DNA interactions of new mixed-ligand complexes of cobalt(III) and nickel(II) that incorporate modified phenanthroline ligands

Four new mixed-ligand complexes, namely [Co(phen)(2)(qdppz)](3+), [Ni(phen)(2)(qdppz)](2+), [Co(phen)(2)(dicnq)](3+) and [Ni(phen)(2)(dicnq)](2+) (phen=1,10-phenanthroline, qdppz=naptho[2,3-a]dipyrido[3,2-H:2',3'-f]phenazine-5,18-dione and dicnq=dicyanodipyrido quinoxaline), were synthesized and characterized by FAB-MS, UV/Vis, IR, 1H NMR, cyclic voltammetry and magnetic susceptibility methods. Absorption and viscometric titration as well as thermal denaturation studies revealed that each of these octahedral complexes is an avid binder of calf-thymus DNA. The apparent binding constants for the dicnq- and qdppz-bearing complexes are in the order of 10(4) and >10(6) M(-1), respectively. Based on the data obtained, an intercalative mode of DNA binding is suggested for these complexes. While both the investigated cobalt(III) complexes and also [Ni(phen)(2)(qdppz)](2+) affected the photocleavage of DNA (supercoiled pBR 322) upon irradiation by 360 nm light, the corresponding dicnq complex of nickel(II) was found to be ineffective under a similar set of experimental conditions. The physico-chemical properties as well as salient features involved in the DNA interactions of the cobalt(III) and nickel(II) complexes investigated here were compared with each other and also with the corresponding properties of the previously reported ruthenium(II) analogues.     

Synthesis, DNA-binding and photocleavage studies of cobalt(III) mixed-polypyridyl complexes: [Co(phen)(2)(dpta)](3+) and [Co(phen)(2)(amtp)](3+)

Two novel cobalt(III) mixed-polypyridyl complexes [Co(phen)(2)(dpta)](3+) and [Co(phen)(2)(amtp)](3+) (phen=1,10-phenanthroline, dpta=dipyrido-[3,2-a;2',3'-c]- thien-[3,4-c]azine, amtp=3-amino-1,2,4-triazino[5,6-f]1,10-phenanthroline) have been synthesized and characterized. The interaction of these complexes with calf thymus DNA was investigated by spectroscopic, cyclic voltammetry, and viscosity measurements. Results suggest that the two complexes bind to DNA via an intercalative mode. Moreover, these Co(III) complexes have been found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365nm. The mechanism studies reveal that hydroxyl radical (OH()) is likely to be the reactive species responsible for the cleavage of plasmid DNA by [Co(phen)(2)(dpta)](3+) and superoxide anion radical (O(2)(-)) acts as the key role in the cleavage reaction of plasmid DNA by [Co(phen)(2)(amtp)](3+).     

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 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.     

Cobalt complexes of terpyridine ligand: crystal structure and photocleavage of DNA

Two new cobalt complexes, [Co(pytpy)(2)](ClO(4))(2), 1, and [Co(pytpy)(2)](ClO(4))(3), 2 where pytpy=pyridine terpyridine, have been synthesized and characterized. Single-crystal X-ray structure of both the complexes has been resolved. The structure shows the complexes to be a monomeric cobalt(II) and cobalt(III) species with two pytpy ligands coordinated to the metal ion to give a six coordinate complex. Both cobalt(II) and cobalt(III) complexes crystallize in meridional configuration. The interaction of these complexes with calf thymus DNA has been explored by using absorption, emission spectral, electrochemical studies and viscosity measurements. From the experimental results the DNA binding constants of 1 and 2 are found to be (1.97+/-0.15)x10(4)M(-1) and (2.7+/-0.20)x10(4)M(-1) respectively. The ratio of DNA binding constants of 1 and 2 have been estimated to be 0.82 from electrochemical studies, which is in close agreement with the value of 0.73 obtained from spectral studies. The observed changes in viscosity of DNA in the presence of increasing amount of complexes 1 and 2 suggest intercalating binding of these complexes to DNA. Results of DNA cleaving experiments reveal that complex 2 efficiently cleaves DNA under photolytic conditions while complex 1 does not cleave DNA under similar conditions.     

Synthesis, characterization, X-ray structure and DNA photocleavage by cis-dichloro bis(diimine) Co(III) complexes

Complexes of the type [Co(LL)2Cl2]Cl, where LL = N,N'-ethylenediamine (en), 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been synthesized and characterized by elemental analyses, IR, UV-visible and NMR spectroscopy. Crystal structure of [Co(phendione)2Cl2]Cl x 0.5 HCl x 3.5 H2O has been solved and refined to R = 0.0552. The crystal is monoclinic with space group C2/c; a = 25.730(2) A, b = 12.375(1) A, c = 18.979(2) A, beta = 119.925(1) degrees and Z = 8. The DNA binding characteristics of the complexes, investigated by covalent binding assay, viscosity measurements and competitive binding fluorescence measurements show that the complexes interact with DNA covalently except the complex containing the planar dppz ligand which intercalates within the base pairs of DNA. The complexes containing en, phen and phendione cleave plasmid pBR 322 DNA upon irradiation under aerobic conditions while the complex containing the dppz ligand cleaves DNA upon irradiation under inert atmosphere. Molecular modeling studies show that the minimized structure of [Co(phendione)2Cl2]+, maintained the octahedral structure while binding to the N7 of guanines and the ligand fits into the major groove without disrupting the helical structure of the B-DNA.     

DNA-binding studies of mixed-ligand (ethylenediamine)ruthenium(II) complexes

A series of mixed-ligand ruthenium(II) complexes of the type [Ru(en)(2)bpy](2+) (bpy=2,2-bipyridine; 1), [Ru(en)(2)phen](2+) (phen=1,10-phenantroline; 2), [Ru(en)(2)IP](2+) (IP=imidazo[4,5-f][1,10]phenanthroline; 3), and [Ru(en)(2)PIP](2+) (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline; 4) have been isolated and characterized by UV/VIS, IR, and (1)H-NMR spectral methods. The binding of the complexes with calf thymus DNA has been investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photo-cleavage. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (=calf thymus DNA) by groove mode. Complex 2 binds more avidly to CT DNA than complex 1, complexes 3 and 4 bind to CT DNA by intercalation mode, 4 binds more avidly to CT DNA than 3. Noticeably, the four complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.     

DNA-binding and cleavage studies of novel copper(II) complex with L-phenylalaninate and 1,4,8,9-tetra-aza-triphenylene ligands

DNA-binding properties of novel copper(II) complex [Cu(l-Phe)(TATP)(H(2)O)](+), where L-Phe=L-phenylalaninate and TATP=1,4,8,9-tetra-aza-triphenylene are investigated using electronic absorption spectroscopy, fluorescence spectroscopy, voltammetry and viscosity measurement. It is found that the presence of calf thymus DNA results in a hypochromism and red shift in the electronic absorption, a quenching effect on fluorescence nature of ethidium bromide-DNA system, an enhanced response on voltammograms of [Co(phen)(3)](3+/2+)-DNA system, and an obvious change in viscosity of DNA. From absorption titration, fluorescence analysis and voltammetric measurement, the binding constant of the complex with DNA is calculated. The latter two methods reveal the stronger binding of [Cu(l-Phe)(TATP)(H(2)O)](+) complex to double strand DNA by the moderate intercalation than [Co(phen)(3)](3+). Such a binding induces the cleavage of plasmid pBR322 DNA in the presence of H(2)O(2).     

DNA-binding and photocleavage studies of cobalt(III) polypyridyl complexes:

Two complexes of [Co(phen)2IP]3+ (IP=imidazo[4,5-f][l,10]phenanthroline) and [Co(phen)2PIP]3+ (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) have been synthesized and characterized by UV/VIS, IR, EA and mass spectra. The binding of the two complexes with calf thymus DNA has been investigated by absorption spectroscopy, cyclic voltammetry, viscosity measurements and DNA cleavage assay. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that both of the complexes bind to CT DNA by intercalation via IP or PIP into the base pairs of DNA. [Co(phen)2PIP]3+ binds more avidly to CT DNA than [Co(phen)2IP]3+, which is consistent with the extended planar and pi system of PIP. Noticeably, the two complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.     

Synthesis, characterization and DNA binding of ruthenium(II) complexes containing the atatp ligand

Acenaphtheno[1,2-b]-1,4,8,9-tetraazatriphenylene (atatp) and its complexes [Ru(L)2atatp](ClO4)2 x nH2O (L = 2,2'-bipyridine (bpy), n=2 (1); 1,10-phenanthroline (phen), n=2 (2); and 2,9-dimethyl-1,10-phenanthroline (dmp), n=1 (3)) have been synthesized and characterized by elemental analyses and 1H NMR. The spectral and electrochemical properties of these complexes are also examined. Complexes 1 and 2 display bright luminescence in acetonitrile but very weak luminescence in water solution. However, complex 3 is not luminescent in either solvent. The interaction of the complexes with calf thymus DNA (CT-DNA) has been studied by absorption, emission and viscosity measurements. The intrinsic binding constants of complexes 1 and 2 are 7.6 x 10(4) and 8.8 x 10(4) M(-1) respectively. The relatively low affinities of complexes 1 and 2 with DNA may arise from the atatp ligand, indicating that the size and shape of the intercalated ligand have a marked effect on the strength of interaction. Complexes 1 and 2 bind with CT-DNA in an intercalative mode but complex 3 in a non-intercalative one, showing that changing the ancillary ligand affects not only the binding magnitude, but also the binding mode of the interaction.     

Syntheses and DNA-binding studies of two ruthenium(II) complexes containing one ancillary ligand of bpy or phen: [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)2

Two new ruthenium(II) complexes of [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)(2) (bpy=2,2'-bipyridine, phen=1,10-phenanthroline, pp[2,3]p=pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis and 1H NMR spectra. The calf thymus DNA-binding properties of the two complexes were investigated by UV-visible and emission spectroscopy, competitive binding experiments with ethidium bromide and viscosity measurements. The results indicate that the two complexes intercalate between the base pairs of the DNA tightly with intrinsic DNA-binding constants of 3.08 x 10(6) and 6.53 x 10(6) M(-1) in buffered 50 mM NaCl, respectively, which are much larger than 6.9 x 10(5) M(-1) for [Ru(bpy)2(pp[2,3]p)](ClO4)2 containing two ancillary ligands of bpy.     

Synthesis, micellar properties, DNA binding and antimicrobial studies of some surfactant-cobalt(III) complexes

A new class of surfactant-cobalt(III) complex ions of the type, cis-[Co(X)(2)(C(14)H(29)NH(2))Cl](2+) (where X=ethylenediamine (en), or 2,2'-bipyridyl (bpy), or 1,10-phenanthroline (phen)) and cis-[Co(trien)(C(14)H(29)NH(2))Cl](2+) (trien=triethylenetetramine) were synthesized and characterized by IR, NMR, UV-visible electronic absorption spectra, elemental analysis and metal analysis. The critical micelle concentration (CMC) values of these surfactant-cobalt(III) complexes in aqueous solution were obtained from conductance measurements. Specific conductivity data (at 298, 308, 318 and 328 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (DeltaG(0)(m), DeltaH(0)(m) and DeltaS(0)(m)). Interactions between calf thymus DNA and the surfactant-cobalt(III) complexes in aqueous solution have been investigated by electronic absorption spectroscopy, emission spectroscopy and viscosity measurements. The electrostatic interactions, van der Waals interactions and/or partial intercalative binding have been observed in these systems. The surfactant-cobalt(III) complexes were screened for their antibacterial and antifungal activities against various microorganisms. The results were compared with the standard drugs, Ciprofloxacin and Fluconazole respectively.     

Synthesis,DNA Binding,and Cleavage Studies of Co(III) Complexes with Fused Aromatic NO/NN-Containing Ligands

Four new Co(III) complexes, namely [Co(cq)₃](PF₆)₃, [Co(phen)₂(cq)](PF₆)₃, [Co(bnp)₃] (PF₆)₃, and [Co(phen)₂(bnp)](PF₆)₃ (where cq = chromeno[2,3-b]quinoline, phen = 1,10-phenanthroline and bnp = dibenzo[b,g][1,8]naphthyridine), were synthesized and structurally characterized. Spectroscopic data suggested an octahedral geometry for all the complexes. Binding studies of these complexes with double-stranded (ds)DNA were analyzed by absorption spectra, viscosity, and thermal denaturation studies. The results revealed that the metal complex intercalates into the DNA base stack as intercalator. The oxidative cleavage activities of the complexes were studied with supercoiled pUC19 DNA using gel electrophoresis and the results show that the complexes have potent nuclease activity.     

DNA-binding and photocleavage studies of cobalt(III) mixed-polypyridyl complexes containing 2-(2-chloro-5-nitrophenyl)imidazo [4,5-f][1,10]phenanthroline

The ligand 2-(2-chloro-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline(CNOIP) and its complexes [Co(bpy)(2)(CNOIP)](3+) (1) and [Co(phen)(2)(CNOIP)](3+) (2) (bpy=2,2'-bipyridine; phen=1,10-phenanthroline) have been synthesized and characterized. Binding of the two complexes with calf thymus DNA has been investigated by spectroscopic methods, cyclic voltammetry, viscosity, and electrophoresis measurements. The experimental results indicate that both complexes bind to DNA through an intercalative mode. In comparison with their parent complexes containing PIP ligand (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline), the introduction of NO(2) and Cl groups to the PIP ligand decreased the binding affinity of complexes 1 and 2 to CT DNA. Both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA, the hydroxyl radical (OH*) is suggested to be the reactive species responsible for the cleavage.     

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.     

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, structure and DNA interaction of cobalt(III) bis-complexes of 1,3-bis(2-pyridylimino)isoindoline and 1,4,7-triazacyclononane

The complex [CoL(2)](ClO(4)).MeOH (1), where HL is the tridentate 3N ligand 1,3-bis(2-pyridylimino)isoindoline, has been isolated and its X-ray crystal structure successfully determined. It possesses a distorted octahedral structure in which both the ligands are coordinated meridionally to cobalt(III) via one deprotonated isoindoline (L(-)) and two pyridine nitrogen atoms. Interestingly, the average dihedral angle between pyridine and isoindoline rings is 25.9 degrees , indicating that the ligand is twisted upon coordination to cobalt(III). The interaction of the complex with calf-thymus DNA has been studied using various spectral methods and viscosity and electrochemical measurements. For comparison, the DNA interaction of [Co(tacn)(2)]Cl(3) (2), where tacn is facially coordinating 1,4,7-triazacyclononane, has been also studied. The ligand-based electronic spectral band of 1 and the N(sigma)-->Co(III) charge transfer band of 2 exhibit moderate hypochromism with small or no blue shift on interaction with DNA. The intrinsic binding constants calculated reveal that the monopositive complex ion [CoL(2)](+) exhibits a DNA-binding affinity lower than the tripositive complex ion [Co(tacn)(2)](3+). The steric clashes with DNA exterior caused by the second L(-) ligand bound to cobalt(III), apart from the lower overall positive charge on the [CoL(2)](+) complex, dictates its DNA-binding mode to be surface binding rather than partial intercalative interaction expected of the extended aromatic chromophore of deprotonated isoindoline anion. An enhancement in relative viscosity of CT DNA on binding to 1 is consistent with its DNA surface binding. On the other hand, a slight decrease in viscosity of CT DNA was observed on binding to 2 revealing that the smaller cation leads to bending (kinking) and hence shortening of DNA chain length. The electrochemical studies indicate that the DNA-bound complexes are stabilised in the higher Co(III) rather than the lower Co(II) oxidation state, suggesting the importance of electrostatic forces of DNA interaction.     

Synthesis, characterization, DNA-binding and spectral properties of complexes [Ru(L)4(dppz)]2+ (L=Im and MeIm)

Two new Ru(II) complexes [Ru(L)(4)(dppz)](2+) (L=imidazole (Im), 1-methylimidazole (MeIm); dppz=dipyrido[3,2-a:2',3'-c]phenazine), have been synthesized and characterized in detail by elemental analysis, (1)H NMR, Electrospray ionization mass spectrometry (ESI-MS) and UV-visible (UV-Vis) spectroscopic techniques. The interaction of these complexes with calf thymus DNA (CT-DNA) has been explored by using electronic absorption titration, competitive binding experiment, circular dichroism (CD), thermal denaturation and viscosity measurements. The experimental results show that: both the two complexes can bind to DNA in an intercalation mode; the DNA-binding affinity of complex [Ru(Im)(4)(dppz)](2+)1 (K(b)=2.5 x 10(6)M(-1)) is greater than that of complex [Ru(MeIm)(4)(dppz)](2+)2 (K(b)=1.1 x 10(6)M(-1)). Moreover, it is very interesting to find that the circular dichroic spectrum of DNA-complex 1 adduct, in which both bands centered at 277 nm and 236 nm are all negative, is very different from those of DNA-complex 2 adduct and other Ru(II) complexes binding to DNA in general intercalation mode. It may be due to the hydrogen-bonding effect or the contribution of induced CD signals of complex 1. Another interesting finding is that the hypochromism of the complexes is not linear relation to their DNA-binding affinities. In order to deeply study these experimental phenomena and trends, the density functional theory (DFT) and time-dependent DFT (TDDFT) computations were carried out, and on the basis of the DFT/TDDFT results and the frontier molecular orbital theory, the trend in DNA-binding affinities, the spectral properties as well as the interesting phenomena of larger extent of hypochromism but relatively smaller K(b) values for the title complexes have been reasonably explained.     

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.     

Spectral and redox studies on mixed ligand complexes of cobalt(III) phenanthroline/bipyridyl and benzoylhydrazones, their DNA binding and antimicrobial activity

Cobalt(III) complexes of the type [Co(N-N)2L](ClO4)2.H2O [where L=anionic form of para-substituted benzaldehyde-benzoylhydrazone (BHBX-); X=H, Me, OMe, OH, Cl or NO2; N-N=2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen)] have been synthesized and characterized through UV-Vis, IR, NMR and electrochemical studies. The IR spectral frequencies support the mode of coordination of BHBX to the metal through the imino nitrogen and enolic oxygen atoms. The electronic absorption spectra exhibit metal to ligand charge transfer (MLCT) transition around 450 nm together with intraligand (IL) bands that are comparable to that of [Co(phen/bpy)3]3+. In acetonitrile solution these complexes show two well defined redox couples corresponding to Co(III/II) and Co(II/I) processes. Binding of these complexes with herring sperm DNA have been investigated by spectroscopic and voltammetric methods. The lower binding constant values of these complexes with respect to the [Co(phen/bpy)3]3+ are ascribed to the polar interaction of the substituted benzoylhydrazone moiety with the sugar-phosphate backbone of the DNA. The UV spectrum shows reasonable hypochromism with slight (2-4 nm) red shift, while the cyclic voltammogram shows decrease in current intensity along with a very small shift in the formal potential of the Co(III/II) redox couple. These experimental results indicate that phen mixed ligand complexes bind to DNA through an intercalative mode more effectively than their bpy counterparts. These complexes are also found to have good antimicrobial activity.