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.

Role of the surface-exposed leucine 155 in the metal ion binding loop of the CuA domain of cytochrome c oxidase from Thermus thermophilus on the function and stability of the protein.

The role of Leu155 in the metal ion binding loop in the soluble CuA binding domain of subunit II of cytochrome c oxidase from Thermus thermophilus (TtCuA) was investigated by site-specific mutations of this residue to arginine (L155R) and glutamic acid (L155E). The UV-visible absorption and electron paramagnetic resonance spectra suggested that the Cu(2)S(2) core of TtCuA was almost unchanged by the mutations. The redox potential of the metal center in the L155R mutant was ~20 mV higher than that in the WT protein, while that of the L155E mutant was almost the same as that of the wild type (WT-TtCuA). The rate of transfer of an electron from cytochrome c(552) to the L155E mutant was much lower than that of transfer to the WT protein, while that for transfer to the L155R mutant was similar to that of WT-TtCuA. The total reorganization energy was increased for both the mutant proteins compared to WT-TtCuA. The results suggest that the presence of a negatively charged residue at the site of Leu155 in TtCuA possibly disfavors the protein-protein interaction between the two redox partners. The mutation also affected the equilibrium pH dependence of the protein. The thermal and thermodynamic stability of TtCuA was drastically decreased upon the mutation, which is most prominent in the L155R mutant. These studies indicate that the hydrophobic patch at the surface of TtCuA consisting of Leu155 is important for the transfer of an electron between cytochrome c(552) and TtCuA.

Synthesis and properties of mononuclear and binuclear molybdenum complexes derived from bis(2-hydroxy-1-naphthaldehyde)oxaloyldihydrazone.

The monomer molybdenum(VI) complex [MoO(2)(napoxlhH(2))].2H(2)O (1) has been synthesized from the reaction of MoO(2)(acac)(2) with bis(2-hydroxy-1-naphthaldehyde)oxaloyldihydrazone (napoxlhH(4)) in 1:1 molar ratio in ethanol under reflux. This complex on reaction with pyridine/3-picoline/4-picoline yielded the dimer molybdenum(VI) complexes [Mo(2)O(4)(napoxlhH(2))(2)(A)(2)].2H(2)O (A=py (2), 3-pic (3), 4-pic (4)), whereas reaction with isonicotinoylhydrazine (inhH(3)) and salicyloylhydrazine (sylshH(3)) lead to the reduction of the metal centre yielding monomeric molybdenum(V) complexes [Mo(napoxlhH(2))(hzid)].2H(2)O (where hzidH(3)=inhH(3) (5) and sylshH(3) (6)). The complexes have been characterized by elemental analyses, molecular weight determinations, molar conductance data, magnetic moment data, electronic, IR, ESR and (1)H NMR spectroscopic studies. The complexes (5) and (6) are paramagnetic to the extent of one unpaired electron. The electronic spectra of the complexes are dominated by strong charge transfer bands. In all of the complexes, the principal dihydrazone ligand has been suggested to coordinate to the metal centres in the anti-cis-configuration. The complexes (1), (5) and (6) are suggested to have six-coordinate octahedral stereochemistry around molybdenum(VI) and molybdenum(V) metal centres, respectively, while the complexes (2)-(4) are suggested to have eight coordinate dodecahedral stereochemistry around molybdenum(VI) metal centre.