Synthesis,Characterization, DNA Binding Studies,Photocleavage, Cytotoxicity and Docking Studies of Ruthenium(II) Light Switch Complexes

A new ligand 3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2yl)phenylboronic acid and its (IPPBA) three ruthenium(II) complexes [Ru(phen)₂(IPPBA)](ClO₄)₂ (1), [Ru(bpy)₂(IPPBA)](ClO₄)₂ (2) and [Ru(dmb)₂(IPPBA)](ClO₄)₂ (3) have been synthesized and characterized by elemental analysis, UV/VIS, IR, ¹H-NMR,¹³C-NMR and mass spectra. The binding behaviors of the three complexes to calf thymus DNA were investigated by absorption spectra, emission spectroscopy, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1, 2 and 3 have been determined to be 7.9?×?10⁵ M^?1, 6.7?×?10⁵ M^?1 and 2.9?×?10⁵ M^?1. The results suggest that these complexes bound to double-stranded DNA in an intercalation mode. Upon irradiation at 365 nm, three ruthenium complexes were found to promote the cleavage of plasmid pBR322 DNA from super coiled form ? to nicked form ??. Further in the presence of Co²⁺, the emission of DNA–Ru(ΙΙ) complexes can be quenched. And when EDTA was added, the emission was recovered. The experimental results show that all three complexes exhibited the “on–off–on” properties of molecular “light switch”. The highest Cytotoxicity potential of the complex1 was observed on the Human alveolar adenocarcinoma (A549) cell line. Good agreement was generally found between the spectroscopic techniques and molecular docked model which provides further evidence of groove binding.     

Synthesis,Characterization and Luminescence Sensitivity with Variance in pH,DNA and BSA Binding Studies of Ru(II) Polypyridyl Complexes

Three ruthenium(II) polypyridyl complexes, [Ru(phen)₂(mip)](ClO₄)₂ (1) (phen =1,10-Phenanthroline), [Ru(bpy)₂(mip)](ClO₄)₂ (2) (bpy = 2,2’bipyridyl) and [Ru(dmb)₂(mip)](ClO₄)₂ (3) (dmb = 4, 4′-dimethyl 2, 2′-bipyridine), were synthesized with an intercalative ligand mip (2-morpholino-1H-imidazo[4,5-f][1, 10]phenanthroline) and characterized by ¹H, ¹³C–NMR, IR, UV-vis, mass spectra and elemental analysis. pH effect, ion selectivity (cations, anions) and solvent sensitivity of complexes were studied. The interaction of these complexes with DNA was performed using absorption, emission spectroscopy and viscosity measurements. The experimental results indicated that the two complexes interacted with calf thymus DNA (CT-DNA) by intercalative mode. BSA (Bovine Serum Albumin) protein binding of these complexes was studied by UV-visible and fluorescence techniques. The binding capacity of these complexes was explained theoretically by molecular docking method.     

Influence of Co(III) Polypyridyl Complexes on Luminescence Behavior,DNA Binding,Photocleavage, Antimicrobial Activity and Molecular Docking Studies

A new ligand FIPB?=?5-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)furan-2-yl-2-boronic acid, having three cobalt(III) polypyridyl complexes [Co(phen)₂(FIPB)]³⁺(1) {FIPB?=?5-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)furan-2-yl-2-boronic acid}, (phen?=?1,10-Phenanthroline), [Co(bpy)₂(FIPB)]³⁺(2) (bpy?=?2,2’bipyridyl), [Co(dmb)₂(FIPB)]³⁺(3) (dmb?=?4, 4′-dimethyl 2, 2′-bipyridine) have been synthesized and characterized by elemental analysis, ES-MS,¹H-NMR, ¹³C-NMR, UV-Vis and FTIR. Their DNA binding behavior has been explored by various spectroscopic titrations and viscosity measurements, which indicated that all the complexes bind to calf thymus DNA by means of intercalation with different binding strengths. The binding properties of these all three complexes towards calf-thymus DNA (CT-DNA) have been investigated by UV-visible, emission spectroscopy and viscosity measurements.The experimental results suggested that three Co(III) complexes can intercalate into DNA base pairs,but with different binding affinities. Photo induced DNA cleavage studies have been performed and results indicate that three complexes efficiently cleave the pBR322-DNA in different forms. The three synthesized compounds were tested for antimicrobial activity by using Staphylococcus aureus and Bacillus subtilis organisms, these results indicated that complex 1 was more activity compared to other two complexes against both tested microbial strains. The in vitro cytotoxicity of these complexes was evaluatedby MTT assay, and complex 1 shows higher cytotoxicity than complex 2 and 3 on HeLa cells.

     

Synthesis,Spectral Characterization,DNA/ Protein Binding,DNA Cleavage,Cytotoxicity, Antioxidative and Molecular Docking Studies of Cu(II)Complexes Containing Schiff Base-bpy/Phen Ligands

Ternary Cu(II) complexes [Cu(II)(L)(bpy)Cl] 1, [Cu(II)(L)(Phen)Cl] 2 [L = 2,3–dimethyl-1-phenyl-4(2 hydroxy-5-methyl benzylideneamino)-pyrazol-5-one, bpy = 2,2^′ bipyridine, phen =1,10 phenanthroline) were synthesized and characterized by elemental analyses, UV-Visible, FT-IR, ESR, Mass, thermogravimetric and SEM EDAX techniques. The complexes exhibit octahedral geometry. The interaction of the Cu(II) with cailf thymus DNA (CT-DNA) was explored by using absorption and fluorescence spectroscopic methods. The results revealed that the complexes have an affinity constant for DNA in the order of 10⁴ M^?1 and mode of interaction is intercalative mode. The DNA cleavage study showed that the complexes cleaved DNA without any external agent. The interaction of Cu(II) complexes with bovine serum albumin (BSA) was also studied using absorption and fluorescence techniques. The cytotoxic activity of the Cu(II) complexes was probed in HeLa (human breast adenocarcinoma cell line), B16F10 (Murine melanoma cell line) and HEPA1–6 celllines, complex 1 has good cytotoxic activity which is comparable with the doxarubicin drug, with IC₅₀ values ranging from 3 to 12.6 μM. A further molecular docking technique was employed to understand the binding of the complexes towards the molecular target DNA. Investigation of the antioxidative properties showed that the metal complexes have significant radical scavenging activity potency against DPPH radical.     

Study of DNA Light Switch Ru(II) Complexes : Synthesis,Characterization, Photocleavage and Antimicrobial Activity

The three Ru(II) complexes of [Ru(phen)₂dppca]²⁺ (1) [Ru(bpy)₂dppca]²⁺ (2) and [Ru(dmb)₂dppca]²⁺ (3) (where phen = 1,10 phenanthroline, bpy = 2,2-bipyridine, dmb = 2 ,2-dimethyl 2′,2′-bipyridine and polypyridyl ligand containing a single carboxylate functionality dppca ligand (dipyridophenazine-11-carboxylic acid) have been synthesized and characterized. These complexes have been shown to act as promising calf thymus DNA intercalators and a new class of DNA light switches, as evidenced by UV-visible and luminescence titrations with Co²⁺ and EDTA, steady-state emission quenching by [Fe(CN)₆]⁴⁻ and KI, DNA competitive binding with ethidium bromide, viscosity measurements, and DNA melting experiments. The results suggest that 1, 2, and 3 complexes bind to CT-DNA through intercalation and follows the order 1 > 2 > 3. Under irradiation at 365 nm, the three complexes have also been found to promote the photocleavage of plasmid pBR322 DNA.     

Synthesis,Characterization, DNA Binding Properties,Fluorescence Studies and Toxic Activity of Cobalt(III) and Ruthenium(II) Polypyridyl Complexes

The new ligand 4-(isopropylbenzaldehyde)imidazo[4,5-f ][1,10]phenanthroline (ippip) and its complexes [Ru(phen)₂(ippip)]²⁺(1),[Co(phen)₂(ippip)]³⁺(2),[Ru(bpy)₂(ippip)]²⁺(3),[Co(bpy)₂(ippip)]³⁺(4)(bpy=2,2-bipyridine) and (phen=1,10-phenanthroline) were synthesized and characterized by ES⁺-MS, ¹H and ¹³C NMR. The DNA binding properties of the four complexes were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that complexes bind to calf thymus DNA (CT-DNA) through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than 2, 3, 4 complexes under comparable experimental conditions. Furthermore, photocleavage studies reveal that singlet oxygen (¹O₂) plays a significant role in the photocleavage.     

Synthesis,Spectroscopic and Antimicrobial Studies of Lead (II) Complexes of Schiff Bases Derived From Amino Acids and Isatins

A new series of lead (II) complexes have been synthesized with Schiff bases derived from isatins and amino acids. These ligands act as bidentate species and coordinate to the metal atom through the azomethine nitrogen and carboxylate oxygen atom via deprotonation. The synthesized complexes have been characterized by elemental analysis, conductance measurements, and molecular weight determinations. The mode of bonding of the complexes has been suggested on the basis of infrared, UV-visible, and ¹H- and ¹³C-NMR spectroscopy, and probable structures have been assigned to these complexes. Few representative ligands and metal complexes have also been screened for their antifungal and antibacterial activities. Molecular modeling and analysis for bond lengths and bond angles have also been carried out for one of the representative compound, [Pb(L³)₂], to substantiate the proposed structures.     

A Biophysical Study of Ru(II) Polypyridyl Complex,Properties and its Interaction with DNA

Mononuclear Ru(II)Polypyridyl complexes of type [Ru(A)₂BPIIP] (ClO₄)₂.2H₂O, where BPIIP?=?2-(3-(4-bromophenyl)isoxazole-5-yl)-1 H-imidazo [4,5-f] [1, 10] phenanthroline and A?=?bpy?=?bipyridyl (1), phen?=?1,10 Phenanthroline (2), dmb?=?4, 4' -dimethyl 2, 2'- bipyridine (3) & dmp?=?4,4'-dimethyl-1,10 –Ortho Phenanthroline (4), were synthesized and their antibacterial activity were examined. The synthesized complexes were characterized and their interaction with DNA was studied using Computational and Biophysical methods (Absorption, emission methods, and viscosity). Molecular modelling studies were carried out for molecular geometry and electronic properties (Frontier molecular orbital HOMO—LUMO). The electrostatic potential surface contours for the complexes were analysed to give their nucleophilic level of sensitivity. The study reveals that the Ru(II) Polypyridyl complexes bind to DNA preponderantly by intercalation. The results recommend that the phen and dmp complex have more effective binding ability than the bpy and dmb, indicating the role of the ancillary ligand in determining their specificity for DNA binding. Further molecular docking studies suggested an octahedral geometry and bind to DNA by preferential binding to Guanine. The docking study additionally sustains the binding constant data acquired with the absorption and emission techniques.The results reveal that the nature of the ancillary Ligand plays a considerable role for the intercalation of the Ru(II) polypyridyl complex to DNA, which subsequently influences the antibacterial activity. Biological studies conducted on Gram‐Negative (E.coli and K.pneumonia) and Gram-Positive (S. aureus and E. faecalis) bacteria establish that complex 1 and 2 were considerably active against S. aureus and E. coli.

     

Spectroscopic,Computational, Antimicrobial,DNA Interaction,In Vitro Anticancer and Molecular Docking Properties of Biochemically Active Cu(II) and Zn(II) Complexes of Pyrimidine-Ligand

Biochemically active Cu(II) and Zn(II) complexes [CuL(ClO₄)₂(1) and ZnL(ClO₄)₂(2)] have been synthesized from N,N donor Schiff base ligand L derived from4,6-dichloropyrimdine-5-carboxaldehyde with 4-(2-aminoethyl)morpholine. The L, complexes 1 and 2 have been structurally characterized by elemental analysis, ¹H-NMR, FTIR, MS, UV-Visible and ESR techniques. The results obtained from the spectral studies supports the complexes 1 and 2 are coordinated with L through square planar geometry. DFT calculations results supports, the ligand to metal charge transfer mechanism can occur between L and metal(II) ions. The antimicrobial efficacy results have been recommended that, complexes 1 and 2 are good anti-pathogenic agents than ligand L. The interaction of complexes 1 and 2 with calf thymus (CT) DNA has been studied by electronic absorption, viscometric, fluorometric and cyclic voltammetric measurements. The calculated K_b values for L, complexes 1 and 2 found from absorption titrations was 4.45?×?10⁴, L; 1.92?×?10⁵, 1 and 1.65?×?10⁵, 2. The Ksv values were found to be 3.0?×?10³, 3.68?×?10³and 3.52?×?10³ for L, complexes 1 and 2 by using competitive binding with ethidium bromide (EB). These results suggest that, the compounds are interacted with DNA may be electrostatic binding. The molecular docking studies have been carried out to confirm the interaction of compounds with DNA. Consequently, in vitro anticancer activities of L, complexes 1 and 2 against selected cancer (lung cancer A549, liver cancer HepG2 and cervical carcinoma HeLa) and normal (NHDF) cell lines were assessed by MTT assay.     

Mononuclear Co(III) and Ni(II) Complexes with Polypyridyl Ligands, [Co(phen)2(taptp)]3+ and [Ni(phen)2(taptp)]2+: Synthesis, Photocleavage and DNA-binding

Two novel, mixed ligand complexes of cobalt(III) and nickel(II), [Co(phen)₂(taptp)]³⁺ (1) and [Ni(phen)₂(taptp)]²⁺ (2) (phen = 1,10-phenanthroline and taptp = 4,5,9,18-tetraazaphenanthreno [9,10-b]triphenylene), were synthesized and characterized by elemental analyses, UV-visible and NMR spectroscopies. The binding interactions of the two complexes with DNA have been investigated using absorption and emission spectroscopy methods and electrophoresis measurement mode. The intrinsic binding constants for these complexes to DNA are in the order of 10⁵. In Tris buffer, the Co(III) complex shows a moderate luminescence which was enhanced after binding to DNA. However for complex Ni(II), no emission was observed in Tris buffer. The [Co(phen)₂(taptp)]³⁺ and [Ni(phen)₂(taptp)]²⁺ can cause the photocleavage of DNA supercoiled pBR322 upon irradiation by 360 nm light. Based on the data, an intercalative mode of DNA binding is suggested for the two complexes.     

Synthesis,Properties and Spectroscopic Studies of Cobalt (II) and Cobalt (III) Complexes with Planar Dithioxamides

The complexes [Coⁱⁱⁱ(LH₂)₃]X₃ (LH₂ = dithiooxamide, N-methyldithiooxamide, N,N′-dimethyldithiooxamide; X = Cl, Br, l) and [CoⁱⁱL]n have been prepared. They were characterized by analyses, thermal techniques, magnetic susceptibilities and spectroscopic (ligand-field, ¹³C-NMR, FT-IR) methods. The vibrational analysis of the prepared complexes is given using NH/ND and CH₃/CD₃ isotopic substitutions. The neutral dithiooxamides exhibit a bidentate chelating S,S-coordination, while the doubly deprotonated dithiooxamido anions act as bis-bidentate bridging S,N/N,S-ligands giving trans polymeric structures. The Co(III) complexes are octahedral with Co^IIIS₆ coordination spheres. A square planar geometry around Co(II) is assigned for the polymeric compounds.     

Synthesis,Spectral Characterization,DNA Binding Studies and Antimicrobial Activity of Co(II), Ni(II), Zn(II), Fe(III) and VO(IV) Complexes with 4-Aminoantipyrine Schiff Base of Ortho-Vanillin

A series of transition metal complexes of Co(II), Ni(II), Zn(II), Fe(III) and VO(IV) have been synthesized involving the Schiff base, 2,3-dimethyl-1-phenyl-4-(2-hydroxy-3-methoxy benzylideneamino)-pyrazol-5-one(L), obtained by condensation of 4-aminoantipyrine with 3-methoxy salicylaldehyde. Structural features were obtained from their FT-IR, UV–vis, NMR, ESI Mass, elemental analysis, magnetic moments, molar conductivity and thermal analysis studies. The Schiff base acts as a monovalent bidentate ligand, coordinating through the azomethine nitrogen and phenolic oxygen atom. Based on elemental and spectral studies six coordinated geometry is assigned to Co(II), Ni(II), Fe(III) and VO(IV) complexes and four coordinated geometry is assigned to Zn(II) complex. The interaction of metal complexes with Calf thymus DNA were carried out by UV–VIS titrations, fluorescence spectroscopy and viscosity measurements. The binding constants (K_b) of the complexes were determined as 5?×?10⁵ M^?1 for Co(II) complex, 1.33?×?10⁴ M^?1 for Ni(II) complex, 3.33?×?10⁵ M^?1 for Zn(II) complex, 1.25?×?10⁵ M^?1 for Fe(III) complex and 8?×?10⁵ M^?1 for VO(IV) complex. Quenching studies of the complexes indicate that these complexes strongly bind to DNA. Viscosity measurements indicate the binding mode of complexes with CT DNA by intercalation through groove. The ligand and it’s metal complexes were screened for their antimicrobial activity against bacteria. The results showed the metal complexes to be biologically active, while the ligand to be inactive.     

Synthesis,Characterization Luminiscence Studies and Microbial Activity of Ethylenediamine Ruthenium (II) Complexes with Dipyridophenazine Ligands

Three symmetric ligands 7-methyl dipyrido-[3,2-a;2′,3′-c]phenazine (dppz-CH₃), 7-nitro dipyrido-[3,2-a;2′,3′-c]phenazine (dppz-NO₂) and benzo[i]dipyrido-[3,2-a;2′,3′-c]phenazine (dppn) and their ruthenium(II) complexes [Ru(en)₂(L)][ClO₄]₂ (en= ethylenediamine), L= dppz-CH₃, dppz-NO₂ and dppn have been synthesized and characterized by IR, ¹H, ¹³C NMR and Mass spectra. The interactions of these complexes with calf thymus DNA have been investigated by spectrophotometric, spectrofluorimetric, circular dichroism, viscosity and thermal denaturation studies. As the planar extension of the intercalative ligand increases, the interaction of the complex with DNA increases, indicating that the size and shape of the intercalalative ligand has a marked effect on the strength of interaction. The plot of log K versus log [Na⁺] yield a slope of -1.26, -1.53, -1.60 for the complexes 1, 2 and 3 respectively. These three complexes have been found to promote the cleavage of plasmid pBR 322 DNA upon irradiation.     

Synthesis and Antitumor,Antioxidant Effects Studies of N-Ethylpiperazine Substitute Thiourea Ligands and Their Copper(II) Complexes

A series of N-ethylpiperazine substitute thioureas [C₆N₂H₁₃NHCSNHR], where R = -C₃H₅ (L ₁ ), -C₁₀H₇ (L ₂ ), and -C₇H₇ (L ₃ ), and their copper (II) complexes have been synthesized. These ligands and complexes have been characterized by elemental analyses, IR, ¹H and ¹³C-NMR spectra, UV-Vis, magnetic susceptibility, thermogravimetrical analyses, and MALDI-TOF MS. In vitro antitumor activity of ligands and their complexes has been screened toward several tumor cell lines. The effects on these complexes of the growth of L1210 and MCF7 were studied comparatively with that of free ligands. Antioxidant and radical scavenging activities of synthesized compounds were determined by various in vitro assays including 1,1-diphenyl-2-picryl-hydrazyl free radicals (DPPH), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid radicals (ABTS+), and ferrous ion (Fe²⁺) chelating activities. Moreover, these activities were compared to synthetic and standard antioxidant trolox. The results showed that the synthesized compounds had effective antioxidant power.     

Novel Bioactive Co(II), Cu(II), Ni(II) and Zn(II) Complexes with Schiff Base Ligand Derived from Histidine and 1,3-Indandione: Synthesis,Structural Elucidation,Biological Investigation and Docking Analysis

Novel bioactive complexes of Co(II), Cu(II), Ni(II) and Zn(II) metal ions with Schiff base ligand derived from histidine and 1,3-indandione were synthesized and thoroughly characterized by various analytical and spectral techniques. The biological investigations were carried out to examine the efficiency of the binding interaction of all the complexes with calf thymus DNA (CT-DNA). The binding properties were studied and evaluated quantitatively by K_b and K_sq values using UV-visible, fluorescence spectroscopy and voltammetric techniques. The experimental results revealed that the mode of binding of all the complexes with CT-DNA is via intercalation. It is further verified by viscosity measurements and thermal denaturation experiments. From the results of the cleavage study with pUC19 DNA it is inferred that all the complexes possess excellent cleaving ability. The present investigation proved that the binding interaction of all the complexes are significantly strong and the order of binding strength of the complexes is [Ni(L)₂] (K_b = 3.11 × 10⁶ M^?1) > [Co(L)₂] (K_b = 2.89 × 10⁶ M^?1) > [Cu(L)₂] (K_b = 2.64 × 10⁶ M^?1) > [Zn(L)₂] (K_b = 2.41 × 10⁵ M^?1). The complexes were also screened for antibacterial and anticandidal activity. The in vitro cytotoxicity of the ligand and complexes on the NIH/3 T3 mouse fibroblast cell lines were examined using CellTiter-Blue® (CTB) Cell viability assay, which unveiled that all the complexes exhibit more potent activities against NIH/3 T3 cells. Among all the complexes [Zn(L)₂] complex showed the maximum efficiency.