DNA binding and gel electrophoresis studies of a new silver(I) complex containing 2,9-dimethyl-1,10-phenanthroline ligands

The silver(I) complex, [Ag(2,9-dimethyl-1,10-phenanthroline)(2)](NO(3)) · H(2)O, has been synthesized and characterized by physicochemical and spectroscopic methods. The binding interactions of this complex with calf thymus DNA (CT-DNA) were investigated using emission, absorption, circular dichroism, viscosity measurements, and gel electrophoresis studies. The calculated binding constant, K(b), obtained from UV-vis absorption studies was 5.3 ± 0.2 × 10(4) M(-1). In fluorimetric studies, the enthalpy and entropy of the reaction between the complex and CT-DNA showed hydrophobic interaction. In addition, in the circular dichroism spectrum, silver(I) complex induces a B → A structural transition of CT-DNA. Gel electrophoresis studies demonstrated that this complex has ability to cleave the supercoiled plasmid DNA. All these results suggest that the complex interacts with CT-DNA via partial intercalative mode of binding.     

Thermodynamic and structural study of phenanthroline derivative ruthenium complex/DNA interactions: probing partial intercalation and binding properties

The binding of [Ru(PDTA-H₂)(phen)]Cl (PDTA = propylene-1,2-diaminetetra-acetic acid; phen = 1,10 phenanthroline) with ctDNA (=calf thymus DNA) has been investigated through intrinsic and induced circular dichroism, UV-visible absorption and fluorescence spectroscopies, steady-state fluorescence, thermal denaturation technique, viscosity and electrochemical measurements. The latter indicate that the cathodic and anodic peak potentials of the ruthenium complex shift to more positive values on increasing the DNA concentration, this behavior being a direct consequence of the interaction of both the reduced and oxidized form with DNA binding. From spectrophotometric titration experiments, the equilibrium binding constant and the number of monomer units of the polymer involved in the binding of one ruthenium molecule (site size) have been quantified. The intrinsic circular dichroism (CD) spectra show an unwinding and a conformational change of the DNA helix upon interaction of the ruthenium complex. Quenching process, thermal denaturation experiments and induced circular dichroism (ICD) are consistent with a partial intercalative binding mode.     

DNA binding, DNA cleavage, and cytotoxicity studies of two new copper (II) complexes

The DNA binding behavior of [Cu(phen)(phen-dione)Cl]Cl (1) and [Cu(bpy)(phen-dione)Cl]Cl (2) was studied with a series of techniques including UV-vis absorption, circular dichroism spectroscopy, and viscometric methods. Cytotoxicity effect and DNA unwinding properties were also investigated. The results indicate that the Cu(II) complexes interact with calf-thymus DNA by both partially intercalative and hydrogen binding. These findings have been further substantiated by the determination of intrinsic binding constants spectrophotometrically, 12.5?×?10(5) and 5?×?10(5) for 1 and 2, respectively. Our findings suggest that the type of ligands and structure of complexes have marked effect on the binding affinity of complexes involving CT-DNA. Circular dichroism results show that complex 1 causes considerable increase in base stacking of DNA, whereas 2 decreases the base stacking, which is related to more extended aromatic area of 1,10-phenanthroline in 1 rather than bipyridine in 2. Slow decrease in DNA viscosity indicates partially intercalative binding in addition to hydrogen binding on the surface of DNA. The second binding mode was also confirmed by additional tests: interaction in denaturation condition and acidic pH. Also, these new complexes induced cleavage in pUC18 plasmid DNA as indicated in gel electrophoresis and showed excellent antitumor activity against K562 (human chronic myeloid leukemia) cells.     

Interaction of two new mixed ligand copper(II) complexes with DNA probed by thermodynamic and spectroscopic studies

The DNA binding behavior of [Cu(4,7-dmp)(phen-dione)Cl]Cl (1) and [Cu(2,9-dmp)(phen-dione)Cl]Cl (2) where dmp and phen-dion stand for dimethyl-1,10-phenanthroline and 1,10-phenanthroline-5,6-dion, respectively, was studied with a series of techniques including Viscometry, UV–Vis absorption, circular dichroism and fluorescence spectroscopy. Cytotoxicity effect was also investigated. Thermodynamic parameters, enthalpy and entropy changes were calculated according to Van’t Hoff equation, which indicated that both reactions are predominantly enthalpically driven. However, these two complexes show different behavior in fluorescence, circular dichroism and viscometry methods which indicate the Cu(II) complexes interact with calf-thymus DNA by different mode of binding. These have further been verified by competition studies using Hoechst as a distinct groove binder. All these results indicate that these two complexes (1) and (2) interact with CT-DNA via groove binding and partially intercalative mode, respectively and the binding affinity of the complex 1 is higher than that of complex 2. Finally, our findings suggest that the type of ligands and structure of complexes have marked effect on the binding affinity of complexes involving CT-DNA. Also, these new complexes showed excellent antitumor activity against human T lymphocyte carcinoma-Jurkat cell line.     

DNA binding studies of antibiotic drug cephalexin using spectroscopic and molecular docking techniques

The purpose of this study was to explore an accurate characterization of the binding interaction of antibiotic drug cephalexin with calf thymus DNA (CT-DNA) as a relevant biological target by using UV absorption, fluorescence spectroscopy and circular dichroism (CD) in vitro under simulated physiological conditions (pH = 7.4) and also through a molecular modeling study. The results showed that the drug interacts with the DNA helix via a minor groove binding mode. The thermodynamic parameters were calculated and showed that the reaction between the drug and CT-DNA was exothermic. In addition, the drug enforced traceable changes in the viscosity of DNA. The molecular modeling results indicated that cephalexin forcefully binds to the minor groove of DNA with a relative binding energy of ?21.02?kJ mol^?1. The obtained theoretical results were in good agreement with those obtained from experimental studies.     

DNA binding of iron(II) mixed-ligand complexes containing 1,10-phenanthroline and 4,7-diphenyl-1,10-phenanthroline

Absorption spectroscopy and circular dichroism (CD) have been used to characterize the DNA binding of [Fe(phen)3]2+, [Fe(phen)2(DIP)]2+ and [Fe(phen)(DIP)2]2+ where phen and DIP stand for 1,10-phenanthroline and 4,7-diphenyl-1,10-phenanthroline, respectively. Both [Fe(phen)3]2+ and [Fe(phen)2(DIP)]2+ bind weakly to calf thymus DNA (CT-DNA) in an electrostatic mode, while [Fe(phen)(DIP)2]2+ binds more strongly to CT-DNA, possibly in an intercalation mode. The hypochromicity, red shift and Kb increase in the order [Fe(phen)3]2+ < [Fe(phen)2(DIP)]2+ < [Fe(phen)(DIP)2]2+ in accordance with the increase in size and hydrophobicity of the iron(II) complexes. The thermodynamic parameters obtained suggest that the DNA binding of both [Fe(phen)3]2+ and [Fe(phen)2(DIP)]2+ is entropically driven, while that of [Fe(phen)(DIP)2]2+ is enthalpically driven. A strong CD spectrum in the UV and visible region develops upon addition of CT-DNA into the racemate solution of each iron(II) complex (Pfeiffer effect). This has revealed that a shift in diastereomeric inversion equilibrium takes place in the solution to yield an excess of one of the DNA-complex diastereomers. The striking resemblance of the CD spectral profiles to those of the pure delta-enantiomer indicates that the delta-enantiomer of the iron(II) complexes is preferentially bound to CT-DNA. The mechanism of the development of Pfeiffer CD is proposed on the basis of kinetic studies on the DNA binding of the racemic iron(II) complexes.     

Synthesis, DNA-binding and photocleavage studies of ruthenium(II) complex with 2-(3'-phenoxyphenyl)imidazo[4,5-f][1,10]phenanthroline

A new polypyridyl ligand MPPIP {MPPIP=2-(3'-phenoxyphenyl)imidazo[4,5-f]-[1,10]phenanthroline} and its ruthenium(II) complexes, [Ru(bpy)(2)MPPIP](2+) (1) (bpy=2,2'-bipyridine) and [Ru(phen)(2)MPPIP](2+) (2) (phen=1,10-phenanthroline) have been synthesized and characterized. The binding of the two complexes to calf thymus DNA (CT-DNA) has been investigated with spectrophotometric methods, viscosity measurements, as well as equilibrium dialysis and circular dichroism spectroscopy. The results suggest that both complexes bind to CT-DNA through intercalation, and enantioselectively interact with CT-DNA in a way. However, complex 2 is a much better candidate as an enantioselective binder to CT-DNA than complex 1. When irradiated at 365nm, both complexes have also been found to promote the photocleavage of plasmid pBR322 DNA.     

DNA interaction studies of a copper (II) complex containing an antiviral drug, valacyclovir: the effect of metal center on the mode of binding

The water-soluble complex, [Cu(Val)(2)(NO(3))(2)]; in which Val = valacyclovir, an antiviral drug, has been synthesized and characterized by elemental analysis, furier transfer-infrared, hydrogen nuclear magnetic resonance (H NMR), and UV-Vis techniques. The binding of this Cu (II) complex to calf thymus DNA was investigated using fluorimetry, spectrophotometry, circular dichroism, and viscosimetry. In fluorimetric studies, the enthalpy and entropy of the reaction between the complex and calf-thymus DNA (CT-DNA) showed that the reaction is endothermic (ΔH = 208.22 kJ mol(-1); ΔS = 851.35 J mol(-1)K(-1)). The complex showed the absorption hyperchromism in its ultra violet-visible (UV-Vis) spectrum with DNA. The calculated binding constant, K(b), obtained from UV-Vis absorption studies was 2 × 10(5) M(-1). Moreover, the complex induced detectable changes in the circular dichroism spectrum of CT-DNA, as well as changes in its viscosity. The results suggest that this copper (II) complex interacts with CT-DNA via a groove-binding mode.     

Spectroscopic studies on the interaction of quercetin-terbium(III) complex with calf thymus DNA

The interaction of native calf thymus DNA (CT-DNA) with quercetin-terbium(III) [Q-Tb(III)] complex at physiological pH was monitored by UV absorption spectrophotometry, circular dichroism, fluorescence spectroscopy, and viscosimetric techniques. The complex displays binding properties to the CT-DNA and was found to interact with CT-DNA through outside binding, demonstrated by a hypochromic effect of Q-Tb(III) on the UV spectra of CT-DNA and the calculated association constants (K). Also, decrease in the specific viscosity of CT-DNA, decrease in the fluorescence intensity of Q-Tb(III) solutions in the presence of increasing amounts of CT-DNA, and detectable changes in the circular dichroism spectrum of CT-DNA are other evidences to indicate that Q-Tb(III) complex interact with CT-DNA through outside binding.     

Effect of substitution pattern of ancillary ligands on the DNA-binding behavior of two new Ru(II)-polypyridyl complexes

The new ligand 2-(4-phenoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (ppip) and its Ru(II) complexes [Ru(2,9-dmp)2(ppip)]2+ (1) and [Ru(4,7-dmp)2(ppip)]2+ (2; 2,9- and 4,7-dmp = 2,9- and 4,7-dimethyl-1,10-phenanthroline, resp.) were synthesized and characterized. The binding properties of the two complexes towards calf-thymus DNA (CT-DNA) in buffered H2O (pH 7.2) were investigated by different spectrophotometric methods and viscosity measurements. Both 1 and 2 strongly bind to CT-DNA by means of intercalation, but with different binding strengths. In contrast to the more tightly bound complex 2, the sterically more-demanding complex 1 showed no fluorescence emission, neither alone nor in the presence of CT-DNA. Our results demonstrate that the position of Me groups on phenanthroline (phen) ancillary ligands significantly affects the overall DNA-recognition propensities of Ru(II)-polypyridyl complexes. Further, the partly resolved complex 2 was shown by circular dichroism (CD) to stereoselectively recognize CT-DNA, in contrast to 1.     

Interaction of polypyridyl ruthenium (II) complex containing asymmetric ligand with DNA

A novel asymmetric bidentate ruthenium (II) complex, [Ru(bpy)(2)(PYNI)](2+) (bpy=2,2'-bipyridine, PYNI=2-(2'-pyridyl)naphthoimidazole), has been synthesized and characterized by elemental analysis, ES-MS (electrospray mass spectra) and (1)H NMR. The electrochemical behaviors of this complex were studied by cyclic voltammetry. DNA interaction studies suggest that [Ru(bpy)(2)(PYNI)](2+) binds to calf thymus DNA (CT-DNA) in an intercalative mode. Interestingly, this new Ru(II) complex has also been found to promote cleavage of plasmid pBR 322 DNA from the supercoiled form I to the open circular form II upon irradiation.     

DNA interaction studies of an antiviral drug, ribavirin, using different instrumental methods

Interaction of ribavirin with CT-DNA was investigated by emission, absorption, circular dichroism, and viscosity studies to determine the binding mode and binding constant of this drug with DNA. The calculated binding constant, K(b), obtained from UV-vis absorption studies was 4.6 × 10(3) M(-1). In fluorimetric studies, the enthalpy (ΔH<0) and entropy (ΔS>0) of the reaction between ribavirin and CT-DNA showed a hydrophobic interaction. In addition, in the circular dichroism spectrum, the drug induces a B → A structural transition of CT-DNA. These results demonstrate that ribavirin interacts with CT-DNA via the groove binding mode. It was observed that the drug has ability to cleave supercoiled plasmid DNA.     

Effects of the substitution positions of Br group in intercalative ligand on the DNA-binding behaviors of Ru(II) polypyridyl complexes

Two new polypyridyl ligands containing substituent Br at different positions in the phenyl ring, PBIP [PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline], OBIP [OBIP=2-(2-bromophenyl)imidazo[4,5-f]1,10-phenanthroline] and their Ru(II) complexes, [Ru(phen)2PBIP]2+ 1, [Ru(phen)2OBIP]2+ 2 (phen=1,10-phenanthroline), have been synthesized and characterized. The binding strength of the two complexes to calf thymus DNA (CT DNA) was investigated with spectrophotometric methods, viscosity measurements, as well as equilibrium dialysis and circular dichroism spectroscopy. The theoretical calculations for these two complexes were also carried out applying the density functional theory (DFT) method. The experimental results show that the Br group substituting H at different positions of the phenyl ring in the intercalated ligand has significant effects on the spectral properties and the DNA-binding behaviors of Ru(II) complexes. Both the complexes can bind to CT DNA in intercalative mode and interact with CT DNA enantioselectively. Moreover, complex 1 can bind to CT DNA more strongly than complex 2, and complex 2 can become a much better candidate as an enantioselective binder to CT DNA than complex 1. The theoretical calculations show that both intercalative ligands, PBIP and OBIP, in these two complexes are essentially planar, and the obtained electronic structures of the complexes can be used to explain reasonably some of their experimental regularities or trends. Such experimental and theoretical information will be useful in design of novel probes of nucleic acid structures.     

Synthesis, characterization, DNA-binding and photocleavage of complexes [Ru(phen)2(6-OH-dppz)]2+ and [Ru(phen)2(6-NO2-dppz)]2+

Two new complexes, ([Ru(phen)(2)(6-OH-dppz)](2+)) (1) and ([Ru(phen)(2)(6-NO(2)-dppz)](2+)) (2) (phen=1,10-phenanthroline; 6-OH-dppz=6-hydroxyl-dipyrido[3,2-a:2',3'-c]phenazine; 6-NO(2)-dppz=6-nitro-dipyrido[3,2-a:2',3'-c]phenazine), have been synthesized and characterized by elemental analysis, ES-MS (electrospray mass spectra), (1)H NMR, UV-Vis (UV-visible) and CV (cyclic voltammetry). The DNA-binding behaviors of both complexes have been studied by spectroscopic methods and viscosity measurements. The results indicate that the two complexes all bind to calf thymus DNA (CT-DNA) in an intercalative mode, and the DNA-binding affinity of complex 2 is greater than that of complex 1. In addition, complex 1 can promote photocleavage of pBR322 DNA upon irradiation, whereas complex 2 can promote cleavage of pBR322 DNA both upon irradiation and in the dark, with more efficient cleavage occurring upon irradiation. Theoretical studies for these complexes have been also carried out with the density functional theory (DFT) method. The difference in the DNA-binding behaviors of the two complexes can be reasonably explained by the DFT calculations.     

Synthesis, characterization, DNA-binding and photocleavage studies of [Ru(bpy)2(PPIP)]2+ and [Ru(phen)2(PPIP)]2+

A novel ligand 2-(4'-phenoxy-phenyl)imidazo[4,5-f][1,10]phenanthroline (PPIP) and its complexes [Ru(bpy)(2)(PPIP)](2+) (1) (bpy = 2,2'-bipyridine) and [Ru(phen)(2)(PPIP)](2+) (2) (phen = 1,10-phenanthroline) have been synthesized and characterized by mass spectroscopy, (1)H NMR and cyclic voltammetry. The interaction of two complexes with calf thymus DNA (CT-DNA) was investigated by spectroscopic and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode. Both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA under irradiated.     

Ruthenium(II) mixed-ligand complex containing 2-(4'-benzyloxy-phenyl)imidazo[4,5-f][1,10]phenanthroline: synthesis, DNA-binding and photocleavage studies

A novel polypyridyl ligand 2-(4'-benzyloxyphenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and its complex [Ru(bpy)2(BPIP)]2+ (1) (bpy=2,2'-bipyridine) and (2) [Ru(phen)2(BPIP)]2+) (phen=1,10-phenanthroline) have been synthesized and characterized by elemental analysis, electrospray mass spectra and 1H NMR. The DNA-binding properties of the two complexes were investigated by spectroscopic and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode. Both complexes can enantioselectively interact with calf thymus DNA (CT-DNA) in a way. The Lambda enantiomer of complex 1 is slightly predominant for binding to CT-DNA to the Delta enantiomer. Under irradiation at 365 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA. Inhibitors studies suggest that singlet oxygen ((1)O2) and hydroxyl radical (*OH) play a significant role in the cleavage mechanism for both complexes. Moreover, the DNA-binding and photocleavage properties of both complexes were compared with that of [Ru(bpy)2(BPIP)]2+ and [Ru(phen)2(BPIP)]2+. The experimental results indicate that methene group existence or not have a significant effect on the DNA-binding and cleavage mechanism of these complexes.     

The interaction of the benzimidazole dye Hoechst 8208 with nucleic acids

The interaction of Hoechst 8208 (H8208) with DNA and synthetic polynucleotides has been studied by absorption, fluorescence, flow dichroism, circular dichroism (CD), and viscosity measurements. The results are compatible with an intercalative mode of H8208 binding.     

Synthesis, characterization, DNA-binding and cleavage studies of [Ru(bpy)2(actatp)]2+ and [Ru(phen)2(actatp)]2+ (actatp=acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence)

New ligand acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence (actatp) and its complexes [Ru(bpy)(2)(actatp)](ClO(4))(2).2H(2)O (1) (bpy=2,2'-bipyridine) and [Ru(phen)(2)(actatp)](ClO(4))(2).2H(2)O (2) (phen=1,10-phenanthroline) have been synthesized and characterized by UV-vis, 1H NMR, and mass spectra. The electrochemical behavior of the two complexes was studied by cyclic voltammetry. The interaction of the two complexes with calf thymus DNA has been investigated by spectrophotometric methods and viscosity measurements. The experimental results suggest that both complexes bind to DNA through an intercalative mode. The circular dichroism signals of the dialysates of the racemic complexes against calf thymus DNA are discussed. When irradiated at 302 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA.     

Mixed-ligand copper(II)-phenanthroline-dipeptide complexes: synthesis, characterization, and DNA-cleavage properties

The mixed-ligand complexes [Cu(II)(HisLeu)(phen)](+) (1) and [Cu(II)(HisSer)(phen)](+) (2; phen=1,10-phenanthroline) were synthesized and characterized. The intercalative interaction of the Cu(II) complexes with calf-thymus DNA (CT-DNA) was probed by UV/VIS and fluorescence titration, as well as by thermal-denaturation experiments, and the intrinsic binding constants (K(b)) for the complexes with 1 and 2 were 4.2x10(3) and 4.9x10(3) M(-1), resp. Both complexes were found to be efficient catalysts for the hydrolytic cleavage of plasmid pUC19 DNA, as tested by gel electrophoresis, converting the DNA from the supercoiled to the nicked-circular form at rate constants of 1.32 and 1.40 h(-1) for 1 and 2, resp.     

Interaction of calf thymus DNA with the antiviral drug Lamivudine

One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. In recent years, some researchers have shown that antiviral drugs, such as ritonavir, saquinavir, and nelfinavir, inhibit the growth of over 60 cancer cell lines derived from nine different tumor types. This article studied the anticancer potential of an antiviral drug, lamivudine (LA). The interaction of LA and calf thymus DNA (CT-DNA) was studied using emission, absorption, circular dichroism (CD), and viscosity techniques. The binding constants evaluated from fluorescence data at different temperatures revealed that fluorescence enhancement is a static process that involves complex-DNA formation in the ground state. Further, the enthalpy and entropy of the reaction between the drug and CT-DNA showed ΔH<0 (-126.38±0.61 kJ mol(-1)) and ΔS<0 (-352.17±2.1?J mol(-1) K(-1)); therefore, van der Waals interactions or hydrogen bonds are the main forces in the binding of LA to CT-DNA. The values of K(f) clearly underscore the high affinity of LA to DNA. In addition, detectable changes in the CD spectrum of CT-DNA in the presence of LA indicated conformational changes. All these results showed that groove binding is the binding mode of this drug and CT-DNA.