Satish S. Bhat

Synthesis, Electronic Structure, DNA and Protein Binding, DNA Cleavage, and Anticancer Activity of Fluorophore-Labeled Copper(II) Complexes

Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)](+)(2) and [Cu(nip)2](2+) (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1-3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal while 3 retains its square planar geometry in the lowest excited state. The interaction of complexes with calf-thymus DNA (CT DNA) has been explored by using absorption, emission, thermal denaturation, and viscosity studies, and the intercalating mode of DNA binding has been proposed. The complexes cleave DNA oxidatively without any exogenous additives. The protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using bovine serum albumin (BSA) as model protein. The compounds showed dynamic quenching behavior. Further, the anticancer activity of the complexes on MCF-7 (human breast cancer), HeLa (human cervical cancer), HL-60 (human promyelocytic leukemia), and MCF-12A (normal epithelial) cell lines has been studied. It has been observed that 3 exhibits higher cytotoxicity than 2, and the cells undergo apoptotic cell death.

Ruthenium(II) polypyridyl complexes as carriers for DNA delivery

Two novel water soluble ruthenium(II) complexes [Ru(bpy)(2)(bqbg)](2+) and [Ru(phen)(2)(bqbg)](2+) have been structurally characterized and their DNA condensation activity, cytotoxicity, and cellular uptake studies of DNA condensates as potential non-viral DNA carriers were evaluated.

Nonheme Fe(IV) Oxo Complexes of Two New Pentadentate Ligands and Their Hydrogen-Atom and Oxygen-Atom Transfer Reactions

Two new pentadentate {N5} donor ligands based on the N4Py (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) framework have been synthesized, viz. [N-(1-methyl-2-benzimidazolyl)methyl-N-(2-pyridyl)methyl-N-(bis-2-pyridyl methyl)amine] (L(1)) and [N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2-pyridylmethyl)amine] (L(2)), where one or two pyridyl arms of N4Py have been replaced by corresponding (N-methyl)benzimidazolyl-containing arms. The complexes [Fe(II)(CH3CN)(L)](2+) (L = L(1) (1); L(2) (2)) were synthesized, and reaction of these ferrous complexes with iodosylbenzene led to the formation of the ferryl complexes [Fe(IV)(O)(L)](2+) (L = L(1) (3); L(2) (4)), which were characterized by UV-vis spectroscopy, high resolution mass spectrometry, and Mössbauer spectroscopy. Complexes 3 and 4 are relatively stable with half-lives at room temperature of 40 h (L = L(1)) and 2.5 h (L = L(2)). The redox potentials of 1 and 2, as well as the visible spectra of 3 and 4, indicate that the ligand field weakens as ligand pyridyl substituents are progressively substituted by (N-methyl)benzimidazolyl moieties. The reactivities of 3 and 4 in hydrogen-atom transfer (HAT) and oxygen-atom transfer (OAT) reactions show that both complexes exhibit enhanced reactivities when compared to the analogous N4Py complex ([Fe(IV)(O)(N4Py)](2+)), and that the normalized HAT rates increase by approximately 1 order of magnitude for each replacement of a pyridyl moiety; i.e., [Fe(IV)(O)(L(2))](2+) exhibits the highest rates. The second-order HAT rate constants can be directly related to the substrate C-H bond dissociation energies. Computational modeling of the HAT reactions indicates that the reaction proceeds via a high spin transition state.

Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ 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-β peptide (Aβ) 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 Aβ (1-40) aggregation is investigated using Thioflavin T fluorescence and Transmission Electron Microscopy. Both complexes efficiently inhibit Aβ (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 Aβ aggregation.

Supramolecular architecture and photophysical and biological properties of ruthenium(II) polypyridyl complexes

Complexes of the type [Ru(N–N)2(tdzp)]Cl2, where N–N is 2,2′-bipyridine (bpy) (1), 1,10-phenathroline (phen) (2), dipyrido[3,2-d:2′,3-f] quinoxaline (dpq) (3), which incorporate the [1,2,5]-thiadiazolo-[3,4-f]-[1,10]-phenanthroline (tdzp) ligand, have been synthesized and characterized by IR, 1H-NMR, 13C-NMR, ESI-MS, elemental analysis, UV-Visible and luminescence spectroscopy. The molecular structure of complex 2 is confirmed by single crystal X-ray structure determination. A two-dimensional cyclic water–chloride anionic {[(H2O)10(Cl)2]2−}n network has been structurally identified in a hydrophobic matrix of 2. Interaction of these complexes with Calf Thymus DNA (CT-DNA) was explored by electronic absorption and emission spectroscopy and circular dichroism spectroscopy. The nucleolytic cleavage activity of complexes 1–3 has been carried out on double stranded circular plasmid pBR322 DNA by gel electrophoresis experiments. The cytotoxicity of the complexes against a cancer cell line has been studied by MTT assay and cellular localization of complexes within the cells has been monitored by fluorescence microscopy. Notably, 1–3 exhibit potent antiproliferative activities against a panel of human cancer cell line.

Efficient DNA condensation by ruthenium(II) polypyridyl complexes containing triptycenyl functionalized 1,10-phenanthroline

A series of luminescent ruthenium(II) polypyridyl complexes containing an extended aromatic moiety derived from triptycene and 1,10-phenanthroline were synthesized and their photophysical, theoretical, and biological properties were investigated. These complexes rapidly condense DNA into nano-aggregates at room temperature. The DNA interactions and DNA condensation properties of these complexes were investigated by absorption and emission spectroscopy, electrophoretic mobility assay, and atomic force microscopy. Their DNA cleavage inactivity and low toxicity of the complexes satisfy the requirements of a good non-viral gene delivery vector.

Synthesis, structural characterization and biological properties of phosphorescent iridium(III) complexes

Two phosphorescent cyclometalated iridium(III)-triptycenyl-1,10-phenanthroline complexes [Ir(ppy)2(tpt-phen)]+ (1) and [Ir(bhq)2(tpt-phen)]+ (2) {ppy=2-phenylpyridine, bhq=Benzo[h]quinoline, tpt-phen=triptycenyl-1,10-phenanthroline} have been synthesized and structurally characterized. The structure of complex 2 has been studied by single crystal X-ray crystallography. The photophysical properties of complexes in a different solvent have also been investigated. The binding of complexes to the double stranded calf thymus (CT-DNA) has been investigated by spectroscopic techniques. These complexes condense originally circular plasmid DNA into particulate structures. The DNA-condensation induced by these complexes have been investigated by electrophoretic mobilty shift assay, dynamic light scattering, and fluorescence microscopy. Furthermore, the cytotoxicity of these complexes towards HeLa cells have been studied and their cellular localisation properties have been investigated by fluorescence microscopy.

Water mediated proton conductance in a hydrogen-bonded Ni(II)-bipyridine-glycoluril chloride self-assembled framework

Proton conducting properties have been investigated in a new Ni(II)-based hydrogen-bonded porous framework synthesized using a urea-fused bipyridine-glycoluril (BPG) tecton. This hydrogen-bonded self-assembled structure encapsulates water molecules in the channels with hydrogen-bonding networks which exhibits a significant temperature dependent proton conductance of 1.5 × 10−4 S cm−1 at 95 °C and 95% RH with a low activation energy (Ea) of 0.54 eV, implying a Grotthuss proton hopping mechanism mediated by hydrogen-bonded water molecules in the channels. In addition, this framework exhibited a very high water uptake under humid conditions. A continuous array of water molecules and chloride ions embedded in the highly hydrophilic porous channels of the hydrogen-bonded framework acts as the proton conducting medium.

Phosphorescent Cyclometalated Iridium(III) Complexes: Synthesis, Photophysics, DNA Interaction, Cellular Internalization and Cytotoxic Activity

Iridium(III) complexes containing quinoline-appended polypyridyl ligands [Ir(ppy)2(qip)]+ (1) and [Ir(bhq)2(qip)]+ (2) {ppy = 2-phenylpyridine, bhq = benzo[h]quinoline, Qip = 2(1H)-quinolinone-3(1H)-imidazo[4,5f][1,10]phenanthrolin-2-yl} have been synthesized and characterized. The structure of complex 2 has been determined by single crystal X-ray crystallography. The experimental photophysical properties of the complexes have been compared with the theoretically obtained results by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) studies. The HOMO of the complexes is mainly localized on the iridium atom while the LUMO is mainly localized on the proximal position of the N–N donor polypyridyl ligand and the LUMO+1 is localized on the distal portion of the N–N donor polypyridyl ligand. The binding of complexes to double-stranded calf thymus DNA (CT-DNA) has been investigated by absorption and emission spectroscopic techniques. The electrophoretic mobility shift assay of plasmid DNA in the presence of complexes shows DNA aggregation at micro-molar concentration. These complexes have low toxicity and their strong intracellular luminescence highlights their potential as theragnostic agents.

Synthesis, crystal structure and biological properties of a cis-dichloridobis(diimine)copper(II) complex

The mechanisms of interaction of inorganic complexes with DNA are important in the design and development of new metal-based drug molecules. The limitations of cis-platin have encouraged the design and development of new metal-based target-specific anticancer drugs having reduced side effects. The complex cis-dichloridobis(1,2,5-thiadiazolo[3,4-f][1,10]phenanthroline-κ2N1,N10)copper(II), [CuCl2(C12H6N4S)2], has been synthesized and characterized. The complex crystallizes in the monoclinic space group C2/c. The covalent binding of the complex with DNA was studied by absorption spectroscopy. The anticancer activity of the complex on the Human Lung Carcinoma (A549) cell line was investigated by MTT assay. The complex exhibits higher toxicity than cis-platin and induces an apoptotic mode of cell death.