M. Kandaswamy

A Series of Oxyimine-Based Macrocyclic Dinuclear Zinc(II) Complexes Enhances Phosphate Ester Hydrolysis, DNA Binding, DNA Hydrolysis, and Lactate Dehydrogenase Inhibition and Induces Apoptosis

A symmetrical macrocyclic dizinc(II) complex (1) has been synthesized by using the ligand (L(1)) [μ-11,24-dimethyl-4,7,16,19-tetraoxa-3,8,15,20-tetraazatricyclo-[20.3.1.1(10,13)] heptacosa-1(25),2,7,9,11,13(27),14,20,22(26),23-decaene-26,27-diol]. A series of unsymmetrical macrocyclic dizinc(II) complexes (2-6) has been synthesized by Schiff base condensation of bicompartmental mononuclear complex [ZnL] [μ-3,16-dimethyl-8,11-dioxa-7,12-diazadicyclo-[1.1(14,18)] heptacosa-1,3,5(20),6,12,14,16,18(19)-octacaene-19,20-diolato)zinc(II)] with various diamines like 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The ligand L(1) and all the zinc(II) complexes were structurally characterized. To corroborate the consequence of the aromatic moiety in comparison to the aliphatic moiety present in the macrocyclic ring on the phosphate ester hydrolysis, DNA binding and cleavage properties have been studied. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate ester reaction are in the range from 2.73 × 10(-2) to 9.86 × 10(-2) s(-1).The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence, and circular dichroism spectroscopy. The DNA binding constant values of the complexes were found in the range from 1.80 × 10(5) to 9.50 × 10(5) M(-1), and the binding affinities are in the following order: 6 > 5 > 1 > 2 > 3 > 4. All the dizinc(II) complexes 1-6 effectively promoted the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 6 under physiological conditions give the observed rate constant (k(obs)) of 4.42 ± 0.2 h(-1), which shows a 10(8)-fold rate acceleration over the uncatalyzed reaction of ds-DNA. The comparison of the dizinc(II) complexes 1-6 with the monozinc(II) complex [ZnL] indicates that the DNA cleavage acceleration promoted by 1-6 are due to the efficient cooperative catalysis of the two close proximate zinc(II) cation centers. The ligand L(1), dizinc(II) complexes 1, 3, and 6 showed cytotoxicity in human hepatoma HepG2 cancer cells, giving IC(50) values of 117, 37.1, 16.5, and 8.32 μM, respectively. The results demonstrated that 6, a dizinc(II) complex with potent antiproliferative activity, is able to induce caspase-dependent apoptosis in human cancer cells. Cytotoxicity of the complexes was further confirmed by the lactate dehydrogenase enzyme level in HepG2 cell lysate and content media.

Synthesis of copper(II) and nickel(II) complexes using compartmental ligands: X-ray, electrochemical and magnetic studies

Abstract Acyclic dicompartmental ligands suitable for the complexation of transition-metal ions which can form mononuclear, homo- or heterodinuclear complexes have been synthesised. The mononuclear complexes ML1 (M=Cu, Ni) where L1=N,N′-bis[2-hydroxy-3-(morpholino-1-ylmethyl)-5-methylbenzyl]alkyldiimine (alkyl=ethylene, L1a; propylene, L1b; butylene, L1c; triethylenetetraamine, L1d); ML2 (M=Cu, Ni) where L2=N,N′-bis[2-hydroxy-3-(morpholino-1-ylmethyl)-5-methylbenzyl]alkyldiamine (alkyl=ethylene, L2a; propylene, L2b); and ML3 (M=Cu, Ni) where L3=N,N′-bis[2-hydroxy-3-(morpholino-1-ylmethyl)-5-bromobenzyl]alkyldiimine (alkyl=ethylene, L3a; propylene, L3b; butylene, L3c) have been synthesised and characterised by C, H, N analysis, IR, electronic and ESR spectra. The complexes CuH2L1a (1), CuH2L2a (4), NiH2L1a (9) and NiH2L1d (12) have been analysed by X-ray crystallography. Complexes 1 and 4 have square pyramidal geometry. The coordination geometry around the metal ion in complex 9 is square planar and in complex 12 it is octahedral. Electrochemical studies of the complexes show a single quasi-reversible electron transfer process at the negative potential region. For copper complexes (1–8) Epc=−1.10 to −0.70 V, for nickel complexes (9–12) Epc=−1.0 to −0.85 V. Copper complexes show a magnetic moment value of μeff=1.70–1.75 BM. The square planar nickel complexes are diamagnetic whereas the nickel complex (12) with octahedral structure has a magnetic moment value of 3.12 BM.

A novel insulin mimetic vanadium–flavonol complex: Synthesis, characterization and in vivo evaluation in STZ-induced rats

Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0.8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium-flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats. The results indicate that the complex is non-toxic and possess anti-diabetic activity.

Synthesis of mononuclear nickel(II) and copper(II) complexes using compartmental ligands: X-ray and electrochemical studies

Abstract A series of mononuclear complexes ML 1 (M=Ni, Cu) where L 1 = N , N ′-bis[2-hydroxy-3-(piperidin-1-ylmethyl)-5-methylbenzyl]alkyldiimine (alkyl=ethylene L 1a , propylene L 1b , butylene L 1c ) and ML 2 (M=Ni, Cu) where L 2 = N , N ′-bis[2-hydroxy-3-(piperidin-1-ylmethyl)-5-bromobenzyl]alkyldiimine (alkyl=ethylene L 2a , propylene L 2b , butylene L 2c ) have been synthesized and characterized by C, H, N analysis, IR, electronic and ESR spectra. The crystal structures of the complexes NiH 2 L 1a ( 1 ) and CuH 2 L 1a ( 6 ) were determined and the geometry around the metal ion is square planar. Electrochemical studies of the complexes show a quasi-reversible single redox wave at negative potential in the range 0 to −1.3 V. For nickel complexes ( 1 – 5 ) E pc =−1.0 to −0.80 V and for copper complexes ( 6 – 9 ) E pc =−0.90 to −0.72 V. The ESR spectra of nickel complexes are inactive due to square planar nature of the complexes whereas copper complexes show an ESR spectrum characteristic of square planar complex with nuclear hyperfine spin 3/2. Copper complexes show a normal magnetic moment value of μ eff =1.70–1.75 B.M. which is close to the spin-only value of 1.73 B.M.

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.

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.

Synthesis, spectral, electrochemical and magnetic properties of new symmetrical and unsymmetrical dinuclear copper(II) complexes derived from binucleating ligands with phenol and benzimidazole donors

Abstract New symmetrical 2,6-bis{N-[2-(2-benzimidazolyl)-phenyl]iminomethyl}-4-methylphenol (L1) and unsymmetrical 2-N-[2-(2-benzimidazoyl)phenyl]iminomethyl-6-[(4-methylpiperazin-1-yl)-methyl]-4-methylphenol (L2) binucleating ligands have been synthesized. Complexation of these ligands with Cu(II) perchlorate and appropriate sodium salt offered the binuclear copper(II) complexes, [Cu2L(X)](ClO4)2, (X=Cl, OH and OAc 1–6). Their spectral, electrochemical and magnetic properties have been studied. Two distinct reduction peaks were observed at negative potentials. The electrochemical data shows that the complexes of L2 undergo reduction at less negative potential (E1pc=−0.15 to −0.25 V, E2pc=−0.45 to −0.65 V) when compared to the complexes of L1 (E1pc=−0.45 to −0.58 V, E2pc=−1.07 to −1.103 V). A variable temperature magnetic study on the complexes of the ligand L1 showed strong antiferromagnetic coupling between the copper atoms (−2J=285–295 cm−1), in contrast, the complexes of the ligand L2 showed weak antiferromagnetic interaction (−2J=60–85 cm−1). Electron spin resonance (ESR) spectra (RT) of the complexes of ligand L1 showed no signal and the complexes of ligand L2 showed a broad feature.

Synthesis, characterisation, electrochemical studies and catecholase activity of a new series of binuclear copper (II) complexes

Abstract New binucleating ligands L (L-, N′-R-bis (methyl-N- (2-pyridinyl) ketoacetamide) where R=ethylene, 1,3-propylene, o-phenylene were prepared by the condensation of 2 equivalents of methyl-N- (2-pyridinyl) ketoacetamide with the diamines. The binuclear copper (II) complexes of the type [Cu2L] X4 where where X=Cl− and Br− were synthesised by refluxing the ligand with 2 equivalents of Cu (II) salts Conductivity studies showed a 1:4 electrolyte for perchlorate complexes and a 1:2 electrolyte for chloro and bromo complexes Room temperature magnetic studies gave moment for the complexes in the range 108 to 145 BM which are less than 173 BM for d 9 system This shows that there is antiferromagnetic coupling between the two copper centers ESR spectra of the complexes show a broad band which is centered at 3300G and the g values obtained were in the range 209–214 Electrochemical studies show a quasireversible two electron reduction occuring at the negative potential in the range −025 to −070 V The initial rate constant for the oxidation of catechol to o-quinone by the complexes are in the range 1504×10−1 to 383×10−1 min−1

Preparation and properties of a triply bridged antiferromagnetically coupled binuclear copper(II) complex [Cu2L(OAc)2]ClO4 {L=2,6-bis[(N-methyl piperazin-1-yl) methyl]-4-bromo phenol}

Abstract The preparation of a pentadentate binucleating ligand 2,6-bis[(N-methyl piperazin-1-yl) methyl]-4-bromo phenol (HL) is described together with the corresponding acetato bridged Cu(II) complex [Cu2L(CH3COO)2]ClO4·H2O. Both the ligand and complex were characterized by elemental analysis and spectral studies. The electrochemical behaviour of the complex is discussed in detail. The structure analysis shows that the ligand is pentadentate donating two nitrogens as well as a bridging oxygen to each copper. Two acetates bridge the coppers through basal and apical positions to yield square–pyramidal coppers with a distorted square base, perchlorates occupy interstitial positions. The structure is held in three-dimensional space by electrostatic attractions and Van der Waal’s forces. The variable temperature magnetic studies reveal weak antiferromagnetic interaction between the two metal centers.

DNA/BSA binding, DNA cleavage and electrochemical properties of new multidentate copper(II) complexes

A new series of multidentate copper(II) complexes [Cu(L1−5)](ClO4) (1–5) were synthesized [where L1−5 represents [N-(salicylaldimine)-N′-[(2-formyl-4-bromo-6-(4-methylpiperazine-1-yl)methyl)phenol] diamines; diamines viz., L1-1,2-diamino ethane, L2-1,3-diamino propane, L3-1,2-diamino benzene, L4-2-aminobenzylamine and L5-1,8-diamino naphthalene] and characterized by elemental analysis and spectroscopic methods. The single crystal X-ray diffraction analysis shows that the multidentate copper(II) complex (1), in which the copper atom exhibits a distorted square planar geometry, coordinates with two phenolic oxygen atoms and two ethylenediamine nitrogen atoms. The assembly of molecular constituents exhibits an interesting supramolecular architecture through the C–H⋯O interactions forming two dimensional supramolecular sheets, and extending infinitely along the (1 0 0) plane. The channels thus formed are large enough to hold the guest (solvent) molecules. Cyclic voltammograms of these copper(II) complexes exhibit one quasi reversible reduction wave in the cathodic region. The DNA/BSA binding, DNA cleavage, antimicrobial activity and MTT assay of these complexes were also investigated. The binding propensities of the complexes toward calf thymus DNA (CT DNA) were also investigated by UV and fluorescent spectroscopy, viscosity measurements and circular dichroism spectral studies. The binding constant (Kb) values are in the range of 0.84 × 104–3.0 × 104 M−1, and the apparent binding constants (Kapp) in the range from 1.9 × 106 M−1 to 4.2 × 106 M−1, as measured by UV and fluorescent methods. The cleavage activities are in the following order (5) > (4) > (3) > (1). The mechanistic investigation suggests that singlet oxygen plays a vital role in the cleavage process. All the copper(II) complexes (1–5) exhibit significant interaction with bovine serum albumin (BSA), and the results show that the binding mechanism is a static quenching process.