Interaction between macrocyclic nickel complexes and the nucleotides GMP,AMP and ApG

Reactions between the nucleotides GMP, AMP and ApG and the complexes Ni(tren), Ni(cyclam) and NiCR in aqueous solution have been monitored by (1)H, (15)N NMR and UV spectroscopy. The three nickel complexes display different properties in reactions with nucleotides. Ni(tren) which has a pseudo-octahedral coordination geometry was shown to bind to all three nucleotides. Ni(cyclam) and NiCR, both with four nitrogen atoms in a square planar arrangement are not able to bind to nucleotides efficiently because of steric hindrance. Oxidation of Ni(cyclam) by KHSO(5) to produce trivalent Ni(III)(cyclam) improves the coordination capacity, while oxidation of NiCR does not produce a similar effect. The nucleotides interact with trivalent nickel complexes to different extent. Ni(III)CR is seen to oxidize GMP gradually but does not affect AMP significantly. Ni(III)(cyclam), on the other hand, does not oxidize either GMP or AMP at the 1:1 concentration of oxidant used. This result is probably due to the lower redox potential of Ni(cyclam). ApG binds less efficiently to the Ni complexes but is easier oxidized than the mononucleotides.     

Synthesis, structural characterization and antimicrobial activities of 4- and 6-coordinate nickel(II) complexes with three thiosemicarbazones and semicarbazone ligands

To investigate the relationship between antimicrobial activities and the molecular structures of nickel(II) complexes with thiosemicarbazone and semicarbazone ligands, nickel(II) complexes with ligands Hmtsc, Hatsc, Hasc and H2dmtsc, were prepared and characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopies, magnetic susceptibility measurements, UV-Vis absorption spectra, TG/DTA and single-crystal X-ray analysis. Their antimicrobial activities were evaluated by the MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 4-coordinate, diamagnetic nickel(II) complexes showed antimicrobial activities which were different from those of free ligands or the starting nickel(II) compounds; [Ni(mtsc)(OAc)] 1 showed selective and effective antimicrobial activities against two Gram-positive bacteria (B. subtilis and S. aureus) and modest activities against a yeast (S. cerevisiae), [Ni(mtsc)Cl] 3 exhibited moderate activities against a Gram-positive bacterium (S. aureus), and [Ni(atsc)(OAc)] 5 showed modest activities against two Gram-positive bacteria (B. subtilis and S. aureus). On the other hand, the 6-coordinate, paramagnetic nickel(II) complexes with two protonated or deprotonated ligands ([Ni(mtsc)2] 2, [Ni(atsc)(mtsc)] 4, [Ni(atsc)2] 6, [Ni(Hatsc)2](NO3)(2)7, [Ni(Hatsc)2]Cl(2)8 and [Ni(Hasc)2](OAc)(2)9) and the sterically crowded 4-coordinate, diamagnetic nickel(II) complex ([Ni(dmtsc)] 10) did not inhibit the growth of the test organisms. The structure-activity correlation in this series of nickel(II) complexes was discussed based on their ligand-replacement abilities.     

Nickel-quinolones interaction. Part 5-Biological evaluation of nickel(II) complexes with first-, second- and third-generation quinolones

The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N′-donor heterocyclic ligand 2,2′-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2′-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2′-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)₂(2,2′-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)₂(H₂O)₂], [Ni(quinolonato)₂(2,2′-bipyridine)] and [Ni(quinolonato)₂(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase.     

DNA Binding and cleavage activity of Ni(II) complex with all-trans retinoic acid

Absorption, fluorescence spectral, cyclic voltammetry and agarose gel electrophoresis studies have been carried out on the interaction of Ni(II) complex with all-trans retinoic acid ([Ni(RA)(2)(H(2)O)(2)] * H(2)O) with DNA. The results indicate that the [Ni(RA)(2)(H(2)O)(2)] * H(2)O can more effectively promote the cleavage of plasmid DNA than that of all-trans retinoic acid (HRA) and Ni(II) at physiological pH and temperature, which may be one of the reasons why the inhibitory effect of [Ni(RA)(2)(H(2)O)(2)] * H(2)O on the human bladder line EJ cells is much greater than that of retinoic acid. It was found that the process of plasmid DNA cleavage was sensitive to ionic strength and pH, however, these radical scavengers almost had no effect on the DNA cleavage reaction. The above results suggested that the cleavage of plasmid DNA by [Ni(RA)(2)(H(2)O)(2)]* H(2)O did not produce diffusible hydroxyl radicals via the Fenton reaction. The results of UV-absorption studies and fluorescence characterization of the interaction of [Ni(RA)(2)(H(2)O)(2)] * H(2)O with Calf thymus DNA show that the [Ni(RA)(2)(H(2)O)(2)] * H(2)O binds to DNA mainly in an intercalating mode.     

Antagonistic effect of magnesium chloride on the nickel chloride-induced inhibition of DNA replication in Chinese hamster ovary cells

The degree of inhibition of semiconservative DNA replication induced by nickel chloride (NiCl2) was analyzed by radiolabeled-thymidine incorporation alone or with cesium chloride (CsCl) density gradient centrifugation. The onset and duration of this Ni2+-induced inhibition was time- and concentration-dependent, but the degree of inhibition was not. A maximal reduction in the rate of DNA synthesis was observed within the first hour of treatment with 2.5 mM NiCl2, which was the highest noncytotoxic concentration utilized. After six hours, 500 microM and 1 mM as well as 2.5 mM NiCl2 all produced the same 50% to 60% reduction in [3H]-thymidine incorporation into DNA. The inhibitory effect of nickel ions on DNA synthesis was reversible. The rate of DNA synthesis following a 500 microM or 1 mM NiCl2 treatment began to increase after washout of nickel, but a six-hour exposure of cells to 2.5 mM NiCl2 produced a sustained 50% to 60% suppression of DNA synthetic activity for at least 36 hours. At all concentrations of NiCl2 used in this study, some inhibition of DNA synthesis persisted for at least 48 hours, but by 72 hours after treatment, the rate of [3H]-thymidine incorporation was actually 10% above the control. Examination of autoradiographic slides of cells treated with 2.5 mM NiCl2 for six hours demonstrated a 60% reduction of silver grains, but there was no preferential reduction in the quantity of grains in the nucleolus or any other region. Cesium chloride density gradient analysis of the replication of nucleolar DNA in cells treated with 2.5 mM nickel supported the autoradiographic findings. The inhibitory effect of NiCl2 on DNA replication was prevented by the addition of magnesium chloride (MgCl2) to cells maintained in a simple salts/glucose medium (SGM). This effect did not appear to be due to an antagonism of the cellular uptake of nickel by Mg2+, since the maximally effective dose of Mg2+ reduced 63Ni2+ uptake by no more than 25% while the inhibition of replication was completely reversed.     

Right- and left-handed helixes of poly[d(A-T)].poly[d(A-T)] investigated by infrared spectroscopy

The secondary structures of double-stranded poly[d(A-T)].poly[d(A-T)] in films have been studied by IR spectroscopy with three different counterions (Na+, Cs+, and Ni2+) and a wide variety of water content conditions (relative humidity between 100 and 47%). In addition to the A-, B-, C-, and D-form spectra, a new IR spectrum has been obtained in the presence of nickel ions. The IR spectra of Ni2+-poly[d(A-T)].poly[d(A-T)] films are analyzed by comparison with previously assigned IR spectra of left-handed poly[d(G-C)].poly[d(G-C)] and poly[d(A-C)].poly[d(G-T)], and it is possible to conclude that they reflect a Z-type structure for poly[d(A-T)].poly[d(A-T)]. The Z conformation has been favored by the high polynucleotide concentration, by the low water content of the films, and by specific interactions of the transition metal ions with the purine bases stabilized in a syn conformation. A structuration of the water hydration molecules around the double-stranded Ni2+-poly[d(A-T)].poly[d(A-T)] is shown by the presence of a strong sharp water band at 1615 cm-1.     

New Ni(II)-sulfonamide complexes: synthesis, structural characterization and antibacterial properties. X-ray diffraction of [Ni(sulfisoxazole)2(H2O)4].2H2O and [Ni(sulfapyridine)2

The synthesis, structural characterization, voltammetric experiments and antibacterial activity of [Ni(sulfisoxazole)(2)(H(2)O)(4)].2H(2)O and [Ni(sulfapyridine)(2)] were studied and compared with similar previously reported copper complexes. [Ni(sulfisoxazole)(2)(H(2)O)(4)].2H(2)O crystallized in a monoclinic system, space group C2/c where the nickel ion was in a slightly distorted octahedral environment, coordinated with two sulfisoxazole molecules through the heterocyclic nitrogen and four water molecules. [Ni(sulfapyridine)(2)] crystallized in a orthorhombic crystal system, space group Pnab. The nickel ion was in a distorted octahedral environment, coordinated by two aryl amine N from two sulfonamides acting as monodentate ligands and four N atoms (two sulfonamidic N and two heterocyclic N) from two different sulfonamide molecules acting as bidentate ligands. Differential pulse voltammograms were recorded showing irreversible peaks at 1040 and 1070 mV, respectively, attributed to Ni(II)/Ni(III) process. [Ni(sulfisoxazole)(2)(H(2)O)(4)].2H(2)O and [Ni(sulfapyridine)(2)] presented different antibacterial behavior against Staphylococcus aureus and Escherichia coli from the similar copper complexes and they were inactive against Mycobacterium tuberculosis.     

Synthesis, structure and biological activity of nickel(II) complexes of 5-methyl 2-furfural thiosemicarbazone

5-Methyl 2-furfuraldehyde thiosemicarbazone (M5HFTSC) with nickel(II) leads to three types of complexes: [Ni(M5HFTSC)(2)X(2)], [Ni(M5FTSC)(2)] and [Ni(M5FTSC)(2)] x 2DMF. In the first type the ligand remains in thione form, while in the two other, the anionic thiolato form is involved. The species [Ni(M5HFTSC)(2)X(2)] has been characterized spectroscopically. The structures of [Ni(M5FTSC)(2)] x 2DMF and [Ni(M5FTSC)(2)] have been solved using X-ray diffraction. Biological studies of [Ni(M5HFTSC)(2)Cl(2)] have been carried out in vitro for antifungal activity on human pathogenic fungi, Aspergillus fumigatus and Candida albicans, and in vivo for toxicity on mice. The results are compared to those of the ligand, the metal salt and a similar copper complex [Cu(M5HFTSC)Cl(2)].     

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.     

Superoxide dismutase activity and novel reactions with hydrogen peroxide of histidine-containing nickel(II)-oligopeptide complexes and nickel(II)-induced structural changes in synthetic DNA

At physiologic pH values, histidine-containing nickel(II) oligopeptides reduced the flux of superoxide anion (O₂) generated in the hypoxanthine/xanthine oxidase system. The postulated involvement of the Ni(III)/Ni(II) redox couple in this apparent dismutation receives indirect support from electron-spin resonance data. These complexes also catalyzed the disproportionation of hydrogen peroxide, a process which generates active intermediates capable of hydroxylating p-nitrophenol and oxidizing uric acid to allantoin. An oxene moiety, namely [Nio]²⁺, is postulated as the active species in these H₂O₂-dependent reactions. Spectral analysis showed that monovalent, divalent and trivalent ions induced cooperative conformational changes in synthetic polydeoxynucleotides. For the nickel(II) ion, resistance to DNase-I activity clearly showed that an alternating G-C sequence is required for the observed transitions. It is concluded that the ability of nickel(II) peptide complexes to participate in active oxygen biochemistry suggests a possible role for nickel as a chemical promoter of cancer, whereas the capacity of the nickel(II) ion to induce conformational changes in DNA could, in principle, affect gene expression. Of course, the validity of both hypotheses require that the observed reactions be verified as biologically significant.     

Ring-substituted diaqua(1,2-diphenylethylenediamine)platinum(II) sulfate reacts with DNA through a dissociable complex.

Ring-substituted diaqua(1,2-diphenylethylenediamine)platinum(II) sulfate shows unusual kinetics in its reaction with salmon testis DNA. The mechanism for diaqua[meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]platinum(II) sulfate, [Pt(H2O)2(meso-6)]2+SO4(2-), a representative of this series, has been investigated and compared with that for cis-[Pt(NH3)2(H2O)2]2+. Reactions were followed by atomic absorption, analytical HPLC of Pt-DNA digests, arrest of enzymatic DNA synthesis/degradation, ultraviolet and fluorescence spectrophotometry. Except for the formation of monofunctional DNA adducts, the kinetics of the platinum(II) complexes are comparable. The pseudo-first-order rate constant for the attack of DNA by [Pt(H2O)2(meso-6)]2+ follows the concentration of DNA in a hyperbolic fashion, which is in contrast to the linear dependence for cis-[Pt(NH3)2(H2O)2]2+. The hyperbolic dependence is typical for a dissociable DNA/drug complex preceding the coordination reaction. By studying the binding of free ligand to DNA, and by correlating ligand structures and electrostatic charges with effects on adduct formation, both the phenyl residues and the positive charge of the platinum(II) complex are shown to be crucial for the stability of the dissociable complex. A non-intercalative mode of binding to the DNA backbone is suggested. At the high concentrations of DNA found in cell nuclei, the reaction of the dissociable complex can, principally, become rate-limiting in the attack of DNA and thus reduce the cytotoxic efficiency of a drug.     

DNA-binding and photocleavage studies of [Ru(phen)2(NMIP)]

A novel ligand 2′-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4′,5′-f][1,10]-phenanthroline (NMIP) and its complex [Ru(phen)₂(NMIP)]²⁺ have been synthesized and characterized by mass spectroscopy, ¹H NMR and cyclic voltammetry. Binding of the complex with calf thymus DNA (CT DNA) has been investigated by spectroscopic methods, viscosity and electrophoresis measurements. The experimental results indicate that [Ru(phen)₂(NMIP)]²⁺ binds to DNA via partial intercalative mode and the individual enantiomers of it bind to DNA in different rates. [Ru(phen)₂(NMIP)]²⁺ 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 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, characterization and the effect of ligand planarity of [Ru(bpy)2L]2+ on DNA binding affinity.

Two structurally related ligands (L) 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene (taptp) and 2,3-diphenyl-1,4,8,9-tetraazatriphenylene (dptatp), and their related complexes of [Ru(bpy)2L]2+ have been synthesized and characterized by elemental analyses, 1H NMR and mass spectra. Their electrochemical properties were also examined. Both complexes emit intense luminescence in organic solvent but are quenched in water to different extents. The interactions of the complexes with calf thymus DNA have been investigated by viscosity, absorption, emission and circular dichroism spectra. The intrinsic binding constants of [Ru(bpy)2(taptp)]2+ and [Ru(bpy)2(dptatp)]2+ are 1.7 x 10(5) and 3.8 x 10(4) M-1, respectively. All data indicate that both complexes bind enantioselectively to double-stranded calf thymus DNA via the intercalative mode, with stronger affinity for the fully planar ligand complex of [Ru(bpy)2(taptp)]2+.     

Conformational characterization of square planar nickel(II) tetraaza macrocyclic complexes by proton NMR. Crystal structure of [Ni(13aneN4)]ZnCl4

Conformations in solution of several diamagnetic nickel(II) complexes of macrocyclic tetraaza ligands are elucidated using proton NMR. There are six possible configurational isomers of planar [Ni(13aneN₄)]²⁺ (13aneN₄ = 1,4,7,10-tetraazacyclotridecane due to the orientation of the N---H protons above or below the plane of the macrocyle. Using NMR it is shown that in aqueous solution the [Ni(13aneN₄)]²⁺ complex has the R,S,R,S or trans-II configuration. A single-crystal X-ray study demonstrates the same configuration of the nitrogen atoms in the complex [Ni(13aneN₄)]ZnCl₄. In the case of the 14-membered ring macrocyle cyclam (cyclam = 1,4,8,11-tetraazacyclotetradecane), previous NMR studies revealed the presence, in aqueous solution, of the previously unobserved trans-I or R,S,R,S isomer, whose spectrum is examined in greater detail here. Solution structures of nickel(II) complexes of bicyclam (1,5,8,12-tetraazabicyclo[10.2.2]hexadecane) and dachden (N, N′-bis(2-aminoethyl)-1,4-diazacycloheptane) are also reported.     

One-pot synthesis of a new 2-substituted 1,2,3-triazole 1-oxide derivative from dipyridyl ketone and isonitrosoacetophenone hydrazone: Nickel(II) complex,DNA binding and cleavage properties

An efficient and simple one-pot synthesis of a new 1,2,3-triazole-1-oxide via reaction between isonitrosoacetophenone hydrazone and dipyridyl ketone in the EtOH/AcOH at room temperature has been developed smoothly in high yield. The reaction proceeds via metal salt free, in-situ formation of asymmetric azine followed by cyclization to provide 1,2,3-triazole 1-oxide compound. It has been structurally characterized. The 1:1 ratio reaction of the 1,2,3-triazole 1-oxide ligand with nickel(II) chloride gives the mononuclear complex [Ni(L)(DMF)Cl₂], hexa-coordinated within an octahedral geometry. Characterization of the 1,2,3-triazole compound and its Ni(II) complex with FTIR, ¹H and ¹³C NMR, UV–vis and elemental analysis also confirms the proposed structures of the compounds. The interactions of the compounds with Calf thymus DNA (CT-DNA) have been investigated by UV–visible spectra and viscosity measurements. The results suggested that both ligand and Ni(II) complex bind to DNA in electrostatic interaction and/or groove binding, also with a slight partial intercalation in the case of ligand. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H₂O₂). Both 1,2,3-triazole 1-oxide ligand and its nickel(II) complex show nuclease activity in the presence of hydrogen peroxide. DNA binding and cleavage affinities of the 1,2,3-triazole 1-oxide ligand is stronger than that of the Ni(II) complex.     

A comparative study of the interaction of two structurally analogue ruthenium(II) complexes with DNA

The binding of the ruthenium(II) complexes of [Ru(bpy)2(CAIP)]Cl2 and [Ru(bpy)2(HCIP)]Cl2 (where bpy=2,2'-bipyridine, CAIP=4-carboxyl-imidado[4,5-f][1,10]-phenanthroline, HCIP=3-hydroxyl-4-carboxyl-imidado[4,5-f][1,10]-phenanthroline) to calf thymus DNA (ct-DNA) has been investigated with UV-visible and emission spectroscopy, steady-state emission quenching, and viscosity measurements. The experimental results indicate that the two complexes bind to ct-DNA through an intercalative mode and [Ru(bpy)2(HCIP)]2+ intercalates into DNA more deeply than [Ru(bpy)2(CAIP)]2+ does.     

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.     

Synthesis, characterization and crystal structures of nickel complexes with dissymmetric tetradentate ligands containing a mixed-donor sphere

Four new nickel(II) complexes of dissymmetric tetradentate ligands, containing mixed-ligand donor sets of NSNS or NSNO, have been synthesized. These complexes were prepared by facile template reactions of the appropriate aldehyde and amine in the presence of [Ni(H₂O)₆](BF₄)₂, resulting directly in the desired nickel compounds. The nickel compounds were characterized by analytical, spectroscopic and electrochemical methods. The structures of [Ni(pyzs)]BF₄, [Ni(pyrs)]BF₄ and [Ni(pyzo)]BF₄ (see Scheme 1) have been determined by single-crystal X-ray crystallography, showing the geometry of the nickel ion to be square-planar. Vis–NIR spectra show that the phenolate-containing complexes [Ni(pyzo)]BF₄ and [Ni(pyro)]BF₄ (see Scheme 1) are essentially square-planar in nitromethane, but tetragonal octahedral in methanol, whereas the thiophenolate-containing compounds [Ni(pyzs)]BF₄ and [Ni(pyrs)]BF₄ remain square-planar in both solvents. Titration of the thiophenolate-containing complexes with 1-methylimidazole results in diamagnetic five-coordinated complexes. Electrochemistry shows quasi-reversible reductions to Ni(I) to occur for [Ni(pyzo)]BF₄, [Ni(pyrs)]BF₄ and [Ni(pyro)]BF₄.     

3H]nitrendipine receptors in skeletal muscle

The richest source of receptors for the organic calcium channel blocker [3H]nitrendipine in muscle is the transverse tubule membrane. The tubular membrane preparation binds [3H]nitrendipine with a high affinity and has a very high number of [3H]nitrendipine binding sites. For example, for the transverse tubule membrane preparation from rabbit muscle, the dissociation constant of the nitrendipine-receptor complex is 1.8 +/- 0.3 nM and the maximum binding capacity Bmax = 50 +/- 6 pmol/mg of protein. Similar results have been found with a membrane preparation from frog muscle. The dissociation constant found at equilibrium is near that determined from the ratio of rate constants for association (kappa 1) and dissociation (kappa-1). Binding of [3H] nitrendipine is pH-dependent and reveals the presence of an essential ionizable group with a pK of 5.4 on the nitrendipine receptor. The binding is destroyed by proteases showing that the receptor is a protein. Three different classes of Ca2+ channel blockers inhibit [3H]nitrendipine to its specific site. (i) The dihydropyridine analogs of nitrendipine which are competitive inhibitors of [3H]nitrendipine. These molecules form tight complexes with the nitrendipine receptor with dissociation constants between 1.4 and 4.0 nM. (ii) Other antiarrhythmic molecules like verapamil, amiodarone, bepridil, and F13004 which are noncompetitive inhibitors of [3H]nitrendipine binding with dissociation constants between 0.2 and 1 microM. (iii) Divalent cations like Ni2+, Co2+, Mn2+, or Ca2+ which are noncompetitive inhibitors of [3H]nitrendipine binding with the following rank order of potency: Ni+ (K0.5 = 1.8 mM) greater than Co2+ (K0.5 = 2.7 mM) greater than Mn2+ (K0.5 = 4.8 mM) greater than Ca2+ (K0.5 = 65 mM).