Pyrazolone incorporating bipyridyl metallointercalators as effective DNA, protein and lung cancer targets: Synthesis, characterization and in vitro biocidal evaluation.

Pyrazolone based metal complexes have strong bio-activity but the anti-cancer mechanism of these derivatives is not fully understood. In recent years, Cu(II) complexes have attracted the interest of researchers increasingly because of their high antitumor activities that are usually related to DNA binding. The reaction of three different derivatives (I) PPMP [3-methyl-1-phenyl-4-propionyl-1H-pyrazol-5(4H)-one], (II) TMCPMP [1-(3-chlorophenyl)-3-methyl-4-(4-methylbenzoyl)-1H-pyrazol-5(4H)-one] and (III) PPTPMP [3-methyl-4-propionyl-1-p-tolyl-1H-pyrazol-5(4H)-one] of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and 2.2' bipyridyl along with Cu(NO3)2·3H2O under methanolic condition allowed us to isolate and characterize a series of new mixed ligand complexes [Cu(TMCPMP) (Bipy)NCS] (1) [Cu(PPMP) (Bipy)NCS] (2) and [Cu(PPTPMP) (Bipy)NCS] (3). All complexes are well characterized by elemental analysis, metal estimation, molar conductivity, FT-IR and UV-Vis spectroscopy. The molecular geometry of these complexes has been determined by single crystal X-ray study. The single-crystal X-ray structures of complexes 1 and 2 exhibit square pyramidal geometry, while complex 3 revealed slightly distorted square-pyramidal geometry. The DNA binding of these compounds with Calf-Thymus DNA (CT-DNA) has been explored by emission titration methods, which revealed that 1-3 could interact with CT-DNA through intercalation mode. The complexes also exhibited a strong binding with Bovine Serum Albumin (BSA) over the ligands. Complexes were evaluated for their in vitro cytotoxic activities against lung cancer cell lines (A549) as well as noncancerous rat cardiomyocytes (H9C2) cell lines, which showed that all three complexes exhibited substantial cytotoxic activity with minimum effect on noncancerous cells. Complex 1 with more hydrophobic environment exhibited relatively high cytotoxic activity towards A549 cells. In summary, this new series of compounds belongs to a class of copper-pyrazolonate complexes that target many biochemical sites and with potential anti-cancer activity. All these results collectively suggested that complexes could serve as promising pharmacologically active substance against lung cancer.

Crystal structure of [1-(3-chloro-phen-yl)-5-hy-droxy-3-methyl-1H-pyrazol-4-yl](p-tol-yl)methanone.

In the title compound C18H15ClN2O2, the dihedral angles between the central pyrazole ring and the pendant chloro-benzene and p-tolyl rings are 17.68 (10) and 51.26 (12)°, respectively. An intra-molecular O-H⋯O hydrogen bond is observed, which closes an S(6) ring.

Pyrazolone as a recognition site: Rhodamine 6G-based fluorescent probe for the selective recognition of Fe3+ in acetonitrile-aqueous solution.

Two novel Rhodamine-pyrazolone-based colorimetric off-on fluorescent chemosensors for Fe(3+) ions were designed and synthesized using pyrazolone as the recognition moiety and Rhodamine 6G as the signalling moiety. The photophysical properties and Fe(3+) -binding properties of sensors L(1) and L(2) in acetonitrile-aqueous solution were also investigated. Both sensors successfully exhibit a remarkably 'turn-on' response, toward Fe(3+) , which was attributed to 1: 2 complex formation between Fe(3+) and L(1) /L(2) . The fluorescent and colorimetric response to Fe(3+) can be detected by the naked eye, which provides a facile method for the visual detection of Fe(3+) .

Crystal structure of (4Z)-1-(3,4-di-chloro-phen-yl)-4-[hy-droxy(4-methyl-phen-yl)methyl-idene]-3-methyl-4,5-di-hydro-1H-pyrazol-5-one.

The title compound, C18H14Cl2N2O2, crystallizes with two mol-ecules, A and B, in the asymmetric unit. In mol-ecule A, the dihedral angles between the central pyrazole ring and pendant di-chloro-benzene and p-tolyl rings are 2.18 (16) and 46.78 (16)°, respectively. In mol-ecule B, the equivalent angles are 27.45 (16) and 40.45 (18)°, respectively. Each mol-ecule features an intra-molecular O-H⋯O hydrogen bond, which closes an S(6) ring and mol-ecule A also features a C-H⋯O inter-action. In the crystal, weak C-H⋯π interactions and aromatic π-π stacking [shortest centroid-centroid separation = 3.707 (2) Å] generate a three-dimensional network.

Crystal structure of (Z)-1-(3,4-dichlorophenyl)-3-methyl-4-[(naphthalen-1-yl-amino)(p-tolyl)methylidene]-1H-pyrazol-5(4H)-one.

The title Schiff base compound, C28H21Cl2N3O, was synthesized by the condensation of 1-(3,4-di-chloro-phen-yl)-3-methyl-4-(4-methyl-benzo-yl)-1H-pyrazol-5(4H)-one with 1-aminona-phthalene. The p-tolyl ring is normal to the pyrazole ring, with a dihedral angle of 88.02 (14)°, and inclined to the naphthalene ring system by 78.60 (12)°. The pyrazole ring is inclined to the naphthalene ring system and the di-chloro-substituted benzene ring by 63.30 (12) and 11.03 (13)°, respectively. The amino group and carbonyl oxygen atom are involved in an intra-molecular N-H⋯O hydrogen bond enclosing an S(6) ring motif. There is also a short C-H⋯O contact involving the carbonyl O atom and the adjacent benzene ring. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming a three-dimensional structure.

A comparative study of experimental and theoretical results of conformations of oxovanadium(IV) complexes with 4-acyl pyrazolone ligands using DFT method.

The optimized structures and electronic properties of the oxovanadium(IV) complexes containing 4-acyl pyrazolone ligands were calculated using density functional theory. The total energies of both the complexes were calculated e.g. syn and anti conformation of complex 1 and complex 2 with and without solvent. The calculated total energy for syn conformation was -10.162 keV, while total energy for anti conformation was -10.155 keV. Similarly, the calculated total energy for complex 2 with solvent was obtained -10.793 keV, while total energy for complex 2 without solvent was -10.158 keV. The total energy calculation shows that syn conformation is more stable in complex 1, while complex 2 is more stable in twisted geometry with solvent. In order to investigate the electronic properties of ligands and complexes, quantum chemical parameters, such as the highest occupied molecular orbital energy (HOMO), the lowest unoccupied molecular orbital energy (LUMO), and energy gap were calculated. The theoretically calculated data of the complexes are in good agreement with the data obtained by the single-crystal X-ray diffraction analysis.

(Z)-3-Methyl-4-[1-(4-methyl-anilino)propyl-idene]-1-phenyl-1H-pyrazol-5(4H)-one.

In the title mol-ecule, C20H21N3O, the central pyrazole ring forms dihedral angles of 4.75 (9) and 49.11 (9)°, respectively, with the phenyl and methyl-substituted benzene rings. The dihedral angle between the phenyl and benzene rings is 51.76 (8)°. The amino group and carbonyl O atom are involved in an intra-molecular N-H⋯O hydrogen bond. In the crystal, π-π inter-actions are observed between benzene rings [centroid-centroid seperation = 3.892 (2) Å] and pyrazole rings [centroid-centroid seperation = 3.626 (2) Å], forming chains along [111]. The H atoms of the methyl group on the p-tolyl substituent were refined as disordered over two sets of sites in a 0.60 (4):0.40 (4) ratio.

(Z)-3-Methyl-1-phenyl-4-[(p-tol-yl)(p-tolyl-amino)-methyl-idene]-1H-pyrazol-5(4H)-one.

In the title mol-ecule, C(25)H(23)N(3)O(2), the pyrazole ring forms dihedral angles of 28.56 (7), 80.35 (7) and 31.99 (7)° with the phenyl ring, the p-tolyl ring and the p-tolyl-amino ring, respectively. The N-H group attached to the exocyclic C=C bond is in a syn arrangement with respect to the C=O bond of the pyrazolone group and an intra-molecular N-H⋯O hydrogen bond is observed. In the crystal, weak C-H⋯π inter-actions link mol-ecules along [100].

Synthesis and crystal structure of an oxovanadium(IV) complex with a pyrazolone ligand and its use as a heterogeneous catalyst for the oxidation of styrene under mild conditions.

1-Phenyl-3-methyl-4-touloyl-5-pyrazolone (ligand) was synthesized and used to prepare an oxovanadium(IV) complex. The complex was characterized by single-crystal X-ray analysis and various spectroscopic techniques. The single-crystal X-ray analysis of the complex shows that the ligands are coordinated in a syn configuration to each other and create a distorted octahedral environment around the metal ion. A heterogeneous catalyst comprising an oxovanadium(IV) complex and hydrous zirconia was synthesized, characterized by various physicochemical techniques, and successfully used for the solvent-free oxidation of styrene. The influence of the reaction parameters (percent loading, molar ratio of the substrate to H(2)O(2), amount of catalyst, and reaction time) was studied. The catalyst was reused three times without any significant loss in the catalytic activity.

Synthesis, spectroscopic characterization and DNA nuclease activity of Cu(II) complexes derived from pyrazolone based NSO-donor Schiff base ligands.

Two neutral mononuclear Cu(II) complexes have been prepared in EtOH using Schiff bases derived from 4-toluoyl pyrazolone and thiosemicarbazide. Both the ligands have been characterized on the basis of elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. The molecular geometry of one of these ligands has been determined by single crystal X-ray study. It reveals that these ligands exist in amine-one tautomeric form in the solid state. Microanalytical data, Cu-estimation, molar conductivity, magnetic measurements, IR, UV-Visible, FAB-Mass, TG-DTA data and ESR spectral studies were used to confirm the structures of the complexes. Electronic absorption and IR spectra of the complexes suggest a square-planar geometry around the central metal ion. The interaction of complexes with pET30a plasmid DNA was investigated by spectroscopic measurements. Results suggest that the copper complexes bind to DNA via an intercalative mode and can quench the fluorescence intensity of EB bound to DNA. The interaction between the complexes and DNA has also been investigated by agarose gel electrophoresis, interestingly, we found that the copper(II) complexes can cleave circular plasmid DNA to nicked and linear forms.

Effect of soda ash industry effluent on agarophytes, alginophytes and carrageenophyte of west coast of India.

This paper presents the results of a study on the impact of the effluent released by the soda ash industry on important red and brown macro algal species Gelidiella acerosa, Gracilaria corticata, Soleria robusta, Sargassum tenerrimum, Padina tetrastromatica in the tidal zone around Veraval, on the west coast of India, in the lowest low water tide of December 2003. The study examined the effect of effluent discharge on availability of biomass and percentage of phyco-colloids extraction such as agar, alginic acid and carrageen of these commercial seaweeds.

Effect of soda ash industry effluent on protein content of two green seaweeds.

The aim of the present study is to check the effect of soda ash industry effluent on the protein content of the seaweed Ulva faciata and Chaetomorpha antennina. Study shows that the effluent has positive effect on the protein content of the alga and thus these species can be used to reduce the effect of soda ash industry pollution because the rise of up to 35% of protein level is found in these species of alga due to uptake of polluted water. Thus, these seaweeds can be cultivated on a large scale in the effluent affected region and thus clean the environment while getting the proteinous food as by product.

Effect of soda ash industry effluent on bioaccumulation of metals by seaweeds of coastal region of Gujarat, India.

The bioaccumulation ability of five species of seaweeds to 15 metals was studied in the seawater polluted by the effluent of soda ash industry. The bioaccumulation of Al, Mn and Fe in these seaweeds increased continuously as distance increased from outfall. However, Padina tetrastromatica showed reverse trend. Quite a number of metals like Au, Co, Hg, Ni, Pb, Pt and Sn were not recorded from any species of seaweeds from all sampling stations. Cr was recorded in Gracillaria acerosa from control site only. Accumulation of Cu in Gracilaria corticata was maximum near effluent discharge point and least at control, whereas its accumulation in P. tetrastromatica was more at station with lower pollution (station-3) than higher polluted station (station-2). Seaweeds had different pattern of bioaccumulation to Cu and Ag under the influence of the effluent. The bioaccumulation of Cd in quite a number of species was in non-detectable range, however in case of red seaweed it was more under polluted condition and non-detectable in control. The biosequestering capacity of different seaweed to different metals and their suitability for bioremediation under the influence of effluent is discussed. Bioconcentration factor for different seaweed species from different distances from outfall has been computed and discussed. The undiluted soda ash industry effluent is characterized by very high pH, density, settleable solids, total dissolved solids, ammonia and nitrate. The specific gravity, density, total suspended solids and total dissolved solids decreased continuously from undiluted effluent to seawater affected up to 1 km.