A new set of penta-coordinated copper(II) hydrazone complexes containing solvated methanol were synthesized by reacting the hydrazone ligands, 2-acetylpyridine benzoyl hydrazone (HL1) and 2-acetylpyridine thiophene-2-carboxylic acid hydrazone (HL2), with [CuCl2(DMSO)2] and characterized by different spectral methods. Single crystal X-ray diffraction studies of the complexes revealed that both of them, [CuCl(L1)(MeOH)] (1) and [CuCl(L2)(MeOH)] (2), have square pyramidal geometry around the cupric ion, in which the hydrazone is coordinated through NNO atoms along with a molecule of methanol in the apical position. Interaction of the ligands HL1 and HL2 along with the corresponding copper complexes 1 and 2 with calf thymus DNA (CT-DNA) has been estimated by absorption and emission titration methods which revealed that the compounds interacted with CT-DNA through intercalation. Binding of the compounds, i.e., free ligands and complexes (1) and (2) with bovine serum albumin (BSA) protein investigated using UV-visible, fluorescence and synchronous fluorescence spectroscopic methods indicated that there occurred strong binding of copper complexes to BSA over the ligands. Further, the cytotoxicity of the compounds examined in vitro on a panel of cancerous cell lines such as a human cervical cancer cell line (HeLa), a pancreatic cancer cell line (PANC-1), an Ehrlich ascites cancer cell line (EAC) and Dalton's lymphoma ascitic cancer cells (DLA) and a normal mouse embryonic fibroblasts cell line (NIH3) demonstrated that the complexes 1 and 2 possessed superior cytotoxicity than that of well-known commercial anticancer drug cisplatin to the tumor cells but are less toxic to the normal cell line and have emerged as potential candidates for further studies.

Potentially cytotoxic new copper(II) hydrazone complexes: synthesis, crystal structure and biological properties

An efficient fluorescent receptor (E)-N-[(2-hydroxy-naphthalen-1-yl)methylene]thiophene-2-carbohydrazide (THN) for Al3+ ions was synthesized and characterized by physicochemical and spectroscopic tools along with single crystal X-ray crystallography. This is the first report showing the crystal structure of THN and its sensing property for Al3+ ions. THN selectively and sensitively detects Al3+ ions without any interference among various cations, Na+, K+, Ca2+, Cr3+, Mg2+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+ and Hg2+ by a strong fluorescent change in ethanol–water medium (EtOH–H2O, 1 : 4 v/v). The THN interacts with Al3+ in a tridentate mode to form a [AlCl2(THN)(H2O)]·H2O complex. The binding constant was determined to be 7.06 × 106 M−1 and the limit of detection (LOD) was calculated to be 1.35 × 10−9 M which is the second highest reported till date in the literature. The 1H NMR titration, ESI-MS and DFT studies have also been performed in support of the binding details of the THN–Al3+ complex.

A highly sensitive and selective fluorescent sensor for Al3+ ions based on thiophene-2-carboxylic acid hydrazide Schiff base

Four new mononuclear Ni(II) complexes [Ni(L1)]ClO4 (1a), [Ni(L2)]ClO4(1b), [Ni(SCN)3(CH3OH)(aminoethylpiperazineH)] (2a), and [Ni(DMSO)4(aminoethylpiperazineH)](ClO4)3(2b)have been synthesized from two Schiff base ligands [L1 = 1-phenyl-3-((2-(piperidin-4-yl)ethyl)imino)but-1-en-1-ol and L2 = 4-((2-(piperazin-1-yl)ethyl)imino)pent-2-en-2-ol] by exploiting the flexibility of the piperazinyl moiety. Structural analysis reveals that 1a and 1b are square planar complexes with piperazine rings in boat conformations whereas hydrolysis of Schiff bases (L1 and L2) occurs during formation of octahedral complexes (2a and 2b) with piperazine rings in chair conformations. Screening tests were conducted to quantify the binding ability of complexes (1a, 1b and 2a) towards DNA, BSA and HSA and it was found that square planar complexes (1a and 1b) showed more effective binding properties over octahedral complex (2a). Furthermore, enzyme kinetic studies reflect that square planar complexes (1a and 1b) are also effective in mimicking catecholase like activities over octahedral complex (2a). Among all the complexes, 1a was found to be the most promising molecule among the series due to its large binding affinity towards different bio-macromolecules and higher T.O.N in the catechol oxidation reaction.

Nickel(II) complexes with a flexible piperazinyl moiety: studies on DNA and protein binding and catecholase like properties

The redox activity of metal ions can lead to the formation of highly reactive species that damage DNA, producing different oxidation products and types of damage depending upon the redox potentials of the DNA bases, formation of intermediate adducts, and identity of the reactive species. Other factors are also important in determining the degree of metal-mediated DNA damage, such as localization and redox chemistry of the metal ions or complexes and lifetimes of the reactive oxygen species generated. This review examines the types of DNA damage mediated by first-row transition metals under oxidative stress conditions, with emphasis on work published in the past ten years. Similarities and differences between DNA damage mechanisms of the first-row transition metals in vitro and in E. coli and human cells are compared and their relationship to disease development are discussed. Methods to detect this metal-mediated DNA damage, including backbone breakage, base oxidation, inter- and intra-strand crosslinking, and DNA–protein crosslinking are also briefly reviewed, as well as detection methods for reactive oxygen species generated by these metal ions. Understanding the conditions that cause metal-mediated DNA damage and metal generation of reactive oxygen species in vitro and in cells is required to develop effective drugs to prevent and treat chronic disease.

Metal-mediated DNA damage and cell death: mechanisms, detection methods, and cellular consequences

A series of four new mixed-ligand copper(II) complexes (1–4) of the type [Cu(L)(diimine)] (ClO4) [where L is 2-((1H-imidazol-2-yl)methylene)-N-phenylhydrazinecarbothioamide and the diimines are 1,10-phenanthroline (phen, 1), 2,2′-bipyridine (bpy, 2), 4,4′-dimethyl-2,2′-bipyridyl (dmbpy, 3), and 2,2′-dipyridylamine (dpa, 4)] have been successfully synthesized and characterized by various spectral techniques. The Kb values were calculated from electronic absorption spectral titration of these complexes with herring sperm DNA, and these varied in the order phen (1) > dmbpy (3) > bpy (2) > dpa (4). Electrophoresis observations revealed that these complexes (1–4) could efficiently induce single-strand breakage of pUC18 plasmid DNA in the presence of ascorbic acid. These copper complexes underwent a static quenching process with BSA. Moreover, their potential free-radical scavenging and anti-inflammatory properties were also determined using DPPH and protein denaturation techniques. These complexes showed efficient antibacterial activities against Staphylococcus aureus (Gram positive) and Pseudomonas aeruginosa (Gram negative). Furthermore, studies of their in vitro cytotoxicity against AGS cancer cells indicated promising antitumor activity with significant IC50 values.

Mixed-ligand copper(II) Schiff base complexes: the vital role of co-ligands in DNA/protein interactions and cytotoxicity

Three new bivalent nickel hydrazone complexes have been synthesised from the reactions of [NiCl2(PPh3)2] with H2L {L = dianion of the hydrazones derived from the condensation of o-hydroxynaphthaldehyde with furoic acid hydrazide (H2L1) (1)/thiophene-2-acid hydrazide (H2L2) (2)/isonicotinic acid hydrazide (H2L3) (3)} and formulated as [Ni(L1)(PPh3)] (4), [Ni(L2)(PPh3)] (5) and [Ni(L3)(PPh3)] (6). Structural characterization of these compounds 4–6 were accomplished by using various physico-chemical techniques. Single crystal X-ray diffraction data of complexes 4 and 5 proved their distorted square planar geometry. In order to ascertain the potential of the above synthesised compounds towards biomolecular interactions, additional experiments involving interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) were carried out. All the ligands and corresponding nickel(II) chelates have been screened for their scavenging effect towards O2−, OH and NO radicals. The efficiency of complexes 4–6 to arrest the growth of HeLa, HepG-2 and A431 tumour cell lines has been studied along with the cell viability test against the non-cancerous NIH 3T3 cells under in vitro conditions.

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Palanissamy Sathyadevi

Papers

Variation in the Biomolecular Interactions of Nickel(Ii) Hydrazone Complexes Upon Tuning the Hydrazide Fragment