Synthesis, characterization, DNA binding and cleavage properties and anticancer studies of ruthenium(III) Schiff base complexes

A Schiff base (HL) has been synthesized and characterized by physico-chemical, spectroscopic and X-ray crystallography studies. Three of its Ru(III) complexes were synthesized and characterized by analytical and spectroscopic studies. The DNA binding properties of HL and its Ru(III) complexes have been investigated by electronic absorption spectroscopy. Also, HL and its Ru(III) complex [RuCl₂(AsPh₃)L] were tested for DNA cleavage properties. The results showed that the complex cleaves DNA more rapidly than the free ligand. Further, an in vitro study of the cytotoxicity of HL and the complex [RuCl₂(AsPh₃)L] was carried out.     

Synthesis,characterization, DNA binding,DNA cleavage,antioxidant and in vitro cytotoxicity studies of ruthenium(II) complexes containing hydrazone ligands

The synthesis, spectral characterization, and biological studies of ruthenium(II) hydrazone complexes [RuCl(CO)(PPh₃)₂L] (where L = hydrazone ligands) have been carried out. The hydrazones are monobasic bidentate ligands with O and N as the donors and are preferably found in the enol form in all the complexes. The molecular structure of the ligands HL¹, HL²_, and HL³ were determined by single-crystal X-ray diffraction. The DNA binding studies of the ligands and complexes were carried out by absorption spectroscopic and viscosity measurements. The results revealed that the ligands and complexes bind to DNA via intercalation. The DNA cleavage activity of the complexes, evaluated by gel electrophoresis assay, revealed that the complexes are good DNA cleaving agents. The antioxidant properties of the complexes were evaluated against DPPH, OH, and NO radicals, which showed that the complexes have strong radical-scavenging. Further, the in vitro cytotoxic effect of the complexes examined on HeLa and MCF-7 cancer cell lines showed that the complexes exhibited significant anticancer activity.     

DNA binding,cleavage, and cytotoxicity of binuclear phenolate nickel(II) complexes

Three binuclear phenolate complexes, [Ni₂(L¹)₂(OAc)](BPh₄)·DMF (1), [Ni₂(L²)₂(OAc)](BPh₄) (2), and [Ni₂(L³)₂(OAc)](OH)·3H₂O (3), where L¹ = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-methyl-phenol, L² = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-methoxy-phenol, and L³ = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-tert-butyl-phenol), have been synthesized. Single-crystal diffraction reveals that all the metal atoms are in a distorted octahedral geometry. The interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated by UV–vis absorption, fluorescence emission, and circular dichroism spectroscopy and viscosity measurements. Furthermore, DNA cleavage mechanism shows that the complexes may be capable to promote DNA cleavage through oxidative DNA damage pathway, which is indicative of the involvement of hydroxyl radical, singlet oxygen, or singlet oxygen-like entity in the cleavage process. Cytotoxicity studies on the Hela and MCF-7 cancer cell lines show that complexes 1–3 exhibit excellent activity toward the tested tumor cell lines with respect to the standard drug carboplatin, revealing that they have the potential to act as effective metal-based anticancer drugs.     

Synthesis, characterization, DNA binding and cleavage studies of chiral Ru(II) salen complexes

Interaction of chiral Ru(II) salen complexes (S)-1 and (R)-1 with Calf Thymus DNA (CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements, CD measurements, thermal denaturation study and cleavage studies by agarose gel electrophoresis. The DNA binding affinity of (S)-1 (6.25 × 10³ M⁻¹) was found to be greater than (R)-1 (3.0 × 10³ M⁻¹). The antimicrobial studies of these complexes on five different gram (+)/(−) bacteria and three different fungal organisms showed selective inhibition of the growth of gram (+) bacteria and were not affective against gram (−) and fungal organisms. Further, the (S)-1 enantiomer inhibited the growth of organisms to a greater extent as compared to (R)-1 enantiomer.     

Synthesis, characterization, DNA binding and cytotoxicity studies of moxifloxacinato complexes

Five metal complexes of the third-generation quinolone antibacterial agent moxifloxacin with Cu(II), Fe(III), Mn(II), Ni(II) and VO(II) have been synthesized and characterized by physicochemical and spectroscopic techniques. In these complexes, moxifloxacin acts as a bidentate deprotonated ligand bound to the metal through ketone and carboxylate oxygens. The interactions between the metal complexes and calf thymus DNA have been studied by UV?CVis, circular dichroism and cyclic voltammetry. Fluorescence competitive binding studies with ethidium bromide (EB) demonstrate the ability of the complexes to displace the EB bound to DNA. The cytotoxicities of the complexes have been evaluated on A549 cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method. [Cu(MFL)₂(H₂O)₂] shows the highest anticancer potency. The apoptosis-inducing activity was assessed by acridine orange/ethidium bromide staining assay.     

Phosphoester binding,DNA binding,DNA cleavage and in vitro cytotoxicity studies of simple heteroleptic copper(II) complexes with bidentate ligands

Abstract

Two mononuclear heteroleptic copper complexes, [Cu(±trans-dach)(bpy)](ClO₄)₂ 1a and [Cu(±trans-dach)(phen)](ClO₄)₂ 2a [dach?=?1,2-diaminocyclohexane, bpy?=?2,2′-bipyridine and phen?=?1,10-phenanthroline], were synthesized and analyzed by CHN analysis, electronic absorption, FT-IR spectroscopy, EPR, and SXRD. The molecular structures of 1a and 2a showed octahedral geometry around Cu(II). Both complexes interacted with phosphoesters and DNA. Their binding affinities with diphenylphosphate, di n-butylphosphate, trimethylphosphate, and triphenylphosphate were studied by UV–vis spectroscopy. For understanding the stereochemical role of dach ligand toward DNA interaction, enantiopure DACH complexes [Cu(R,R-trans-dach(bpy)](ClO₄)₂ 1b, [Cu(S,S-trans-dach)(bpy)](ClO₄)₂ 1c, [Cu(cis-dach)(bpy)](ClO₄)₂ 1d, [Cu(R,R-trans-dach)(phen)](ClO₄)₂ 2b, [Cu(S,S-trans-dach)(phen)](ClO₄)₂ 2c, and [Cu(cis-dach)(phen)](ClO₄)₂ 2d were synthesized and analyzed. All complexes interacted with calf thymus-DNA (CT-DNA) as studied by UV–vis spectroscopy. The nature of binding to CT-DNA was groove/electrostatic as supported by circular dichroism, cyclic voltammetry, and docking studies. Complexes were able to cleave plasmid DNA at 12.5 µM (1a–d) and 6 µM (2a–d), where 2d showed 64% Form II and 36% Form III. The in vitro cytotoxic studies of two different cancer cell lines showed inhibition with low IC₅₀ value in comparison to reference control (cisplatin). These complexes are efficient in inducing apoptosis in cancer cells, making them viable for potent anticancer activity.     

Synthesis,crystal structures,DNA/bovine serum albumin binding,DNA cleavage and cytotoxicity of five mononuclear zinc(II) complexes

Five new mononuclear zinc(II) complexes containing ligands with extended planar phenanthroline moieties (dipyrido‐[3,2‐a:2′,3′‐c]phenazine (dppz) or dipyrido[3,2‐d:2′,3′‐f] quinoxaline (dpq)), namely [Zn(dppz)(acac)₂]⋅CH₃OH ( 1 ), [Zn(dppz)(dbm)(OAc)] ( 2 ), [Zn(dpq)(dbm) (OAc)] 1.5H₂O ( 3 ), [Zn(dpq)(tfnb)(OAc)] ( 4 ) and [Zn(dpq)(tfnb)₂] ( 5 ), where acac = acetylacetonate, tfnb = benzoyltrifluoroacetone and dbm = dibenzoylmethane, were synthesized and structurally characterized. The binding ability of complexes 1 – 5 with calf thymus DNA was investigated by spectroscopic titration methods and viscosity measurements. Results indicate that all complexes bind to calf thymus DNA via intercalative mode, and the DNA binding affinities of dppz complexes 1 and 2 are apparently stronger than those of dpq complexes 3 – 5 . DNA photocleavage experiments reveal that these complexes are efficient DNA cleaving agents and they are more active in UV‐A (365 nm) than in visible light. In particular, the in vitro cytotoxicity of the complexes for human cancer cell line A549 demonstrates that the five compounds have anticancer activity with low IC₅₀ values. Meanwhile, interaction of the complexes with bovine serum albumin investigated using UV–visible and fluorescence methods indicates that all complexes can quench the intrinsic fluorescence of bovine serum albumin in a static quenching process.     

Metal(II) complexes of bioactive aminonaphthoquinone-based ligand: synthesis,characterization and BSA binding,DNA binding/cleavage,and cytotoxicity studies

An aminonaphthoquinone ligand, L, and its metal complexes of general formula [MLCl₂] {M = Co(II), Ni(II), Cu(II) and Zn(II)} have been synthesized and characterized by analytical and spectral techniques. Tetrahedral geometry has been assigned to Ni(II) and Zn(II) complexes and square planar geometry to Co(II) and Cu(II) complexes on the basis of electronic spectral and magnetic susceptibility data. The binding of complexes with bovine serum albumin (BSA) is relatively stronger than that of free ligand and alters the conformation of the protein molecule. Interaction of these complexes with CT-DNA has been investigated using UV-Vis and fluorescence quenching experiments, which show that the complexes bind strongly to DNA through intercalative mode of binding (K_app 10⁵ M^?1). Molecular docking studies reiterate the mode of binding of these compounds with DNA, proposed by spectral studies. The ligand and its complexes cleave plasmid DNA pUC18 to nicked (Form II) and linear (Form III) forms in the presence of H₂O₂ oxidant. The in vitro cytotoxicity screening shows that Cu(II) complex is more potent against MCF-7 cells and Zn(II) complex exhibits marked cytotoxicity against A-549 cells equal to that of cisplatin. Cell imaging studies suggested apoptosis mode of cell death in these two chosen cell lines.     

Ternary Cu(II) complexes: synthesis,structural elucidation,and biological studies (DNA binding,cleavage, antibacterial,cytotoxicity)

Research on Chemical Intermediates - The present work focused on the assembly of 2-((2-(4-chlorophenylamino)phenylimino)methyl)-6-methoxyphenol as primary ligand (VBL) and bidentate nitrogen...     

Synthesis,characterization, DNA binding,photo-induced DNA cleavage,and antimicrobial activity of metal complexes of a Schiff base derived from bis(3-aminophenyl)malonamide

The peptide linkage Schiff base (H₂L) and its complexes have been synthesized and fully characterized by elemental analysis, UV–Vis, FTIR, ¹H-NMR, ¹³C-NMR, EPR, and FAB-mass spectra. The stoichiometry of the complexes is [ML] (where M = Cu(II), Co(II), Ni(II), Zn(II), and VO(IV)). All the complexes exhibit square-planar geometry except the vanadyl complex which has square-pyramidal geometry. Interactions of the complexes and free ligand with double-stranded calf thymus DNA (CT-DNA) are studied by UV-spectrophotometric, electrochemical, and viscosity measurements. The data suggest that all the complexes form adducts with DNA and distort the double helix by changing the base stacking. Vanadyl complex forms a weaker adduct to CT-DNA than other complexes, probably due to the square-pyramidal geometry. CT-DNA induces extensive distortion in the planarity of vanadyl complex as EPR spectral calculations reveal. The intrinsic binding constants (K _b) of [ZnL], [CuL], [CoL], and [NiL] are 1.1 × 10⁵, 1.4 × 10⁵, 0.8 × 10⁵, and 0.6 × 10⁵ M^?1, respectively. Photo-induced DNA cleavage indicates that all complexes cleave DNA effectively. Control DNA cleavage experiments using pUC19 supercoiled (SC) DNA and minor groove binder distamycin suggest major groove binding for the synthesized complexes. The antimicrobial results indicate that the complexes inhibit the growth of bacteria and fungi more than the free ligand.     

Organoruthenium(II) thiosemicarbazone complexes: synthesis, spectral characterization, DNA binding and DNA cleavage studies

A series of new ruthenium(II) complexes were synthesized with Schiff bases derived from salicylaldehyde / o-hydroxyacetophenone/ o-vanillin / 2-hydroxy-1-naphthaldehyde with thiosemicarbazide and acetyl furan. They are characterized by elemental analysis, IR, electronic, ¹H NMR, ¹³C NMR and mass spectral studies. The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). Four of these complexes were tested for its binding with CT-DNA using absorption spectroscopic studies and two of these complexes exhibit efficient DNA cleavage activity.      

Synthesis,DNA-binding,cytotoxicity, and cleavage studies of unsymmetrical oxovanadium complexes

An unsymmetrical oxovanadium complex [VO(SAA)(phen)] (1) (SAA?=?salicylidene anthranilic acid, phen?=?phenanthroline) and its derivative [VO(MOSAA)(phen)] (2) (MOSAA?=?2-hydroxy-4-methoxysalicylidene anthranilic) have been synthesized and characterized by elemental analysis, UV-Vis, ES-MS, IR, and ¹H NMR. The interaction of these two complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence spectra, viscosity measurements, and thermal denaturation. Their photocleavage reactions with pBR322 supercoiled plasmid DNA were investigated by gel electrophoresis. The cytotoxicity of these two complexes against myeloma cell (Ag8.653) and gliomas cell (U251) have been assessed by MTT assay. The results show that both 1 and 2 bind to CT-DNA in classical intercalation, and the DNA-binding affinity of 1 is larger than that of 2. These complexes enhance the oxidative cleavage of supercoiled pBR322 DNA and both complexes have cytotoxic activities against Ag8.653 and U251 cell lines. Complex 1 has more potent inhibitory effect against the two cell lines than 2.     

Synthesis,characterization, catalytic,antimicrobial, DNA binding and cleavage studies of N-functionalized tetraazamacrocyclic binuclear copper(II) complexes

A series of binuclear copper(II) complexes of N-functionalized cyclam derivatives has been prepared by the Schiff base condensation of 1,8-[bis(3-formyl-2-hydroxy-5-methyl)benzyl]-l,4,8,11-tetraazacyclo-tetradecane (PC-a), 1,8-[bis(3-formyl-2-hydroxy-5-bromo)benzyl]-l,4,8,11-tetraazacyclo-tetradecane (PC-b) with appropriate aliphatic diamines, and copper(II) perchlorate. All the complexes were characterized by elemental, FT-IR, UV–Vis, ESI and ESR spectral analysis. The room temperature magnetic moment studies depicts the presence of an antiferromagnetic interaction in the binuclear complexes, which is also observed from the broad ESR spectra with a g value of 2.10–2.11. Variable-temperature magnetic susceptibility study of the complex [Cu₂L^2a](ClO₄)₂ shows that the calculated ?2J value is 219 cm^?1, which conveys a spin–spin interaction between the two copper(II) ions. The catechol oxidation and hydrolysis of 4-nitrophenylphosphate were carried out by using the complexes as a catalyst. All the above metal complexes were screened for antimicrobial and human pathogenic fungal activity. The binding of the complexes to calf thymus DNA (CT-DNA) has been investigated with UV–Vis and fluorescence spectroscopy. All complexes display significant cleavage property of circular plasmid pBR322 DNA into linear form. Spectral, electrochemical, magnetic and catalytic studies support the distortion of the copper ion geometry that arises as the macrocyclic ring size increases.     

DNA binding, nuclease activity and cytotoxicity studies of Cu(II) complexes of tridentate ligands

Cu(II) complexes of three tridentate ligands, L(1), L(2) and L(3), [L(1), N-((1H-imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(2), N-((1-methyl-1H-imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(3), 2-(pyridine-2-yl)-N-((pyridine-2-yl)methyl)ethanamine] respectively, were synthesized and characterized. The single crystal X-ray structure of complex 1 reveals the pseudo octahedral coordination geometry around the copper center. Absorption and fluorescence experimental evidence show good DNA binding propensity (in the order of 10(5) M(-1)) of the complexes. Thermal denaturation and circular dichroism (CD) analyses reveal minor structural changes of calf thymus (CT) DNA in presence of complexes and groove and/or surface binding of the complexes to CT-DNA. Kinetic DNA cleavage assay shows pseudo-first-order kinetic reaction between the complex and supercoiled (SC) DNA. In addition, mechanistic SC DNA cleavage results show higher DNA cleavage activity in presence of reducing agent, due to the presence of hydroxyl radicals. In vitro cytotoxicity assay of the complexes demonstrate that the complexes have low toxicity for different cancer cell lines and IC(50) values were between 37 and 156 μM.     

Novel metal-based pharmacologically dynamic agents of transition metal(II) complexes: Designing,synthesis, structural elucidation,DNA binding and photo-induced DNA cleavage activity

Novel Schiff base Cu(II), Ni(II), Co(II) and Zn(II) complexes have been designed and synthesized using the macrocyclic ligand derived from the condensation of diethylphthalate with Schiff base, obtained from benzene-1,2-diamine and 3-benzylidene-pentane-2,4-dione. The ligand and its complexes have been characterized by analytical and spectral techniques. DNA binding properties of these complexes have been investigated by UV–vis, viscosity measurements, cyclic voltammetric and differential pulse voltammogram studies. The intrinsic binding constants for Co(II), Ni(II), Cu(II) and Zn(II) complexes are 1.6 × 10⁶, 1.8 × 10⁶, 2.0 × 10⁶ and 1.5 × 10⁶ M^?1 respectively which are obtained from electronic absorption experiment. Control DNA cleavage experiments using pUC19 supercoiled (SC) DNA and minor groove binder (distamycin) suggest the major groove binding tendency for the synthesized complexes. In the presence of a reducing agent like 3-mercaptopropionic acid (MPA), the synthesized complexes show chemical nuclease activity under dark reaction condition. The complexes also show efficient photo-induced DNA cleavage activity on irradiation with a monochromatic UV light of 360 nm in the presence of inhibitors. Control experiments show inhibition of cleavage in the presence of singlet oxygen quencher like sodium azide and enhancement of cleavage in D₂O, suggesting the formation of singlet oxygen as a reactive species in a type-II process.     

Synthesis,structural characterization,antimicrobial, DNA-binding,and photo-induced DNA cleavage activity of some bio-sensitive Schiff base copper(II) complexes

Schiff base mixed-ligand copper complexes [CuL¹(phen)Cl₂], [CuL¹(bipy)Cl₂], [Cu(L¹)₂Cl₂], [Cu(L²)₂Cl₂], [CuL²(bipy)Cl₂], and [CuL²(phen)Cl₂] (where L^1?=?4-[3,4-dimethoxy-benzylidene]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazole-3-one; L^2?=?4-[3-hydroxy-4-nitro-benzylidene]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazole-3-one; phen?=?1,10-phenanthroline; and bipy?=?2,2′-bipyridine) have been synthesized and characterized. Their DNA-binding properties have been studied by electronic absorption spectra, viscosity, and electrochemical measurements. The absorption spectral and viscosity results suggest that the copper(II) complexes bind to DNA via partial intercalation. The addition of DNA resulting in the decrease of the peak current of the copper(II) complexes indicates their interaction. Interaction between the complexes and DNA has also been investigated by submarine gel electrophoresis. The copper complexes cleave supercoiled pUC19 DNA to nicked and linear forms through hydroxyl radical and singlet oxygen in the presence of 3-mercaptopropionic acid as the reducing agent. These copper complexes promote the photocleavage of pUC19 DNA under irradiation at 360?nm. Mechanistic study reveals that singlet oxygen is likely to be the reactive species responsible for the cleavage of plasmid DNA by the synthesized complexes. The in vitro antimicrobial study indicates that the metal chelates have higher activity against the bacterial and fungal strains than the free ligands.     

Synthesis,characterization, DNA binding studies and in vitro cytotoxicity of platinum(II)-dihalogenido complexes containing bidentate chelating N-donor ligands

Platinum(II) complexes, [Pt(L_x)X₂] (1–6), where X = Br or I and L_x = 2,2′-bipyridine or 1,10-phenanthroline derivatives (5,5′-dimethyl-2,2′-bipyridine (5-Mebpy), 4,4′-dimethyl-2,2′-bipyridine (4-Mebpy), and 5-amino-1,10-phenanthroline (5-NH₂phen)) were prepared. The complexes were characterized by the elemental analysis, mass spectrometry, infrared, and multinuclear (¹H, ¹³C and ¹⁹⁵Pt) 1-D and 2-D NMR spectroscopies, and by single-crystal X-ray analysis of [Pt(4-Mebpy)I₂] (4). All the platinum(II) complexes (1–6) were evaluated for in vitro cytotoxicity against human cancer cell lines A2780 and A2780R, and against non-malignant MRC5 cell line. All the complexes were nontoxic up to the 50 μM concentration, although they were found to readily bind to calf-thymus DNA (CT-DNA), as determined by spectrophotometric titration (K_b ≈ 10⁷ M^?1) and ethidium bromide displacement assay.