Chun-Yan Gao

Synthesis, structure, and DNA binding of three reduced amino-acid Schiff-base zinc(II), nickel(II), and cadmium(II) complexes

Three new reduced amino-acid Schiff-base complexes, [Zn(HL)2] · H2O (1), [Ni(HL)2] · H2O (2), and [Cd(HL)2] · H2O (3), where H2L is a reduced Schiff base derived from condensation of N-(2-hydroxybenzaldehyde) and L-histidine, have been synthesized and characterized by elemental analysis, UV-Vis absorption spectra and single crystal X-ray diffraction. Complexes 1–3 are isostructural. All metal centers are six-coordinate with O2N4 donor sets in slightly distorted octahedra. Unlike its Schiff-base counterpart, the deprotonated monoanionic ligand HL− has a more flexible backbone and two HL− are tridentate to one metal. Moreover, the binding interactions of these complexes with calf thymus DNA (CT-DNA) have been investigated by UV-Vis spectra and fluorescence quenching, which show that the complexes bind in an intercalative mode.

Synthesis, DNA binding, photo-induced DNA cleavage and cell cytotoxicity studies of a family of light rare earth complexes

A family of light rare earth complexes, [RE(acac)(3)(dpq)] (RE=La (1), Ce (2), Pr (3), Nd (4), Sm (5)) and [RE(acac)(3)(dppz)].CH(3)OH (RE=La (6), Ce (7), Pr (8), Nd (9), Sm (10) viz. acetylacetonate (acac), dipyrido[3,2-d:20,30-f]quinoxaline (dpq), dipyrido[3,2-a:20,30-c] phenazine (dppz)), have been synthesized and structurally characterized. Binding interactions of these complexes with CT-DNA and their photo-induced DNA cleavage activity with pBR 322 DNA are also investigated. These complexes have strong DNA binding interaction (K(b)≈10(5)M(-1) and K(app)≈10(5)M(-1))and the binding propensity to CT-DNA decrease with the order: dppz complexes>dpq complexes. Furthermore, DNA photocleavage experiments indicate that these complexes are efficient DNA cleaving agents in UV-A (365 nm) and ambient light in the absence of any external reagents. Hydroxyl radical (HO(•)) and singlet oxygen ((1)O(2)) are the major cleavage active species from the machanistic studies. Moreover, cell cytotoxicity studies of these complexes on HeLa, K562 and MDA-MB-231 cells indicate that they have the potential to act as effective metal-based anti-cancer drugs.

Synthesis, structure, DNA binding, and cleavage activity of two copper(II) complexes

Two copper(II) complexes, [Cu2(L1)2(H2O)]∞ (1) and {[Cu2(L2)2(H2O)] · H2O}∞ (2), have been synthesized and characterized by elemental analysis, UV-visible absorption spectra, and single-crystal X-ray diffraction. H2L1 is an amino acid Schiff base derived from condensation of N-(2-hydroxybenzaldehyde) and L-methionine. H2L2 is a reduced product of H2L1 by sodium borohydride (scheme 1). Both complexes consist of one-dimensional covalently bonded polymeric chains. Complex 1 has two crystallographic independent copper centers. Cu1 has a distorted octahedral geometry and Cu2 a square pyramid. The copper(II)s are bridged by carboxylate with a Cu1–Cu2 separation of 3.6399(5) Å. Complex 2 is a double phenolate-bridged complex with a Cu1–Cu2 separation of 3.0148(7) Å, where each copper is square pyramidal. Binding of the complexes with Calf thymus DNA (CT-DNA) has been investigated by UV-visible spectra and fluorescence quenching, showing intercalation to CT-DNA. DNA cleavage experiments have been also investigated by agarose gel electrophoresis. Both complexes show oxidative DNA cleavage in the presence of H2O2/sodium ascorbate. The reactive oxygen species responsible for the DNA cleavage is likely singlet oxygen ( ). Scheme 1. Schematic structures of H2L1 and H2L2.

Four related mixed-ligand nickel(II) complexes: effect of steric encumbrance on the structure, DNA/BSA binding, DNA cleavage and cytotoxicity

Four closely related mononuclear nickel(II) complexes [Ni(L)(diimine)Cl](ClO4) (1–4), where L is a tridentate polypyridyl ligand of 4-methyl-N,N-bis(pyridin-2-ylmethyl)aniline and diimine is 2,2′-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:20,30-f]quinoxaline (dpq, 3) or dipyrido[3,2-a:20,30-c]phenazine (dppz, 4), have been synthesized and characterized using various physico-chemical techniques. All Ni centers adopt a distorted octahedral geometry with N5Cl donor sets. From 1 to 4, the dihedral angles between the benzene ring of L and the plane of the diimine gradually decline (52.5–6.8°), leading to increasing steric encumbrance. The interactions of the complexes with CT-DNA and BSA have been explored using absorption and emission spectral methods. These complexes display binding propensity to CT-DNA in the order: 4 (dppz) > 3 (dpq) > 2 (phen) > 1 (bpy), and the quenching mechanisms of BSA by all the complexes are static procedures. In the absence of any external agents, only 1 (bpy) and 4 (dppz) exhibit apparent DNA cleavage activity, while with the addition of GSH or on the irradiation with UV-A light of 365 nm, the DNA cleavage abilities of the complexes are obviously enhanced, which vary as 1 > 2 > 3 > 4 (GSH) and 4 > 3 > 2 > 1 (UV-A). In addition, the in vitro cytotoxicity of the complexes on tumor cells lines (MCF-7, HepG-2 and SGC-7901) have been examined by MTT and the morphological assessment obtained using Hoechst 33342 staining reveals that 4 induces apoptosis against HepG-2.

Two dpa-based zinc(II) complexes as potential anticancer agents: nuclease activity, cytotoxicity and apoptosis studies

Two new mononuclear zinc(II) complexes [ZnLX2]2·CH3OH (X = Br for 1, Cl for 2) of a tridentate polypyridyl ligand L (L = 4-methyl-N,N-bis(pyridin-2-ylmethyl)aniline) have been synthesized and structurally characterized. The interactions of two complexes with CT-DNA, pBR322 plasmid DNA and BSA have been explored respectively by using various physico-chemical techniques. Furthermore, the anticancer activities of the complexes towards three human tumor cells lines (HeLa, MCF-7 and RL952) have been studied. The IC50 values of 1 (on MCF-7 cells) and 2 (on RL952 cells) are 12.58 μM and 11.71 μM, respectively. The apoptosis-inducing activity of 1 was assessed by Hoechst 33342 staining, Annexin V binding and cell cycle analyses.

Step-Controlled Povarov-Type Reaction with 1,2-Dihydroquinolines as Precursors of Dienophiles: Direct Synthesis of Spirocyclic Bi-tetrahydroquinolines and Functionalized 1,2-Dihydroquinolines

A novel Povarov-type reaction for straightforward synthesis of novel spiro bi-tetrahydroquinolines with readily available 1,2-DHQs (1,2-dihydroquinolines) and aromatic imines was developed. The reaction could be selectively stopped at the first stage under a Brønsted acid catalyst to afford the corresponding functionalized 1,2-DHQs conveniently.