Anupa A. Kumbhar

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.

Monitoring Cellular Uptake and Cytotoxicity of Copper(II) Complex Using a Fluorescent Anthracene Thiosemicarbazone Ligand

The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase.

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.

Light uncages a copper complex to induce nonapoptotic cell death

Cu3G is a Cu(II) complex of a photoactive tetradentate ligand that is cleaved upon UV irradiation to release Cu. Here we show that the cytotoxicity of Cu3G increases in response to brief UV stimulation to result in extensive cytoplasmic vacuolization that is indicative of nonapoptotic cell death.

Synthesis, DNA interaction and anticancer activity of 2-anthryl substituted benzimidazole derivatives

2-Anthryl benzimidazole derivatives (5–7) with hydrogen, carboxyl and benzoyl substituents at the 5th position have been synthesized using a silica supported periodic acid catalyst. The DNA cleavage activity of 5–7 was studied in the presence of light using pBR322 plasmid DNA and was shown to vary with substitution at the 5th position of benzimidazole derivatives. DNA binding studies using ethidium bromide displacement assay demonstrated the non-intercalative binding mode of 5–7. The anticancer activity of these target molecules was tested against MCF-7 and HL-60 cell lines, and they exhibited remarkable activity in the micromolar range. Cellular uptake and morphological changes were confirmed by fluorescence and confocal microscopy. A molecular docking study was carried out to explore the DNA binding mechanism of 5–7.

Structural and DNA cleavage of sugar-derived Schiff base ligands and their dinuclear Cu(II) complexes

Neutral dinuclear Cu(II) complexes of Schiff base ligands derived from D-glucose have been synthesized and structurally characterized. These complexes were evaluated for their interaction with DNA, and DNA cleavage was observed even in the presence of radical inhibitors.

Synthesis and biological evaluation of copper(II) pyrenethiosemicarbazone

Pyrenethiosemicarbazone (PyTSC) and its copper(II) complex (CuPyTSC) have been synthesized and characterized by elemental analysis, 1H-NMR, IR, ESI-MS, cyclic voltammetry, UV-Visible and fluorescence spectroscopy. Both the compounds interact with calf thymus (CT) DNA via intercalation with apparent binding constants, Kb, of the order of 105. CuPyTSC shows better photo-induced DNA cleavage of plasmid pBR322 DNA (74%) than PyTSC (14%). Mechanistic investigations revealed the involvement of singlet oxygen species in the DNA cleavage by both the compounds. DFT calculations demonstrated more efficient generation of singlet oxygen by CuPyTSC with a decreased HOMO–LUMO gap (0.332 eV) than PyTSC (0.629 eV). The protein binding ability has been monitored using Bovine Serum Albumin (BSA). The compounds show green fluorescence revealing their uptake by the cells under a fluorescence microscope. CuPyTSC displayed better cytotoxic activity on photoexposure to B16F10 melanoma cells.

Aryl-1H-imidazole[4,5f][1,10]phenanthroline Cu(II) complexes: Electrochemical and DNA interaction studies

The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO3)2 lead to the formation of Cu(II) complexes of the type [Cu(L)(NO3)2] where L=PIP, 2-(phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f] phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The interaction of these complexes with calf thymus DNA has been studied using viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical nuclease activity of these complexes has also been investigated. All complexes cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking studies revealed that these complexes bind to DNA through minor groove.

Interaction of a Hydrated Electron with Anthracenethiosemicarbazone: A Pulse Radiolysis Study

The thiosemicarbazide derivative of anthracene, ATSC, has been synthesized and characterized by elemental analysis, IR, UV-visible, (1)H NMR, fluorescence, and mass spectroscopy experiments. The interaction of hydrated electron (e(-)aq) with ATSC proceeds via radical anion formation followed by intramolecular transfer that cleaves the thiosemicarbazide side chain on the anthracene moiety. HPLC and ESI-MS experiments suggested that the anthrylmethyl radical combines with different ATSC fragments during the reaction. ATSC, its one-electron reduction products, and dimers were analyzed combining experiments with density functional theory.

Anthracene-based fluorescence turn-on chemodosimeter for the recognition of persulfate anion

The anthracene thiosemicarbazone (ATSC) fluorescence ‘turn-on’ chemodosimeter for the detection of the persulfate anion (S2O82−) in 90% DMSO has been developed. ATSC is simple and exhibits high selectivity toward S2O82− anion in the presence of large interferences from other anions or cations. A fluorescence change from blue to green visualized under the UV light makes it possible to detect the persulfate anion with naked-eye. A mechanism underlying the molecular recognition has been explained from the 1H-NMR and single crystal X-ray structure experiments.