC. The correspondence between the two models of triplets, CGC+ and CGC, unambiguously assigned that protonation at N3 cytosine in low pH to be the first step in triplet formation, but a donor acceptor triplet (CGC) can be designed without involving a proton in the Hoogsteen H-bond. Further, the bases of cytosine analogue also show the capability of forming Watson Crick (WC) H-bonds with guanine.