Synthesis,DNA binding,and antimicrobial studies of novel metal complexes containing a pyrazolone derivative Schiff base

A novel series of Co(II), Ni(II), Cu(II), Zn(II), and VO(IV) complexes has been synthesized from the Schiff base derived from 4-[(3,4-dimethoxybenzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one and 1,2-diaminobenzene. Structural features were determined by analytical and spectral techniques. Binding of synthesized complexes with calf thymus DNA (CT DNA) was studied by spectroscopic methods and viscosity measurements. Experimental results indicate that the complexes are able to form adducts with DNA and to distort the double helix by changing the base stacking. Lower DNA affinity of the VO(IV) complex is caused by the change of coordination geometry by the vanadyl ion resulting in a somewhat unfavorable configuration for the DNA binding. Oxidative DNA cleavage activities of the complexes were studied with supercoiled (SC) pUC19 DNA using gel electrophoresis; the mechanism studies revealed that the hydroxyl radical is likely to be the reactive species responsible for the cleavage of pUC19 DNA by the synthesized complexes. The in vitro antimicrobial screening effects of the investigated compounds were monitored by the disc diffusion method. The synthesized Schiff base complexes exhibit higher antimicrobial activity than the respective free Schiff base.     

Structure of a copper-mediated base pair in DNA.

Stable and selective DNA base pairing by metal coordination was recently demonstrated with nucleotides containing complementary pyridine-2,6-dicarboxylate (Dipic) and pyridine (Py) bases (Meggers, E.; Holland, P. L.; Tolman; W. B.; Romesberg, F. E.; Schultz, P. G. J. Am. Chem. Soc. 2000, 122, 10714-10715). To understand the structural consequences of introducing this novel base pair into DNA we have solved the crystal structure of a duplex containing the metallo-base pair. The structure shows that the bases pair as designed, but in a Z-DNA conformation. The structure also provides a structural explanation for the B- to Z-DNA transition in this duplex. Further solution studies demonstrate that the metallo-base pair is compatible with Z- or B-DNA conformations, depending on the duplex sequence.     

Solution structure of a DNA duplex containing a biphenyl pair

Hydrogen-bonding and stacking interactions between nucleobases are considered to be the major noncovalent interactions that stabilize the DNA and RNA double helices. In recent work we found that one or multiple biphenyl pairs, devoid of any potential for hydrogen bond formation, can be introduced into a DNA double helix without loss of duplex stability. We hypothesized that interstrand stacking interactions of the biphenyl residues maintain duplex stability. Here we present an NMR structure of the decamer duplex d(GTGACXGCAG) d(CTGCYGTCAC) that contains one such X/Y biaryl pair. X represents a 3',5'-dinitrobiphenyl- and Y a 3',4'-dimethoxybiphenyl C-nucleoside unit. The experimentally determined solution structure shows a B-DNA duplex with a slight kink at the site of modification. The biphenyl groups are intercalated side by side as a pair between the natural base pairs and are stacked head to tail in van der Waals contact with each other. The first phenyl rings of the biphenyl units each show tight intrastrand stacking to their natural base neighbors on the 3'-side, thus strongly favoring one of two possible interstrand intercalation structures. In order to accommodate the biphenyl units in the duplex the helical pitch is widened while the helical twist at the site of modification is reduced. Interestingly, the biphenyl rings are not static in the duplex but are in dynamic motion even at 294 K.     

DNA deformability at the base pair level

A complete set of harmonic force constants describing the DNA deformation energetics at the base pair level was obtained using unrestrained atomic-resolution molecular dynamics simulations of selected duplex oligonucleotides and subsequent analysis of structural fluctuations from the simulated trajectories. The deformation was described by the six base pair conformational parameters (buckle, propeller, opening, shear, stretch, stagger). The results for 13 AT pairs and 11 GC pairs in different sequence contexts suggest that buckle and propeller are very flexible (more than roll in TA dinucleotide steps), while stretch is exceptionally stiff. Only stretch and opening stiffness were found to depend unambiguously on the base pair identity (AT vs GC). The relationship of the results to a simple plates-and-springs model of base-base interactions is discussed.     

Efficient incorporation of a copper hydroxypyridone base pair in DNA

Recently, we reported the first artificial nucleoside for alternative DNA base pairing through metal complexation (J. Org. Chem. 1999, 64, 5002-5003). In this regard, we report here the synthesis of a hydroxypyridone-bearing nucleoside and the incorporation of a neutral Cu(2+)-mediated base pair of hydroxypyridone nucleobases (H-Cu-H) in a DNA duplex. When the hydroxypyridone bases are incorporated into the middle of a 15 nucleotide duplex, the duplex displays high thermal stabilization in the presence of equimolar Cu(2+) ions in comparison with a duplex containing an A-T pair in place of the H-H pair. Monitoring temperature dependence of UV-absorption changes verified that a Cu(2+)-mediated base pair is stoichiometrically formed inside the duplex and dissociates upon thermal denaturation at elevated temperature. In addition, EPR and CD studies suggested that the radical site of a Cu(2+) center is formed within the right-handed double-strand structure of the oligonucleotide. The present strategy could be developed for controlled and periodic spacing of neutral metallobase pairs along the helix axis of DNA.     

Drug-induced stabilisation of a mismatched C-T base pair in a DNA hairpin

We have shown that a key feature of drug binding, namely specific G-C base pair recognition at a 5'-TG step, can induce a number of novel structural features when an extrahelical base is inserted in close proximity to the drug binding site; we have clearly demonstrated the formation of a stabilised C-T mismatched base pair at a non-terminal site.     

Antimicrobial polyesters containing Schiff-base metal complexes

Antimicrobial polyesters containing Schiff-base metal complexes (PSB) were prepared by polycondensation of adipoyl chloride with chelated Schiff-base diol {bis-(2-hydroxy-5-methylol-benzaldehyde)ethylenediamine}. All the metal chelated polyesters were characterized by elemental analysis, UV–Visible, FTIR, ¹³C and ¹H NMR spectra and thermogravimetric analysis. The analytical data of the polyesters agreed with 1 : 1 molar ratio (metal chelated diols to adipoyl chloride). The geometry of the chelated polyesters was confirmed by magnetic susceptibility measurements and UV–Visible spectroscopy. The thermal behaviors of these chelated polyesters were studied by TGA (Thermogravimetric analyzer) in a nitrogen atmosphere up to 800°C. The TGA results revealed that the Cu(II) chelated polyester has better heat resistant properties than the other polyesters. The antimicrobial properties of these polyesters were investigated with agar diffusion methods against selected microorganisms Bacillus subtelillis, Bacillus megaterium, Streptococcus aureus, Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, Shigella boydii and for antifungal activity against Candida albicans, Trichophyton longifusus, Aspergillus flavus, Aspergillus niger, Fusarium solani, Microsporum canis, Puccinia graminis. The antimicrobial activity of these polyesters was higher than standard drugs Kanamycin and Miconazol.     

Synthesis,characterization, and biological evaluation of new polyester containing Schiff base metal complexes

The production of new biocidal polyester Schiff base metal complexes [PESB–M(II)] via polycondensation reaction between chelated Schiff base diol and adipoyl chloride is reported. The resulting polyesters were characterized by physico-chemical and spectroscopic methods. The analytical data of all the synthesized polyesters were found to be in good agreement with 1:1 molar ratio of chelated Schiff base diol to adipoyl chloride. Thermogravimetric analyses of synthesized polyesters were studied by TG in nitrogen atmosphere up to 1073 K and results indicate that Cu(II) polyester complex exhibited better heat resistant properties than the other polyesters complexes. Magnetic moment and UV–visible spectra were examined to explain the structure of all the polyesters which reveled that Mn(II), Co(II), Ni(II) have octahedral geometry while Cu(II) possess a distorted octahedral geometry. These newly developed polyesters were also tested for their antibacterial activity against several bacteria and fungi. Among all the tested compounds PESB–Cu(II) possess the highest bactericidal and fungicidal activity.     

Transition metal complexes of heterocyclic Schiff base

Metal complexes of Schiff base derived from 2-furancarboxaldehyde and 2-aminobenzoic acid (HL) are reported and characterized based on elemental analyses, IR, ¹H NMR, UV-Vis, solid reflectance, magnetic moment, molar conductance and thermal analysis. The ligand dissociation as well as the metal-ligand stability constants have been calculated pH-metrically at 25°C and ionic strength μ=0.1 (1 M NaCl). The complexes are found to have the formulae [M(HL)₂](X)_n·yH₂O (where M=Fe(III) (X=Cl, n=3, y=4), Co(II) (X=Cl, n=y=2), Ni(II) (X=Cl, n=y=2), Cu(II) (X=Cl, n=y=2) and Zn(II) (X=AcO, n=y=2)) and [UO₂(L)₂]·2H₂O. The thermal behaviour of these chelates is studied and the activation thermodynamic parameters are calculated using Coats-Redfern method. The ligand and its metal complexes show a biological activity against some bacterial species.     

Schiff碱金属配合物的研究进展

简要介绍了Schiff碱金属配合物的发展历程、缩合反应机理、合成方法及其在材料、医药、催化等领域的研究、应用概况,并展望了其发展、应用前景.     

Redox, thermodynamic and spectroscopic of some transition metal complexes containing heterocyclic Schiff base ligands

Complexes of two series of Schiff base ligands, H₂L_a and H₂L_bderived from the reaction of 2,6-diacetyl pyridine with semicarbazide, H₂L_a and thiosemicarbazide, H₂L_b, with the metal ions, Co(II), Ni(II), Cu(II), VO(IV) and UO₂(VI) have been prepared. The ligands are characterized by elemental analysis, IR, UV–vis and ¹H NMR. The structures of the complexes are investigated with the IR, UV–vis, X-band ESR spectra, ¹H NMR and thermal gravimetric analysis as well as conductivity and magnetic moment measurements. The IR-spectra reveal the presence of variable modes of chelation for the investigated ligands. A variety of binuclear or mononuclear complexes were obtained with the two ligands in tri-, tetra or pentadentate forms. The bonding sites are the pyridine nitrogen, two azomethine nitrogen atoms and ketonic oxygen in case of H₂L_a or sulphur atoms in case of H₂L_b. The Coats–Redfern equation has been used to calculate the kinetic and thermodynamic parameters for the different thermal decomposition steps of some complexes. Cyclic voltammograms of Co(II) and Ni(II) show quasi-reversible peaks. The redox properties and the nature of the electro-active species of the complexes have been characterized.     

A comparative DFT study of some N-based aromatic ligand metal complexes as anticancer agents and analysis of their mode of interaction with DNA base pair

Metal complexed anticancer agents interact with DNA nucleobase pairs (AT and GC) through different types of binding mode such as intercalation, groove binding, covalent binding, etc. Minor and major groove binding mechanism of DNA base pair is the key factor for all kinds of anticancer agent; as metal complexes have a great affinity to bind with DNA nucleobase either through minor or major groove. Ligands in metal complexes also play a vital role during the interaction with DNA base pairs; these ligands directly interact with DNA through different interacting modes. Generally, anticancer agents with less sterically hindered N-based aromatic and planar ligands are the key component for DNA binding; as the structure of such ligands are quite compatible for following intercalation and groove binding mechanism. Since, the experimental investigation for drug-DNA nucleobase complexes are extremely complicated, therefore; quantum mechanical calculations might be very helpful for computing the actual interactions in drug-DNA complexes. Quantum mechanical approaches such as density functional theory (DFT) might be a very important and useful tool to investigate the actual mode of interaction of metal complexed antitumor agents with DNA nucleobase. Herein, we have taken some metal complexes with N-based aromatic ligands as antitumor agents to investigate the proper mode of interaction between drug-DNA complexes.     

The elusive atomic rationale for DNA base pair stability

A systematic analysis of the electrostatic interaction between 27 natural DNA base pairs was carried out, based on ab initio correlated wave functions and the topology of the electron density. Using high rank multipole moments we show that the atomic partitioning of the interaction energy contains many substantial contributions between distant atoms. Profiles of cumulative energy versus internuclear distance show large fluctuations and provide an electrostatic fingerprint of the partitioning of interaction energy in a complex. A quantified comparison between each pair of energy profiles, one for each base pair, makes clear that there is no correlation between the total base pair interaction energy and the shape of the profile. In other words, base pairs with similar interaction energy are not stable for the same reasons in terms of atomic partitioning. In summary, simple rules to rationalize the pattern of energetic stability of naturally occurring base pairs in terms of subsets of atoms are elusive. Our work cautions against inappropriate use of Jorgensen's secondary interaction hypothesis.     

A pyrimidine-like nickel(II) DNA base pair

4-(2'-Pyridyl)-pyrimidinone deoxyriboside is synthesized and characterized as a DNA metallo base-pair; this novel nucleoside forms a self-pair in the presence of Ni(II) and stabilizes double helical DNA to the same extent as a G.C pair.     

Synthesis of transition metal complexes containing a Schiff base ligand derived from 1,10-phenanthroline-2,9-dicarboxaldehyde and 2-aminobenzenethiol

The synthesis of a new Schiff base containing 1,10-phenanthroline-2,9-dicarboxaldehyde and 2-aminobenzenethiol subunits is described. The reaction of 1,10-phenanthroline-2,9-dicarboxaldehyde with 2-aminobenzenethiol leads to the isolation of 2,9-bis(2-benzothiazolinyl)-1,10-phenanthroline (I) which undergoes rearrangement when reacted with cobalt, nickel, copper or zinc ions to produce complexes of the tautomeric Schiff base 2,9-bis[2-(2-mercaptophenyl)-2-azaethene]-1,10-phenanthroline (L). The [Cu(L)ClO₄][ClO₄] and [M(L)X₂] complexes (where M = Co(II), Ni(II) and Zn(II) and X = Br) were characterized by physical and spectroscopic measurements which indicated that the ligand is acting probably as a tetradentate N₄ chelating agent.     

Designing,structural elucidation,comparison of DNA cleavage,and antibacterial activity of metal(II) complexes containing tetradentate Schiff base

Macrocyclic complexes of Cu(II), Ni(II), Co(II), and Zn(II)of a tetradentate Schiff base ligand derived from 3-benzalideneacetoacetanilide and N-(2-aminoethyl)-1,3-ropanediamine were synthesized. The nature of the complexes and the geometry have been inferred from their microanalytical data, magnetic susceptibility measurements, IR, UV-Vis, ¹H NMR, ESR, and mass spectral techniques. The low electrical conductance of the complexes supports the neutral nature. Monomeric nature of the complexes is assessed from their magnetic susceptibility values.The in vitro biological screening effects of the investigated compounds were tested against the bacteria E. coli, S. aureus, S. typhi, and K. pneumoniae by the well diffusion method using agar nutrient as the medium. A comparative study of minimum inhibitory concentration (MIC) values of the Schiff base and its complexes indicate that the metal complexes exhibit higher antibacterial activity than the free ligand and the control (streptomycin). The cyclic voltammetry method was used to probe the interaction of a Cu(II) complex with pUC18 DNA. Information of the binding ratio and intercalation mode can be obtained from its electrochemical data. Cyclic voltammetric measurements showed that the Cu(II) complex undergoes a reversible reduction at biologically accessible potentials. From the study, it is understood that the copper complex prefers to bind with DNA in Cu(II) rather than Cu(I) oxidation state. The DNA cleavage ability of the complexes was monitored by gel electrophoresis using supercoiled pUC18 DNA in tris-HCl buffer. The text was submitted by the authors in English     

Polyoxometalate tri-supported transition metal complexes containing mixed-valent transition metal ions

Three compounds, [AsMo₈V₆O₄₂][Cu(2,2?-bpy)₂]₂[Cu(2,2?-bpy)]·4H₂O (1), [PMo₈V₆O₄₂][Cu(2,2?-bpy)₂]₂[Cu(2,2?-bpy)]·3H₂O (2) and [PMo₈V₆O₄₂][Cu(2,2?-bpy)₂]₂[Cu(2,2?-bpy)]·3.5H₂O (3), have been synthesized under hydrothermal conditions and characterized by IR, UV–vis, XRD, TG, elemental analysis, and X-ray diffraction analysis. Single-crystal X-ray structure analysis reveals that 1 and 2 are isostructural and isomorphous, whereas 2 and 3 are polymorphs. Polymorphs of 1 have not been synthesized yet. The mixed-valent transition metal ion in 1–3 has been further confirmed by TG analyses. Catalytic properties of 1 and 2 have also been studied.     

Transition metal complexes of bidentate Schiff base ligands

New Schiff base ligands derived from vanillin (HL¹), 4-dimethylaminobenzaldehyde (HL²) and 3,5-di-t-butyl-4-hydroxybenzaldehyde (HL³) with N-(pyridyl)-3-methoxy-4-hydroxy-5-aminobenzylamine (2) and their copper(II), cobalt(II), nickel(II), oxovanadium(IV) and zinc(II) transition metal complexes have been synthesized and characterized by elemental analyses, electronic and i.r. spectra, molar conductance data and by 1H and ¹³C n.m.r. spectra. The results indicate that the ligands coordinate through azomethine nitrogen and phenolic oxygen to the metal ions. In like manner, it was found that the pyridine and amine nitrogen atoms are not coordinated to the metal ions. The ¹H and ¹³C n.m.r. spectral data confirmed the suggested structure for the Schiff base ligands, and the mass spectra results confirmed the proposed structure of the ligands. The antimicrobial activity properties of the ligands and their metal complexes have been studied.