Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action.

BACKGROUND: Malaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed. METHODS: The dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains. RESULTS: Copper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis. CONCLUSION: The dinuclear [Cu(phen)-4,4'-bipy-Cu(phen)](NO3)4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets.

The Thermoluminescence Response of Ge-Doped Flat Fibers to Gamma Radiation.

Study has been undertaken of the thermoluminescence (TL) yield of various tailor-made flat cross-section 6 mol% Ge-doped silica fibers, differing only in respect of external dimensions. Key TL dosimetric characteristics have been investigated, including glow curves, dose response, sensitivity, fading and reproducibility. Using a (60)Co source, the samples were irradiated to doses within the range 1 to 10 Gy. Prior to irradiation, the flat fibers were sectioned into 6 mm lengths, weighed, and annealed at 400 °C for 1 h. TL readout was by means of a Harshaw Model 3500 TLD reader, with TLD-100 chips (LiF:Mg, Ti) used as a reference dosimeter to allow the relative response of the fibers to be evaluated. The fibers have been found to provide highly linear dose response and excellent reproducibility over the range of doses investigated, demonstrating high potential as TL-mode detectors in radiation medicine applications. Mass for mass, the results show the greatest TL yield to be provided by fibers of the smallest cross-section, analysis indicating this to be due to minimal light loss in transport of the TL through the bulk of the silica medium.

Comparative study of tributyltin adsorption onto mesoporous silica functionalized with calix[4]arene, p-tert-butylcalix[4]arene and p-sulfonatocalix[4]arene.

The adsorption of tributyltin (TBT), onto three mesoporous silica adsorbents functionalized with calix[4]arene, p-tert-butylcalix[4]arene and p-sulfonatocalix[4]arene (MCM-TDI-C4, MCM-TDI-PC4 and MCM-TDI-C4S, respectively) has been compared. Batch adsorption experiments were carried out and the effect of contact time, initial TBT concentration, pH and temperature were studied. The Koble-Corrigan isotherm was the most suitable for data fitting. Based on a Langmuir isotherm model, the maximum adsorption capacities were 12.1212, 16.4204 and 7.5757 mg/g for MCM-TDI-C4, MCM-TDI-PC4 and MCM-TDI-C4S, respectively. The larger uptake and stronger affinity of MCM-TDI-PC4 than MCM-TDI-C4 and MCM-TDI-C4S probably results from van der Waals interactions and the pore size distribution of MCM-TDI-PC4. Gibbs free energies for the three adsorption processes of TBT presented a negative value, reflecting that TBT/surface interactions are thermodynamic favorable and spontaneous. The interaction processes were accompanied by an increase of entropy value for MCM-TDI-C4 and MCM-TDI-C4S (43.7192 and 120.7609 J/mol K, respectively) and a decrease for MCM-TDI-PC4 (-37.4704 J/mol K). It is obviously observed that MCM-TDI-PC4 spontaneously adsorbs TBT driven mainly by enthalpy change, while MCM-TDI-C4 and MCM-TDI-C4S do so driven mainly by entropy changes.

[Zn(phen)(O,N,O)(H2O)] and [Zn(phen)(O,N)(H2O)] with O,N,O is 2,6-dipicolinate and N,O is L-threoninate: synthesis, characterization, and biomedical properties.

Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.

Morphology, geology and water quality assessment of former tin mining catchment.

Bestari Jaya, former tin mining catchment covers an area of 2656.31 hectares comprised of four hundred and forty-two different-size lakes and ponds. The present study area comprise of 92 hectares of the catchment that include four large size lakes. Arc GIS version 9.2 used to develop bathymetric map, Global Positioning System (GPS) for hydrographical survey and flow meter was utilized for water discharge analysis (flow routing) of the catchment. The water quality parameters (pH, temperature, electric conductivity, dissolved oxygen DO, total dissolved solids TDS, chlorides, ammonium, nitrates) were analyzed by using Hydrolab. Quality assurance (QA) and quality control (QC) procedures were strictly followed throughout the field work and data analysis. Different procedures were employed to evaluate the analytical data and to check for possible transcription or dilution errors, changes during analysis, or unusual or unlikely values. The results obtained are compared with interim national water quality standards for Malaysia indicates that water quality of area is highly degraded. It is concluded that Bestri Jaya ex-mining catchment has a high pollution potential due to mining activities and River Ayer Hitam, recipient of catchment water, is a highly polluted river.

Synthesis and characterization of mesoporous silica functionalized with calix[4]arene derivatives.

This work reports a new method to covalently attach calix[4]arene derivatives onto MCM-41, using a diisocyanate as a linker. The modified mesoporous silicates were characterized by fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and elemental analysis. The FTIR spectra and TGA analysis verified that the calix[4]arene derivates are covalently attached to the mesoporous silica. The preservation of the MCM-41 channel system was checked by X-ray diffraction and nitrogen adsorption analysis.

Removal of organochlorine pesticides using zerovalent iron supported on biochar nanocomposite from Nephelium lappaceum (Rambutan) fruit peel waste.

Unique zerovalent iron (Fe0) supported on biochar nanocomposite (Fe0-BRtP) was synthesized from Nephelium lappaceum (Rambutan) fruit peel waste and were applied for the simultaneous removal of 6 selected organochlorine pesticides (OCPs) from aqueous medium. During facile synthesis of Fe0-BRtP, Rambutan peel extract was used as the green reducing mediator to reduce Fe2+ to zerovalent iron (Fe0), instead of toxic sodium borohydride which were used for chemical synthesis. For comparison, chemically synthesized Fe0-BChe nanocomposite was also prepared in this work. Characterization study confirmed the successful synthesis and dispersion of Fe0 nanoparticles on biochar surface. Batch experiments revealed that Fe0-BRtP and Fe0-BChe nanocomposites combine the advantage of adsorption and dechlorination of OCPs in aqueous medium and up to 96-99% and 83-91% removal was obtained within 120 and 150 min, respectively at initial pH 4. Nevertheless, the reactivity of Fe0-BChe nanocomposite decreased 2 folds after being aged in air for one month, whilst Fe0-BRtP almost remained the same. Adsorption isotherm of OCPs were fitted well to Langmuir isotherm and then to Freundlich isotherm. The experimental kinetic data were fitted first to pseudo-second-order adsorption kinetic model and then to pseudo-first-order reduction kinetic model. The adsorption mechanism involves π-π electron-donor-acceptor interaction and adsorption is facilitated by the hydrophobic sorption and pore filling. After being reused five times, the removal efficiency of regenerated Fe0-BChe and Fe0-BRtP was 5-13% and 89-92%, respectively. The application of this Fe0-BRtP nanocomposite could represent a green and low-cost potential material for adsorption and subsequent reduction of OCPs in aquatic system.

Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid.

Crystal structure analysis of the zinc complex establishes it as a distorted octahedral complex, bis(3-methylpicolinato-kappa(2) N,O)(2)(1,10-phenanthroline-kappa(2) N,N)-zinc(II) pentahydrate, [Zn(3-Me-pic)(2)(phen)]x5H(2)O. The trans-configuration of carbonyl oxygen atoms of the carboxylate moieties and orientation of the two planar picolinate ligands above and before the phen ligand plane seems to confer DNA sequence recognition to the complex. It cannot cleave DNA under hydrolytic condition but can slightly be activated by hydrogen peroxide or sodium ascorbate. Circular Dichroism and Fluorescence spectroscopic analysis of its interaction with various duplex polynucleotides reveals its binding mode as mainly intercalation. It shows distinct DNA sequence binding selectivity and the order of decreasing selectivity is ATAT > AATT > CGCG. Docking studies lead to the same conclusion on this sequence selectivity. It binds strongly with G-quadruplex with human tolemeric sequence 5'-AG(3)(T(2)AG(3))(3)-3', can inhibit topoisomerase I efficiently and is cytotoxic against MCF-7 cell line.

Bis[(4-chloro-benz-yl)triphenyl-phospho-nium] tetra-chloridozincate(II) trihydrate.

The crystal structure of the title compound, (C(25)H(21)ClP)(2)[ZnCl(4)]·3H(2)O, consists of tetra-hedral phosphonium cations and tetra-hedral zincate anions; the water mol-ecules form weak hydrogen bonds to the anions. Two of the water mol-ecules are disordered over three sites in a 0.68:0.55:0.77 ratio.

{6,6'-Dibromo-4,4'-dichloro-2,2'-[o-phenyl-enebis(nitrilo-methyl-idyne)]diphenolato}nickel(II).

In the title complex, [Ni(C(20)H(10)Br(2)Cl(2)N(2)O(2))], the Ni(II) ion is coordinated by two phen-oxy O atoms and two imino N atoms of the tetradentate ligand, forming a slightly distorted square-planar environment. The mol-ecule is essentially planar, with an r.m.s. deviation of 0.088 Šfor the mean plane defined by all non-H atoms in the mol-ecule.

(2,2'-Bipyridine-κN,N')(4-hydr-oxy-2-oxidobenzaldehyde thio-semicar-ba-zon-ato-κO,N,S)zinc(II).

The Zn(II) atom in the title compound, [Zn(C(8)H(7)N(3)O(2)S)(C(10)H(8)N(2))], is N,N'-chelated by the heterocycle and N,O,S-chelated by the doubly deprotonated Schiff base ligand in a distorted square-pyramidal environment. O-H⋯O and N-H⋯N hydrogen bonds link adjacent mol-ecules into a layer structure.

[1-(4-Hydr-oxy-2-oxidobenzyl-idene)-4-phenyl-thio-semicarbazonato-κN,O,S](1,10-phenanthroline-κN,N')zinc(II)-4,4'-bipyridine (2/1).

The Zn(II) atom in the title compound, [Zn(C(14)H(11)N(3)O(2)S)(C(12)H(8)N(2))]·0.5C(10)H(8)N(2), is N,N'-chelated by the N-heterocycle and N,O,S-chelated by the deprotonated Schiff base in a square-pyramidal environment. The hydr-oxy group of the Schiff base is a hydrogen-bond donor to 4,4'-bipyridine, which is located about a center of inversion, resulting in the formation of a supra-molecular trimeric unit.

Bis(acetone 4-phenyl-thio-semi-carbazonato-κN,S)zinc(II).

The Zn(II) atom in the title compound, [Zn(C(10)H(12)N(3)S)(2)], is N,S-chelated by the deprotonated Schiff base in a tetra-hedral environment. The metal atom lies on a twofold rotation axis that relates one anion to the other. The amino H atom forms an intermolecular N-H⋯π inter-action to an aromatic ring.

Bis(µ-4-hydr-oxy-2-oxidobenzaldehyde 4-ethyl-thio-semicarbazone)-κO,N,S:O;κO:O,N,S-bis-[chloridozinc(II)] dimethyl sulfoxide tris-olvate.

The two Zn(II) atoms in the title compound, [Zn(2)(C(10)H(12)N(3)O(2)S)(2)Cl(2)]·3C(2)H(6)OS, are each N,O,S-chelated by a mono-deprotonated Schiff base ligand. The Zn atoms are bridged through the phenolate O atom, leading to a central Zn(2)O(2) core. Each Zn atom has a Cl atom in the apical position of a distorted square-pyramidal environment. Hydr-oxy-DMSO (DMSO is dimethyl sulfoxide) O-H⋯O and amide-DMSO N-H⋯O hydrogen bonds link the components of the crystal structure. Two of the DMSO mol-ecules are partially disordered, with each modelled over two sites of equal weight.

Enantiomeric pairs of ternary copper(ii) complexes and their aldol-type condensation products: synthesis, characterization, and anticancer and epigenetic properties.

Chiral enantiomers [Cu(phen)(l-ser)(H2O)]NO31 and [Cu(phen)(d-ser)(H2O)]NO32 (ser = serinato) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(ii) complexes, viz. l- and d-[Cu(phen)(OCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; OCA = oxazolidine-4-carboxylate; x = 1/2, 0-2) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. The crystal structures of 1 and 3 showed both the cationic complexes to have a square pyramidal geometry. These complexes were about nine fold more potent than cisplatin against metastatic MDA-MB-231 breast cancer cells, inducing apoptotic cell death via ROS generation and a massive drop in mitochondrial membrane potential. The results of monitoring EZH1, EZH2 and H3K27me3 revealed that the mode of action of 1-4 also involved the downregulation of EZH2 and it seemed to be independent of the H3K27me3 status.

2,5-Dihydroxy-benzaldehyde 4-methyl-thio-semicarbazone.

The planar mol-ecules of the title compound, C(9)H(11)N(3)O(2)S, are linked into a supra-molecualr chain via O-H⋯S hydrogen bonds. These chains are connected into a two-dimensional array via N-H⋯O hydrogen bonds; an intra-molecular O-H⋯N hydrogen bond is also present.

Chlorido(2-methyl-4-oxo-4H-pyran-3-olato-κO,O)(1,10-phenanthroline-κN,N')copper(II).

The copper(II) atoms in the two independent mol-ecules of the title compound, [Cu(C(6)H(5)O(3))Cl(C(12)H(8)N(2))], both adopt square-pyramidal geometries. The two coordinating atoms of the two heterocyclic ligands comprise the square plane, and the chlorine atom occupies the apical position of the coordination environment.

2,4-Dihydroxy-benzaldehyde 4-ethyl-thio-semicarbazone.

The mol-ecular conformation of the title compound, C(10)H(13)N(3)O(2)S, is stabilized by an intramolecular O-H⋯N hydrogen bond. Adjacent mol-ecules are linked by O-H⋯O hydrogen bonds to furnish a zigzag chain.

2,4-Dihydroxy-benzaldehyde 4-methyl-thio-semicarbazone.

The approximately planar mol-ecule of the title compound, C(9)H(11)N(3)O(2)S, is linked to adjacent mol-ecules by O-H⋯S hydrogen bonds to form a zigzag chain. Adjacent chains are consolidated by N-H⋯O hydrogen bonds into a two-dimensional array. An intramolecular O-H⋯N link is also present.

(4-Hydr-oxy-2-oxidobenzaldehyde thio-semicarbazonato-κO,N,S)(1,10-phenanthroline-κN,N')zinc(II) dimethyl sulfoxide disolvate monohydrate.

The Zn(II) atom in the title compound, [Zn(C(8)H(7)N(3)O(2)S)(C(12)H(8)N(2))]·2C(2)H(6)OS·H(2)O, is N,N'-chelated by the N-heterocycle and N,O,S-chelated by the deprotonated Schiff base in a distorted square-pyramidal enviroment. Hydrogen bonds link the mononuclear mol-ecule, the water and the dimethyl sulfoxide (DMSO) mol-ecules into a linear chain motif. One DMSO mol-ecule is disordered over two positions in respect of the S atom in an approximate 1:1 ratio.