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 interaction studies of a platinum(II) complex containing L-histidine and 1,10-phenanthroline ligands

The aim of this study was developing coordination complexes that can be used as inorganic medicinal agents. The water soluble [Pt(phen)(His)]NO(3)·3H(2)O complex in which phen=1,10-phenantheroline and His=L-histidine was synthesized and characterized using physicochemical methods. Binding interaction of this complex with calf thymus (CT) DNA was investigated by emission, absorption, circular dichroism, and viscosity measurement techniques. Upon addition of CT-DNA, changes were observed in the characteristic ultraviolet-visible (UV-Vis) bands (hypochromism) of the complex. The complex binds to CT-DNA in an intercalative mode. The calculated binding constant, K(b), was 8 ± 0.2 × 10(4) M(-1). In addition, circular dichroism (CD) study showed that the phenanthroline ligand was inserted between the base pair stack of the double-helical structure of DNA. Also, the fluorescence spectral characteristics showed an increase in fluorescence intensity of the platinum complex in the presence of increasing amounts of DNA solution. The experimental results showed that the platinum complex binds to DNA via intercalative and hydrogen bonding mode.     

DNA interaction studies of cobalt (II) mixed-ligand complexes containing dimethyl-1, 10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine: the role of methyl substitutions on the mode of binding

Two cobalt (II) complexes containing a dipyrido[3,2-a:2',3'-c]phenazine (dppz) base with the general formulation [Co(dppz)(dmp)(2)]Cl(2), where dmp is 4,7-dimethyl-1,10-phenanthroline ligand (4,7-dmp) (1) and 2,9-dimethyl-1,10-phenanthroline ligand (2,9-dmp) (2) were synthesized and characterized. Binding interactions of these complexes with calf thymus DNA were investigated by emission, absorption, circular dichroism, and viscosity studies, and the effects of the positions of methyl substitutions in phenanthroline coligands were investigated. The DNA binding constants obtained from the absorption spectral titrations decrease in the order of 1?>?2, which is consistent with the trend in apparent emission enhancement of the complexes on binding to calf thymus DNA. These observations were supported by circular dichroism spectroscopy and viscosity measurements and reveal that DNA binding affinity of the complexes depends on the position of methyl groups on the phenanthroline ligands.     

Synthesis,characterization, DNA interaction,and cytotoxicity of novel Pd(II) and Pt(II) complexes

Four complexes [Pd(L)(bipy)Cl]·4H₂O (1), [Pd(L)(phen)Cl]·4H₂O (2), [Pt(L)(bipy)Cl]·4H₂O (3), and [Pt(L)(phen)Cl]·4H₂O (4), where L = quinolinic acid, bipy = 2,2’-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, ¹H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5?×?10⁴ M^?1, 3.9?×?10⁴ M^?1, 6.1?×?10⁴ M^?1, and 1.4?×?10⁵ M^?1, respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.     

Synthesis, characterization and DNA binding studies of two mixed ligand complexes of ruthenium(II)

Two mixed ligand complexes [Ru(bpy)(2)(DMHBT)]Cl(2)(1) and [Ru(phen)(2)(DMHBT)]Cl(2) (2) (where DMHBT is 11,13-dimethyl-13H-4,5,9,11,14-hexaaza-benzo[b]triphenylene-10,12-dione) have been synthesized and characterized by electrospray ionization (ESI) mass, (1)H-(1)H correlation spectroscopy (COSY), electronic spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Spectroscopic titration and viscosity changes of calf thymus (CT)-DNA in the presence of incremental amount of complexes 1 and 2 clearly demonstrate that both these complexes bind intercalatively to DNA, with binding constant 2.87+/-0.20 x 10(4)M(-1) and 1.01+/-0.20 x 10(5)M(-1) for complexes 1 and 2, respectively. All the experimental evidences suggest that the ancillary ligand 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) influences the intercalative binding of these complexes to DNA.     

Cationic 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin fully intercalates at 5'-CG-3' steps of duplex DNA in solution

The interaction of 5,10,15, 20-tetrakis(N-methylpyridinium-4-yl)porphyrin (T4MPyP(4+)) with the oligonucleotide DNA duplex [d(GCACGTGC)](2) was studied by two-dimensional (1)H NMR spectroscopy, optical absorbance, circular dichroism, and molecular dynamics simulation employing particle mesh Ewald methods. T4MPyP(4+) is one of the largest aromatic molecules for which intercalative binding to DNA has been proposed, although this has been called into question by recent X-ray crystallographic work [Lipscomb et al. (1996) Biochemistry 35, 2818-2823]. T4MPyP(4+) binding to [d(GCACGTGC)](2) produced a single set of (mostly) upfield-shifted DNA resonances in slow exchange with the resonances of the free DNA. Intra- and intermolecular NOEs observed in the complex showed that the porphyrin intercalates at the central 5'-CG-3' step of the DNA duplex without disrupting the flanking base pairs. Absorption and circular dichroism spectra of the complex also support intercalative binding. Molecular dynamics simulations (using explicit solvent and PME methods), carried out for fully and partially intercalated complexes, yielded stable trajectories and plausible structures, but only the symmetrical, fully intercalated model agreed with NOESY data. Stable hydrogen bonding was observed during 600 ps of MD simulation for the base pairs flanking the binding site.     

2‐Hydroxynaphthalene‐1‐carbaldehyde‐ and 2‐(Aminomethyl)pyridine‐Based Schiff Base CuII Complexes for DNA Binding and Cleavage

Three mononuclear Cu^II complexes, [CuCl(naph‐pa)] ( 1 ), [Cu(bipy)(naph‐pa)]Cl ( 2 ), and [Cu(naph‐pa)(phen)]Cl ( 3 ) ((naph‐pa)=Schiff base derived from the condensation of 2‐hydroxynaphthalene‐1‐carbaldehyde and 2‐picolylamine (=2‐(aminomethyl)pyridine), bipy=2,2′‐bypiridine, and phen=1,10‐phenanthroline) were synthesized and characterized. Complex 1 exhibits square‐planar geometry, and 2 and 3 exhibit square pyramidal geometry, where Schiff base and bipy/phen act as NNO and as NN donor ligands, respectively. CT (Calf thymus)‐DNA‐binding studies revealed that the complexes bind through intercalative mode and show good binding propensity (intrinsic binding constant K_b: 0.98×10⁵, 2.22×10⁵, and 2.67×10⁵ M ^?1 for 1 – 3 , resp.). The oxidative and hydrolytic DNA‐cleavage activity of these complexes has been studied by gel electrophoresis: all the complexes displayed chemical nuclease activity in the presence and absence of H₂O₂. From the kinetic experiments, hydrolytic DNA cleavage rate constants were determined as 2.48, 3.32, and 4.10 h^?1 for 1 – 3 , respectively. It amounts to (0.68–1.14)×10⁸‐fold rate enhancement compared to non‐catalyzed DNA cleavage, which is impressive. The complexes display binding and cleavage propensity to DNA in the order of 3 > 2 > 1 .     

Crystal structure, magnetic and electrochemical properties of five-coordinate copper (II) complexes with 1,10-phenanthroline-5,6-dione

Three new five-coordinate Cu^II complexes, [Cu(tpy)(phen-dione)](PF₆)₂, [Cu(phen)(phen-dione)Cl]PF₆ and [Cu(bpy)(phen-dione)Cl]PF₆ (tpy = 2,2′;6′,2″-terpyridine, phen = 1,10-phenanthroline and phen-dione = 1,10-phenanthroline-5,6-dione) have been prepared and characterized by elemental analysis, IR and UV-Vis spectroscopies and cyclic voltammetry.The complex of [Cu(tpy)(phen-dione)](PF₆)₂ crystallized with one molecule of acetonitrile. The ortep drawing of [Cu(tpy)(phen-dione)](PF₆)₂ · CH₃CN shows that the coordination geometry around Cu^II is a distorted trigonal- bipyramid. Due to the steric hindrance of in the unit cell, the tpy ligands in each complex cation cannot interact in a π-π fashion. The effective magnetic moment (μ_eff) of the complexes was measured by the Evans method. The cyclic voltammograms at Pt disk electrode for these complexes display only one reversible Cu(II)/Cu(I) redox couple.     

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.     

DNA binding and cleavage properties of certain tetrammine ruthenium(II) complexes of modified 1,10-phenanthrolines--effect of hydrogen-bonding on DNA-binding affinity

A series of ruthenium(II) mixed ligand complexes of the type [Ru(NH(3))(4)(L)](2+), where L=imidazo[4,5-f][1,10]phenanthroline (ip), 2-phenylimidazo[4,5-f][1,10]phenanthroline (pip), 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (hpip), 4,7-diphenyl-1,10-phenanthroline (dip), naphtha[2,3-a]dipyrido[3,2-h:2',3'-f]phenazine-5,18-dione (qdppz), 5,18-dihydroxynaphtho[2,3-a]dipyrido[3,2-H:2',3'-f]phenazine (hqdppz), have been isolated and characterized. The interaction of these complexes with calf thymus DNA (CT DNA) has been explored by using absorption, emission, and circular dichroic spectral methods, thermal denaturation studies and viscometry. All these studies suggest the involvement of the modified phenanthroline 'face' rather than the ammonia 'face' of the complexes in DNA binding. An intercalative mode of DNA binding, which involves the insertion of the modified phenanthroline ligands in between the base pairs, is suggested. The results from absorption spectral titration and circular dichroism (CD), thermal denaturation and viscosity experiments indicate that the qdppz and hqdppz complexes (K(b) approximately 10(6) and Delta T(m)=11-13 degrees C) bind more avidly than the ip, pip and hpip complexes (K(b) approximately 10(5), Delta T(m)=6-8 degrees C). Intramolecular hydrogen bonding in the hpip and hqdppz complexes increases the surface area of the intercalating diimines and enhances the DNA binding affinity substantially. The ammonia co-ligands of the complexes are possibly involved in hydrogen bonding with the intrastrand nucleobases to favour intercalation of the extended aromatic ligands. Circular dichroism spectral studies reveal that all the complexes effect certain structural changes on DNA duplex; [Ru(NH(3))(4)(ip)](2+) induces a B to A transition while [Ru(NH(3))(4)(qdppz)](2+) a B to Psi conformational change on CT DNA. Cleavage efficiency of the complexes were determined using pBR322 supercoiled plasmid DNA. All the complexes, except hqdppz complex, promote the cleavage of supercoiled plasmid (form I) to relaxed circular form (form II).     

Synthesis,crystal structure,and nuclease activity of planar mono-heterocyclic base copper(II) complexes

A series of mononuclear copper(II) complexes having a 1:1 molar ratio of copper and the planar heterocyclic base like 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) are prepared from a reaction of copper(II) nitrate.trihydrate and the base (L) in ethanol or aqueous ethanol at different temperatures. The complexes [Cu(dpq)(NO(3))(2)] (2), [Cu(dpq)(NO(3))(H(2)O)(2)](NO(3)) (3), [Cu(dpq)(NO(3))(2)(H(2)O)(2)].2H(2)O (4.2H(2)O) and [Cu(dppz)(NO(3))(2)(H(2)O)].H(2)O (5.H(2)O) have been characterized by X-ray crystallography. The crystal structures show the presence of the heterocyclic base in the basal plane. The coordination geometries of the copper(II) centers are axially elongated square-pyramidal (4+1) in 2, 3 and 5, and octahedral (4+2) in 4. The nitrate anion in the coordination sphere displays unidentate and bidentate chelating bonding modes. The axial ligand is either H(2)O or NO(3) in these structures giving a Cu-L(ax) distance of approximately 2.4 A. The one-electron paramagnetic complexes (mu approximately 1.8 mu(B)) exhibit axial EPR spectra in DMF glass at 77 K giving g(parallel)>g( perpendicular ) with an A(parallel) value of approximately 170G indicating a [d(x)2(-y)2](1) ground state. The complexes are redox active and display a quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.0 V vs. SCE giving an order of the E(1/2) values as 5(dppz)>2-4 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). The complexes bind to calf thymus DNA giving an order 5 (dppz)>2 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). An effect of the extended planar ring in dpq and dppz is observed in the DNA binding. The complexes show nuclease activity with pUC19 supercoiled DNA in DMF/Tris-HCl buffer containing NaCl in presence of mercaptopropanoic acid as a reducing agent. The extent of cleavage follows the order: [Cu(phen)(2)(H(2)O)](ClO(4))(2)>5>2 approximately 3 approximately 4>1. The bis-phen complex is a better cleaver of SC DNA than 1-5 having mono-heterocyclic base. Mechanistic investigations using distamycin reveal minor groove biding for the phen, dpq complexes, and a major groove binding for the dppz complex 5. The cleavage reactions are found to be inhibited in the presence of hydroxyl radical scavenger DMSO and the reactions are proposed to proceed via sugar hydrogen abstraction pathway. The ancillary ligand is found to have less effect in DNA binding but are of importance in DNA cleavage reactions.     

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.     

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: the novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

The coordination geometry around copper(II) in [Cu(imda)(phen)(H2O)] (1) (H2imda = iminodiacetic acid, phen = 1,10-phenanthroline) is described as distorted octahedral while those in [Cu(imda)(5,6-dmp)] (2) (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline) and [Cu(imda)(dpq)] (3) (dpq = dipyrido-[3,2-d:2',3'-f]-quinoxaline) as trigonal bipyramidal distorted square-based pyramidal with the imda anion facially coordinated to copper(II). Absorption spectral (Kb: 1, 0.60+/-0.04x10(3); 2, 3.9+/-0.3x10(3); 3, 1.7+/-0.5x10(4) M(-1)) and thermal denaturation studies (deltaTm: 1, 5.70+/-0.05; 2, 5.5+/-10; 3, 10.6+/-10 degrees C) and viscosity measurements indicate that 3 interacts with calf thymus DNA more strongly than 1 and 2. The relative viscosities of DNA bound to 1 and 3 increase while that of DNA bound to 2 decreases indicating formation of kinks or bends and/or conversion of B to A conformation as revealed by the decrease in intensity of the helicity band in the circular dichroism spectrum of DNA. While 1 and 3 are bound to DNA through partial intercalation, respectively, of phen ring and the extended planar ring of dpq with DNA base stack, the complex 2 is involved in groove binding. All the complexes show cleavage of pBR322 supercoiled DNA in the presence of ascorbic acid with the cleavage efficiency varying in the order 3 > 1 > 2. The highest oxidative DNA cleavage of dpq complex is ascribed to its highest Cu(II)/Cu(I) redox potential. Oxidative cleavage studies using distamycin reveal minor groove binding for the dpq complex but a major groove binding for the phen and 5,6-dmp complexes. Also, all the complexes show hydrolytic DNA cleavage activity in the absence of light or a reducing agent with cleavage efficiency varying in the order 1 > 3 > 2.     

DNA binding and nucleolytic properties of Cu(ii) complexes of salicylaldehyde semicarbazones

The copper(ii) complexes of two salicylaldehyde semicarbazones, HOC(6)H(4)CH[double bond, length as m-dash]N-NHCONR(2) [H(2)Bnz(2) (R = CH(2)Ph) and H(2)Bu(2) (R = Bu)], were evaluated for their DNA binding and cleavage properties by spectrophotometric DNA titration, ethidium bromide displacement assay and electrophoretic mobility shift assay. Results showed that the Cu(ii) complexes can bind to DNA via a partial intercalation mode with binding constants of 1.1 × 10(4) and 9.5 × 10(3) M(-1) for [Cu(HBnz(2))Cl] and [Cu(HBu(2))Cl], respectively. These complexes also cleave DNA in the presence of ascorbic acid, most likely through hydroxyl radicals that are generated via the reduction of a Cu(ii) to a Cu(i) species. The complexes show similar DNA cleavage activity, which is reflected in the similarity of their frontier molecular orbital energies calculated by density functional theory. These results are discussed in relation to the anticancer properties of the complexes.     

Synthesis, characterization, DFT studies and DNA binding of mixed platinum (II) complexes containing quinoxaline and 1,2-dithiolate ligands

The complexes Pt(pq)Cl2(1) and Pt(pq)(bdt) (2) (where pq = 2-(2'pyridyl)quinoxaline and bdt=benzene-1,2-dithiolate) have been synthesized and fully characterized by UV-visible (UV-Vis), Fourier Transformer Infrared Spectra (FTIR), 1 and 2D NMR and cyclic voltammetry (CV). Interactions of the tested systems (the aforementioned complexes 1 and 2) and the free ligands pq and bdt with double stranded calf thymus DNA (CT-DNA) were studied by UV-spectrophotometric (melting curves) and circular dichroism (CD) measurements. The results suggest that both complexes 1 and 2, are able to form adducts with DNA and to distort the double helix by changing the base stacking. Complex 2 forms stronger adducts to CT-DNA than complex 1 and this is probably due to the substitution of the chlorine atoms of 1 by the 1,2-dithiolate ligand (bdt) in 2. The latter induces an extensive distortion in the planarity of 2 as density functional theory (DFT) calculations reveal. Besides, the light absorbing complex 2 possess intense mixed metal ligand to ligand charge transfer (MM'LLCT) transition in the visible region of the spectrum and could act as photoluminescent metal-based probe for the study of DNA binding. Thus, the photocleavage of DNA by 2 has been studied by UV-Vis and CD spectra and monitored by agarose gel electrophoresis. Under our experimental conditions, it is unclear that complex 2 can photocleave DNA. Furthermore, the ability of 2 to inhibit proliferation of human tumor cell lines was tested and the results indicate some cytoxytic effect on the SF-286 cells.     

Copper(II)-fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability

Copper(II) complexes of fluoroquinolone antibacterial agents levofloxacin (LEV) and sparfloxacin (SPAR), containing or not a nitrogen donor heterocyclic ligand, 2,2'-bipyridine (bipy) or 1,10-phenathroline (phen), were prepared and characterized. The complexes are of the type [CuCl(2)(H(2)O)(L)], [CuCl(bipy)(L)]Cl and [CuCl(2)(phen)(L)], where L?=?LEV or SPAR. The data suggest that LEV and SPAR act as zwitterionic bidentade ligands coordinated to Cu(II) through the carboxylate and ketone oxygen atoms. The electron paramagnetic resonance spectra of the [CuCl(bipy)(L)]Cl and [CuCl(2)(phen)(L)] complexes (L?=?LEV and SPAR) in aqueous and DMSO solutions indicate mixture of mononuclear and binuclear forms. The Cu(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activity in vitro against Trypanosoma cruzi, the causative agent of Chagas disease. The assays performed against bloodstream trypomastigotes showed that all complexes were more active than their corresponding ligands. Complexes [CuCl(2)(phen)(LEV)] and [CuCl(2)(phen)(SPAR)] were revealed, among all studied compounds, to be the most active with IC(50)?=?1.6 and 4.7?μM, respectively, both presenting a superior effect than benznidazole. The interactions of fluoroquinolones and their Cu(II) complexes with calf-thymus DNA were investigated. These compounds showed binding properties towards DNA, with moderated binding constants values, suggesting that this structure may represent a parasite target.     

Synthesis and DNA binding/cleavage of mononuclear copper(II) phenanthroline/bipyridine proline complexes

The complexes [Cu(II)(phen)(L-Pro)(H2O)]+ ClO4(-) (1; phen = 1,10-phenanthroline) and [Cu(II)(bipy)(L-Pro)(H2O)]+ ClO4(-) (2; bipy = 2,2'-bipyridine) were synthesized and characterized by IR, magnetic susceptibility, UV/VIS, EPR, ESI-MS, elemental analysis, and theoretical calculations. The metal center was found in a square-pyramidal geometry. UV/VIS, thermal-denaturation, and fluorescence-spectroscopic studies were conducted to assess the interaction of the complexes with CT-DNA. An intercalative mode of binding was found, with intrinsic binding constants (Kb) of 3.86x10(3) and 4.6x10(3) M(-1) and Stern-Volmer quenching constants (K) of 0.15 and 0.11 for 1 and 2, respectively. Interestingly, none of the Cu(II) complexes was able to cleave pUC-19 DNA, which is attributed to the absence of a Pro amide H-atom and inhibition of the formation of an OH radical from the axially coordinated H2O molecule.     

Synthesis, crystal structure, DNA binding and photo-induced DNA cleavage activity of (S-methyl-L-cysteine)copper(II) complexes of heterocyclic bases

Ternary S-methyl-L-cysteine (SMe-l-cys) copper(II) complexes [Cu(SMe-L-cys)(B)(H(2)O)](X) (1-4), where the heterocyclic base B is 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyridoquinoxaline (dpq, 3) and dipyridophenazine (dppz, 4), and X is ClO(4)(-) (1-3) or NO(3)(-) (4), are prepared and their DNA binding and cleavage properties studied. Complexes 2 and 4 are structurally characterized by X-ray crystallography. Both the crystal structures show distorted square-pyramidal (4+1) CuN(3)O(2) coordination geometry of the complexes in which the N,O-donor S-methyl-L-cysteine and N,N-donor heterocyclic base bind at the basal plane with a water molecule as the axial ligand. In addition, the dppz structure shows the presence of a 1D-chain formed due to covalent linkage of the carboxylate oxygen atom belonging to another molecule at the elongated axial site. The crystal structures show chemically significant non-covalent interactions like hydrogen bonding involving the axial aqua ligand and pi-pi interactions between dppz ligands. The complexes display a d-d band in the range of 605-654 nm in aqueous dimethylformamide (DMF) solution (9:1 v/v). The redox active complexes show quasireversible cyclic voltammetric response near 0.1 V in DMF assignable to the Cu(II)/Cu(I) couple. The complexes show good binding affinity to calf thymus (CT) DNA giving the order: 4 (dppz)>3 (dpq)>2 (phen)>1 (bpy). The intrinsic binding constants, obtained from UV-visible spectroscopic studies, are 1.3x10(4) and 2.15 x 10(4) M(-1) for 3 and 4, respectively. Control DNA cleavage experiments using pUC19 supercoiled (SC) DNA and minor groove binder distamycin suggest major groove binding propensity for the dppz complex, while the phen and dpq complexes bind at the minor groove of DNA. Complexes 2-4 show DNA cleavage activity in dark in the presence of a reducing agent 3-mercaptopropionic acid (MPA) via a mechanistic pathway involving formation of hydroxyl radical as the reactive species. The complexes also show efficient photo-induced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency follows the order: 3>4>2. The complexes exhibit significant DNA cleavage activity on irradiation with visible light of 633 nm. Control experiments show inhibition of cleavage in presence of singlet oxygen quenchers like sodium azide, histidine and enhancement of cleavage in D(2)O, suggesting formation of singlet oxygen as a reactive species in a type-II process. The photosensitizing effect of the thiomethyl group of the amino acid is evidenced from the observation of significant DNA photocleavage activity of the phen complex 2 as the phen ligand itself is not a photosensitizer.     

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.     

Mononuclear copper(II) complexes with quinolones and nitrogen-donor heterocyclic ligands: Synthesis, characterization, biological activity and interaction with DNA

The neutral mononuclear copper(II) complexes with the quinolone antibacterial drugs, pipemidic acid and N-propyl-norfloxacin, in the presence or absence of nitrogen-donor heterocyclic ligands, 2,2′-bipyridine, 1,10-phenanthroline or 2,2′-dipyridylamine, have been prepared and characterized spectroscopically. The interaction of copper(II) with the deprotonated quinolone ligand leads to the formation of the neutral mononuclear complexes of the type [Cu(quinolone)₂(H₂O)] (1)–(2) while the presence of the N-donor ligand leads to the formation of the neutral mononuclear complexes of the type [Cu(quinolone)(N-donor)Cl] (3)–(8). In all the complexes, copper(II) is pentacoordinate having a distorted square pyramidal geometry. The electron paramagnetic resonance spectra of 1 and 2 are typical of mononuclear Cu(II) complexes, while for the mixed-ligands complexes 3–8 a mixture of dimeric and monomeric species is indicated. The interaction of the complexes with calf-thymus DNA has been investigated with diverse spectroscopic techniques and has shown that the complexes can be bound to calf-thymus DNA by the intercalative mode. The antimicrobial activity of the complexes has been tested on three different microorganisms. All the complexes show an increased biological activity in comparison to the corresponding free quinolone ligand.