Promising Anticancer Activity of [Bis(1,8-quinolato)palladium (II)] Alone and in Combination.

Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds as well have been investigated for their anticancer activity. In the present study, we describe synthesis, characterization, and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumor activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines. Also, NH3 has the lower IC50 value in HT-29 colorectal cancer cell line. The higher antitumor activity of NH3 is due to the presence of bulky 8-Hydroxyquinoline ligand, thus reducing its reactivity. Proteomic study has identified significantly expressed proteins which have been validated through bioinformatics. NH3 has been found to be less toxic than cisplatin at 2.5 mg/kg and 5 mg/kg dosages on mice models. Binary combinations of NH3 with curcumin and epigallocatechin gallate (EGCG) have demonstrated dose and sequence-dependent synergism in ovarian and colorectal cancer models. All of the preclinical studies indicate promising therapeutic potential of NH3 [Bis(1,8-quinolato)palladium (II)] as an anticancer drug.

Synthesis and Photophysical Properties of a Series of Dimeric Indium Quinolinates.

A novel class of quinolinol-based dimeric indium complexes (1-6) was synthesized and characterized using 1H and 13C(1H) NMR spectroscopy and elemental analysis. Compounds 1-6 exhibited typical low-energy absorption bands assignable to quinolinol-centered π-π* charge transfer (CT) transition. The emission spectra of 1-6 exhibited slight bathochromic shifts with increasing solvent polarity (p-xylene < tetrahydrofuran (THF) < dichloromethane (DCM)). The emission bands also showed a gradual redshift, with an increase in the electron-donating effect of substituents at the C5 position of the quinoline groups. The absolute emission quantum yields (ΦPL) of compounds 1 (11.2% in THF and 17.2% in film) and 4 (17.8% in THF and 36.2% in film) with methyl substituents at the C5 position of the quinoline moieties were higher than those of the indium complexes with other substituents.

Regulation of quinolinic acid neosynthesis in mouse, rat and human brain by iron and iron chelators in vitro.

Several lines of evidence indicate that excess iron may play an etiologically significant role in neurodegenerative disorders. This idea is supported, for example, by experimental studies in animals demonstrating significant neuroprotection by iron chelation. Here, we tested whether this effect might be related to a functional link between iron and the endogenous excitotoxin quinolinic acid (QUIN), a presumed pathogen in several neurological disorders. In particular, the present in vitro study was designed to examine the effects of Fe(2+), a known co-factor of oxygenases, on the activity of QUIN's immediate biosynthetic enzyme, 3-hydroxyanthranilic acid dioxygenase (3HAO), in the brain. In crude tissue homogenate, addition of Fe(2+) (2-40 µM) stimulated 3HAO activity 4- to 6-fold in all three species tested (mouse, rat and human). The slope of the iron curve was steepest in rat brain where an increase from 6 to 14 µM resulted in a more than fivefold higher enzyme activity. In all species, the Fe(2+)-induced increase in 3HAO activity was dose-dependently attenuated by the addition of ferritin, the main iron storage protein in the brain. The effect of iron was also readily prevented by N,N'-bis(2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED), a synthetic iron chelator with neuroprotective properties in vivo. All these effects were reproduced using neostriatal tissue obtained postmortem from normal individuals and patients with end-stage Huntington's disease. Our results suggest that QUIN levels and function in the mammalian brain might be tightly controlled by endogenous iron and proteins that regulate the bioavailability of iron.

Structural and photophysical studies of highly stable lanthanide complexes of tripodal 8-hydroxyquinolinate ligands based on 1,4,7-triazacyclononane.

The tripodal H(3)thqtcn ligand allows the synthesis of well-defined neutral monomeric syn-tris(hydroxyquinolinate) complexes of lanthanides. Pure [Ln(thqtcn)] complexes (Ln = Nd, 1; Er, 2; Yb, 3) of the triply deprotonated ligand thqtcn(3-) were prepared. Crystallographic characterization was carried out for complexes 1 and 3, showing that the ligand is flexible enough to wrap around Ln(III) of different size with a tricapped trigonal-prism coordination geometry. The partially protonated H(1.5)thqtcn(1.5-) ligand also binds strongly to Ln(III) ions in methanol and water (at pH approximately 5). The X-ray diffraction study shows that protonated complexes crystallize as chiral dimers of formula [Ln(H(1.5)thqtcn)](2)(OTf)(3) x 3 MeOH (Ln = Nd, 4; Yb, 5) in which two equivalent monomeric complexes of the partially protonated H(1.5)thqtcn(1.5-) are bridged by very strong hydrogen bonds between the phenol oxygen atoms. The ligand thqtcn(3-) sensitizes efficiently the near-infrared emission of Er, Nd (0.10% Qy), and Yb (0.60% Qy). For the first time, the effect of ligand protonation on the efficiency of the solid-state luminescence emission of lanthanides complexes is demonstrated by the decrease of the luminescence quantum yield observed for [Yb(H(1.5)thqtcn)](2)(OTf)(3) (0.26%) with respect to [Yb(thqtcn)] (0.60%). The water-soluble H(3)thqtcn-SO(3) analogue of H(3)thqtcn and its lanthanide complexes has been prepared. The solution quantum yields of the thqtcn-SO(3)(3-) complexes were measured in water at pH 7.4 (0.016% for Nd(III) and 0.14% for Yb(III)) and in deuterated water (Nd, 0.047%; Yb, 0.55%), and they are among the highest reported in the literature for Yb(III) in aqueous solutions. The high thermodynamic and kinetic stability in water at physiological pH of the gadolinium complex of thqtcn-SO(3)(3-) indicate that the lanthanide complexes of thqtcn(3-) and thqtcn-SO(3)(3-) are highly resistant to hydrolysis and therefore are well suited for the development of luminescent devices and for application as probes in biomedical imaging.

Luminescence quenching by photoinduced charge transfer between metal complexes in peptide nucleic acids.

A new scaffold for studying photoinduced charge transfer has been constructed by connecting a [Ru(Bpy)3](2+) donor to a bis(8-hydroxyquinolinate)2 copper [CuQ2] acceptor through a peptide nucleic acid (PNA) bridge. The luminescence of the [Ru(Bpy)3](2+*) donor is quenched by electron transfer to the [CuQ2] acceptor. Photoluminescence studies of these donor-bridge-acceptor systems reveal a dependence of the charge transfer on the length and sequence of the PNA bridge and on the position of the donor and acceptor in the PNA. In cases where the [Ru(Bpy)3](2+) can access the π base stack at the terminus of the duplex, the luminescence decay is described well by a single exponential; but if the donor is sterically hindered from accessing the π base stack of the PNA duplex, a distribution of luminescence lifetimes for the donor [Ru(Bpy)3](2+*) is observed. Molecular dynamics simulations are used to explore the donor-PNA-acceptor structure and the resulting conformational distribution provides a possible explanation for the distribution of electron transfer rates.

Successive ion layer adsorption and reaction (SILAR) technique synthesis of Al(III)-8-hydroxy-5-nitrosoquinolate nano-sized thin films: characterization and factors optimization.

Nano Al(III)-8-hydroxy-5-nitrosoquinolate [Al(III)-(HNOQ)(3)] thin films were synthesized by the rapid, direct, simple and efficient successive ion layer adsorption and reaction (SILAR) technique. Thin film formation optimized factors were evaluated. Stoichiometry and structure were confirmed by elemental analysis and FT-IR. The particle size (27-71 nm) was determined using scanning electron microscope (SEM). Thermal stability and thermal parameters were determined by thermal gravimetric analysis (TGA). Optical properties were investigated using spectrophotometric measurements of transmittance and reflectance at normal incidence. Refractive index, n, and absorption index, k, were determined. Spectral behavior of the absorption coefficient in the intrinsic absorption region revealed a direct allowed transition with 2.45 eV band gap. The current-voltage (I-V) characteristics of [Al(III)-(HNOQ)(3)]/p-Si heterojunction was measured at room temperature. The forward and reverse I-V characteristics were analyzed. The calculated zero-bias barrier height (Φ(b)) and ideality factor (n) showed strong bias dependence. Energy distribution of interface states (N(ss)) was obtained.