Chew Hee Ng

Ternary copper(II)-polypyridyl enantiomers: aldol-type condensation, characterization, DNA-binding recognition, BSA-binding and anticancer property

Chiral enantiomers [Cu(phen)(L-threo)(H2O)]NO3 1 and [Cu(phen)(D-threo)(H2O)]NO3 2 (threo = threoninate) 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)(5MeOCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; 5MeOCA = 5-methyloxazolidine-4-carboxylate; x = 0-3) 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. Analysis of restriction enzyme inhibition by these four complexes revealed modulation of DNA binding selectivity by the type of ligand, ligand modification and chirality. Their interaction with bovine serum albumin was investigated by FL and electronic spectroscopy. With the aid of the crystal structure of BSA, spectroscopic evidence suggested their binding at the cavity containing Trp134 with numerous Tyr residues in subdomain IA. The products were more antiproliferative than cisplatin against cancer cell lines HK-1, MCF-7, HCT116, HSC-2 and C666-1 except HL-60, and were selective towards nasopharyngeal cancer HK-1 cells over normal NP69 cells of the same organ type.

Factors affecting nucleolytic efficiency of some ternary metal complexes with DNA binding and recognition domains. Crystal and molecular structure of Zn(phen)(edda)

The binding selectivity of the M(phen)(edda) (M=Cu, Co, Ni, Zn; phen=1,10-phenanthroline, edda=ethylenediaminediacetic acid) complexes towards ds(CG)(6), ds(AT)(6) and ds(CGCGAATTCGCG) B-form oligonucleotide duplexes were studied by CD spectroscopy and molecular modeling. The binding mode is intercalation and there is selectivity towards AT-sequence and stacking preference for A/A parallel or diagonal adjacent base steps in their intercalation. The nucleolytic properties of these complexes were investigated and the factors affecting the extent of cleavage were determined to be: concentration of complex, the nature of metal(II) ion, type of buffer, pH of buffer, incubation time, incubation temperature, and the presence of hydrogen peroxide or ascorbic acid as exogenous reagents. The fluorescence property of these complexes and its origin were also investigated. The crystal structure of the Zn(phen)(edda) complex is reported in which the zinc atom displays a distorted trans-N(4)O(2) octahedral geometry; the crystal packing features double layers of complex molecules held together by extensive hydrogen bonding that inter-digitate with adjacent double layers via pi...pi interactions between 1,10-phenanthroline residues. The structure is compared with that of the recently described copper(II) analogue and, with the latter, included in molecular modeling.

Synthesis, characterization and biological properties of cobalt(II) complexes of 1,10-phenanthroline and maltol

The synthesis and characterization of two cobalt(II) complexes, Co(phen)(ma)Cl 1 and Co(ma)(2)(phen) 2, (phen=1,10-phenanthroline, ma(-)=maltolate or 2-methyl-4-oxo-4H-pyran-3-olate) are reported herein. The complexes have been characterized by FTIR, CHN analysis, fluorescence spectroscopy, UV-visible spectroscopy, conductivity measurement and X-ray crystallography. The number of chelated maltolate ligands seems to influence their DNA recognition, topoisomerase I inhibition and antiproliferative properties.

Interaction of DNA with Simple and Mixed Ligand Copper(II) Complexes of 1,10-Phenanthrolines as Studied by DNA-Fiber EPR Spectroscopy

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related to the DNA binding modes of the complexes such as intercalation, groove binding, and electrostatic surface binding. A variety of spectroscopic methods have been used to study the DNA binding mode of the Cu(II) complexes. Of all these methods, DNA-fiber electron paramagnetic resonance (EPR) spectroscopy affords unique information on the DNA binding structures of the complexes. In this review we summarize the results of our DNA-fiber EPR studies on the DNA binding structure of the complexes and discuss them together with the data accumulated by using other measurements.

Synthesis, characterization and nucleolytic property of bis(N,N′-dimethylglycinato)copper(II)

Aquabis(N,N-dimethylglycinato)copper(II) dihydrate, [Cu(dmg)2(H2O)]·2H2O, has been synthesized and characterized by elemental analysis, FT-IR, magnetic data, thermal analysis, solution UV-visible spectroscopy, X-ray crystal structure analysis and electrospray ionization mass spectroscopy. The square pyramidal copper(II) complex crystallizes in the orthorhombic space group P212121. The complex cleaves circular plasmid DNA (pBR322) in the presence of H2O2. The extent of cleavage varies with the concentration range of the complex, the type of buffer used, pH of buffer and the concentration of H2O2. Hydroxyl radical scavenger can inhibit the nucleolytic ability of this complex.

Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of chirality on their interaction with biomolecules.

Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3(-); ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl(-); ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)](+) and [Cu(phen)(d-ala)(H2O)](+), have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin.

(4-Hydr­oxy-2-oxidobenzaldehyde thio­semicarbazonato-κ3O2,N1,S)(1,10-phenanthroline-κ2N,N′)zinc(II) dimethyl sulfoxide disolvate monohydrate

The ZnII atom in the title compound, [Zn(C8H7N3O2S)(C12H8N2)]·2C2H6OS·H2O, 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 molecule, the water and the dimethyl sulfoxide (DMSO) molecules into a linear chain motif. One DMSO molecule is disordered over two positions in respect of the S atom in an approximate 1:1 ratio.

Ternary and binary copper(II) complexes: synthesis, characterization, ROS-inductive, proteasome inhibitory, and anticancer properties

Abstract Three ternary copper(II) complexes, [Cu(phen)(L-phe)Cl]·2H2O, [Cu(phen)(L-leu)Cl]·4½H2O, and [Cu(phen)(L-tyr)Cl]·3H2O, and four binary copper(II) complexes, [Cu(phen)Cl2], Cu(L-phe)2·½H2O, Cu(L-leu)2·½H2O, and Cu(L-tyr)2·H2O (where phen = 110-phenanthroline, L-phe = L-phenylalanine, L-tyr = L-tyrosine, L-leu = L-leucine and Cl- = chloride), were synthesized and characterized by elemental analysis, spectroscopic techniques (FTIR, UV–visible, fluorescence spectroscopy), magnetic susceptibility, molar conductivity, and lipophilicity measurement. X-ray diffraction determination of a single crystal of [Cu(phen)(L-tyr)Cl] showed two independent molecules in the asymmetric unit, each with the same distorted square pyramidal geometry about copper(II). p-Nitrosodimethylaniline assay revealed that the three ternary complexes were better inducers of reactive oxygen species over time than binary complexes, CuCl2, and free ligands. All the copper(II) complexes in this series inhibited the three proteolytic activities in the order Trypsin-like > Caspase-like > Chymotrypsin-like. In terms of anticancer properties, the copper(II)-phen complexes had GI50 values of less than 4 μM against MCF-7, HepG2, CNE1 and A549 cancer cell lines, more potent than cisplatin.

Structural, infrared spectral and thermogravimetric analysis of a hydrogen-bonded assembly of cobalt(II) and nickel(II) mixed complex cations with hexamethylenetetraamine and aqua ligands: {[M(hmt)2(H2O)4][M(H2O)6]}(SO4)2·6H2O

The synthesized cobalt(II) and nickel(II) complexes {[M(hmt)2(H2O)4][M(H2O)6]}(SO4)2·6H2O [M = Co(II) (1) and Ni(II) (2), hmt = hexamethylenetetraamine] share the same general formula and chemical name {[bis(hexamethylenetetraamine)tetraaquametal(II)][hexaaquametal(II)]} disulfate hexahydrate. Complexes 1 and 2 have been characterized by elemental analysis, infrared spectroscopy, thermal analysis and magnetic moment determination. Each complex has two different cationic complexes co-crystallizing with the sulfate anions. The crystal structure of 1has been determined. Both complex cations in 1 have distorted octahedral geometry and they are linked to the sulfate anions through the coordinated and lattice water molecules. Each sulfate anion is hydrogen bonded to ten water molecules; two of its oxygen atoms have two hydrogen bonds each while the other two oxygen atoms have three hydrogen bonds each. The three uncoordinated nitrogen atoms of hmt in each [Co(hmt)2(H2O)4]2+ cation are hydrogen bonded to water molecules of adjacent [Co(H2O)6]2+ cations. The thermal decomposition of 1 has been investigated further by analyzing the FTIR spectra of the residues formed from each decomposition step, and the data have contributed to establishing the thermal decomposition pathway of both 1and 2.

3,4-Dihydroxy­benzaldehyde thio­semi­carbazone

The asymmetric unit of the title compound, C8H9N3O2S, contains three independent molecules which are stacked approximately over each other. In the crystal structure, centrosymmetric pairs of molecules are formed through intermolecular hydroxy–hydroxy O—H⋯O and hydroxy–sulfur O—H⋯S hydrogen bonds which are, in turn, linked into a two-dimensional network by N—H⋯O(hydroxy) hydrogen bonds.