Structure-activity relationships of highly cytotoxic copper(II) complexes with modified indolo[3,2-c]quinoline ligands

A number of indolo[3,2-c]quinolines were synthesized and modified at the lactam unit to provide a peripheral binding site able to accommodate metal ions. Potentially tridentate ligands HL(1a)-HL(4a) and HL(1b)-HL(4b) were reacted with copper(II) chloride in isopropanol/methanol to give novel five-coordinate copper(II) complexes [Cu(HL(1a-4a))Cl(2)] and [Cu(HL(1b-4b))Cl(2)]. In addition, a new complex [Cu(HL(5b))Cl(2)] and two previously reported compounds [Cu(HL(6a))Cl(2)] and [Cu(HL(6b))Cl(2)] with modified paullone ligands HL(5b), HL(6a), and HL(6b), which can be regarded as close analogues of indoloquinolines HL(1b), HL(4a), and HL(4b), in which the pyridine ring was formally substituted by a seven-membered azepine ring, were synthesized for comparison. The new ligands and copper(II) complexes were characterized by (1)H and (13)C NMR, IR and electronic absorption spectroscopy, ESI mass spectrometry, magnetic susceptibility measurements in solution at 298 K ([Cu(HL(1a))Cl(2)] and [Cu(HL(4b))Cl(2)]), and X-ray crystallography ([Cu(HL(3b))Cl(2)]·3DMF, [Cu(HL(4b))Cl(2)]·2.4DMF, HL(5b) and [Cu(HL(5b))Cl(2)]·0.5CH(3)OH). All complexes were tested for cytotoxicity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (non-small cell lung cancer), and SW480 (colon carcinoma). The compounds are highly cytotoxic, with IC(50) values ranging from nanomolar to very low micromolar concentrations. Substitution of the seven-membered azepine ring in paullones by a pyridine ring resulted in a six- to nine-fold increase of cytotoxicity in SW480 cells. Electron-releasing or electron-withdrawing substituents in position 8 of the indoloquinoline backbone do not exert any effect on cytotoxicity of copper(II) complexes, whereas copper(II) compounds with Schiff bases obtained from 2-acetylpyridine and indoloquinoline hydrazines are 10 to 50 times more cytotoxic than those with ligands prepared from 2-formylpyridine and indoloquinoline hydrazines.     

A rational design for imidazolate-bridged linear trinuclear compounds from mononuclear copper(II) complexes with 2-[((imidazol-2-ylmethylidene)amino)ethyl]pyridine (HL): syntheses, structures, and magnetic properties of [Cu(L)(hfac)M(hfac)2Cu(hfac)(L)] (M = ZnII, CuII, MnII)

Two mononuclear copper(II) complexes with the unsymmetrical tridentate ligand 2-[((imidazol-2-ylmethylidene)amino)ethyl]pyridine (HL), [Cu(HL)(H2O)](ClO4)2.2H2O (1) and [Cu(HL)Cl2] (2), have been prepared and characterized. The X-ray analysis of 2 revealed that the copper(II) ion assumes a pentacoordinated square pyramidal geometry with an N3Cl2 donor set. When 1 and 2 are treated with an equimolecular amount of potassium hydroxide, the deprotonation of the imidazole moiety promotes a self-assembled process, by coordination of the imidazolate nitrogen atom to a Cu(II) center of an adjacent unit, leading to the polynuclear complexes [[Cu(L)(H2O)](ClO4)]n (3) and [[Cu(L)Cl].2H2O]n (4). Variable-temperature magnetic data are well reproduced for one-dimensional infinite regular chain systems with J = -60.3 cm(-1) and g = 2.02 for 3 and J = -69.5 cm(-1) and g = 2.06, for 4. When 1 is used as a "ligand complex" for [M(hfac)2] (M = Cu(II), Ni(II), Mn(II), Zn(II)) in a basic medium, only the imidazolate-bridged trinuclear complexes [Cu(L)(hfac)M(hfac)2Cu(hfac)(L)] (M = Zn(II), Cu(II)) (5, 6) can be isolated. Nevertheless, the analogous complex containing Mn(II) as the central metal (7) can be prepared from the precursor [Cu(HL)Cl2] (2). All the trinuclear complexes are isostructural. The structures of 5 and 6 have been solved by X-ray crystallographic methods and consist of well-isolated molecules with Ci symmetry, the center of symmetry being located at the central metal. Thus, the copper(II) fragments are in trans positions, leading to a linear conformation. The magnetic susceptibility data (2-300 K), which reveal the occurrence of antiferromagnetic interactions between copper(II) ions and the central metal, were quantitatively analyzed for symmetrical three-spin systems to give the coupling parameters JCuCu = -37.2 and JCuMn = -3.7 cm(-1) with D = +/-0.4 cm(-1) for 6 and 7, respectively. These magnetic behaviors are compared with those for analogous systems and discussed on the basis of a localized-orbital model of exchange interactions.     

Green Oxidative Degradation of Methyl Orange with Copper(II) Schiff Base Complexes as Photo‐Fenton‐Like Catalysts

Two copper(II) complexes, namely [Cu(HL)Cl] ( 1 ) and [Cu(HL)Br] ( 2 ), where HL is the multidentate Schiff base N‐[(2‐oxy‐acetate)benzyl]‐2‐aminothanol, were synthesized and fully characterized. The Cu^II ions in 1 and 2 are pentacoordinate and the coordination arrangement is best described as distorted square‐pyramidal. The degradation of methyl orange (MO) was investigated using 1 and 2 as homogeneous photo‐Fenton‐like catalysts. 1 and 2 exhibited similar catalytic activity at neutral pH. The results suggest that they have advantages on catalyzing efficient degradation of organic dye through photo‐Fenton‐like reaction.     

Copper(II) Complexes with N,O-Hybrid Ligands based on Pyridyl-Containing Phospholane Oxides

Russian Journal of Coordination Chemistry - New water-soluble copper(II) bis-N,O-chelate complexes [Cu(L2)2Cl2] (I), [Cu2(L1)2Cl4] (II), and [Cu(L1)2Cl]2[CuCl4] (III) (L1, L2 = pyridyl-containing...     

Copper(II) complexes of formyl- and acetylpyrazine N(4)- (2–methylpyridinyl)-, N(4)-(2–ethylpyridinyl)- and N(4)-methyl- (2–ethylpyridinyl)thiosemicarbazones

The title complexes of general formula [Cu(HL)Cl2] or [Cu(L)Cl] were isolated from boiling EtOH. The thiosemicarbazones have been characterized by their 1H- and 13C-n.m.r., i.r. and electronic spectra. The i.r., electronic and e.s.r. spectra of the copper(II) complexes are compared with data on previously studied complexes. The antitumour and antiviral activities of the thiosemicarbazones and their complexes are discussed. This revised version was published online in June 2006 with corrections to the Cover Date.     

Oxidative double dehalogenation of tetrachlorocatechol by a bio-inspired CuII complex: formation of chloranilic acid

Copper(II) complexes of the potentially tripodal N,N,O ligand 3,3-bis(1-methylimidazol-2-yl)propionate (L1) and its conjugate acid HL1 have been synthesised and structurally and spectroscopically characterised. The reaction of equimolar amounts of ligand and CuII resulted in the complexes [Cu(L1)]n(X)n (X=OTf-, PF6(-); n=1,2), for which a new bridging coordination mode of L1 is inferred. Although these complexes showed moderate catecholase activity in the oxidation of 3,5-di-tert-butylcatechol, surprising reactivity with the pseudo-substrate tetrachlorocatechol was observed. A chloranilato-bridged dinuclear CuII complex was isolated from the reaction of [Cu(L1)]n(PF6)n with tetrachlorocatechol. This stoichiometric oxidative double dehalogenation of tetrachlorocatechol to chloranilic acid by a biomimetic copper(II) complex is unprecedented. The crystal structure of the product, [Cu2(ca)Cl2(HL1)2], shows a bridging bis-bidentate chloranilato (ca) ligand and ligand L1 coordinated as its conjugate acid (HL1) in a tridentate fashion. Magnetic susceptibility studies revealed weak antiferromagnetic coupling (J= -35 cm(-1)) between the two copper centres in the dinuclear complex. Dissolution of the green complex [Cu2(ca)Cl2(HL1)2] resulted in the formation of new pink-purple mononuclear compound [Cu(ca)(HL1)(H2O)], the crystal structure of which was determined. It showed a terminal bidentate chloranilato ligand and N,N-bidentate coordination of ligand HL1, which illustrates the flexible coordination chemistry of ligand L1.     

Mononuclear to polynuclear transition induced by ligand coordination: synthesis, X-ray structure, and properties of mono-, di-, and polynuclear copper(II) complexes of pyridyl-containing azo ligands

Reactions of two hydrated cupric salts (CuCl(2).2H(2)O and Cu(ClO(4))(2).6H(2)O) with three azopyridyl ligands, viz. 2-[(arylamino)phenylazo]pyridine [aryl = phenyl (HL(1a)), p-tolyl (HL(1b)), and 2-thiomethyl phenyl (HL(1c))], 2-[2-(pyridylamino)phenylazo]pyridine (HL(2)), and 2-[3-(pyridylamino)phenylazo]pyridine (HL(3)), afford the mononuclear [CuClL(1)] (1), dinuclear [Cu(2)X(2)L(2)(2)](n)()(+) (X = Cl, H(2)O, ClO(4); n = 0, 1; 2, 3), and polynuclear [CuClL(3)](n)() (4) complexes, respectively, in high yields. Representative X-ray structures of these complexes 1-4 are reported. X-ray structure analysis of 4 reveals an infinite 1D zigzag chain that adopts a saw-tooth-like structure. Variable-temperature cryomagnetic measurements (2-300 K) on the complexes 2-4 have revealed weak magnetic interactions between the copper centers with J values -1.04, 9.88, and -1.31 cm(-1), respectively. Positive ion ESI mass spectra of the soluble complexes 1-3 are studied which provide the evidence for the integrity of the complexes also in solution. Visible range spectra of the complexes 1-3 in solution consist of intense and broad transitions in the range 700-600 nm. The solid-state spectrum of the insoluble copper complex 4, on the other hand, shows a structured band near 700 nm. The intensities of the transitions of the dinuclear complexes are much higher than those of the corresponding mononuclear copper complexes. Redox properties of the present copper complexes are reported. Notably, the dinuclear complex, 3, displays two successive redox processes: Cu(II)Cu(II) right harpoon over left harpoon Cu(II)Cu(I) right harpoon over left harpoon Cu(I)Cu(I). It catalyzes aerial oxidation of L-ascorbic acid. The catalytic cycle is most effective up to H(2)A/3 (H(2)A = L-ascorbic acid) molar ratio of 20:1.     

Amine mediated proton transfer reaction and C-Cl bond activation of solvent chloroform by a trinuclear copper(II) complex of a glucopyranosylamine derived ligand

An amine mediated C-Cl bond activation process of the solvent chloroform has been explored by a coordinatively labile trinuclear Cu(II) complex, [Cu3(L1)2(MeOH)(H2O)] (1), derived from N-(3-tert-butyl-2-hydroxybenzylidene)-4,6-O-ethylidene--D-glucopyranosylamine (H3L1). The effect of activation is extremely high with methylamine, resulting in the formation of [Cu(MeNH2)5]Cl2 (2) and [Cu(L2)2] (3; HL2 = 2-tert-butyl-6-[(methylimino)methyl]phenol), however, under identical conditions it is moderate with ethylamine resulting in the isolation of crystals of the intermediate amine bound trinuclear copper(II) complex, [Cu3(L1)2(EtNH2)2(MeOH)2] (5), which was further converted into the mononuclear complex, [Cu(HL1)(EtNH2)] (6), in a novel crystal-to-crystal transformation. The successive isolation of the ethylamine-bound tri- and mononuclear complexes, 5 and 6, supported the occurrence of proton transfer reactions, which might be a key step in C-Cl bond activation. The primary and secondary amines, 2-aminomethylpyridine, N,N-dimethylethylenediamine, and 1,4,7-triazacyclononane, also having chelating features further enhance the rate of activation. No activation has been noted in the case of triethylamine and N,N,N,N-tetramethylethylenediamine. Formation of a carbene-trapped compound, 2,6-xylyl isocyanide, was confirmed in the reaction of complex 1 with 1,4,7-triazacyclononane and 2,6-xylidine in CHCl3, suggesting that the C-Cl bond cleavage led to the generation of dichlorocarbene. In addition, the mononuclear complex 6 has been transformed into a homotrinuclear complex [Cu3(L1)2(MeOH)2] by treatment with Cu(II) ions in MeOH/CHCl3, suggesting the possibility that the former could be regarded as a suitable metalloligand for heterotrimetallic complex synthesis.     

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.     

Spectral and structural studies of copper(II) complexes of thiosemicarbazones derived from salicylaldehyde and containing ring incorporated at N(4)-position

Mononuclear and binuclear copper(II) complexes (1-8) with two ONS donor thiosemicarbazone ligands {salicylaldehyde 3-hexamethyleneiminyl thiosemicarbazone [H2L1] and salicylaldehyde 3-tetramethyleneiminyl thiosemicarbazone [H2L2]} have been prepared and physico-chemically characterized. IR, electronic and EPR spectra of the complexes have been obtained. The thiosemicarbazones bind to metal as dianionic ONS donor ligands in all the complexes except in [Cu(HL1)2] (2) and [Cu(HL2)2] (6). In compounds 2 and 6 the ligands are coordinated as monoanionic HL- ones. The magnetic susceptibility measurements indicate that all the complexes are paramagnetic. In complex [(CuL1)2] (1), the magnetic moment value is lower than the expected spin only value. In all the complexes g(||)>g( perpendicular)>2.0023 and G values within the range 2.5-3.5 are consistent with dx2-y2 ground state. The complexes were given the formula as [(CuL1)2] (1); [Cu(HL1)2] (2); [CuL1bpy] (3); [CuL1phen] (4); [CuL1gamma-pic].2H2O (5); [Cu(HL2)2] (6); [CuL2py].3H2O (7); [CuL2bipy] (8). The structure of the compound 8 have been solved by single crystal X-ray crystallography and was found to be distorted square pyramid around copper(II) ion.     

Copper(I) coordination chemistry of (pyridylmethyl)amide ligands

Copper(I) chloro complexes were synthesized with a family of ligands, HL(R) [HL(R) = N-(2-pyridylmethyl)acetamide, R = null; 2-phenyl-N-(2-pyridylmethyl)acetamide, R = Ph; 2,2-dimethyl-N-(2-pyridylmethyl)propionamide, R = Me3; 2,2,2-triphenyl-N-(2-pyridylmethyl)acetamide, R = Ph3)]. Five complexes were synthesized from the respective ligand and cuprous chloride: [Cu(HL)Cl]n (1), [Cu2(HL)4Cl2] (2), [Cu2(HL(Ph))2(CH3CN)2Cl2] (3), [Cu2(HL(Ph)3)2Cl2] (4), and [Cu(HL(Me)3)2Cl] (5). X-ray crystal structures reveal that for all complexes the ligands coordinate to the Cu in a monodentate fashion, and inter- or intramolecular hydrogen-bonding interactions formed between the amide NH group and either amide C=O or chloro groups stabilize these complexes in the solid state and strongly influence the structures formed. Complexes 1-5 display a range of structural motifs, depending on the size of the ligand substituent groups, hydrogen bonding, and the stoichiometry of the starting materials, including a one-dimensional coordination polymer chain (1) and binuclear (2-4) or mononuclear (5) structures.     

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.     

Monopicolinate cyclen and cyclam derivatives for stable copper(II) complexation

The syntheses of a new 1,4,7,10-tetraazacyclododecane (cyclen) derivative bearing a picolinate pendant arm (HL1), and its 1,4,8,11-tetraazacyclotetradecane (cyclam) analogue HL2, were achieved by using two different selective-protection methods involving the preparation of cyclen-bisaminal or phosphoryl cyclam derivatives. The acid-base properties of both compounds were investigated as well as their coordination chemistry, especially with Cu(2+), in aqueous solution and in solid state. The copper(II) complexes were synthesized, and the single crystal X-ray diffraction structures of compounds of formula [Cu(HL)](ClO(4))(2)·H(2)O (L = L1 or L2), [CuL1](ClO(4)) and [CuL2]Cl·2H(2)O, were determined. These studies revealed that protonation of the complexes occurs on the carboxylate group of the picolinate moiety. Stability constants of the complexes were determined at 25.0 °C and ionic strength 0.10 M in KNO(3) using potentiometric titrations. Both ligands form complexes with Cu(2+) that are thermodynamically very stable. Additionally, both HL1 and HL2 exhibit an important selectivity for Cu(2+) over Zn(2+). The kinetic inertness in acidic medium of both complexes of Cu(2+) was evaluated by spectrophotometry revealing that [CuL2](+) is much more inert than [CuL1](+). The determined half-life values also demonstrate the very high kinetic inertness of [CuL2](+) when compared to a list of copper(II) complexes of other macrocyclic ligands. The coordination geometry of the copper center in the complexes was established in aqueous solution from UV-visible and electron paramagnetic resonance (EPR) spectroscopy, showing that the solution structures of both complexes are in excellent agreement with those of crystallographic data. Cyclic voltammetry experiments point to a good stability of the complexes with respect to metal ion dissociation upon reduction of the metal ion to Cu(+) at about neutral pH. Our results revealed that the cyclam-based ligand HL2 is a very attractive receptor for copper(II), presenting a fast complexation process, a high kinetic inertness, and important thermodynamic and electrochemical stability.     

Syntheses,Structures, and Catalytic Activities of Copper(I) Complexes with the Ligand 2(4,5‐Diphenyl‐1H‐imidazol‐2‐yl)­pyridine

Two copper(I) complexes of compositions [Cu(HL)I]₂ · EtOH ( 1 ) and [Cu(HL)₃]I · MeOH ( 2 ) were synthesized via the reactions of HL [HL = 2(4,5‐diphenyl‐1H‐imidazol‐2‐yl)pyridine] and CuI in EtOH and MeOH, respectively, under solvothermal conditions. The complexes were characterized by X‐ray single crystal diffraction, IR spectroscopy, and elemental analysis. Compounds 1 and 2 are catalytically active towards ketalization reaction, giving various ketals under mild conditions.     

l- and d-Proline Thiosemicarbazone Conjugates: Coordination Behavior in Solution and the Effect of Copper(II) Coordination on Their Antiproliferative Activity

Two enantiomerically pure thiosemicarbazone-proline conjugates with enhanced aqueous solubility, namely, 2-hydroxy-3-methyl-(S)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [l-Pro-STSC or (S)-H(2)L] and 2-hydroxy-3-methyl-(R)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [d-Pro-STSC or (R)-H(2)L] have been synthesized and characterized by elemental analysis, spectroscopic methods (UV-vis and (1)H and (13)C NMR), and electrospray ionization mass spectrometry. The metal complexation behavior of l-Pro-STSC, stoichiometry, and thermodynamic stability of iron(II), iron(III), copper(II), and zinc(II) complexes in 30% (w/w) dimethyl sulfoxide/H(2)O solvent mixture have been studied by pH-potentiometric, UV-vis-spectrophotometric, circular dichroism, electron paramagnetic resonance, (1)H NMR spectroscopic, and spectrofluorimetric measurements. By the reaction of CuCl(2)·2H(2)O with (S)-H(2)L and (R)-H(2)L, respectively, the complexes [Cu[(S)-H(2)L]Cl]Cl and [Cu[(R)-H(2)L]Cl]Cl have been prepared and comprehensively characterized. An X-ray diffraction study of [Cu[(R)-H(2)L]Cl]Cl showed the formation of a square-planar copper(II) complex, which builds up stacks with interplanar separation of 3.3 ?. The antiproliferative activity of two chiral ligands and their corresponding copper(II) complexes has been tested in two human cancer cell lines, namely, SW480 (colon carcinoma) and CH1 (ovarian carcinoma). The thiosemicarbazone-proline conjugates l- and d-Pro-STSC show only moderate cytotoxic potency with IC(50) values of 62 and 75 μM, respectively, in CH1 cells and >100 μM in SW480 cells. However, the corresponding copper(II) complexes are 13 and 5 times more potent in CH1 cells, based on a comparison of IC(50) values, and in SW480 cells the increase in the antiproliferative activity is even higher. In both tested cell lines, l-Pro-STSC as well as its copper(II) complex show slightly stronger antiproliferative activity than the compounds with a d-Pro moiety, yielding IC(50) values of 4.6 and 5.5 μM for [Cu(l-Pro-STSC)Cl]Cl in CH1 and SW480 cells, respectively.     

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.     

Synthesis,magnetochemical studies and X-ray molecular structures of some mononuclear copper(II)–1H-pyrazole adducts and mono(μ-pyrazolate) bridged dicopper(II) complexes derived from N-salicylidenearoylhydrazines

1H-Pyrazole complexes, [Cu(HL)HPz Cl] nH₂O and [Cu(L)HPz] nH₂O were prepared and characterized, where HL and L, respectively, refer to the mononegative and dinegative N-salicylidenearoylhydrazine anions. The X-ray crystal and molecular structure of [monochloro(N-salicylidenebenzoylhydrazinato)ONO(−1)monopyrazole] copper(II) monohydrate, [Cu(HSBzh)HPz Cl] H₂O, and [(N-salicylidenebenzoylhydrazinato)ONO(−2)monopyrazole] copper(II) hemihydrate, [Cu(SBzh)HPz] 1/2H₂O, were determined. The Cu(II) in [Cu(HSBzh)HPz Cl] H₂O is in a distorted square pyramidal environment and is bound in the equatorial plane with the mononegative tridentate aroylhydrazone anion and pyrazole nitrogen, the axial fifth coordination site is occupied by a chloride ion. On the other hand, the complex [Cu(SBzh)HPz] 1/2H₂O consists of two monomeric crystallographically independent but chemically similar molecules. In each molecule, the Cu(II) is in a distorted square planar geometry and is coordinated to the dinegative tridentate aroylhydrazone via the phenoxy oxygen, azomethine nitrogen and enolimide oxygen, and the fourth coordination site is occupied by the pyrazole nitrogen. The mono(μ-pyrazolate) dicopper(II) complexes, K[Cu₂(L)₂Pz] nH₂O, were also prepared and the X-ray molecular structure of K₂[Cu₄(SBzh)₄(Pz)₂] 2H₂O 1/2CH₃OH was determined. In this complex, two copper(II) atoms are bridged by only one pyrazolate anion forming a dicopper mono(μ-pyrazolate) unit. Each two units are connected together by a five coordinate K⁺ cation forming a tetranuclear assembly. These tetranuclear assemblies are connected together by another K⁺ cation forming a supramolecular structure. Variable temperature magnetic studies on these pyrazolate complexes indicated antiferromagnetic behaviour with −2J values varying from 25 to 36 cm⁻¹.     

Synthesis,magnetic moments and X-band e.p.r. spectra of binuclear and trinuclear copper(II) complexes

The imidazole-bridged binuclear copper(II) complex, [(Cl)2(imH)2Cu(imH)2Cu(bipy)(Cl)2] and the trinuclear copper (II) complex [(Cl)2(bipy)Cu(imH)2Cu(imH)2Cu(bipy)(Cl)2] have been synthesized by direct coupling between [Cu(imH)4(Cl)2] and [Cu(bipy)Cl2] in the appropriate stoichiometric ratios. The complexes show subnormal magnetic moments and e.p.r. spectra, characteristic of the triplet state. The antiferromagnetic coupling constant, J, has been obtained for both the complexes.     

Copper(II) mediated anion dependent formation of Schiff base complexes

A tetranuclear mixed ligand copper(II) complex of a pyrazole containing Schiff base and a hydroxyhexahydropyrimidylpyrazole and copper(II) and nickel(II) complexes of the Schiff base having N-donor atoms have been investigated. A 2 equiv amount of 5-methyl-3-formylpyrazole (MPA) and 2 equiv of 1,3-diamino-2-propanol (1,3-DAP) on reaction with 1 equiv of copper(II) nitrate produce an unusual tetranuclear mixed ligand complex [Cu4(L1)2(L2)2(NO3)2] (1), where H2L1 = 1,3-bis(5-methyl-3-formylpyrazolylmethinimino)propane-2-ol and HL2 = 5-methyl-3-(5-hydroxyhexahydro-2-pyrimidyl)pyrazole. In contrast, a similar reaction with nickel(II) nitrate leads to the formation of a hygroscopic intractable material. On the other hand, the reaction involving 2 equiv of MPA and 1 equiv each of 1,3-DAP and various copper(II) salts gives rise to two types of products, viz. [Cu(T3-porphyrinogen)(H2O)]X2 (X = ClO4, NO3, BF4 (2)) (T3-porphyrinogen = 1,6,11,16-tetraza-5,10,15,20-tetrahydroxy-2,7,12,17-tetramethylporphyrinogen) and [Cu(H2L1)X]X x H2O (X = Cl (3), Br (4)). The same reaction carried out with nickel(II) salts also produces two types of compounds [Ni(H2L1)(H2O)2]X2 [X = ClO4 (5), NO3 (6), BF4 (7)] and [Ni(H2L1)X2] x H2O [X = Cl (8), Br (9)]. Among the above species 1, 3, and 5 are crystallographically characterized. In 1, all four copper atoms are in distorted square pyramidal geometry with N4O chromophore around two terminal copper atoms and N5 chromophore around two inner copper atoms. In 3, the copper atom is also in distorted square pyramidal geometry with N4Cl chromophore. The nickel atom in 5 is in a distorted octahedral geometry with N4O2 chromophore, where the metal atom is slightly pulled toward one of the axial coordinated water molecules. Variable-temperature (300 to 2 K) magnetic susceptibility measurements have been carried out for complex 1. The separations between the metal centers, viz., Cu(1)...Cu(2), Cu(2)...Cu(2)A, and Cu(2)A...Cu(1)A are 3.858, 3.89, and 3.858 A, respectively. The overall magnetic behavior is consistent with strong antiferromagnetic interactions between the spin centers. The exchange coupling constants between Cu(1)...Cu(2) and Cu(2)...Cu(2A) centers have turned out to be -305.3 and -400.7 cm(-1), respectively, resulting in a S = 1/2 ground state. The complexes are further characterized by UV-vis, IR, electron paramagnetic resonance, and electrochemical studies.     

Synthesis, spectroscopic, thermal and antimicrobial studies of some novel metal complexes of Schiff base derived from [N1-(4-methoxy-1,2,5-thiadiazol-3-yl)sulfanilamide] and 2-thiophene carboxaldehyde

Keeping in view the chemotherapeutic of the sulfa-drugs, Schiff base namely 2-thiophene carboxaldehyde-sulfametrole (HL) and its tri-positive and di-positive metal complexes have been synthesized and characterized by elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance, mass spectra, UV-vis and thermal analysis (TGA and DrTG). The low molar conductance values suggest the non-electrolytic nature of these complexes. IR spectra show that HL is coordinated to the metal ions in a tetradentate manner through hetero five-membered ring-S and azomethine-N, enolic sulfonamide-OH and thiadiazole-N, respectively. Zn(II), Cd(II) and UO2(II) complexes are found to be diamagnetic (as expected). The proposed general formulae of the prepared complexes are [M2X4(HL)(H2O)4] (where M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II), X=Cl, [Fe2Cl6(HL)(H2O)2], [(FeSO4)2(HL)(H2O)4] and [(UO2)2(HL) (NO3)4].H2O. The thermal behaviour of these chelates shows that the hydrated complexes loss water of hydration in first step in case of uranium complexes followed loss coordinated water followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. The activation thermodynamic parameters, such as DeltaE*, DeltaH*, DeltaS*, and DeltaG* are calculated from the DrTG curves using Coats-Redfern method. The antimicrobial activity of the obtained products was performed using Chloramphenicol and Grisofluvine as standards, indicate that in some cases metallation increase activity than the ligand.