New insights into the visible-light-induced DNA cleavage activity of dipyridoquinoxaline complexes of bivalent 3d-metal ions

Dipyridoquinoxaline (dpq) complexes of bivalent 3d-metal ions, viz., [FeII(dpq)3](PF6)2 (1), [CoII(dpq)3](ClO4)2 (2), [NiII(dpq)3](ClO4)2 (3), [CuII(dpq)2(H2O)](ClO4)2 (4), [ZnII(dpq)3](ClO4)2 (5), and [ZnII(dpq)2(DMF)2](ClO4)2 (5a) (DMF = N,N-dimethylformamide), are prepared and their photoinduced DNA cleavage activity studied. Structural characterization for the complexes 1 and 5a is done by single-crystal X-ray crystallography. All the complexes show efficient binding propensity to calf thymus DNA with a binding constant (K) value of approximately 10(5) M(-1). Complexes 1, 2, and 4 show metal-based cyclic voltammetric responses at 1.2, 0.4, and 0.09 V (vs SCE) in DMF 0.1 M [Bun4N](ClO4) assignable to the respective FeIII/FeII, CoIII/CoII, and CuII/CuI couples. The NiII and ZnII complexes do not show any metal-based redox process. The dpq-based reductions are observed in the potential range of -1.0 to -1.7 V vs SCE. DNA melting and viscosity data indicate the groove-binding nature of the complexes. Control experiments using distamycin-A suggest a minor groove-binding propensity of the complexes. The complexes exhibit photoinduced cleavage of supercoiled pUC19 DNA in UV light of 365 nm. The diamagnetic d6-FeII and d10-ZnII complexes are cleavage-inactive on irradiation with visible light. The paramagnetic d7-CoII and d9-CuII complexes exhibit efficient DNA cleavage activity on photoirradiation at their respective d-d band. The paramagnetic d8-NiII complex displays only minor DNA cleavage activity on irradiation at its d-d band. The DNA cleavage reactions at visible light under aerobic conditions involve the formation of hydroxyl radical. The CoII complex shows photocleavage of DNA under an argon atmosphere. Theoretical calculations on the complexes suggest a photoredox pathway in preference to a type-2 process forming singlet oxygen for the visible-light-induced DNA cleavage activity of the 3d-metal complexes. The theoretical data also predict that the photoredox pathway is favorable for the 3d7-CoII and 3d9-CuII complexes to exhibit DNA cleavage activity, while the analogous 3d6-FeII and 3d8-NiII complexes are energetically unfavorable for the exhibition of such activity under visible light. The CoII and CuII complexes are better suited for designing and developing new metal-based PDT agents than their cleavage-inactive FeII, NiII, and ZnII analogues.     

Structure and DNA cleavage properties of two copper(II) complexes of the pyridine-pyrazole-containing ligands mbpzbpy and Hmpzbpya

The DNA-cleavage properties of the two copper(II) complexes, [Cu(mbpzbpy)Br(2)](H(2)O)(2.5) (1) and [Cu(mpzbpya)Cl](CH(3)OH) (2), obtained from the ligands 6,6'-bis(3,5-dimethyl-N-pyrazolmethyl)-2,2'-bipyridine) (mbpzbpy) and 6'-(3,5-dimethyl-N-pyrazolmethyl)-2,2'-bipyridine-6-carboxylic acid) (Hmpzbpya), respectively, are reported. Upon coordination to Cu(II) chloride in methanol, one arm of the ligand mbpzbpy is hydrolyzed to form mpzbpya. Under the same experimental conditions, the reaction of mbpzbpy with CuBr(2) does not lead to ligand hydrolysis. The ligand mpzbpya is coordinated to a copper(ii) ion generating a CuN(3)OCl chromophore, resulting in a distorted square-pyramidal environment, whereas with the N(4) mbpzbpy ligand, the Cu(II) ion is four-coordinated in a distorted square planar geometry. Both complexes promote the oxidative DNA cleavage of phiX174 phage DNA in the absence of reductant. The oxidative nature of the DNA cleavage reaction has been confirmed by religation and cell-transformation experiments. Studies using standard radical scavengers suggest the involvement of hydroxyl radicals in the oxidative cleavage of DNA. Although both compounds do convert form I (supercoiled) DNA to form II (nicked, relaxed form), only complex 1 is able to produce small amounts of form III (linearized DNA). This observation may be explained either by the attack of the copper(ii) complexes to only one single strand of DNA, or by a single cleavage event. Statistical analysis of relative DNA quantities present after the treatment with both copper(ii) complexes supports a random mode of DNA cleavage.     

Double-strand DNA cleavage by copper complexes of 2,2'-dipyridyl with guanidinium/ammonium pendants

Two ligands with guanidinium/ammonium groups were synthesized and their copper complexes, [Cu(L1)Cl2](ClO4)2.H2O (1) and [Cu(L2)Cl2](ClO4)2 (2) (L1 = 5,5'-di[1-(guanidyl)methyl]-2,2'-bipyridyl cation and L2 = 5,5'-di[1-(amino)methyl]-2,2'-bipyridyl cation), were prepared to serve as nuclease mimics. X-Ray analysis revealed that Cu(II) ion in 1 has a planar square CuN2Cl2-configuration. The shortest distance between the nitrogen of guanidinium and copper atoms is 6.5408(5) A, which is coincident with that of adjacent phosphodiesters in DNA (ca. 6 A). In the absence of reducing agent, supercoiled plasmid DNA cleavage by the complexes were performed and their hydrolytic mechanisms were demonstrated with radical scavengers and T4 ligase. The pseudo-Michaelis-Menten kinetic parameters (kcat, KM) were calculated to be 4.42 h(-1), 7.46 x 10(-5) M for 1, and 4.21 h(-1), 1.07 x 10(-4) M for 2, respectively. The result shows that their cleavage efficiency is about 10-fold higher than the simple analogue [Cu(bipy)Cl2] (3) (0.50 h(-1), 3.5 x 10(-4) M). The pH dependence of DNA cleavage by 1 and its hydroxide species in solution indicates that mononuclear [Cu(L1)(OH)(H2O)]3+ ion is the active species. Highly effective DNA cleavage ability of is attributed to the effective cooperation of the metal moiety and two guanidinium pendants with the phosphodiester backbone of nucleic acid.     

Metal-based netropsin mimics showing AT-selective DNA binding and DNA cleavage activity at red light

Copper(II) bis-arginate [Cu(l-arg)2](NO3)2 (1) and [Cu(l-arg)(phen)Cl]Cl (2) as mimics of the minor-groove-binding natural antibiotic netropsin show preferential binding to the AT-rich region of double-stranded DNA. The complexes with a d-d band near 600 nm display oxidative DNA cleavage activity on photoirradiation at UV-A light of 365 nm and at red light of 647.1 nm (Ar-Kr laser) in a metal-assisted photoexcitation process forming singlet oxygen (1O2) species in a type-2 pathway.     

DNA cleavage on photoexposure at the d-d band in ternary copper(II) complexes using red-light laser

Ternary copper(II) complexes [Cu(L1)B](ClO4) (1, 2) and [Cu(L2)B](ClO4) (3, 4), where HL1 and HL2 are tridentate NSO- and ONO-donor Schiff bases and B is a heterocyclic base, viz. dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 1 and 3) or dipyrido[3,2-a:2',3'-c]phenazine (dppz, 2 and 4), were prepared and their DNA binding and photoinduced DNA cleavage activity studied. Complex 1, structurally characterized by single-crystal X-ray crystallography, shows an axially elongated square-pyramidal (4 + 1) coordination geometry in which the monoanionic L1 binds at the equatorial plane. The NN-donor dpq ligand exhibits an axial-equatorial binding mode. The complexes display good binding propensity to calf thymus DNA, giving a relative order 2 (NSO-dppz) > 4 (ONO-dppz) > 1 (NSO-dpq) > 3 (ONO-dpq). They cleave supercoiled pUC19 DNA to its nicked circular form when treated with 3-mercaptopropionic acid (MPA) by formation of hydroxyl radicals as the cleavage active species under dark reaction conditions. The photoinduced DNA cleavage activity of the complexes was investigated using UV radiation of 365 nm and red light of 633, 647.1, and 676.4 nm (CW He-Ne and Ar-Kr mixed gas ion laser sources) in the absence of MPA. Complexes 1 and 2, having photoactive NSO-donor Schiff base and dpq/dppz ligands, show dual photosensitizing effects involving both the photoactive ligands in the ternary structure with significantly better cleavage properties when compared to those of 3 and 4, having only photoactive dpq/dppz ligands. Involvement of singlet oxygen in the light-induced DNA cleavage reactions is proposed. A significant enhancement of the red-light-induced DNA cleavage activity is observed for the dpq and dppz complexes containing the sulfur ligand when compared to their earlier reported phen (1,10-phenanthroline) analogue. Enhancement of the cleavage activity on photoexposure at the d-d band indicates the occurrence of metal-assisted photosensitization processes involving the LMCT and d-d band in the ternary structure.     

手性钌(Ⅱ)配合物对DNA的立体选择性断裂

八面体钌(Ⅱ)多吡啶配合物与双螺旋DNA插入结合后具有较强的结合能力,并且含有一个具有氧化一还原活性的中心金属离子．它们对氧化剂相对比较稳定,但对光比较敏感,因此可利用光辐射使之产生单线态氧或羟基自由基等而使DNA裂解．此外,这些配合物具有左手∧-和右手△-两种构型,与同样具有手性的DNA作用时,存在着立体选择性结合．并且在对DNA的断裂反应中也存在一定的立体选择性,可作为不同构型DNA的结构探针．     

A series of oxyimine-based macrocyclic dinuclear zinc(II) complexes enhances phosphate ester hydrolysis, DNA binding, DNA hydrolysis, and lactate dehydrogenase inhibition and induces apoptosis

A symmetrical macrocyclic dizinc(II) complex (1) has been synthesized by using the ligand (L(1)) [μ-11,24-dimethyl-4,7,16,19-tetraoxa-3,8,15,20-tetraazatricyclo-[20.3.1.1(10,13)] heptacosa-1(25),2,7,9,11,13(27),14,20,22(26),23-decaene-26,27-diol]. A series of unsymmetrical macrocyclic dizinc(II) complexes (2-6) has been synthesized by Schiff base condensation of bicompartmental mononuclear complex [ZnL] [μ-3,16-dimethyl-8,11-dioxa-7,12-diazadicyclo-[1.1(14,18)] heptacosa-1,3,5(20),6,12,14,16,18(19)-octacaene-19,20-diolato)zinc(II)] with various diamines like 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The ligand L(1) and all the zinc(II) complexes were structurally characterized. To corroborate the consequence of the aromatic moiety in comparison to the aliphatic moiety present in the macrocyclic ring on the phosphate ester hydrolysis, DNA binding and cleavage properties have been studied. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate ester reaction are in the range from 2.73 × 10(-2) to 9.86 × 10(-2) s(-1).The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence, and circular dichroism spectroscopy. The DNA binding constant values of the complexes were found in the range from 1.80 × 10(5) to 9.50 × 10(5) M(-1), and the binding affinities are in the following order: 6 > 5 > 1 > 2 > 3 > 4. All the dizinc(II) complexes 1-6 effectively promoted the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 6 under physiological conditions give the observed rate constant (k(obs)) of 4.42 ± 0.2 h(-1), which shows a 10(8)-fold rate acceleration over the uncatalyzed reaction of ds-DNA. The comparison of the dizinc(II) complexes 1-6 with the monozinc(II) complex [ZnL] indicates that the DNA cleavage acceleration promoted by 1-6 are due to the efficient cooperative catalysis of the two close proximate zinc(II) cation centers. The ligand L(1), dizinc(II) complexes 1, 3, and 6 showed cytotoxicity in human hepatoma HepG2 cancer cells, giving IC(50) values of 117, 37.1, 16.5, and 8.32 μM, respectively. The results demonstrated that 6, a dizinc(II) complex with potent antiproliferative activity, is able to induce caspase-dependent apoptosis in human cancer cells. Cytotoxicity of the complexes was further confirmed by the lactate dehydrogenase enzyme level in HepG2 cell lysate and content media.     

Inactivation of human angiotensin converting enzyme by copper peptide complexes containing ATCUN motifs

The copper complex [KGHK-Cu]+ demonstrates catalytic inactivation of human angiotensin converting enzyme at sub-saturating concentrations, under oxidative conditions, with an observed rate constant k approximately 2.9 +/- 0.5 x 10(-2) min(-1).     

Oxidative DNA cleavage promoted by multinuclear copper complexes: activity dependence on the complex structure

Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]3 H2O (1), [Cu2(pTPXA)Cl4]3 H2O (2), [Cu3(HPTAB)Cl5]Cl3 H2O (3) (mTPXA = N,N,N',N'-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N',N'-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N',N',N',N'-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.     

Synthesis,crystal structure,DNA binding,and oxidative cleavage activity of copper(II)-bipyridyl complexes containing tetraalkylammonium groups

Two copper(II) complexes of disubstituted 2,2′-bipyridine (bpy = 2, 2′-bipyridine) with tetraalkylammonium groups, [Cu(L¹)₂Br](ClO₄)₅·2H₂O (1) and [Cu(L²)₂Br](ClO₄)₅·H₂O (2) (L¹ = [4, 4′-(Et₃NCH₂)₂-bpy]²⁺, L² = [4, 4′-((n-Bu)₃NCH₂)₂-bpy]²⁺), have been synthesized and characterized. X-ray crystallographic study of 1 indicates that Cu(II) is a distorted trigonal bipyramidal or square pyramid. DNA binding of both complexes was studied by UV spectroscopic titration. In the presence of reducing reagents, the cleavage of plasmid pBR322 DNA mediated by both complexes was investigated and efficient oxidative cleavage of DNA was observed. Mechanistic study with reactive oxygen scavengers indicates that hydrogen peroxide and singlet oxygen participate in DNA cleavage.     

Carbon-halogen bond activation mechanism by copper(I) complexes of (2-pyridyl)alkylamine ligands

The reaction of p-substituted benzyl halides ((Y)BnX; X = Cl, Br, and I; Y = p-substituent, OMe, t-Bu, Me, H, F, Cl, and NO(2)) and copper(I) complexes supported by a series of (2-pyridyl)alkylamine ligands has been investigated to shed light on the mechanism of copper(I) complex mediated carbon-halogen bond activation, including ligand effects on the redox reactivity of copper(I) complexes which are relevant to the chemistry. For both the tridentate ligand (Phe)L(Pym2) [N,N-bis(2-pyridylmethyl)-2-phenylethylamine] and tetradentate ligand TMPA [tris(2-pyridylmethyl)amine] complexes, the C-C coupling reaction of benzyl halides proceeded smoothly to give corresponding 1,2-diphenylethane derivatives and copper(II)-halide complex products. Kinetic analysis revealed that the reaction obeys second-order kinetics both on the copper complex and the substrate; rate = k[Cu](2)[(Y)BnX](2). A reaction mechanism involving a dinuclear copper(III)-halide organometallic intermediate is proposed, on the basis of the kinetic results, including observed electronic effects of p-substituents (Hammett plot) and the rate dependence on the BDE (bond dissociation energy) of the C-X bond, as well as the ligand effects.     

DNA cleavage by new oxovanadium(IV) complexes of N-salicylidene alpha-amino acids and phenanthroline bases in the photodynamic therapy window

Oxovanadium(IV) complexes [VO(salmet)(B)] (1-3) and [VO(saltrp)(B)] (4-6), where salmet and saltrp are N-salicylidene-l-methionate and N-salicylidene-l-tryptophanate, respectively, and B is a N,N-donor heterocyclic base (viz. 1,10-phenanthroline (phen, 1, 4), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2, 5), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3, 6)) are prepared and characterized and their DNA binding and photoinduced DNA cleavage activity studied. Complexes 1, 2, and 4 are structurally characterized by single-crystal X-ray crystallography. The molecular structure shows the presence of a vanadyl group in the VO3N3 coordination geometry. The dianionic alpha-amino acid Schiff base acts as a tridentate O,N,O-donor ligand in a meridional binding mode. The N,N-donor heterocyclic base displays a chelating mode of bonding with a N-donor site trans to the oxo group. The complexes show a d-d band in the range of 680-710 nm in DMF with a shoulder near 840 nm. They exhibit an irreversible oxidative cyclic voltammetric response near 0.8 V assignable to the V(V)/V(IV) couple and a quasi-reversible V(IV)/V(III) redox couple near -1.1 V vs SCE in DMF-0.1 M TBAP. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 5.2 x 10(4) to 7.2 x 10(5) M(-1). The binding site size, thermal melting, and viscosity data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor "chemical nuclease" activity in the dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide. The dpq and dppz complexes show efficient DNA cleavage activity on irradiation with UV-A light of 365 nm via a mechanistic pathway involving formation of singlet oxygen as the reactive species. They also show significant DNA cleavage activity on photoexcitation in red light (>750 nm) by (1)O2 species. Observation of red-light-induced cleavage of DNA is unprecedented in the vanadium chemistry. The DNA cleavage activity is metal promoted as the ligands or vanadyl sulfate alone are cleavage inactive on photoirradiation at these wavelengths.     

Formation,preservation, and cleavage of the disulfide bond by vanadium

Reaction of the disulfide [HpicanS](2) (HpicanS is the carboxamide based on picolinate (pic) and o-mercaptoaniline (anS); the [] brackets are used to denote disulfides) with [VOCl(2)(thf)(2)] leads to reductive scission of the disulfide bond and formation of the mixed-valence (V(IV)/V(V)) complex anion [(OVpicanS)(2)mu-O](-) (1), with the dianionic ligand coordinating through the pyridine-N atom, the deprotonated amide-N atom, and thiophenolate-S atom. Reductive cleavage of the SbondS bond is also observed as [VCl(2)(tmeda)(2)] (tmeda=tetramethylethylenediamine) is treated with the disulfides [HsalanS](2) or [HvananS](2) (HsalanS and HvananS are the Schiff bases formed between o-mercaptoaniline and salicylaldehyde (Hsal) or vanillin (Hvan), respectively), yielding the V(III) complexes [VCl(tmeda)(salanS)] (2 a), or [VCl(tmeda)(vananS)] (2 b). The disulfide bond remains intact in the aerial reaction between [HsalanS](2) and [VCl(3)(thf)(3)] to yield the V(V) complex [VOCl[salanS](2)] (3), where (salanS)(2-) coordinates through the two phenolate and one of the imine functions. The S-S bond is also preserved as [VO(van)(2)] or [VO(nap)(2)] (Hnap=2-hydroxynaphthalene-1-carbaldehyde) is treated with bis(2-aminophenyl)disulfide, [anS](2), a reaction which is accompanied by condensation of the aldehyde and the diamine, and complexation of the resulting bis(Schiff bases) [HvananS](2) or [HnapanS](2) to form the complexes [VO[vananS](2)] (4 a) or [VO[napanS](2)] (4 b). In 4 a and 4 b, the phenolate and imine functions, and presumably also one of the disulfide-S atoms, coordinate to V(IV). 2-Mercaptophenyl-2'-pyridinecarboxamide (H(2)picanS) retains its identity in the presence of V(III); reaction between [VCl(3)(thf)(3)] and H(2)picanS yields [V[picanS](2)](-) (5). The dithiophenolate 2,6-bis(mercaptophenylthio)dimethylpyridine (6 a) is oxidized, mediated by VO(2+), to the bis(disulfide) octathiadiaza-cyclo-hexaeicosane 6 b. The relevance of these reactions for the speciation of vanadium under physiological conditions is addressed. [HNEt(3)]-1.0.5 NEt(3,) 3.3 CH(2)Cl(2), [HsalanS](2), [HNEt(3)]-5, and 6 b.4 THF have been characterized by X-ray diffraction analysis.     

Disulfide bond cleavage induced by a platinum(II) methionine complex

The cleavage of a disulfide bond and the redox equilibrium of thiol/disulfide are strongly related to the levels of glutathione (GSH)/oxidized glutathione (GSSG) or mixed disulfides in vivo. In this work, the cleavage of a disulfide bond in GSSG induced by a platinum(II) complex [Pt(Met)Cl2] (where Met = methionine) was studied and the cleavage fragments or their platinated adducts were identified by means of electrospray mass spectrometry, high-performance liquid chromatography, and ultraviolet techniques. The second-order rate constant for the reaction between [Pt(Met)Cl2] and GSSG was determined to be 0.4 M(-1) s(-1) at 310 K and pH 7.4, which is 100- and 12-fold faster than those of cisplatin and its monoaqua species, respectively. Different complexes were formed in the reaction of [Pt(Met)Cl2] with GSSG, mainly mono- and dinuclear platinum complexes with the cleavage fragments of GSSG. This study demonstrated that [Pt(Met)Cl2] can promote the cleavage of disulfide bonds. The mechanistic insight obtained from this study may provide a deeper understanding on the potential involvement of platinum complexes in the intracellular GSH/GSSG systems.     

Mechanistic studies of the O2-dependent aliphatic carbon-carbon bond cleavage reaction of a nickel enolate complex

The mononuclear nickel(II) enolate complex [(6-Ph(2)TPA)Ni(PhC(O)C(OH)C(O)Ph]ClO(4) (I) was the first reactive model complex for the enzyme/substrate (ES) adduct in nickel(II)-containing acireductone dioxygenases (ARDs) to be reported. In this contribution, the mechanism of its O(2)-dependent aliphatic carbon-carbon bond cleavage reactivity was further investigated. Stopped-flow kinetic studies revealed that the reaction of I with O(2) is second-order overall and is ～80 times slower at 25 °C than the reaction involving the enolate salt [Me(4)N][PhC(O)C(OH)C(O)Ph]. Computational studies of the reaction of the anion [PhC(O)C(OH)C(O)Ph](-) with O(2) support a hydroperoxide mechanism wherein the first step is a redox process that results in the formation of 1,3-diphenylpropanetrione and HOO(-). Independent experiments indicate that the reaction between 1,3-diphenylpropanetrione and HOO(-) results in oxidative aliphatic carbon-carbon bond cleavage and the formation of benzoic acid, benzoate, and CO:CO(2) (～12:1). Experiments in the presence of a nickel(II) complex gave a similar product distribution, albeit benzil [PhC(O)C(O)Ph] is also formed, and the CO:CO(2) ratio is ～1.5:1. The results for the nickel(II)-containing reaction match those found for the reaction of I with O(2) and provide support for a trione/HOO(-) pathway for aliphatic carbon-carbon bond cleavage. Overall, I is a reasonable structural model for the ES adduct formed in the active site of Ni(II)ARD. However, the presence of phenyl appendages at both C(1) and C(3) in the [PhC(O)C(OH)C(O)Ph](-) anion results in a reaction pathway for O(2)-dependent aliphatic carbon-carbon bond cleavage (via a trione intermediate) that differs from that accessible to C(1)-H acireductone species. This study, as the first detailed investigation of the O(2) reactivity of a nickel(II) enolate complex of relevance to Ni(II)ARD, provides insight toward understanding the chemical factors involved in the O(2) reactivity of metal acireductone species.     

Rapid three-step cleavage of RNA and DNA model systems promoted by a dinuclear Cu(II) complex in methanol. energetic origins of the catalytic efficacy

A dinuclear Cu(II) complex of 1,3-bis-N(1)-(1,5,9-triazacyclododecyl)propane with an associated methoxide (2-Cu(II)(2):(-OCH(3))) was prepared, and its kinetics of reaction with an RNA model (2-hydroxypropyl-p-nitrophenyl phosphate (1, HPNPP)) and two DNA models (methyl p-nitrophenyl phosphate (3) and iso-butyl p-chlorophenyl phosphate (4)) were studied in methanol solution at (s)(s)pH 7.2 +/- 0.2. X-ray diffraction structures of 2-Cu(II)(2):(-OH)(H(2)O)(CF(3)SO(3)-)(3):0.5CH(3)CH(2)OCH(2)CH(3) and 2-Cu(II)(2):(-OH)((C(6)H(5)CH(2)O)(2)PO(2)-)(CF(3)SO(3)-)2 show the mode of coordination of the bridging -OH and H(2)O between the two Cu(II) ions in the first complex and bridging -OH and phosphate groups in the second. The kinetic studies with 1 and 3 reveal some common preliminary steps prior to the chemical one of the catalyzed formation of p-nitrophenol. With 3, and also with the far less reactive substrate (4), two relatively fast events are cleanly observed via stopped-flow kinetics. The first of these is interpreted as a binding step which is linearly dependent on [catalyst] while the second is a unimolecular step independent of [catalyst] proposed to be a rearrangement that forms a doubly Cu(II)-coordinated phosphate. The catalysis of the cleavage of 1 and 3 is very strong, the first-order rate constants for formation of p-nitrophenol from the complex being approximately 0.7 s(-1) and 2.4 x 10(-3) s(-1), respectively. With substrate 3, 2-Cu(II)(2):(-OCH(3)) exhibits Michaelis-Mentin kinetics with a k(cat)/K(M) value of 30 M(-1) s(-1) which is 3.8 x 10(7)-fold greater than the methoxide promoted reaction of 3 (7.9 x 10(-7) M(-1) s(-1)). A free energy calculation indicates that the binding of 2-Cu(II)(2):(-OCH(3)) to the transition states for 1 and 3 cleavage stabilizes them by -21 and -24 kcal/mol, respectively, relative to that of the methoxide promoted reactions. The results are compared with a literature example where the cleavage of 1 in water is promoted by a dinuclear Zn(II) catalyst, and the energetic origins of the exalted catalysis of the 2-Cu(II)(2) and 2-Zn(II)(2) methanol systems are discussed.     

席夫碱大环铜配合物的化学核酸酶活性研究

对3种结构相近的席夫碱四氮大环草酰胺铜配合物（CuL^1～3）的化学核酸酶活性进行比较研究。结果表明：这类配合物的化学核酸酶活性与中心金属离子的类型、配体的结构、溶液的pH值、离子强度及配合物的浓度等都有关系。3种配合物表现出来的化学核酸酶活性顺序为CuL³＞CuL²＞CuL¹。CuL³的DNA切割反应表现为典型的假一级连续反应。在80 μmol·L^-1 CuL³和2 mmol·L^-1 H₂O₂的存在下,就超螺旋DNA向切口开环型DNA进而向线型DNA的转化而言,反应速率常数分别为0.044 0±0.001 5 min^-1(k₁)和0.003 52±0.000 18 min^-1(k₂)。     

DNA-binding and photoactivated cleavage of enantiomeric ruthenium(II) complexes

A set of enantiomeric Ru^II complexes Δ- and Λ-[Ru(bpy)₂TAPTP](PF₆)₂(bpy=2,2’-bipyridine, TAPTP=4,5,9,18-tetraazaphenanthreno[9,10-b]triphenylene) have been synthesized and characterized. Binding of both enantiomers to calf thymus DNA has been studied by spectroscopic methods, viscosity, and equilibrium dialysis. The experimental results indicated that both enantiomers bind to DNA by intercalation. Upon irradiation at 302 nm, both enantiomers were found to promote the cleavage of plasmid pBR 322 DNA from supercoiled form I to a nicked form II, and obvious enantioselectively was observed on DNA cleavage, the Λ- enantiomer exhibiting higher cleaving efficiency. The mechanisms for DNA cleavage by the two enantiomers are also proposed.     

The first dinuclear copper(II) and zinc(II) complexes containing novel Bis-TACN: syntheses, structures, and DNA cleavage activities

Two novel binuclear complexes [Cu(2)(L)].(ClO(4))(2) (1) and [Zn(2)(L)].(ClO(4))(2) (2) were synthesized and crystallographically characterized {L = 1(4),5(4)-dimethyl-1(2),5(2)-dihydroxy-1(1,3),5(1,3)-dibenzene-3(1,4),7(1,4)-di-1,4,7-triazacyclononane}. The cation [Cu(2)(L)](2+) structure of 1 is similar to that of [Zn(2)(L)](2+) of 2. The central ion is bridged by the di-phenoxo of L and lies in a close to perfect square pyramidal geometry. 1 and 2 crystallize in the triclinic space group P1. The two complexes effectively promote the cleavage of plasmid DNA in the presence of activating agents at physiological pH and temperature. The pseudo-Michaelis-Menten kinetic parameters k(cat) = 1.61 h(-1), K(m) = 1.35 x 10(-5) M for complex 1 in the presence of mercaptoethanol; k(cat) = 2.48 h(-1), K(m) = 5.5 x 10(-5)M for complex 2 in the presence of hydrogen peroxide were obtained. The mechanism of plasmid DNA cleavage was studied by adding standard radical scavengers. DNA cleavage reaction by the binuclear Zn(II)/H(2)O(2) system is a hydrolytic mechanism.     

On the origin of selective nitrous oxide N-N bond cleavage by three-coordinate molybdenum(III) complexes

Reaction of Mo(N[R]Ar)(3) (R = (t)Bu or C(CD(3))(2)CH(3)) with N(2)O gives rise exclusively to a 1:1 mixture of nitride NMo(N[R]Ar)(3) and nitrosyl ONMo(N[R]Ar)(3), rather than the known oxo complex OMo(N[R]Ar)(3) and dinitrogen. Solution calorimetry measurements were used to determine the heat of reaction of Mo(N[R]Ar)(3) with N(2)O and, independently, the heat of reaction of Mo(N[R]Ar)(3) with NO. Derived from the latter measurements is an estimate (155.3 +/- 3.3 kcal.mol(-1)) of the molybdenum-nitrogen bond dissociation enthalpy for the terminal nitrido complex, NMo(N[R]Ar)(3). Comparison of the new calorimetry data with those obtained previously for oxo transfer to Mo(N[R]Ar)(3) shows that the nitrous oxide N-N bond cleavage reaction is under kinetic control. Stopped-flow kinetic measurements revealed the reaction to be first order in both Mo(N[R]Ar)(3) and N(2)O, consistent with a mechanism featuring post-rate-determining dinuclear N-N bond scission, but also consistent with cleavage of the N-N bond at a single metal center in a mechanism requiring the intermediacy of nitric oxide. The new 2-adamantyl-substituted molybdenum complex Mo(N[2-Ad]Ar)(3) was synthesized and found also to split N(2)O, resulting in a 1:1 mixture of nitrosyl and nitride products; the reaction exhibited first-order kinetics and was found to be ca. 6 times slower than that for the tert-butyl-substituted derivative. Discussed in conjunction with studies of the 2-adamantyl derivative Mo(N[2-Ad]Ar)(3) is the role of ligand-imposed steric constraints on small-molecule, e.g. N(2) and N(2)O, activation reactivity. Bradley's chromium complex Cr(N(i)Pr(2))(3) was found to be competitive with Mo(N[R]Ar)(3) for NO binding, while on its own exhibiting no reaction with N(2)O. Competition experiments permitted determination of ratios of second-order rate constants for NO binding by the two molybdenum complexes and the chromium complex. Analysis of the product mixtures resulting from carrying out the N(2)O cleavage reactions with Cr(N(i)Pr(2))(3) present as an in situ NO scavenger rules out as dominant any mechanism involving the intermediacy of NO. Simplest and consistent with all the available data is a post-rate-determining bimetallic N-N scission process. Kinetic funneling of the reaction as indicated is taken to be governed by the properties of nitrous oxide as a ligand, coupled with the azophilic nature of three-coordinate molybdenum(III) complexes.