Nuclease activity and interaction studies of unsymmetrical binuclear Ni(II) complexes with CT-DNA and BSA.

New unsymmetrical binuclear nickel(II) complexes [Ni2L(1-5)] (ClO4)2 (1-5) were synthesized by using [NiL] [(3-((9E)-(2-((E)-(3-formyl-2-olato-5-methylbenzylideneamino)methyl) phenylimino)methyl)-3-formyl-5-methyl-2-olato)nickel(II)] with various diamines like 1,2-diaminoethane (L(1)), 1,3-diaminopropane (L(2)), 1,4-diaminobutane (L(3)), 1,2-diaminobenzene (L(4)) and 1,8-diaminonaphthalene (L(5)) and characterized by elemental analysis and spectroscopic methods. The molecular structure of binuclear nickel(II) complex 1 is determined by a single crystal X-ray diffraction method. Cyclic voltammograms of binuclear Ni(II) complexes exhibit two quasi-reversible reduction waves in the cathodic region and two oxidation waves in the anodic region. DNA binding, protein binding and DNA cleavage studies were investigated. The interactions of complexes (1-5) with calf thymus DNA were studied by spectroscopic techniques, including absorption and fluorescence methods. The binding affinities of complexes (1-5) with CT-DNA and nuclease activities are in the following order: 5> 4>3 >2>1 . Binuclear Ni(II) complex 1 cleaved the plasmid DNA by a hydrolytic pathway. The hydrolytic cleavage of DNA by the complexes is supported by evidence from free radical quenching and T4 ligase ligation. Binuclear Ni(II) complexes (1-5) displayed significant protein (bovine serum albumin) interactions. The experimental results showed that the interaction between binuclear Ni(II) complexes and BSA was mainly a static quenching process.

2,2'-{[(1E,1'E)-(Cyclo-hexane-1,4-diyl)-bis(aza-nylyl-idene)]bis-(ethan-1-yl-1-yl-idene)}diphenol.

The title compound, C22H26N2O2, crystallizes with three independent mol-ecules, two of which are situated on inversion centers, so the asymmetric unit contains two independent half-mol-ecules and one mol-ecule in a general position. The two hy-droxy groups in each mol-ecule are involved in intra-molecular O-H⋯N hydrogen bonds, which generate S(6) rings. In the crystal, weak inter-molecular C-H⋯π inter-actions link the mol-ecules into two crystallographically independent columns propagating along [001]; one column consists of mol-ecules in general positions, while the other column is built from alternating independent centrosymmetric mol-ecules.

Wound healing properties of Indian propolis studied on excision wound-induced rats.

CONTEXT: In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken. OBJECTIVE: The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats. MATERIALS AND METHODS: Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. RESULTS: Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone. DISCUSSION AND CONCLUSION: It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.

A new chitosan biopolymer derivative as metal-complexing agent: synthesis, characterization, and metal(II) ion adsorption studies.

In this study, a new chitosan biopolymer derivative (CTSL) has been synthesized by anchoring a new vanillin-based complexing agent or ligand, namely 4-hydroxy-3-methoxy-5-[(4-methylpiperazin-1-yl)methyl] benzaldehyde, (L) with chitosan (CTS) by means of condensation. The new material was characterized by elemental (CHN), spectral (FTIR and solid state (13)C NMR), thermal (TG-DTA and DSC), structural (powder XRD), and morphological (SEM) analyses. The CTSL was employed to study the equilibrium adsorption of various metal ions, namely, Mn(II), Fe(II), Co(II), Cu(II), Ni(II), Cd(II), and Pb(II), as functions of pH of the solutions. Its kinetics of adsorption was evaluated utilizing the pseudo first order and pseudo second order equation models and the equilibrium data were analyzed by Langmuir isotherm model. The CTSL shows good adsorption capacity for metal ions studied in the order Cu(II)>Ni(II)>Cd(II)> or =Co> or =Mn(II)>Fe(II)>Pb(II) in all studied pH ranges due to the presence of many coordinating moieties present in it.

Synthesis and characterization of a crosslinked chitosan derivative with a complexing agent and its adsorption studies toward metal(II) ions.

A new chitosan derivative has been synthesized by crosslinking a metal complexing agent, [6,6'-piperazine-1,4-diyldimethylenebis (4-methyl-2-formyl) phenol] (L), with chitosan (CTS). The resulting material (CCTSL) was characterized by elemental (CHN), spectral (FTIR and solid-state NMR), thermal (TGA and DTA), and structural (powder XRD and SEM) analyses. Adsorption experiments (pH dependency, kinetics, and equilibrium) of CCTSL toward various metal ions such as Mn(II), Fe(II), Co(II), Cu(II), Ni(II), Cd(II), and Pb(II) were carried out at 25 degrees C. The results showed that the adsorption was dependent on the pH of the solution, with a maximum capacity between pHs 6.5 and 8.5. The kinetics was evaluated by applying the pseudo-first-order and pseudo-second-order equation models and the equilibrium data were analyzed by Langmuir isotherm model. The maximum adsorption capacity was 1.21 mmol g(-1) for Cu(II) and the order of adsorption capacities for the metal(II) ions studied was found to be Cu(II)>Ni(II)>Cd(II)> or =Co(II)> or =Mn(II)> or =Fe(II)> or =Pb(II).

Structural, magnetic, electrochemical, catalytic, DNA binding and cleavage studies of new macrocyclic binuclear copper(II) complexes.

The macrocyclic symmetrical and a series of unsymmetrical binuclear copper(II) complexes have been synthesized by using mononuclear complex [CuL] [3,3'-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)copper(II)]. Another compartment of the [CuL] have been condensed with various diamines like 1,2-bis(aminooxy)ethane (L(1)), 1,2-diamino ethane(L(2a)), 1,3-diamino propane(L(2b)), 1,4-diamino butane(L(2c)), 1,2-diamino benzene(L(2d)), 1,8-diamino naphthalene(L(2e)) and characterized by elemental, spectroscopic, and X-ray crystallographic methods. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, magnetic, catecholase activity, DNA binding and cleavage properties have been studied. The molecular structures of the symmetrical binuclear complex [Cu(2)L(1)(H(2)O)(2)](ClO(4))(2) (1) and unsymmetrical binuclear complex [Cu(2)L(2b)(ClO(4))(H(2)O)]ClO(4) (2b) were determined by X-ray crystallography. Both of them were discrete binuclear species in which each Cu(II) ions are in distorted square pyramid. The Cu...Cu distances vary from 3.0308 (2b) to 3.0361 A (1). Electrochemical studies evidenced that two quasi-reversible one electron-transfer reduction waves (E(pc)(1)) -0.91 to -1.01 V, (E(pc)(2)) -1.26 to -1.55 V) for binuclear complexes are obtained in the cathodic region. Cryomagnetic investigation of the binuclear complexes reveals a weak antiferromagnetic spin exchange interaction between the Cu(II) ions within the complexes (-2J=104.4-127.5 cm(-1)). The initial rate (V(in)) for the oxidation of 3,5-di-tert-butylcatechol to o-quinone by the binuclear Cu(II)complexes are in the range 3.6 x 10(-5) to 7.3 x 10(-5)Ms(-1). The binuclear Cu(II) complexes are avid binders to calf thymus DNA. The complexes display significant oxidative cleavage of circular plasmid pBR322 DNA in the presence of mercaptoethanol using the singlet oxygen as a reactive species. The aromatic diamine condensed macrocyclic ligands of copper(II) complexes display better DNA interaction and significant chemical nuclease activity than the aliphatic diamine condensed macrocyclic Cu(II) complexes.

1-[2-(2,4-Dinitro-benzyl-ideneamino)phen-yl]-3-phenyl-thio-urea.

In the title compound, C(20)H(15)N(5)O(4)S, the central benzene ring makes dihedral angles of 59.5 (1) and 51.7 (1)°, respectively, with the terminal phenyl and benzene rings. The mol-ecular structure exhibits weak intra-molecular N-H⋯N and C-H⋯S inter-actions. In the crystal structure, mol-ecules are linked by weak inter-molecular N-H⋯S and C-H⋯O inter-actions, forming a chain along [11].

Synthesis and characterization of a chitosan-bearing binucleating ligand and its pH dependency on copper(II) adsorption.

A novel chitosan derivative has been synthesized by the condensation of a binucleating ligand, 2,6-bis[(N-methylpiperazine-1-yl)methyl]-4-formylphenol (BNL), with chitosan (CTS). The resulting material (CTS-BNL) was characterized and its adsorption properties towards copper(II) ions in aqueous solutions of various pH have been studied, the adsorption capacity (Q(e)) is about 0.94 mmol g(-1) at pH 6 and 1.45 mmol g(-1) at pH 8.5. This higher adsorption capacity may be due to the binucleating ligand anchored to chitosan.

1-(2,4-Dinitro-phen-yl)-5-ferrocenyl-3-methyl-1H-pyrazole.

In the title compound, [Fe(C(5)H(5))(C(15)H(11)N(4)O(4))], the dinitro-phenyl and cyclo-penta-dienyl rings make dihedral angles of 53.61 (6) and 23.11 (9)°, respectively, with the pyrazole unit. The two cyclo-penta-dienyl rings are in an eclipsed conformation. The crystal structure is stabilized by inter-molecular C-H⋯O inter-actions, which link mol-ecules into chains parallel to the b axis.

1-{2-[(Anthracen-10-yl)methyl-ene-amino]phen-yl}-3-phenyl-thio-urea.

The title compound, C(28)H(21)N(3)S, crystallizes with two mol-ecules in the asymmetric unit. There are only very slight differences in the torsion angles between the two molecules. The two mol-ecules are stabilized by intra-molecular N-H⋯N inter-actions and the crystal packing is stabilized by inter-molecular N-H⋯S inter-actions.

Synthesis of new oxamide-based ligand and its coordination behavior towards copper(II) ion: spectral and electrochemical studies.

A new ligand N,N'-bis{3-(2-formyl-4-methyl-phenol)-6-iminopropyl}oxamide (L) and its mono- and binuclear copper(II) complexes have been synthesized and characterized. The ligand shows absorption maxima at 249 and 360 with a weak transition at 455 nm. The ligand was found to be fluorescent and shows an emission maximum at 516 nm on excitation at 360 nm. The electronic spectra of the mono- and binuclear Cu(II) complexes exhibited a d-d transition in the region 520-560 nm characteristic of square planar geometry around Cu(II) ion. The ESR spectrum of the mononuclear complex showed four lines with nuclear hyperfine splitting. The binuclear complex showed a broad ESR spectrum with g=2.10 due to antiferromagnetic interaction between the two Cu(II) ions. The room-temperature magnetic moment values (micro(eff)) for the mono- and binuclear Cu(II) complexes are found to be 1.70 micro(B) and 1.45 micro(B), respectively. The electrochemical studies of the mononuclear Cu(II) complex showed a single irreversible one-electron wave at -0.70 V (E(pc)) and the binuclear Cu(II) complex showed two irreversible one-electron reduction waves at -0.75 V (E(pc)(1)) and -1.27 V (E(pc)(2)) in the cathodic region.

Anti-inflammatory and lysosomal stability actions of Cleome gynandra L. studied in adjuvant induced arthritic rats.

The present study was aimed to assess the anti-arthritic nature of Cleome gynandra L. (Cat's whiskers) against Freund's complete adjuvant induced arthritis in rats. The ethanolic extract of C. gynandra was administered orally at a dose of 150 mg/kg body weight for 30 days to the experimental rats after the induction of adjuvant arthritis. The anti-inflammatory activity of C. gynandra leaves was assessed by paw volume measurement, and its capacity to stabilize lysosomal enzyme activities in the plasma and liver of control and experimental rats. The activity of pathophysiological enzymes such as AST, ALT, ALP, cathepsin-D, beta-glucuronidase, N-acetyl-beta-glucosaminidase LDH and the levels of glycoproteins were also estimated in plasma and liver. The increased levels of both lysosomal enzymes and protein-bound carbohydrates in arthritic rats were significantly suppressed to near normal level by the administration of C. gynandra extract. Further, the significantly elevated plasma levels of TNF-alpha found in arthritic rats were found to be significantly restored back to near normal levels by the extract in experimental animals. The membrane stabilizing activity of the extract was further evidenced by histological observations made on the limb tissue. Recently, we have reported the presence of many biologically active phyto chemicals such as triterpenes, tannins, anthroquinones, flavonoids, saponins, steroids, resins, lectins, glycosides, sugars, phenolic compounds, and alkaloids in the extract of C. gynandra and these compounds might be responsible for the anti-arthritic properties observed in the present study. The possible mechanism of action of the C. gynandra extract may be through its stabilizing action on lysosomal membranes and there by preventing the spread of inflammation.

Biochemical evaluation of antidiabetogenic properties of some commonly used Indian plants on streptozotocin-induced diabetes in experimental rats.

1. Diabetes mellitus is a serious metabolic disorder with micro- and macrovascular complications that results in significant morbidity and mortality. 2. The aim of the present study was to evaluate the hypoglycaemic efficacy of commonly used traditional Indian plants, such as Murraya koenigii, Mentha piperitae, Ocimum sanctum and Aegle marmelos, in streptozotocin (STZ)-induced experimental rats. 3. Oral administration of the ethanolic extract of these plants resulted in a significant decrease in the levels of blood glucose, glycosylated haemoglobin and urea, with a concomitant increase in glycogen, haemoglobin and protein, in diabetic rats. Treatment with these plant extracts also resulted in an increase in insulin and C-peptide levels and glucose tolerance. 4. The decreased activities of carbohydrate-metabolising enzymes, such as hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthase, in diabetic rats were significantly elevated towards near normal in rats treated with extracts of M. koenigii, O. sanctum and A. marmelos; the increased activities of lactate dehydrogenase, fructose-1,6-bisphosphatase, glucose-6-phosphatase and glycogen phosphorylase in STZ diabetic rats were significantly reduced following treatment with the plant extracts. 5. Elevated specific binding of [(125)I]-labelled insulin to the receptor found in diabetic rats was markedly decreased in extract-treated groups. However, treatment of diabetic rats with M. piperitae did not result in any significant modification in all parameters. 6. Phytochemical screening conducted by us revealed the presence of biologically active ingredients in the ethanolic extracts of M. koenigii, O. sanctum and A. marmelos, which may readily account for the observed hypoglycaemic activity.

Free radical scavenging activity of Cleome gynandra L. leaves on adjuvant induced arthritis in rats.

The generation of free radicals has been implicated in the causation of several diseases of known and unknown etiologies such as, rheumatoid arthritis, diabetes, cancer, etc., and compounds that can scavenge free radicals have great potential in ameliorating these disease processes. The present study was aimed to investigate the possible anti-oxidant potential of Cleome gynandra leaf extract at a dose of 150 mg/kg body weight for 30 days on adjuvant induced arthritis in experimental rats. Oral administration of C. gynandra leaf extract significantly increased the levels of lipid peroxides and activities of catalase, glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological observations made on the limb tissue. The presence of biologically active ingredients and vital trace elements in the leaves readily account for free radical scavenging property of C. gynandra.

Anti-inflammatory activity of Cleome gynandra L. on hematological and cellular constituents in adjuvant-induced arthritic rats.

Cleome gynandra L. (cat whiskers) has traditionally been used for the treatment of rheumatic and other inflammatory conditions. In this work, the methanolic extract of the leaves of C. gynandra exhibited significant anti-inflammatory activity in adjuvant-induced arthritic rats. Phytochemical screening was carried out to ascertain the qualitative composition of the leaves. Arthritis was induced by Freund's complete adjuvant. A significant decrease in paw edema with a remarkable increase in body weight was observed following oral administration of the leaf extract (150 mg/kg of body weight). The alterations in hematological and other biochemical parameters were restored to near normal after a treatment period of 30 days. These results demonstrate that the plant extract has no harmful effect and exerts in vivo anti-inflammatory properties against adjuvant-induced arthritis.

Mineral content of some medicinal plants used in the treatment of diabetes mellitus.

It is known that certain inorganic trace elements such as vanadium, zinc, chromium, copper, iron, potassium, sodium, and nickel play an important role in the maintenance of normoglycemia by activating the beta-cells of the pancreas. In the present study, the elemental composition in the leaves of four traditional medicinal plants (Murraya koenigii, Mentha piperitae, Ocimum sanctum, and Aegle marmelos) widely used in the treatment of diabetes-related metabolic disorders has been studied using atomic absorption spectroscopy. The levels of Cu, Ni, Zn, K, and Na were found to be in trace amounts, whereas Fe, Cr, and V levels were found in marginal levels. The importance of these elements in disorders related to diabetes is also briefly discussed.

Hypoglycemic effect of macrocyclic binuclear oxovanadium (IV) complex on streptozotocin-induced diabetic rats.

Though vanadium complexes mimic the action of insulin, owing to their toxicity, research is still in progress for a new vanadium complex with maximum efficacy at low concentration and without any side effects. A novel macrocyclic binuclear oxovanadium complex was synthesized, its composition and structure were confirmed by spectral studies and its efficacy was studied in streptozotocin-induced diabetic rats over a period of 30 days. The oral administration of the complex normalizes the blood glucose level in the diabetic rats and also maintains normoglycemia after a glucose load. The biochemical studies revealed that the complex is not toxic to the system. The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact form. The study highlights the nontoxic and hypoglycemic effects of the new macrocyclic binuclear oxovanadium complex.

Insulin mimetic effects of macrocyclic binuclear oxovanadium complexes on streptozotocin-induced experimental diabetes in rats.

AIM: The vanadium complexes so far tested for their insulin mimetic effects are either mono- or binuclear and contain only acyclic ligands. The leaching or hydrolysis of vanadyl ions from these complexes is much easier, and hence they elicit side effects. In the present study, a new binuclear macrocyclic oxovanadium complex was synthesized, and its efficacy was studied on streptozotocin (STZ)-induced diabetic rats over a period of 30 days. METHODS: The insulin mimetic effect of the complex was tested on the blood sugar level in the STZ-diabetic rats and on the activities of the carbohydrate-metabolizing enzymes present in the liver. RESULTS: Administration of vanadium complex to STZ-induced diabetic rats decreased blood glucose levels from hyperglycaemic to normoglycaemic when compared to diabetic rats. The activity of carbohydrate-metabolizing enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen content were increased to near normal in vanadium complex-administered diabetic rats. The biochemical studies such as assay of blood urea and glutamate oxaloacetate transaminases revealed that the complex is not toxic to the system. CONCLUSION: The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact macrocyclic form. Further, the vanadyl ions present in the macrocyclic binuclear oxovanadium complex are very close to each other, and this may enhance the insulin mimetic activity by synergic effect.

Synthesis of lateral macrobicyclic compartmental ligands: structural, magnetic, electrochemical, and catalytic studies of mono- and binuclear copper(II) complexes.

A series of putative mono- and binuclear copper(II) complexes, of general formulas [CuL](ClO(4)) and [Cu(2)L](ClO(4))(2), respectively, have been synthesized from lateral macrocyclic ligands that have different compartments, originated from their corresponding precursor compounds (PC-1, 3,4:9,10-dibenzo-1,12-[N,N'-bis[(3-formyl-2-hydroxy-5-methyl)benzyl]diaza]-5,8-dioxacyclotetradecane; and PC-2, 3,4:9,10-dibenzo-1,12-[N,N'-bis[(3-formyl-2-hydroxy-5-methyl)benzyl]diaza]-5,8-dioxacyclopentadecane). The precursor compound PC-1 crystallized in the triclinic system with space group P(-)1. The mononuclear copper(II) complex [CuL(1a)](ClO(4)) is crystallized in the monoclinic system with space group P2(1)/c. The binuclear copper(II) complex [Cu(2)L(2c)](ClO(4))(2) is crystallized in the triclinic system with space group P(-)1; the two Cu ions have two different geometries. Electrochemical studies evidenced that one quasi-reversible reduction wave (E(pc) = -0.78 to -0.87 V) for mononuclear complexes and two quasi-reversible one-electron-transfer reduction waves (E(1)(pc) = -0.83 to -0.92 V, E(2)(pc) = -1.07 to -1.38 V) for binuclear complexes are obtained in the cathodic region. Room-temperature magnetic-moment studies convey the presence of antiferromagnetic coupling in binuclear complexes [mu(eff) = (1.45-1.55)mu(B)], which is also suggested from the broad ESR spectra with g = 2.10-2.11, whereas mononuclear complexes show hyperfine splitting in ESR spectra and they have magnetic-moment values that are similar to the spin-only value [mu(eff) = (1.69-1.72)mu(B)]. Variable-temperature magnetic susceptibility study of the complex shows that the observed -2J value for the binuclear complex [Cu(2)L(1b)](ClO(4))(2) is 214 cm(-1). The observed initial rate-constant values of catechol oxidation, using complexes as catalysts, range from 4.89 x 10(-3) to 5.32 x 10(-2) min(-1) and the values are found to be higher for binuclear complexes than for the corresponding mononuclear complexes.

Synthesis and Characterization of New Symmetrical Binucleating Ligands and Their &mgr;-Phenoxo-Bridged Bicopper(II) Complexes: Structural, Electrochemical, and Magnetic Studies.

The new pentadentate binucleating ligands 2,6-Bis[N-(3,5-dimethyl-2-hydroxybenzyl)-N-methylaminomethyl]-4-chlorophenol, H(3)L(1), and 2,6-bis[N-(3,5-dichloro-2-hydroxybenzyl)-N-cyclohexylaminomethyl]-4-methylphenol, H(3)L(2), and their binuclear copper(II) complexes of the general formulas [Cu(2)L(1)(X)] (X = OMe, OH, Br (1-3)) and [Cu(2)L(2)(X)] (X = OMe, OH, Br (4-6)) have been prepared. The molecular structure of the complex [Cu(2)L(1)(OMe)].MeOH was studied by X-ray crystallography. It exists as a discrete binuclear species in which the copper atoms are in a distorted square planar environment with two oxygen bridges provided by the phenolate of the ligand and methoxy exogenous donor and the Cu.Cu distance is 3.030 Å. A cyclic voltammetric study of the complexes shows two quasireversible reduction waves at negative potentials. A cryomagnetic investigation on powdered samples of the complexes (1-6) shows moderately strong antiferromagnetic coupling (-2J in the range 120-300 cm(-)(1)). A comparison of the electrochemical and magnetic properties of the complexes prepared from both ligands is discussed. Crystal data for the complex [Cu(2)L(1)(OMe)].MeOH: molecular formula C(30)H(39)ClCu(2)N(2)O(5), monoclinic, space group P2(1)/c with a = 13.222(1) Å, b = 15.912(1) Å, c = 14.149(1) Å, beta = 91.64(1) degrees, and Z = 4.