Liang-Nian Ji

Targeting topoisomerase II with the chiral DNA-intercalating ruthenium(II) polypyridyl complexes

Many antitumor drugs act as topoisomerase inhibitors, and the inhibitions are usually related to DNA binding. Here we designed and synthesized DNA-intercalating Ru(II) polypyridyl complexes Δ--[Ru(bpy)2(uip)]2+ and Λ-[Ru(bpy)2(uip)]2+ (bpy is 2,2′-bipyridyl, uip is 2-(5-uracil)-1H-imidazo[4,5-f][1,10]phenanthroline). The DNA binding, photocleavage, topoisomerase inhibition, and cytotoxicity of the complexes were studied. As we expected, the synthesized Ru(II) complexes can intercalate into DNA base pairs and cleave the pBR322 DNA with high activity upon irradiation. The mechanism studies reveal that singlet oxygen (1O2) and superoxide anion radical (O2•−) may play an important role in the photocleavage. The inhibition of topoisomerases I and II by the Ru(II) complexes has been studied. The results suggest that both complexes are efficient inhibitors towards topoisomerase II by interference with the DNA religation and direct topoisomerase II binding. Both complexes show antitumor activity towards HELA, hepG2, BEL-7402, and CNE-1 tumor cells.

Increased thermostability and phenol removal efficiency by chemical modified horseradish peroxidase

Horseradish peroxidase was modified by phthalic anhydride and glucosamine hydrochloride. The thermostabilities and removal efficiencies of phenolics by native and modified HRP were assayed. The chemical modification of horseradish peroxidase increased their thermostability (about 10- and 9-fold, respectively) and in turn also increased the removal efficiency of phenolics. The quantitative relationships between removal efficiency of phenol and reaction conditions were also investigated using modified enzyme. The optimum pH for phenol removal is 9.0 for both native and modified forms of the enzyme. Both modified enzyme could suffer from higher temperature than native enzyme in phenol removal reaction. The optimum molar ratio of hydrogen peroxide to phenol was 2.0. The phthalic anhydride modified enzyme required lower dose of enzyme than native horseradish peroxidase to obtain the same removal efficiency. Both modified horseradish peroxidase show greater affinity and specificity of phenol.

DNA binding and photocleavage properties of a novel cationic porphyrin-anthraquinone hybrid.

A novel cationic porphyrin-anthraquinone (Por-AQ) hybrid has been synthesized and characterized. Using the combination of absorption titration, fluorescence spectra, circular dichroism (CD) as well as viscosity measurements, the binding properties of the hybrid to calf thymus (CT) DNA have been investigated compared with its parent porphyrin. The experimental results show that at low [Por]/[DNA] ratios, the parent porphyrin binds to DNA in an intercalative mode while the hybrid binds in a combined mode of outside binding (for porphyrin moiety) and partial intercalation (for anthraquinone). Ethidium bromide (EB) competition experiment determined the binding affinity constants (K(app)) of the compounds for CT DNA. Theoretical calculational results applying the density functional theory (DFT) can explain the different DNA binding behaviors reasonably. (1)O(2) was suggested to be the reactive species responsible for the DNA photocleavage of porphyrin moieties in both two compounds. The wavelength-depending cleavage activities of the compounds were also investigated.

Synthesis, crystal structure and cyclic voltammetry of square- pyramidal acetatoaqua [(4-methylimidazol-5-yl)methylene] histamine copper(II) perchlorate

The copper atom in acetatoaqua[[(4-methylimidazol-5- yl)methylene]histamine]-copper(II) perchlorate (1) is N,N,N-chelated by the [(4-methylimidazol- 5-yl)methylene]histamine [Cu–N=1.969(3) ∼2.019(3) Å] donor ligand. The aqua ligand occupies the apical site of the square-pyramidal coordination polyhedron [Cu–O= 2.365(3) Å], whose fifth site is occupied by the carboxy oxygen atom of the monodentate acetato anion [Cu–O=1.960(3)Å]. Cyclic voltammetry in MeCN and N,N-dimethylformamide (DMF) gives a voltage of −0.39 and −0.37 V versus s.c.e, which compares well with the value obtained for Cu,Zn superoxide dimuthase itself.

The effect of the perturbation of hydrogen bonding on the Zn(II) coordination geometry: synthesis and structure of Zn(BIP) (H2O)(2) (ClO4)(2) (BIP=1,3-bis (4-methyl-5-imidazol-1-yl)ethylideneamino propane)

Abstract A polydentate ligand comprising imidazole donor 1,3-bis[(4-methyl-5-imidazol-1-yl)ethylideneamino]propane (BIP) was synthesized, and the crystal structure of its Zn(II) complex [Zn(BIP)(H2O)2](ClO4)2 has been reported, in which the Zn(II) atom adopts a distorted octahedral coordination geometry with the equatorial positions occupied by four nitrogen atoms of BIP and the axial positions by two aqua molecules. The effect of hydrogen bonding of the aqua ligand on the coordination geometry is discussed.

Syntheses, crystal structures and properties of copper(II) complexes of 1,3-bis (4-methyl-5-imidazol-1-yl)ethylideneamino propan-2-ol and 1,3-bis (4-methyl-5-imidazol-1-yl)ethylideneamino propane

The syntheses of two polydentate ligands comprising imidazole donors, 1,3-bis[(4-methyl-5-imidazol-1-yl) ethylideneamino]propan-2-ol (BIPO), 1,3-bis[(4-methyl-5-imidazol-1-yl)ethylideneamino]propane (BIP), and their copper(II) complexes [Cu(BIPO)(ClO4)(H2O)] (NO3) · H2O (1) and [Cu(BIP)(ClO4)](ClO4) · 2H2O (2) are reported. Single-crystal structural analyses show that (1) adopts an elongated octahedral geometry with the axial positions occupied by a perchlorate oxygen atom and an aqua ligand, while (2) adopts a distorted square-pyramidal geometry with the axial positions occupied by a perchlorate oxygen atom. Electronic spectra in aqueous solution indicate that both (1) and (2) adopt square-pyramidal geometry. Cyclic voltammetry in aqueous solution gives reduction waves at −0.07 and −0.08 V versus s.c.e. for (1) and (2), respectively. The low reduction potential and general reversibility of the redox reaction of (1) and (2) indicate that BIPO and BIP are flexible enough to stabilize both CuII and CuI forms of the complexes.

Catalytic studies of 2-benzthiazolethiol (BzTa)-linked manganese(III) and cobalt(II) porphyrin complexes

Four 2-benzthiazolethiol (BzTa)-linked porphyrins (1)–(4), and their complexes with CoII and MnIII, (5)–(12), were prepared and characterized by elemental analysis, 1H-n.m.r., i.r., u.v.–vis. and mass spectra. The hydroxylation of cyclohexane in the presence of these complexes and PhIO under mild conditions was investigated. The catalytic activities of these complexes were higher than that of corresponding TPPMnIIICl and TPPCoII species respectively, which indicated that the terminal group, BzTa, played an important role in the catalysis. A possible mechanism is proposed.