Mingchang Zhu

Current Development of Pd(II) Complexes as Potential Antitumor Agents

Research has proven that the most effective and widely used metal-containing chemotherapy anticancer drugs are cisplatin ([cis-PtCl(2)(NH(3))(2)]) and many platinum complexes, however, these compounds have significant disadvantages including poor water solubility and serious side effects. Thus researches in order to overcome these shortcomings have never interrupted. Many non-platinum complexes have been synthesized and tested, in which some palladium complexes show significant antitumor activity in normal tumor cells and lower resistance of tumor cells to clinical treatments as well as lower side effects. Mononuclear palladium complexes with aromatic N-containing ligands, amino acid ligands, S-donor ligands, and P-containing ligands have respective qualities and properties due to the different structures and properties of the ligands; some dinuclear palladium complexes possess interesting steric structures and good antitumor activity; a try to modify natural medicines with Pd(2+) leads the research to a new route. In this review, medicinal chemistry, the development status and interactions of palladium complexes with DNA are discussed in order to provide guidance and determine structure and antitumor activity relationships for continuing studies of these systems.

Synthesis, characterization, interaction with DNA and cytotoxicity in vitro of the complexes [M(dmphen)(CO3)]·H2O [M = Pt(II), Pd(II)]

The complexes [Pt(dmphen)CO3].H2O (1), [Pd(dmphen)CO3].H2O (2) (dmphen is 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The binding of the complexes with FS-DNA was investigated by UV spectrum and fluorescence spectrum, showing that the complexes have the ability of interaction with DNA of intercalative mode. The intrinsic binding constant K of the complexes with FS-DNA is 1.8 x 10(5) M(-1) (1) and 1.6 x 10(4) M(-1) (2), respectively. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR 322 plasmid DNA. Evaluation of cytotoxic activity of the complexes against four different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate.

New pH-dependent complexes, from mononuclear Pd(II) monomer to heteronuclear [Pd(II),K(I)]Polymer: DNA cleavage and cytotoxicity in vitro.

Two novel complexes, namely, [Pd(pdc)(2)].(dmp).6H(2)O (1) and [Pd(pdc)(2)K(H(2)O)(5).3H(2)O]n (2) [H(2)pdc=pyridine-2,3-dicarboxylate acid, dmp=2,9-Dimethyl-1,10-phenanthroline] were synthesized and characterized as pH-dependent products. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR 322 plasmid DNA. Values of IC(50) calculated for complexes 1 and 2 show that the two complexes exhibit good cytotoxic activity against different cell lines tested in general, especially more effective against HL-60 and A2780(cisR) cell lines.

Hairpin-shaped tetranuclear palladium(II) complex: synthesis, crystal structure, DNA binding and cytotoxicity activity studies.

A novel tetranuclear palladium(II) complex [Pd(4)(phen)(4) (micro-pydc)(4)].10H(2)O (phen = 1,10-phenanthroline, pydc = pyridine-3,4-dicarboxylate) has been synthesized and characterized. In the tetranuclear complex, two pairs of dipalladated [Pd(phen)] moieties are bridged together by four pydc, presenting a hairpin molecular shape. The binding of the title complex with fish sperm DNA (FS-DNA) has been investigated by UV spectrum and fluorescence spectrum. All the results indicate that the complex bind to DNA in an intercalative mode and considerating the molecular shape and size, the dipalladated phenanthroline moieties bisintercalate to the base pairs of DNA. Agarose gel electrophoresis assay demonstrates the ability of the complex to cleave the pBR322 plasmid DNA. Cytotoxic activity studies show the complex exhibited good cytotoxic activity against four different cancer cell lines.

Hydrothermal synthesis, structure, and photoluminescence of four complexes based on 1H-imidazole-4,5-dicarboxylate or 1H-imidazole-2-carboxylate ligands

Four complexes, [Ag4(bipy)2(Himdc)2(H2O)2] n (1), [Ag(H2imdc)] n (2), [K(H3imdc)(H2imdc)(H2O)2] n (3), and [Cu(Himc)2] (4) (H3imdc = 1H-imidazole-4,5-dicarboxylic acid, H2imc = 1H-imidazole-2-carboxylic acid, and bipy = 4,4′-bipyridine), were hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis and elemental analysis. The obtained complexes exhibit different coordination structures; 1 contains a 2-D supramolecular layer based on two chains arraying uniformly in an ABAB manner. Compound 2 displays sawtooth-shaped 1-D chains extending to 2-D layers via hydrogen bond interactions. Compound 3 possesses a 3-D framework structure based on a 1-D chain via hydrogen bonding interactions. Compound 4 has a 3-D framework structure bearing a pcu-type topology. In addition, the photoluminescence for 1 has been investigated.

Synthesis, interaction with double-helical DNA and biological activity of new Pt(II) and Pd(II) complexes with phenylglycine

The mononuclear palladium(II) (1) and platinum(II) (2) complexes containing phenylglycine have been synthesized and characterized by elemental analysis, IR spectra, and 1H NMR spectra. The structure of 1 was determined by X-ray diffractometry. The interaction between the complexes and fish sperm DNA (FS-DNA), adenosine-5′-triphosphate (ATP), and adenine (Ade) were investigated by UV absorption spectra, the interaction mode of the complex binding to DNA was studied by fluorescence spectra and viscometry. The results indicate that the two complexes have different binding affinities to DNA, complex 2 > complex 1. Gel electrophoresis assay demonstrates that the two complexes have the ability to cleave pBR322 plasmid DNA. Cytotoxicity experiments were carried out toward four different cancer cell lines, and 1 shows lower inhibitory efficiency than 2, consistent with the binding affinities towards DNA.

Synthesis, characterization, and study on HeLa cells activity of a dinuclear complex [Cu4(phen)4(H2O)2]·(pyri)·3H2O

The complex [Cu4(phen)4(H2O)2]·(pyri)·3H2O(where phen=1,10-phenanthroline and pyri=3,5-pyridine dicarboxylic acid)has been synthesized and characterized. IR spectra, elemental analysis and X-ray single-crystal diffraction were carried out to determine the composition and crystal structure of the complex. The binding of the complex with HC-DNA (HeLa cells DNA, which was extracted by ourselves) was investigated by fluorescence spectrum. Gel electrophoresis assay demonstrates the ability of the complex to cleave the extracted HC-DNA. Additionally, the complex exhibited a significant cytotoxic specificity and cancer cell inhibitory rate. The apoptotic tests indicate that the complex have an apoptotic effect on HeLa cells.

Cadmium(II) complex with 2-methyl-1H-4,5-imidazoledicarboxylic acid ligand: synthesis, characterization, and biological activity

A coordination polymer, [Cd(L)2(H2O)2]n (HL = 2-methyl-1H-4,5-imidazoledicarboxylic acid), was prepared from reactions of Cd(NO3)2 with L at room temperature. It was characterized by IR spectra and elemental analysis. The complex was structurally characterized by X-ray single-crystal diffraction revealing that the complex crystallizes in monoclinic with P2(1)/c space group, a = 12.203(10) Å, b = 9.332(8) Å, c = 7.554(7) Å, β = 100.894(2) Å, V = 844.7(13) Å3, Z = 2. Fluorescence and UV absorption spectroscopy indicated that the complex can bind to fish sperm DNA. Gel electrophoresis assay demonstrated the ability to cleave the HL-60 plasmid DNA. Apoptotic study showed that the complex exhibited significant cancer cell (JEKO and KB) inhibitory rate. Graphical Abstract Complex binding to DNA in an intercalative mode

Effect of carbon chain length on biological activity of novel palladium (II) complexes

A series of complexes [Pd(L1)(Phen)]·2H2O (1), [Pd(L2)(Phen)]·H2O (2), [Pd(L3)(Phen)]·H2O (3), [Pd(L4)(Phen)]·2H2O (4) and [Pd(L5)(Phen)]·2H2O (5) were prepared. The complexes were characterized by IR, (1)H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes was investigated by fluorescence spectrum and UV spectrum, showing the ability of interaction with DNA of intercalative mode. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 DNA. Moreover, the five complexes bind to DNA with different binding affinities, in ascending order: complex 1 < 2<3 < 4 < 5. Evaluation of cytotoxic activity of the complexes against five different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate.

Zigzag-shaped supramolecular networks formed via hydrogen bonding. Crystal structures, DNA binding, and cytotoxic activity of a new palladium(II) complex

A single-ligand complex Pd(II)-L-aspartic acid was synthesized and characterized by elemental ana-lysis and IR spectra. The crystal structure of the complex was determined by single crystal X-ray diffraction (crystallizing in orthorhombic crystal system, space group P212121 with unit cell parameters a = 5.3145(11) Å, b = 9.6294(19) Å, c = 22.233(4) Å, and Z = 4). The Pd atom was four-coordinated with N(1), N(2), O(4), and O(5) from two L-aspartic ligands and formed a slightly distorted parallelogram geometry. 2D “zigzag” shaped supramolecular networks are constructed via hydrogen bonding. The binding of the title complex with fish sperm DNA (FS-DNA) has been investigated by absorption and fluorescence spectra and the results indicate that the complex bind to FS-DNA in an intercalative mode. Gel electrophoresis shows the cleavage of both supercoiled and circular pBR322 DNA to form a small molecular fragment under the action of the title complex. The cytotoxicity assay proves that the complex has strong anticancer activity to human cervix epitheloid carcinoma cell lines (HeLa).