Nickel(II) and copper(II) complexes of tetradentate unsymmetrical Schiff base ligands: First evidence of positional isomerism in such system

The 1:1 condensation of 2,4-pentanedione and 1,2-diaminopropane gives a mixture two positional isomers of tridentate mono-condensed product 7-amino-4-methyl-5-aza-3-octene-2-one (HAMAO) and 7-amino-4,6-dimethyl-5-aza-3-heptene-2-one (HADAH) that reacted readily with Ni(II) thiocyanate to yield exclusively a single product, [Ni(AMAO)NCS] (1) in which the methyl substituent of diamine is ‘remote’ from the imino nitrogen. The mixture of terdentate ligands has been used for further condensation with pyridine-2-carboxaldehyde or 2-acetylpyridine to obtain the unsymmetrical tetradentate Schiff base ligands. The tetradentate ligands formed by the condensation of it and pyridine-2-carboxaldehyde readily yielded complexes with Cu(II) and Ni(II) (2 and 3, respectively). Crystal structure analysis shows that in 2 the condensation site of the diamine with 2,4-pentanedione is the same as in 1 but that in 3 is different (the methyl group of the diamine is located in the vicinity of 2,4-pentanedione), i.e., the tetradentate ligand is in two different isomeric forms in complexes 2 and 3. Another tetradentate ligand, obtained by the condensation of the tridentate ligands and 2-acetylpyridine yielded a Ni(II) complex (4) where the methyl group is in the vicinity of 2,4-pentanedione as in 3. The isomerization in the Ni(II) complexes has been studied by NMR spectroscopy.     

Metal complexes with unsymmetrical tetradentate schiff bases

A simple method for the synthesis of 1-amino-3-aza-4-methylhept-4-ene-6-one is presented. The dominant tautomeric form of the compound in CDCl₃ has been established. Using this compound eight (five new) unsymmetrical tetradentate Schiff bases and their nickel(II), palladium(II) and copper(II) complexes have been prepared and characterized by various physical techniques. Data for the complexes indicate that they are all of square-planar geometry. High resolution ¹H nmr studies, including lanthanide shift reagents on nickel and palladium chelates, allowed us to assign almost all proton resonances. Data for nickel(II) and palladium(II) chelates with 1-(2′-hydroxyphenyl)-1-phenyl-2,5-diaza-6-methylnona-1,6-diene-8-one are consistent with the ketoenamine structure of both the acetylacetone and hydroxybenzophenone portions of the molecules. Good resolved nitrogen hyperfine splitting was observed in the esr spectrum of the copper complex with the aforementioned ligand.     

A novel copper(II) complex with a pendant Schiff base: An unprecedented monodentate bonding mode of the potentially tridentate ligand

The 1:1 condensation of 1-benzoylacetone and 1,2-diaminopropane yields 6-amino-3-methyl-1-phenyl-4-azahept-2-en-1-one (HL). When copper(II) perchlorate is added to the methanolic solution of HL, followed by triethylamine in 1:2:1 molar ratio, an unusual copper(II) complex, [Cu(L)(HL)]ClO₄, is separated out where the deprotonated ligand, L, is coordinated in the usual chelating tridentate manner but HL is coordinated to Cu(II) only through the amine N, i.e. it acts as a pendant ligand. The complex is characterized by X-ray crystal structure analysis.     

Nickel(II) complexes of terdentate or symmetrical tetradentate Schiff bases: Evidence of the influence of the counter anions in the hydrolysis of the imine bond in Schiff base complexes

Two sets of ligands, set-1 and set-2, have been prepared by mixing 1,3-diaminopentane and carbonyl compounds (2-acetylpyridine or pyridine-2-carboxaldehyde) in 1:1 and 1:2 ratios, respectively, and employed for the synthesis of complexes with Ni(II) perchlorate, Ni(II) thiocyanate and Ni(II) chloride. Ni(II) perchlorate yields the complexes having general formula [NiL₂](ClO₄)₂(L = L¹ [N³-(1-pyridin-2-yl-ethylidene)-pentane-1,3-diamine] for complex 1 or L²[N³-pyridin-2-ylmethylene-pentane-1,3-diamine] for complex 2) in which the Schiff bases are monocondensed terdentate, whereas Ni(II) thiocyanate results in the formation of tetradentate Schiff base complexes, [NiL(SCN)₂] (L = L³[N,N′-bis-(1-pyridin-2-yl-ethylidine)-pentane-1,3-diamine] for complex 3 or L⁴ [N,N′-bis(pyridin-2-ylmethyline)-pentane-1,3-diamine] for complex 4) irrespective of the sets of ligands used. Complexes 5 {[NiL³(N₃)₂]} and 6 {[NiL⁴(N₃)₂]} are prepared by adding sodium azide to the methanol solution of complexes 1 and 2. Addition of Ni(II) chloride to the set-1 or set-2 ligands produces [Ni(pn)₂]Cl₂, 7, as the major product, where pn = 1,3-diaminopentane. Formation of the complexes has been explained by the activation of the imine bond by the counter anion and thereby favouring the hydrolysis of the Schiff base. All the complexes have been characterized by elemental analyses and spectral data. Single crystal X-ray diffraction studies confirm the structures of three representative members, 1, 4 and 7; all of them have distorted octahedral geometry around Ni(II). The bis-complex of terdentate ligands, 1, is the mer isomer, and complexes 4 and 7 possess trans geometry.     

Synthesis,Physico-Chemical investigations of Co(II), Ni(II) and Cu(II) complexes and their in vitro microbial,cytotoxic, DNA cleavage studies

A series of metal complexes of cobalt(II), nickel(II), and copper(II) have been synthesized with newly derived biologically active ligands. These ligands were synthesized by the condensation of 2-amino-4-phenyl-1,3-thiazole with 8-formyl-7-hydroxy- 4-methylcoumarin. The probable structure of the complexes has been proposed on the basis of analytical and spectroscopic data (IR, UV-Vis, ESR, FAB-mass, and thermoanalytical). Electrochemical study of the complexes is also reported. Elemental analysis of the complexes confined them to stoichiometry of the type ML₂.2H₂O [M = Co(II), Ni(II), and Cu(II)]. The Schiff base and its metal(II) complexes have been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Staphylococcus pyogenes, and Pseudomonas aeruginosa) and antifungal activities (Aspergillus niger, Aspergillus flavus, and Cladosporium) by the MIC method. The brine shrimp bioassay was carried out to study their in vitro cytotoxic properties, and also the Schiff base and its metal(II) complexes have been studied for DNA cleavage.     

Antibacterial and antifungal metal based triazole Schiff bases

A new series of four biologically active triazole derived Schiff base ligands (L¹–L⁴) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1–16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Synthesis, characterization and X-ray crystal structures of copper(II) and nickel(II) complexes with potentially hexadentate Schiff base ligands

Copper(II) and nickel(II) complexes of potentially N₂O₄ Schiff base ligands 2-({[2-(2-{2-[(1-{2-hydroxy-5-[2-phenyl-1-diazenyl]phenyl}methylidene)amino] phenoxy}ethoxy) phenyl]imino}methyl)4-[2-phenyl-1-diazenyl]phenol (H₂L¹) and 2-({[2-(4-{2-[(1-{2-hydroxy-5-[2-phenyl-1-diazenyl]phenyl}methylidene)amino] phenoxy}butoxy) phenyl]imino}methyl)4-[2-phenyl-1-diazenyl]phenol (H₂L²) prepared of 5-phenylazo salicylaldehyde (1) and two various diamines 2-[2-(2-aminophenoxy)ethoxy]aniline (2) and 2-[4-(2-aminophenoxy)butoxy]aniline (3) were synthesized and characterized by a variety of physico-chemical techniques. The single-crystal X-ray diffractions are reported for CuL¹ and NiL². The CuL¹ complex contains copper(II) in a near square-planar environment of N₂O₂ donors. The NiL² complex contains nickel(II) in a distorted octahedral geometry coordination of N₂O₄ donors. In all complexes, H₂L¹ behaves as a tetradentate and H₂L² acts as a hexadentate ligand. Cyclic voltammetry of copper(II) complexes indicate a quasi-reversible redox wave in the negative potential range.     

Syntheses, characterization and X-ray crystal structures of a mono- and a penta-nuclear nickel(II) complex with oximato Schiff base ligands

A mononuclear octahedral nickel(II) complex [Ni(HL¹)₂](SCN)₂ (1) and an unusual penta-nuclear complex [{(NiL²)(μ-SCN)}₄Ni(NCS)₂]·2CH₃CN (2) where HL¹ = 3-(2-aminoethylimino)butan-2-one oxime and HL² = 3-(hydroxyimino)butan-2-ylidene)amino)propylimino)butan-2-one oxime have been prepared and characterized by X-ray crystallography. The mono-condensed ligand, HL¹, was prepared by the 1:1 condensation of the 1,2-diaminoethane with diacetylmonoxime in methanol under high dilution. Complex 1 is found to be a mer isomer and the amine hydrogen atoms are involved in extensive hydrogen bonding with the thiocyanate anions. The dicondensed ligand, HL², was prepared by the 1:2 condensation of the 1,3-diaminopropane with diacetylmonoxime in methanol. The central nickel(II) in 2 is coordinated by six nitrogen atoms of six thiocyanate groups, four of which utilize their sulphur atoms to connect four NiL² moieties to form a penta-nuclear complex and it is unique in the sense that this is the first thiocyanato bridged penta-nuclear nickel(II) compound with Schiff base ligands.     

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2-14). The copper(II) complexes (2a-14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, ¹H and ¹³C NMR, AAS, UV-Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2-8 and 2a-8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G₂. Several derivatives were shown to be active comparable to that of cisplatin.     

Asymmetric catalysis 87. Enantioselective allylation of 1,5-dimethylbarbituric acid with Pd catalysts and new optically active PN ligands

The new PN ligands 5, 6 and 7 were prepared by Schiff base condensation of 2-formylphenyl(diphenyl)phosphine (1) with the optically active amines (R)-(−)-2-aminobutanol (2), (S)-(+)-2-aminobutanol (3) and (1S,2S)-2-amino- 1-phenyl-1,3-propanediol (4). These new ligands were used in the Pd catalysed allylation of 1,5-dimethylbarbituric acid with allylacetate. 5-Allyl-1,5-dimethylbarbituric acid was obtained with an optical induction of up to 12.7% ee.     

Copper(II) complexes of coumarin-derived Schiff bases and their anti-Candida activity

The condensation of 7-amino-4-methyl-coumarin (1) with a number of substituted salicylaldehydes yielded a series of Schiff bases (2a–2k) in good yields. Subsequent reaction of these ligands with copper(II) acetate yielded Cu(II) complexes (3a–3k) and some were characterised using X-ray crystallography. All of the free ligands and their metal complexes were tested for their anti-Candida activity. A number of the ligands and complexes exhibited anti-Candida activity comparable to that of the commercially available antifungal drugs, ketoconazole and Amphotericin B.     

Preparation, separation and characterisation of two regioisomers of a N-hydroxyalkylpyridylpyrazole ligand: A structural investigation of their coordination to Pd(II), Pt(II) and Zn(II) centres

The reaction of the β-diketone 1-phenyl-3-(pyridyn-2-yl)propane-1,3-dione, and the monosubstituted hydrazine 2-hydroxyethylhydrazine has been investigated. Two regioisomers were identified, 2-(3-phenyl-5-(pyridyn-2-yl)-1H-pyrazol-1-yl)ethanol (pzol.1) and 2-(5-phenyl-3-(pyridyn-2-yl)-1H-pyrazol-1-yl)ethanol (pzol.2) in 57:43 ratio. The separation of the regioisomers was done by silica column chromatography using ethyl acetate as eluent.Palladium(II) and platinum(II), [MCl₂(pzol.1)₂], [MCl₂(pzol.2)], and zinc(II), [ZnCl₂(pzol.1)], [ZnCl₂(pzol.2)] complexes were synthesised and characterised. The crystals and molecular structures of [PdCl₂(pzol.2)]·H₂O and [ZnCl₂(pzol.2)] were solved by X-ray diffraction, and consist of mononuclear complexes. In complex [PdCl₂(pzol.2)]·H₂O, the Pd(II) centre has a typical square planar geometry, with a slight tetrahedral distortion. The tetra-coordinated atom is bonded to one pyridinic nitrogen, one pyrazolic nitrogen and two chlorine atoms in cis disposition. The pzol.2 ligand acts as a bidentate chelate forming a five-membered metallocycle ring. In complex [ZnCl₂(pzol.2)], the Zn(II) is five-coordinated with two Zn-N bonds (Zn-N_pz and Zn-N_py), one Zn-OH bond and two Zn-Cl bonds. The coordination geometry is intermediate between a trigonal bipyramid and a square pyramid. In this complex, the ligand pzol.2 is tridentated and forms two metallocycle rings.     

Electroporation Enhances the Anticancer Effects of Novel Cu(II) and Fe(II) Complexes in Chemotherapy-Resistant Glioblastoma Cancer Cells

Schiff base ligand (L) was obtained by condensation reaction between 4-aminopyrimidin-2(1H)-one (cytosine) with 2-hydroxybenzaldehyde. The synthesized Schiff base was used for complexation with Cu(II) and Fe(II) ions used by a molar (2 : 1 mmol ration) in methanol solvent. The structural features of ligand, Cu(II), and Fe(II) metal complexes were determined by standard spectroscopic methods (FT-IR, elemental analysis, proton and carbon NMR spectra, UV/VIS, and mass spectroscopy, magnetic susceptibility, thermal analysis, and powder X-ray diffraction). The synthesized compounds (Schiff base and its metal complexes) were screened in terms of their anti-proliferative activities in U118 and T98G human glioblastoma cell lines alone or in combination with electroporation (EP). Moreover, the human HDF (human dermal fibroblast) cell lines was used to check the bio-compatibility of the compounds. Anti-proliferative activities of all compounds were ascertained using an MTT assay. The complexes exhibited a good anti-proliferative effect on U118 and T98G glioblastoma cell lines. In addition, these compounds had a negligible cytotoxic effect on the fibroblast HDF cell lines. The use of compounds in combination with EP significantly decreased the IC₅₀ values compared to the use of compounds alone (p<0.05). These results show that newly synthesized Cu(II) and Fe(II) complexes can be developed for use in the treatment of chemotherapy-resistant U118 and T98G glioblastoma cells and that treatment with lower doses can be provided when used in combination with EP.     

Antibacterial Schiff bases of oxalyl-hydrazine/diamide incorporating pyrrolyl and salicylyl moieties and of their zinc(II) complexes

Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms.     

Antibacterial cobalt(II), nickel(II) and zinc(II) complexes of nicotinic acid-derived Schiff-bases

Nicotinic acid derived Schiff bases and their transition metal [cobalt(II), nickel(II) and zinc(II)] complexes have been prepared and characterized by physical, spectral and analytical data. The Schiff bases act as deprotonated tridentate ligands for the complexation of the above mentioned metal ions. These complexes, possessing the general formula [M(L)2] [where M = Co(II), Ni(II) and Zn(II) and L = HL1-HL4] showed an octahedral geometry of the metal ions. For determining the effect of metal ions upon chelation, the Schiff bases and their complexes have been screened for antibacterial activity against several pathogenic strains of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The new metal derivatives reported here were more bactericidal against one or more bacterial species as compared to the uncomplexed Schiff bases.     

(E)-2-(2-(2-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione: Tautomery and coordination to copper(II)

(E)-2-(2-(2-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione (H₂L) was synthesized by azocoupling of diazonium salt of 2-hydroxyaniline with 1-phenylbutane-1,3-dione and characterized by IR, ¹H and ¹³C NMR spectroscopies and X-ray diffraction analysis. In solution, H₂L exists as a mixture of the enol-azo and hydrazone tautomeric forms and a decrease of temperature and of solvent polarity shifts the tautomeric balance to the hydrazone form. In the solid state, H₂L crystallizes from ethanol-water in the monohydrate hydrazone form, as shown by X-ray analysis. The dissociation constants of H₂L (pK₁ = 5.98 ± 0.04, pK₂ = 9.72 ± 0.03) and the stability constants of its copper(II) complex (log β₁ = 11.01 ± 0.07, log β₂ = 20.19 ± 0.08) were determined by the potentiometric method in aqueous-ethanol solution. The copper(II) complex [Cu₂(μ-L)₂]_n was isolated in the solid state and found by X-rays to be a coordination polymer of a binuclear core with a distorted square pyramidal metal coordination geometry.     

A systematic study of ligand intermolecular interactions in crystals of copper(II) complexes of bidentate guanidino derivatives

The synthesis and X-ray structures of copper(II) complexes of the bidentate ligands, N-(4-oxo-5,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-N′-phenylguanidino, 2-uanidinobenzimidazolo and N-(4-oxo-3-phenyl-1,3-diazaspiro[4.4]non-1-en-2-yl)guanidino, are reported. These complexes, which possess potential doublet (DA) or triplet (DAD) hydrogen bonding motifs, can form supramolecular structures based on synthons involving hydrogen bonding or phenyl embraces. The changes in supramolecular structure resulting from small changes in ligand structure, as well as from the use of different solvents for their crystallisation, are examined. The structures adopted are compared with others reported previously for complexes of related ligands.     

Unsymmetrical tetradentate ligand complexes of copper(II) and nickel(II) with N3O donor sets and ethylenediamine bridges

Novel non-symmetrical tetradentate Schiff base complexes with N₃O donor sites have been obtained using the ‘half-unit’ 7-amino-4-methyl-5-aza-hept-3-ene-2-one (AEH). Two reaction pathways have been used: (i) preparation of the free ligand which is then reacted with the desired metal salt, and (ii) template synthesis without isolation of the free ligand. The so prepared nickel and copper complexes have been characterized (infrared, visible, EPR and NMR spectroscopies).     

Antibacterial Co(II), Cu(II), Ni(II) and Zn(II) Complexes of Thiadiazole Derived Furanyl,Thiophenyl and Pyrrolyl Schiff Bases

2-Amino-1,3,4-thiadiazole undergoes a condensation reaction with furane-, thiophene- and pyrrole-2-carboxaldehyde to form tridentate NNO, NNS and NNN donor Schiff bases. These Schiff bases were further used to obtain complexes of the type [M(L) 2] X, where M=Co(II), Cu(II), Ni(II) or Zn(II), L=L 1, L 2 or L 3 and X=Cl 2. The new compounds described here have been characterized by their physical, spectral and analytical data, and have been screened for antibacterial activity against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of the Schiff bases increased upon chelation/complexation in comparison to the uncomplexed Schiff bases against the tested bacterial species thus, opening new approaches to find new ways in the fight against antibiotic-resistant strains.     

Antibacterial Schiff Bases of Oxalyl-hydrazine/diamide Incorporating Pyrrolyl and Salicylyl Moieties and of Their Zinc(II) Complexes

Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms.