Investigation on the interaction of newly designed potential antibacterial Zn(II) complexes with CT-DNA and HSA

Two Zn(II) complexes of formula [Zn(bpy)(Gly)]NO₃ (I) and [Zn(phen)(Gly)]NO₃ (II) (where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and Gly = glycine) were synthesized and characterized by elemental analysis, molar conductance measurements, UV–vis, FT-IR, and ¹H NMR spectra. The interaction ability of these complexes with calf thymus DNA was monitored using spectroscopic methods, including UV–vis absorption spectroscopy, ethidium bromide displacement, Fourier transform infrared, and electrophoretic mobility assay. Further, the human serum albumin interactions of complexes I and II were investigated using UV–vis absorption spectroscopy, fluorescence quenching, circular dichroism, and Fourier transform infrared. The results obtained from these analyses indicated that both complexes interact effectively with CT-DNA and HSA. The binding constant (K_b), the Stern–Volmer constant (K_sv), and the number of binding sites (n) at different temperatures were determined for CT-DNA and HSA. Also, the negative ΔH° and ΔS° values showed that both hydrogen bonds and van der Waals forces played major roles in the association of CT-DNA-Zn(II) and HSA-Zn(II) complex formation. The displacement experiments suggested that Zn(II)-complexes primarily bound to Sudlow’s site II of HSA. The distance between the donor (HSA) and the acceptor (Zn(II) complexes) was estimated on the basis of the Forster resonance energy transfer (FRET) and the alteration of HSA secondary structure induced by the compounds were confirmed by FT-IR spectroscopy. The complexes follow the binding affinity order of I > II with DNA and II > I with HSA. Finally, Antibacterial activity of complexes I and II have been screened against gram positive and gram negative bacteria.     

Antibacterial combination therapy using Co3+, Cu2+, Zn2+ and Pd2+ complexes: Their calf thymus DNA binding studies

Four Co(III)-, Cu(II)-, Zn(II)-, and Pd(II)-based potent antibacterial complexes of formula K₃[Co(ox)₃].3H₂O (I), [Cu(bpy)₂Cl]Cl.5H₂O (II), [Zn(bpy)₃]Cl₂ (III), and [Pd(bpy)₂](NO₃)₂ (IV) (where ox is oxalate and bpy is 2,2′-bipyridine) were synthesized. They were characterized by elemental analyses, molar conductance measurements, UV–Vis, FTIR, ¹H NMR, and ¹³C NMR spectra. These metal complexes were ordered in three combination series of I + II, I + II + III, and I + II + III + IV. Antibacterial activity was tested for each of these four metal complexes and their combinations against Gram-positive and Gram-negative bacteria. All compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV and the activity of their combinations followed the order of I + II + III + IV > I + II + III > I + II. CT-DNA binding studies of complex I and its three combinations were carried out using UV–vis spectral titration, displacement of ethidium bromide (EB), and electrophoretic mobility assay. The results obtained from UV–vis studies indicated that all series interact effectively with CT-DNA. Fluorescence titration revealed that the complexes quench DNA-EB strongly through the static quenching procedures. The binding constant (K_b), the Stern–Volmer constant (K_sv), and the number of binding sites (n) were determined at different temperatures of 293, 300, and 310 K, respectively. The calculated thermodynamic parameters supported that hydrogen binding and Van der Waals forces play a major role in association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series.     

Synthesis and X-ray crystal structure of [Ag(phendio)<Subscript>2</Subscript>]ClO<Subscript>4</Subscript> (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells

The Cu(II) and Ag(I) complexes, [Cu(phendio)₃](ClO₄)₂4H₂O and [Ag(phendio)₂]ClO₄ (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. `Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH<sub>3</sub>CO<sub>2</sub>, AgNO<sub>3</sub> and AgClO<sub>4</sub>.H<sub>2</sub>O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to `metal-free' phendio, simple Ag(I) salts and [Ag(phendio)₂]ClO₄ causes extensive, non-specific DNA cleavage. `Metal-free' phendio and [Ag(phendio)₂]ClO₄ induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells.     

Alteration of molecular conformations and spectral properties for nickel(II), zinc(II) and copper(II) complexes having 3,8-di(thiophen-2′,2′′-yl)-1,10-phenanthroline ligands

Four transition metal complexes of 3,8-di(thiophen-2′,2″-yl)-1,10-phenanthroline (dtphen), formulated as [Ni(dtphen)₂(H₂O)₂]·(ClO₄)₂ (1), [Zn(dtphen)₂(H₂O)]·(ClO₄)₂ (2) [Cu(dtphen)₂(H₂O)]·(ClO₄)₂ (3), [Cu(dtphen)(phen)₂]·(ClO₄)₂ (4) (phen = 1,10-phenanthroline) with different metal-to-ligand ratios, were synthesized and characterized herein. The X-ray single-crystal diffraction studies of 1-4 exhibit that different molecular configurations for the dtphen ligand can be observed where the side thiophene rings adopt the trans/trans, trans/cis, trans/disorder and cis/cis conformations relative to the central 1,10-phenanthroline unit in different compounds. Fluorescence emission spectra of 1-4 in methanol show that the fluorescence emission of 2 is much stronger than the other three metal complexes, which is mainly due to its full d¹⁰ electronic configuration of Zn(II) ion.     

Structural forms in complexes of 2,9-dimethyl-1,10-phenanthroline with simple salts of copper(I) and other univalent ‘closed shell’ species

Syntheses, spectroscopic and structural characterizations of a series of Cu(I)-phenanthroline complexes are reported. A single crystal X-ray structure determination is recorded for CuNO₃:dmp:MeCN (1:1:1), ‘dmp’ = 2,9-dimethyl-1,10-phenanthroline, showing it to be isomorphous with its previously studied tetrafluoroborate, perchlorate and hexafluorophosphate, and silver(I) perchlorate counterparts, the metal atom lying in a trigonal planar [(N^∧N)Cu(NCMe)] coordination environment, the anion not being coordinated. Structure (re-) determinations are also reported for a number of salts of the [Cu(dmp)₂]⁺ cation: the perchlorate, isomorphous with numerous other salts, not only of copper(I), but also lithium(I)), also the unsolvated nitrate, and a solvated form of the chloride.     

Study on Interaction of DNA from Calf Thymus with 1,10-phenanthrolinehexyldithiocarbamatopalladium(II) nitrate as Potential Antitumor Agent

Abstract

A novel palladium(II) complex has been synthesized with hexyldithiocarbamate (Hex-dtc) and 1,10-phenanthroline (phen) by the reaction of [Pd(phen)(H₂O)₂](NO₃)₂ with sodium salt of hexyldithiocarbamate and a complex of type [Pd(Hex-dtc) (phen)]NO₃ has been obtained. The complex has been characterized by elemental analysis, molar conductance, ¹H NMR, IR and electronic spectroscopic studies. The dithiocarbamate ligand acts in bidentate fashion. This water-soluble complex was screened against chronic myelogenous leukemia cell line, K562, for cytotoxic effects and showed significant antitumor activity much lower than that of cisplatin. The interaction of this complex with calf thymus DNA (ctDNA) was extensively investigated by a variety of spectroscopic techniques. Absorbance titration experiments imply the interaction of 4 Pd(II) complex molecules per 1000 nucleotides on DNA with positive cooperativity in the binding process and the complex denature the DNA at very low concentration (～14.3 μM). Fluorescence titration spectra and fluorescence Scatchard plots suggest that the Pd(II) complex intercalate in DNA. The gel chromatograms obtained from Sephadex G-25 column experiments showed that the binding of metal complex with DNA is so strong that it does not readily break. Furthermore, some thermodynamic and binding parameters found in the process of UV-Visible studies are described. They may provide specificity of the compound with ctDNA.     

Synthesis and biological evaluation of a new dysprosium(III) complex containing 2,9-dimethyl 1,10-phenanthroline

The binding of [Dy(dmp)₂Cl₃(OH₂)], where dmp is 2,9-dimethyl 1,10-phenanthroline, with Fish salmon DNA (FS-DNA) is investigated by absorption and emission spectroscopy, quenching studies, salt dependent, and gel electrophoresis. The binding constant (K_b) of the interaction is calculated as (1.27 ± .05) × 10⁵ M^?1 from absorption spectral titration data. The Stern–Volmer constant (K_SV), thermodynamic parameters involves ΔG°, ?H°, and ?S° are calculated by fluorescent data and Van’t Hoff equation. The thermodynamic studies show that the reaction for the binding of the complex with FS-DNA is endothermic and entropically driven (ΔS° > 0, ΔH° > 0). The effect of the complex concentration on FS-DNA cleavage reactions is also investigated by gel electrophoresis. Furthermore, the Dy(III) complex has been screened for its antibacterial activity. The experimental results suggest that the Dy(III) complex binds significantly to FS-DNA by hydrophobic groove binding mode and the complex has more efficient antibacterial activity compared to its metal salt.     

Synthesis,DNA Binding,and Oxidative Cleavage Studies of Fe(II) and Co(III) Complexes Containing Bioactive Ligands

The two complexes containing bioactive ligands of the type and [Fe(L)] (PF₆)₂ (1) (where L = [1-{[2-{[2-hydroxynaphthalen-1-yl)methylidine]amino}phenyl)imino] methyl}naphthalene-2-ol]) and [Co(L₁L₂)] (PF₆)₃ (2) (where L₁L₂ = mixed ligand of 2-seleno-4-methylquinoline and 1,10-phenanthroline in the ratio 1:2, respectively) were synthesized and structurally characterized. The DNA binding property of the complexes with calf thymus DNA has been investigated using absorption spectra, viscosity measurements, and thermal denaturation experiments. Intrinsic binding constant K_b has been estimated at room temperature. The absorption spectral studies indicate that the complexes intercalate between the base pairs of the CT-DNA tightly with intrinsic DNA binding constant of 2.8 × 10⁵ M^?1 for (1) and 4.8 × 10⁵ M^?1 for (2) in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2, respectively. The oxidative cleavage activity of (1) and (2) were studied by using gel electrophoresis and the results show that complexes have potent nuclease activity.     

Synthesis and antimicrobial activity of copper(II) and manganese(II) α,ω-dicarboxylate complexes

Copper(II) ,-dicarboxylate complexes of general formulae, [Cu(O₂C(CH₂)_nCO₂)]·xH₂O, [Cu(O₂C(CH₂)_nCO₂) (phen)₂]·xH₂O and [Cu(O₂C(CH₂)_nCO₂)(bipy)_y]·xH₂O (n=1–8; y=1, 2; phen = 1,10-phenanthroline; bipy = 2,2-bipyridine) were synthesised. These copper complexes, some related manganese(II) complexes and the metal-free ligands were screened in vitro for their ability to inhibit the growth of Candida albicans. Metal-free 1,10-phenanthroline and all of the copper(II) and manganese(II) phenanthroline complexes were potent growth inhibitors, with only one bipyridine complex, [Cu(O₂C(CH₂)CO₂)(bipy)₂]·2H₂O, having moderate activity. The remaining substances were effectively inactive. Complexes which were active against C. albicans also proved effective against C. glabrata, C. tropicalis and C. kreusi with the manganese complexes retaining superior activity. For the phenanthroline complexes the active drug species is thought to be the dication [M(phen)₂(H₂O)_n]²⁺ (M = Cu, Mn). Escherichia coli and Staphylococcus aureus were resistant to all of the metal complexes and also to metal-free 1,10-phenanthroline. Only the copper phenanthroline complexes showed intermediate activity against Pseudomonas aeruginosa.     

Kinetics of the complexation of nickel(II) with 1,10-phenanthroline and its derivatives in acetonitrile-water mixed solvents

The kinetics of the complexation of Ni(II) with 1,10-phenanthroline(phen), 4,7-dimethyl-1,10-phenanthroline(dmphen), and 5-nitro-1,10-phenanthroline(NO₂phen) in acetonitrile-water mixed solvents of acetonitrile mole fraction x_AN = 0, 0.05, 0.1, 0.2 and 0.3 at 288, 293, 298 and 303 K have been studied by stopped-flow method at ionic strength of 1.0 (NaClO₄) and pH 7.4. The corresponding activation enthalpy, entropy, and free energy were determined from the observed rate constants. The complexation of Ni(II) with the three ligands has comparable observed rate constants; in pure water the observed rate constants are (×10³ dm³ mol⁻¹ s⁻¹) 2.31, 2.57, and 1.38 for phen, dmphen and NO₂phen, respectively. The corresponding activation parameters for the three ligands are, however, considerably different; in pure water the ΔH^‡/ΔS^‡ (kJ mol⁻¹/J K⁻¹ mol⁻¹) are 44.7/−30.2, 19.5/−114.1, and 32.2/−76.9 for phen, dmphen, and NO₂phen, respectively. The effects of solvent composition on the kinetics are also markedly different for the three ligands. The ΔH^‡ and ΔS^‡ showed a minimum at x_AN = 0.1 for phen; for dmphen and NO₂phen, however, maxima at x_AN = 0.2 were observed. Nevertheless, there is an effective enthalpy-entropy compensation for the ΔH^‡/ΔS^‡ of all the three ligands, demonstrating the significant effects of the changes in solvation and solvent structure on the complexation kinetics. As the rate-determining step of Ni(II) complexation is the dissociation of a water molecule from Ni(II), the solvent and ligand dependencies in the Ni(II) complexation kinetics are ascribed to the change in solvation status of the ligands and the altered solvent structures upon changing solvent composition.     

Ordering selected Zn(II), Cu(II), Pd(II) and Co(III) complex compounds: their separately and combinedly antibacterial therapy and DNA-binding studies

Abstract

In this study, four Co(III)-, Cu(II)-, Zn(II)- and Pd(II)-based potent antibacterial complexes of formula K₃[Co(ox)₃]·3H₂O (I), [Cu(phen)₂Cl]Cl·6.5H₂O (II), [Zn(phen)₃]Cl₂ (III) and [Pd(phen)₂](NO₃)₂ (IV) (where ox is oxalato and phen is 1,10-phenanthroline) were synthesized. They were characterized by elemental analysis, molar conductivity measurements, UV–vis, Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (¹H-NMR) techniques. These metal complexes were ordered in three combination series of I+II, I+II+III and I+II+III+IV. Antibacterial screening for each metal complex and their combinations against Gram-positive and Gram-negative bacteria revealed that all compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV, and the activity of their combinations followed the order of I+II+III+IV > I+II+III > I+II. The DNA-binding properties of complex (I) and its three combinations were studied using electronic absorption and fluorescence (ethidium bromide displacement assay) spectroscopy. The results obtained indicated that all series interact effectively with calf thymus DNA (CT-DNA). The binding constant (K_b), the number of binding sites (n) and the Stern–Volmer constant (K_sv) were obtained based on the results of fluorescence measurements. The calculated thermodynamic parameters supported that hydrogen bonding and van der Waals forces play a major role in the association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series.

Communicated by Ramaswamy H. Sarma     

Example of two novel thiocyanato bridged copper (II) complexes derived from substituted thiosemicarbazone ligand: structural elucidation,DNA/albumin binding,biological profile analysis,and molecular docking study

Two novel copper (II) substituted thiosemicarbazone Schiff base complexes [Cu(L₁)(µ-SCN)]_n(NO₃)₂ (1) and [Cu₂(µ-SCN)(SCN)(L₂)₂](NO₃) (2) have been synthesized by condensing substituted thiosemicarbazides like 4-methyl-3-thiosemicarbazide or 4-ethyl-3-thiosemicarbazide with 2-acetylpyridine. Both the metal complexes 1 and 2 are characterized using different spectroscopic techniques like IR, UV-Vis, ESR spectroscopy followed by elemental analysis, cyclic voltammetric measurement and single crystal X-ray structure analysis. X-ray crystal structure analysis reveal that complex 1 is polymeric while complex 2 is dimeric in nature. The coordination geometry around Cu(II) are square pyramidal in which thiosemicarbazone Schiff base ligand coordinate to the central Cu(II) atom in tridentate fashion. The prominent interaction patterns of 1 and 2 with CT-DNA were examined by employing electronic absorption and emission spectral titrations, cyclic voltammetry and viscosity measurements. All the results show that CT-DNA binds with both copper (II) complexes 1 and 2. Furthermore, protein binding ability in vitro of complexes 1 and 2 with both BSA and HSA were carried out using multispectroscopic techniques and a static quenching pattern was observed in both cases. Molecular docking study was employed to ascertain the exact mechanism of action of 1 and 2 with DNA and protein molecules (BSA and HSA). In vitro cytotoxicity activity of complexes 1 and 2 toward AGS and A549 was evaluated using MTT assay which demonstrates that both complexes 1 and 2 have superior prospectus to act as anticancer agents.

Communicated by Ramaswamy H. Sarma     

Antiproliferative activity and QSAR study of copper(II) mixed chelate [Cu(N-N)(acetylacetonato)]NO3 and [Cu(N-N)(glycinato)]NO3 complexes, (Casiopeínas)

Mixed chelate copper(II) complexes patented and mark title registered as Casiopeínas^® are antineoplastic agents with general formulas [Cu(N-N)(α-l-amino acidato)]NO₃ and [Cu(N-N)(O-O)]NO₃, where the N-N donor is an aromatic substituted diimine (1,10-phenanthroline (phen) or 2,2′-bipyridine (bpy)) and the O-O donor is acetylacetonate (acac) or salicylaldehydate (salal). In the present work, the series of complexes [Cu(N-N)(acac)]NO₃ and [Cu(N-N)(gly)]NO₃ with several substituents on the diimine ligand were selected to perform a quantitative structure-activity relationship (QSAR) study. Two main analysis were performed: (1) the study of the influence of the substituents on diimine ligand on physicochemical properties such as half-wave potential (E_1/2) and their relationship with medial lethal dose (LD50) or medial inhibitory concentration (IC50) on several tumor cell lines and (2) the study of the influence of the secondary ligand when acac is changed for glycinate (gly). Results showed that the presence of the central fused aromatic ring in the phen containing complexes is necessary to preserve the antiproliferative activity. The QSAR equations showed a strong relationship between the IC50 and E_1/2; the most active complexes are the weaker oxidants. The change of secondary ligand from acac to gly has less influence on biological activity than the changes on the diimine ligand.     

Effect of lipophilicity of amylamine and amylglycine ligands on biological activity of new anticancer cisplatin analog

Investigation of side effects and solubility of anticancer drugs is a major challenge in chemotherapy science. Thus, design and synthesis of cisplatin analogs with higher lipophilicity as novel water-soluble anticancer drugs is valuable. In this work, two new Pt(II) complexes were synthesized with formula cis-[Pt(NH₃)₂(amylgly)]NO₃ and cis-[Pt(amylamine)₂(amylgly)]NO₃, where gly is penthyl glycine as an amino acid. The new compounds were synthesized and extensively characterized using analytical techniques; spectroscopic methods, and conductivity measurement. The anticancer activity of synthesized complexes was investigated against colon cancer cell line HCT116 using MTT assay and results showed excellent anticancer activity with Cc₅₀ values of 36 and 270 M after 24-h incubation time for cis-[Pt(NH₃)₂(amylgly)]NO₃ and cis-[Pt(NH₂-amyl)₂(amylgly)]NO₃, respectively; which is lower than that for cisplatin. These complexes were also interacted with highly polymerized calf thymus DNA and the binding mode of the complexes to CT-DNA was evaluated by fluorescence, circular dichroism, and UV spectroscopy. The calculation of binding and thermodynamic of Pt(II) complexes with CT-DNA can provide deeper insight into mechanism of the action of these types of complexes with nucleic acids. So, thermodynamic parameters were also determined according to isothermal titration. In comparison with cis-[Pt(NH₃)₂(amylgly)]NO₃ in DNA interaction, the result show that cis-[Pt(NH₂-amyl)₂(amylgly)]NO₃ has higher affinity with binding constant K_f = 8.72 mM to CT-DNA. The results indicate that cis-[Pt(amylamine)₂(amylgly)]NO₃ with large and bulky aliphatic group bind to CT-DNA by different modes and covalent and groove bindings were preferred mode of interaction with DNA.     

Synthesis,Characterization, Cellular Uptake,Apoptosis, Cytotoxicity,Dna-Binding,and Antioxidant Activity Studies of Ruthenium(II) Complexes

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)₂(HECIP)](ClO₄)₂ (1) (HECIP = N-ethyl-4-[(1,10)-phenanthroline(5,6-f)imidazol-2-yl]carbazole, dmb = 4,4’-dimethyl-2,2’-bipyridine) and [Ru(dmp)₂(HECIP)](ClO₄)₂ (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of the two complexes were investigated by absorption spectra, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 were determined to be 8.03 (± 0.12) × 10⁴ M^?1 (s = 1.62) and 2.97 (± 0.15) × 10⁴ M^?1 (s = 1.82), respectively. The results suggest that these complexes interact with DNA through intercalative mode. The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 has been evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)] method. Complex 1 shows higher anticancer potency than 2 against the four tumor cell lines. Apoptosis and cellular uptake were investigated. The antioxidant activities of the ligand and these complexes were also performed.     

Extended structures of three new coordination polymers based on 1,10-phenanthroline derivatives and 1,4-benzenedicarboxylate mixed ligands: Preparation, structural characterization and properties

Three coordination polymers, namely, [Cd(HOIP)₂(1,4-bdc)] (1), [Cu(HOIP)(1,4-bdc)] (2) and [Cu(PDIP)(1,4-bdc)] (3) (HOIP = 2-(4-hydroxylbenzene) imidazo[4,5-f]1,10-phenanthroline, PDIP = 2-(3-pyridine) imidazo[4,5-f]1,10-phenanthroline, and 1,4-bdc = 1,4-benzenedicarboxylate), have been synthesized under the hydrothermal conditions. All complexes have been characterized by elemental analyses, IR and single-crystal X-ray diffraction. Structural analyses reveal that complex 1 possesses infinite one-dimensional (1D) chain bridged by 1,4-bdc ligands, complexes 2 and 3 both exhibit two-dimensional (2D) (4,4) network structures based on dinuclear [Cu₂O₂] units. However, the weak interactions are different in complexes 1-3. Moreover, the thermal properties of all complexes, fluorescence property of 1, and the electrochemical behavior of 3 are also reported in this paper.     

Synthesis and crystal structures of cobalt(II), cadmium(II), and zinc(II) complexes of 4-nitro phenylcyanamide: enhancing the biological properties through bound to human serum albumin

Metal complexes of the type [Co(phen)₂(4-NO₂pcyd)₂].CH₃OH, 1, [Zn(phen)₂(4-NO₂pcyd)₂].CH₃OH, 2, [Cd(phen)₂(4-NO₂pcyd)₂], and 3, (phen?=?1,10-phenanthroline, 4-NO₂pcyd?=?4-nitro phenylcyanamide) have been studied. The synthesis, characterization, and the biological activities of complexes 1-3 have been investigated. The geometries of complexes 1-3 were confirmed by single-crystal X-ray crystallography. The interactions of complexes 1-3 with human serum albumin (HSA) were studied using fluorescence and circular dichroism spectroscopy. The thermodynamic studies have showed the reaction for the binding of complexes 1-3 with HSA is hydrophobic (ΔH_0???0 and ΔS₀ > 0). The in vitro cytotoxic potential of complexes 1-3 and their complexes with HSA were examined. The complexes 1-3 with HSA enhance about 3-fold cytotoxicity in cancer cells lines.     

New ternary copper(II) complexes of l-alanine and heterocyclic bases: DNA binding and oxidative DNA cleavage activity

Four new ternary copper(II) complexes of α-amino acid having polypyridyl bases of general formulation [Cu(l-ala)(B)(H₂O)](X) (1-4), where l-ala is l-alanine, B is an N,N-donor heterocyclic base, viz. 2,2′-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2) and 5,6-phenanthroline dione (dione, 3), dipyrido[3,2:2′,3′-f]quinoxaline (dpq, 4), and X = / are synthesized, characterized by various spectroscopic and X-ray crystallographic methods. The complexes show a distorted square-pyramidal (4 + 1) CuN₃O₂ coordination geometry. The one-electron paramagnetic complexes (1-4) display a low energy d-d band near 600 nm in aqueous medium and show a quasi-reversible cyclic voltammetric response due to one-electron Cu(II)/Cu(I) reduction near −100 mV (versus SCE) in DMF-0.1 M TBAP. Binding interactions of the complexes with calf thymus DNA (CT-DNA) were investigated by UV-Vis absorption titration, ethidium bromide displacement assay, viscometric titration experiment and DNA melting studies. All the complexes barring the complexes 1 and 3 are avid binder to the CT-DNA in the DNA minor groove giving an order: 4 > 2 ? 1, 3. The complexes 2 and 4 show appreciable chemical nuclease activity in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent. Hydroxyl radical was investigated to be the DNA cleavage active species. Control experiments in the presence of distamycin-A show primarily minor groove-binding propensity for the complexes 2 and 4 to the DNA.     

Synthesis and characterization of tris(heteroleptic) diimine complexes of chromium(III)

A preparative procedure of potentially wide applicability is described for the synthesis of previously unreported tris(heteroleptic) [Cr(diimine)₃]³⁺ complexes. The synthetic scheme involves the sequential addition of three different diimine ligands, and employs CrCl₃ · 6H₂O as the initial Cr(III) reagent. The synthesis and characterization of the complexes [Cr(TMP)(phen)(diimine′)]³⁺ are reported (where TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline, phen = 1,10-phenanthroline; and diimine′ is either bpy = 2,2′-bipyridine, Me₂bpy = 4,4′-dimethyl-2,2′-bipyridine, 5-Clphen = 5-chloro-1,10-phenanthroline, or DPPZ = dipyridophenazine). Chiral capillary electrophoresis and electrospray mass spectrometry were essential aids in determining the presence or absence of diimine ligand scrambling. Utilizing emission and electrochemical data obtained on these compounds, the oxidizing power of the lowest lying excited state (²E_g(O_h)) was calculated, and was found to vary in a systematic fashion with diimine ligand type.     

Phenoxyl-copper(II) complexes: models for the active site of galactose oxidase

 The reaction of the macrocycles 1,4,7-tris (3,5-di-tert-butyl-2-hydroxy-benzyl)-1,4,7-triazacyclononane, L¹H₃, or 1,4,7-tris(3-tert-butyl-5-methoxy-2-hydroxy-benzyl)-1,4,7-triazacyclononane, L²H₃, with Cu(ClO₄)₂·6H₂O in methanol (in the presence of Et₃N) affords the green complexes [Cu^II(L¹H)] (1), [Cu^II(L²H)]·CH₃OH (2) and (in the presence of HClO₄) [Cu^II(L¹H₂)](ClO₄) (3) and [Cu^II(L²H₂)] (ClO₄) (4). The Cu^II ions in these complexes are five-coordinate (square-base pyramidal), and each contains a dangling, uncoordinated pendent arm (phenol). Complexes 1 and 2 contain two equatorially coordinated phenolato ligands, whereas in 3 and 4 one of these is protonated, affording a coordinated phenol. Electrochemically, these complexes can be oxidized by one electron, generating the phenoxyl-copper(II) species [Cu^II(L¹H)]^+ ·, [Cu(L²H)]^+ ·, [Cu^II(L¹H₂)]^2+ ·, and [Cu^II(L²H₂)]^2+ ·, all of which are EPR-silent. These species are excellent models for the active form of the enzyme galactose oxidase (GO). Their spectroscopic features (UV-VIS, resonance Raman) are very similar to those reported for GO and unambiguously show that the complexes are phenoxyl-copper(II) rather than phenolato-copper(III) species. Received: 10 February 1997 / Accepted: 7 April 1997