Ruthenium(II) complexes of bipyridine-glycoluril and their interactions with DNA.

Nine complexes of the type [Ru(N-N)(2)(BPG)]Cl(2) 1-4, [Ru(N-N)(BPG)(2)]Cl(2) 5-8, and [Ru(BPG)(3)]Cl(2) 9 where N-N is 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz), which incorporates bipyridine-glycoluril (BPG-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione) as the ancillary ligand, have been synthesized and characterized. These complexes with the peripheral polypyridyl ligands have the ability to form conjugates with DNA. The DNA binding (absorption spectroscopy, steady-state and time-resolved emission measurements, steady-state emission quenching measurements) and cleavage (under dark and irradiated conditions) by these complexes has been studied to investigate the influence of the ancillary ligand. The binding ability of these complexes to DNA is dependent on the planarity of the intercalative polypyridyl ligand, which is further affected by the ancillary bipyridine-glycoluril ligand. The complexes 3, 4, 7, and 8 bind to CT-DNA with binding constants on the order of 10(4) M(-1). Time-resolved emission measurements on the DNA-bound complexes 1, 3, 5-7, and 9 show monoexponential decay of the excited states, whereas complexes 2, 4, and 8 show biexponential decay with short- and long-lived components. Interaction of complexes 2-9 with plasmid pBR322 DNA studied by gel electrophoresis experiments reveals that all complexes cleave DNA efficiently at micromolar concentrations under dark and anaerobic conditions probably by a hydrolytic mechanism. Complexes 3, 4, 7, 8, and [Ru(bpy)(2)(dppz)](2+) show extensive DNA cleavage in the presence of light with a shift in mobility of form I of DNA probably due to the high molecular weight of DNA-complex conjugates. However, the extent of the cleavage is augmented on irradiation in the case of complexes 3, 4, 7, and 8, which include the planar dpq and dppz ligands, suggesting a combination of hydrolytic and oxidative mechanism for the DNA scission. Molecular mechanics calculations of these systems corroborate the DNA binding and cleavage mechanisms.

Synthesis, characterization, X-ray structure and DNA photocleavage by cis-dichloro bis(diimine) Co(III) complexes.

Complexes of the type [Co(LL)2Cl2]Cl, where LL = N,N'-ethylenediamine (en), 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been synthesized and characterized by elemental analyses, IR, UV-visible and NMR spectroscopy. Crystal structure of [Co(phendione)2Cl2]Cl x 0.5 HCl x 3.5 H2O has been solved and refined to R = 0.0552. The crystal is monoclinic with space group C2/c; a = 25.730(2) A, b = 12.375(1) A, c = 18.979(2) A, beta = 119.925(1) degrees and Z = 8. The DNA binding characteristics of the complexes, investigated by covalent binding assay, viscosity measurements and competitive binding fluorescence measurements show that the complexes interact with DNA covalently except the complex containing the planar dppz ligand which intercalates within the base pairs of DNA. The complexes containing en, phen and phendione cleave plasmid pBR 322 DNA upon irradiation under aerobic conditions while the complex containing the dppz ligand cleaves DNA upon irradiation under inert atmosphere. Molecular modeling studies show that the minimized structure of [Co(phendione)2Cl2]+, maintained the octahedral structure while binding to the N7 of guanines and the ligand fits into the major groove without disrupting the helical structure of the B-DNA.

Ruthenium(II) polypyridyl complexes with hydrophobic ancillary ligand as Aß aggregation inhibitors.

The synthesis, spectral and electrochemical characterization of the complexes of the type [Ru(NN)2(txbg)](2+) where NN is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), dipyrido [3,2-d:2',3f] quinoxaline (dpq) (3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4) which incorporate the tetra-xylene bipyridine glycoluril (txbg) as the ancillary ligand are described in detail. Crystal structures of ligand txbg and complex 2 were solved by single crystal X-ray diffraction. Thioflavin T (ThT) fluorescence and Transmission Electron Microscopy (TEM) results indicated that at micromolar concentration all complexes exhibit significant potential of Aß aggregation inhibition, while the ligand txbg displayed weak activity towards Aß aggregation. Complex 1 showed relatively low inhibition (70%) while complexes 2-4 inhibited nearly 100% Aß aggregation after 240 h of incubation. The similar potential of complexes 2-4 and absence of any trend in their activity with the planarity of polypyridyl ligands suggests there is no marked effect of planarity of coligands on their inhibitory potential. Further studies on acetylcholinesterase (AChE) inhibition indicated very weak activity of these complexes against AChE. Detailed interactions of Aß with both ligand and complex 2 have been studied by molecular modeling. Complex 2 showed interactions involving all three polypyridyl ligands with hydrophobic region of Aß. Furthermore, the toxicity of these complexes towards human neuroblastoma cells was evaluated by MTT assay and except complex 4, the complexes displayed very low toxicity.

Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aß aggregation.

Two ruthenium(II) polypyridyl complexes [Ru(phen)3](2+) (1) and [Ru(phen)2(bxbg)](2+) (2) (where phen = 1,10 phenanthroline, bxbg = bis(o-xylene)bipyridine glycoluril) have been evaluated for acetylcholinesterase (AChE) and Amyloid-ß peptide (Aß) aggregation inhibition. Complex 2 exhibits higher potency of AChE inhibition and kinetics and molecular modeling studies indicate that ancillary ligand plays significant role in inhibitory potency exhibited by complex 2. The inhibitory effect of these complexes on Aß (1-40) aggregation is investigated using Thioflavin T fluorescence and Transmission Electron Microscopy. Both complexes efficiently inhibit Aß (1-40) aggregation and are negligibly toxic to human neuroblastoma cells. This is the first demonstration that ruthenium(II) polypyridyl complexes simultaneously inhibit AChE and Aß aggregation.

Mixed ligand cobalt(II) picolinate complexes: synthesis, characterization, DNA binding and photocleavage.

Complexes of the type [Co(pic)(2)(NN)], where pic = picolinate, NN = dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (4) and 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]-phenanthroline-6,13-dione (bipyridyl-glycoluril) (bpg) (6) have been synthesized and characterized by elemental analysis, IR, UV-vis, NMR and ESI-MS spectroscopy and thermogravimetic analysis (TGA). Their physicochemical properties are compared with previously synthesized complexes, where NN = (H(2)O)(2) (1), 2,2'-bipyridine (bpy) (2), 1,10-phenanthroline (phen) (3) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (5). The crystal structures of the complexes 4-6 were solved by single-crystal X-ray diffraction. The complexes 4 and 5 crystallize from a mixture of chloroform and methanol in monoclinic and orthorhombic crystal systems, respectively, whereas complex 6 crystallizes from dimethyl sulfoxide (DMSO) in a tetragonal crystal system. The coordination sphere consists of two oxygen atoms and two nitrogen atoms from the two picolinates and two nitrogen atoms from the dpq, dppz or bpg ligand, respectively. Co(ii)/Co(iii) oxidation potentials have been determined by cyclic voltammetry. The DNA binding of complexes 1-5 has been investigated using thermal melting, fluorescence quenching and viscosity measurements, which indicate the partial intercalation of complex 5 with an apparent binding constant (k(app)) of 8.3 × 10(5) M(-1). DNA cleavage studies of complexes 1-5 have been investigated using gel electrophoresis in the presence of H(2)O(2) as an oxidizing agent and also by photoirradiation at 365 nm. The mechanistic investigations suggest that singlet oxygen ((1)O(2)) is the major species involved in the DNA cleavage by these complexes. The structures of complexes 2-6 were optimized with density functional theory (DFT) method (B3LYP/6-31G(d,p)). The low vertical ionization potential values indicate photoredox pathways for the DNA cleavage activity by complexes 4 and 5, which is corroborated by DNA cleavage experiments.