Copper complexes with bioactive ligands. Part II--Antifungal activity

Antifungal activity of new copper(II) complexes of 2-methylthionicotinate (2-MeSNic) of the composition Cu(2-MeSNic)₂(MeNia)₂·4H₂O (where MeNia isN-methylnicotinamide), and Cu(2-MeSNic)₂(Nia)₂·2H₂O (where Nia is nicotinamide) and Cu(2-MeSNic)₂L₂ (where L is isonicotinamide, iNia, or ethyl nicotinate, EtNic) were tested on various strains of filamentous fungi by the macrodilution method. Most sensitive against copper(II) adducts with bioactive ligands wereRhizopus oryzae andMicrosporum gypseum (IC₅₀ 1.5–2.3 mmol/L). The adducts with Nia, MeNia and EtNic at 5 mmol/L induced morphological changes in growing hyphae ofBotrytis cinerea, mainly their intensive branching attached to release of cytoplasm with partial growth inhibition. Inhibition of sporulation (>90%) ofAlternaria alternata by Cu(2-MeSNic)₂·H₂O was observed as a change in the color of the colonies. The highest resistance was marked byB. cinerea andFusarium moniliforme (average IC₅₀ values 4.25 and 3.13 mmol/L, respectively). The presence of all bioactive ligands in copper(II) complexes caused an increase in the inhibition effect against model fungi (except significant inhibition activity of EtNic onR. oryzae). Part I: Copper complexes with bioactive ligands. Antimicrobial activity.Folia Microbiol.46, 379–384 (2001).     

Antibacterial,antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones

1‐phenyl‐3‐methyl‐4‐benzoyl‐5‐pyrazolone 4‐ethyl‐thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C₂H₅OH·( 1 ), [Cu(L)₂]·H₂O ( 2 ), [Cu(L)(Br)]·H₂O·CH₃OH ( 3 ), [Cu(L)(NO₃)]·2C₂H₅OH ( 4 ), [VO₂(L)]·2H₂O ( 5 ), [Ni(L)₂]·H₂O ( 6 ), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, ¹H NMR and ¹³C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico‐chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) ( 2 , 4 ), and vanadium(V) ( 5 ) complexes have been determined by single‐crystal X‐ray diffraction. The composition of the coordination polyhedron of the central atom in 2 , 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4 , it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL‐60 cells was tested.     

Microcalorimetric Study of <Emphasis Type="Italic">Tetrahymena</Emphasis> Growth Affected by Copper(II) Complexes

By means of microcalorimetry, the effect of four copper(II) complexes on Tetrahymena growth was investigated. The extent and duration of the inhibitory effect on the metabolism, judged by the rate constant, k, and the half inhibition concentration, IC₅₀, varied with the different complexes. The results showed that the half inhibition concentrations IC₅₀ of CuCl₂, (C₉H₆NO)₂Cu and [Cu(phen)₂]Cl₂⋅6H₂O were 9.9 × 10⁻⁴, 2.0 × 10⁻⁴, and 2.6 × 10⁻⁴ mol/L, respectively. The sequence of antibiotic activity of these three complexes was: (C₉H₆NO)₂Cu > [Cu(phen)₂]Cl₂⋅6H₂O > CuCl₂. The growth rate constants of [Cu(phen)₃]Cl₂⋅6H₂O did not change obviously with the increase of concentrations, but [Cu(phen)₃]Cl₂⋅6H₂O also can prolong the time of Tetrahymena growth.     

The Cu/ligand stoichiometry effect on the coordination behavior of aroyl hydrazone with copper(II): Structure,anticancer activity and anticancer mechanism

In an effort to better understand the biological efficacy of the tridentate aroyl hydrazone Cu(II) complexes, three Cu(II) complexes of acetylpyridine benzoyl hydrazone (HL), [Cu(L)(NO₃) (H₂O)]·H₂O (C1), [Cu(L)₂] (C2) and [Cu(L)(HL)]·(NO₃)(Sas) (C3) (Sas = salicylic acid) were synthesized and characterized. X-ray crystal structures and infrared (IR) spectra of the complexes reveal that the L⁻ ligand of C1 and C2 are predominantly in the enolate resonance form, while one L⁻ ligand in C3 is represented enolate resonance form and the other HL ligand exhibits keto resonance form. All Cu(II) complexes showed significantly more anticancer activity than the ligand alone. Interestingly, the Cu complexes where the ligand/metal ratio was 1:1 (C1) rather than 2:1 (C2 and C3) had higher antitumor efficacy. Moreover, the 1:1 Cu/ligand complex, C1, promotes A549 cell apoptosis possibly through the intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.     

New binary copper(II) complexes containing intercalating ligands: DNA interactions,an unusual static quenching mechanism of BSA and cytotoxic activities

New binary copper(II) complexes – [Cu(4-mphen)₂(NO₃)]NO₃·H₂O (1), [Cu(5-mphen)₂ (NO₃)]NO₃·H₂O (2), the known complex [Cu(dmphen)₂(NO₃)]NO₃ (3) and [Cu(tmphen)₂ (NO₃)]NO₃·H₂O (4) - (4-mphen: 4-methyl-1,10-phenanthroline, 5-mphen: 5-methyl-1,10-phenanthroline, dmphen: 4,7-dimethyl-1,10-phenanthroline, tmphen: 3,4,7,8-tetramethyl-1,10-phenanthroline), have been synthesized and characterized by CHN analysis, ESI-MS, FTIR and single-crystal X-ray diffraction techniques. Interaction of these complexes with calf thymus DNA (CT-DNA) has been investigated by absorption spectral titration, ethidium bromide (EB) and Hoechst 33,258 displacement assay and thermal denaturation measurement. These complexes cleaved pUC19 plasmid DNA in the absence and presence of an external agent. Notably, in the presence of H₂O₂ as an activator, the cleavage abilities of these complexes are obviously enhanced at low concentration. Addition of hydroxyl radical scavengers like DMSO shows significant inhibition of the DNA cleavage activity of these complexes. BSA quenching mechanism was investigated with regard to the type of quenching, binding constant, number of binding locations and the thermodynamic parameters. The experimental results suggested that the probable quenching mechanism was an unusual static process and hydrophobic forces play a dominant role. The CT-DNA and BSA binding efficiencies of these complexes follow the order: 4 > 3 > 1 > 2. Furthermore, in vitro cytotoxicities of these complexes on tumor cells lines (Caco-2, MCF-7 and A549) and healthy cell line (BEAS-2B) showed that these complexes exhibited anticancer activity with low IC₅₀ values. The effect of hydrophobicity of the methyl-substituted phenanthrolines on DNA and protein binding activities of these complexes is discussed.     

Anti-oxidant,in vitro,in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II)

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)₂(H₂O)₂], 1, [Co(mef)₂(H₂O)₂], 2, [Ni(mef)₂(H₂O)₂], 3, [Cu(mef)₂(H₂O)]₂, 4 and [Zn(mef)₂], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl₃ solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, β-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)₂(H₂O)₂] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)₂] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 ± 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 ± 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC₅₀ values in a μM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.     

Studies on metal carboxylates. VIII. Reactions of acetylacetonates of the first row transition elements with pyridine-2,6-dicarboxylic acid

The acetylacetonates VO(acac)₂, M(acac)₃, where M = V, Mn or Fe and [M′(acac)₂]_n, where M′ = Co, Ni or Cu, have been reacted with pyridine-2,6-dicarboxylic acid (dipicH₂) in acetone to afford the complexes VO(dipic)·2H₂O, M(acac)(dipic)·xH₂O [M = V, Mn or Fe and x = 1 or 0] and M₂(dipic) (dipicH)₂·yH₂O [M = Co, Ni or Cu and y = 2 or 0]. The cobalt(II) and nickel(II) complexes are converted to polymeric [M(dipic)]_n in ethanol and all three complexes formulated as M₂(dipic)(dipicH)₂ react with 2,2′2″-terpyridyl to yield M(dipic)(terpy)·3H₂O. The vanadium(III) complex V(acac)(dipic) is oxidized to VO(dipic)·4H₂O in aqueous solution via the vanadium(III) intermediate V(OH)(dipic)·2H₂O. Tentative structural conclusions are drawn for certain of these new complexes based upon room temperature spectral and magnetic measurements. The characterization of these complexes has included selected studies of their X-ray photoelectron spectra.     

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     

Syntheses,characterization, antimicrobial and cytotoxic activities of pyridine-2,5-dicarboxylate complexes with 1,10-phenanthroline

In this study, four mononuclear M(II)-pyridine-2,5-dicarboxylate (M = Co(II), Ni(II), Cu(II) and Zn(II) complexes with pyridine-2,5-dicarboxylic acid or isocinchomeronic acid, 1,10-phenanthroline (phen), [Co(Hpydc)₂(phen)]·H₂O (1), [Ni(pydc)(phen)₂]·6.5H₂O (2) [Cu(pydc)(phen)(H₂O)₂] (3) and [Zn(pydc)(phen)(H₂O)₂]·H₂O (4) have been synthesized. Elemental, thermal and mass analyses, molar conductance, magnetic susceptibilities, IR and UV/vis spectroscopic studies have been performed to characterize the complexes. Subsequently, these ligands and complexes were tested for antimicrobial activity by disc diffusion method on Gram positive, negative bacteria and yeast. In addition, cytotoxic activity tests were performed on rat glioma (C6) cells by MTT viability assay for 24 and 48 h. Antimicrobial activity results demonstrated that when compared to the standard antibiotics, phen displayed the most effective antimicrobial effect. The effect of synthesized complexes was close to phen or less. Cytotoxic activity results showed that IC₅₀ value of phen was determined as 31 μM for 48 h. (1) and (2) compared to the alone ligand had less toxic activity. IC₅₀ values of (3) for 24 and 48 h treatments were 2.5 and 0.6 μM, respectively. IC₅₀ value of (4) for 48 h was 15 μM. In conclusion, phen, (3) and (4) may be useful as antibacterial and antiproliferative agents in the future.     

Hypoglycemic effect of copper(II) acetate imidazole complexes

The effect of copper(II) complexes on glucose metabolism was studied in normal and streptozotocin-induced diabetic rats. The copper(II) complexes used were bis(acetato)tetrakis(imidazole) copper (II), [Cu(OAc)₂(Im)₄], bis(acetato)bis(2-methylimidazole) copper(II), [Cu(OAc)₂(1,2dmIm)₂], and bis)acetato)bis(μ-acetato)tetrakis(N-methylimidazole) copper(II) hexaaquo, [Cu₂(OAc)₄-(NmIm)₄]·6H₂O. Intramuscular administration of various doses of Cu(OAc)₂(Im)₄ ranging from 10 to 100 mg/kg body mass to overnight fasted rats decreased blood glucose levels in a dose-dependent manner. Maximum hypoglycemic effect was observed 3 h after administration and lasted for at least 6 h. Treatment with 100 mg/kg body mass of Cu(OAc)₂(Im)4 caused hypoglycemic shock, which was irreversible and even lethal. Blood insulin levels were reduced sharply during this hypoglycemic shock. Similar changes in blood glucose level were achieved using Cu(OAc)₂)2mIm)₂. The same pattern of hypoglycemia, although less pronouned, was observed for Cu₂(OAc)₄(NmIm)₄·6H₂O and Cu (OAc)₂(1,2dmIm)₂. Binary copper(II) acetate complex, the ligand imidazole, and the inorganic form of copper, such as copper(II) chloride, had no significant effect on blood glucose level. These results indicate that the hypoglycemic activity of these complexes varies with the imidazole ligand and structure of the complex. Intramuscular administration of Cu(OAc)₂(Im)₄ to diabetic rats caused a reduction in blood glucose levels and improved their tolerance for glucose.     

Synthesis of copper(II) and nickel(II) complexes of N-(hydroxyalkylaminoalkyl)salicylamides

Copper(II) and nickel(II) complexes are prepared of potentially quadridentate ligands (LH₃), N-{2-(2- hydroxyethylamino)ethyl}- (seeH₃), N-{3-(2-hydroxy- ethylamino)propyl}- (steH₃), and N-{2-(3-hydroxypropylamino)ethyl}-salicylamide (setH₃). The nickel complexes Na[Ni(see)] and Na[Ni(set)]·1/2H₂O are diamagnetic and square-planar, in which the ligands act as a quadridentate one coordinated through secondary amino-N, and deprotonated phenolic-O, alcoholic-O, and amido-N atoms. The three copper complexes Na [CuL]·H₂O (L = see, ste, set) with a normal magnetic moment have a similar square-planar structure. In another type complexes Cu(LH)·H₂O (LH = seeH, setH) an alcohol group is not deprotonated. Two isomers are present in Cu(seeH)·H₂O: one has a normal and the other a subnormal magnetic moment. The difficulty of complex formation of steH₃ may be attributed to an unfavourably fused 6-6-5 membered chelate ring with strain.     

Superoxide dismutase–mimicking activities of dinuclear Cu(II) complexes with ligands containing a tetrathioether-tetraamino moiety

The superoxide scavenging activities of copper(II) complexes with the ligands, 6,6′-methylene-bis(5′-amino-3′,4′-benzo-2′-thiapentyl)-1,11-diamino-2,3:9,10-dibenzo-4,8-dithiaundecane (H₄L), and 6,6′-bis(5′-amino-3′,4′-benzo-2′-thiapentyl)-1,11-diamino-2,3:9,10-dibenzo-4,8-dithiaundecane (H₄L′), were investigated by xanthine–xanthine oxidase (X/XO) assays using nitroblue tetrazolium (NBT) as indicator molecule, and the results were compared with respect to the particular type of anion (ClO·4, Cl^·, NO·3) on the apical site of the copper(II) complexes. All of the complexes inhibited the reduction of NBT by superoxide radicals, with the [Cu₂(L′)](ClO₄)₂ complex exhibiting the highest scavenging activity against superoxide radicals among the complexes examined. The catalytic efficiency of the complexes for dismutation of superoxide radicals depends on the particular anion liganded to Cu(II) ion in the complexes, and the order of potency was observed to be ClO₄ > Cl > NO·3 in phosphate buffer at pH 7.40. The Cu(II)-H₄L′ complexes had the lowest IC₅₀ and catalytic rate constant values indicating that the distorted geometry of the Cu(II)-H₄L′ complexes influence their catalytic activities for dismutation of superoxide radicals more efficiently. The difference in the activities of the complexes toward superoxide radicals can also be attributed to the nature of the anions on the apical site of the copper(II) complexes and the superoxide dismutase-like activity. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 53–59, 1998     

Copper(II) complexes of methimazole,an anti Grave’s disease drug. Synthesis,characterization and its potential biological behavior as alkaline phosphatase inhibitor

Methimazole (MeimzH) is an anti-thyroid drug and the first choice for patients with Grave’s disease. Two new copper(II) complexes of this drug: [Cu(MeimzH)₂(NO₃)₂].0.5H₂O and [Cu(MeimzH)₂(H₂O)₂](NO₃)₂·H₂O were synthesized and characterized by elemental analysis, dissolution behavior, thermogravimetric analysis and UV-vis, diffuse reflectance, FTIR and EPR spectroscopies. As it is known that copper(II) cation can act as an inhibitor of alkaline phosphatase (ALP), the inhibitory effect of methimazole and its copper(II) complexes on ALP activity has also been investigated.     

Synthesis,spectral characterization,in vitro microbial and cytotoxic studies of lanthanum(III) and thorium(IV) complexes with 1,2,4-triazole Schiff bases

A series of metal complexes of La(III) and Th(IV) have been synthesized with newly derived biologically active ligands. These ligands were synthesized by the condensation of 3-substituted-4-amino-5-hydrazino-1,2,4-triazole with 8-formyl-7-hydroxy- 4-methylcoumarin. The structure of the complexes has been proposed by elemental analyses, spectroscopic data i.e. i.r., ¹H nmr, Uv-Vis, FAB-mass and thermal studies. The elemental analyses of the complexes conform to the stoichiometry of the type [La(L)·3H₂O]·2H₂O and [Th(L)(NO₃)·2H₂O]·2H₂O where (L = L^I-L^IV). All the complexes are soluble in DMF and DMSO and are non-electrolytes in DMF and DMSO. All these ligands and their complexes have also been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Staphylococcus pyogenes and Pseudomonas aeruginosa) and antifungal activities (Aspergillus niger, Aspergillus flavus and cladosporium) by the MIC method. The brine shrimp bioassay was also carried out to study their invitro cytotoxic properties.     

Metal complexes of 1-methyl-3,4-diphenylpyrazole,a ligand formed by the reaction between benzil and N,N,-dimethylhydrazine

New complexes of the general formulae MnX₂L₂ (X = Cl,Br), MnBr₂L₃, CoX₂L₂ (X = Cl, Br, I, NCS, NO₃), NiX₂L₂ (X = Cl, NO₃), NiBr₂L₃·H₂O, NiL₂L₄·H₂O, CuCl₂L, CuBr₂L₂·H₂O, Cu(NO₃)₂L₂, ZnX₂L₂ (X = Cl, Br, NO₃, Zn(NCS)₂L₂·H₂O, CdX₂L₂ (X = I, NO₃) and HgCl₂L, where L is 1-methyl-3,4-diphenylpyrazole, have been prepared and characterized by elemental analysis, conductivity measurements, magnetic moments and spectral (¹H-NMR, IR and electronic) studies. The ligands is formed by the reaction between benzil and N,N-dimethylhydrazine. The nitrogen of the >CN bond is the donor atom to the metal ions. The bis-ligand halide complexes are pseudotetrahedral, while the nitrate complexes contain octahedrally coordinated metal ions. The IR spectra of MCl₂L (M = Cu, Hg) are indicative of the presence of both terminal and bridging metal-halogen bonds supporting polymeric structures. The stereochemistry and the nature of the nickel(II) complexes are markedly dependent upon the anions; the chloride complex is pseudotetrahedral, the iodide square planar, the nitrate polymeric octahedral, while the proposed structural formula for NiBr₂L₃·H₂O comprises Nickel(II) atoms present in both square planar and octahedral coordination environments.     

Immobilization of whole cells ofStreptomyces kanamyceticus containing glucose isomerase by a combination of heat treatment in the presence of minerals and entrapment in calcium alginate gels

A method of immobilization of whole cells ofStreptomyces kanamyceticus containing glucose isomerase was devised, based on techniques of heat fixation in the presence of minerals and, entrapment in calcium alginate gels. The optimum activity of the enzyme was obtained when the cells were heat-fixed at 60°C for 10 min in the presence of 50 mmol/L MgSO₄·7H₂O and 5 mmol/L CoCl₂·6H₂O and then cast into calcium alginate beads using 2% sodium alginate.     

Chronotoxicity of a Copper (II) Complex with a Linear Tetradentate Ligand in Mice

In vitro copper (II) complex presents antimitotic effects. In this work, we have studied the in vivo seasonal toxic effects of copper (II), ligand (H₂L) and the complex [Cu(H₂L)(H₂O)₂]Cl₂·4H₂O in male Swiss mice. During spring, an i.p. injection of CuCl₂ in aqueous NaCl (9 g·l^-1) up to 0.05 µmol·kg^-1 b.w. (body weight) killed 60% of the rodents after 6 days. LD100 was up to 0.3 µmol·kg^-1; H₂L was well tolerated, while the complex was 30% lethal with 50 µmol·kg^-1. In autumn, mice were less sensitive to CuCl₂, and both ligand and complex were equally tolerated and this leads to the conclusion that, in vivo, chronotoxicities of copper (II) and complex in NaCl aqueous solutions are quite different in spring and autumn seasons.     

Multispectroscopic insight,morphological analysis and molecular docking studies of CuII-based chemotherapeutic drug entity with human serum albumin (HSA) and bovine serum albumin (BSA)

The interaction studies of Cu^II nalidixic acid–DACH chemotherapeutic drug entity, [C₃₆H₅₀N₈O₆Cu] with serum albumin proteins, viz., human serum albumin (HSA) and bovine serum albumin (BSA) employing UV–vis, fluorescence, CD, FTIR and molecular docking techniques have been carried out. Complex [C₃₆H₅₀N₈O₆Cu] demonstrated strong binding affinity towards serum albumin proteins via hydrophobic contacts with binding constants, K?=?3.18?×?10⁵ and 7.44?×?10⁴ M^–1 for HSA and BSA, respectively implicating a higher binding affinity for HSA. The thermodynamic parameters ΔG, ΔH and ΔS at different temperatures were also calculated and the interaction of complex [C₃₆H₅₀N₈O₆Cu] with HSA and BSA was found to be enthalpy and entropy favoured, nevertheless, complex [C₃₆H₅₀N₈O₆Cu] demonstrated higher binding affinity towards HSA than BSA evidenced from its higher binding constant values. Time resolved fluorescence spectroscopy (TRFS) was carried out to validate the static quenching mechanism of HSA/BSA fluorescence. The collaborative results of spectroscopic studies indicated that the microenvironment and the conformation of HSA and BSA (α–helix) were significantly perturbed upon interaction with complex [C₃₆H₅₀N₈O₆Cu]. Hirshfeld surfaces analysis and fingerprint plots revealed various intermolecular interactions viz., N–H····O, O–H····O and C–H····O linkages in a 2–dimensional framework that provide crucial information about the supramolecular architectures in the complex. Molecular docking studies were carried out to ascertain the preferential binding mode and affinity of complex [C₃₆H₅₀N₈O₆Cu] at the target site of HSA and BSA. Furthermore, only for Transmission electroscopy microscopy micrographs of HSA and BSA in presence of complex [C₃₆H₅₀N₈O₆Cu] revealed major protein morphological transitions and aggregation which validates efficient delivery of complex by serum proteins to the target site.

Communicated by Ramaswamy H. Sarma     

Metal—phenoxyalkanoic acid interactions. Part 14. The crystal and molecular structures of diaquabis(4-fluorophenoxyacetato)copper(II) bis(4-fluorophenoxyacetic acid)dihydrate and tetra-μ-(4-fluorophenoxyacetato-0,0′)-bis[(2-aminopyrimidine)copper(II)]

The crystal structures of two copper(II) complexes of 4-fluorophenoxyacetic acid (4-FPAH) have been determined by X-ray diffraction. [Cu(4-FPA)₂(H₂O)₂]·2(4-FPAH)·2H₂O (1) is triclinic, space group P1 with Z = 1 in a cell of dimensions a = 14.808(2), b = 9.832(2), c = 6.847(2) Å, α = 87.77(2), β = 98.41(2), γ = 112.33(2)° and was refined to a residual of 0.038 for 1697 ‘observed’ reflections. The coordination sphere in this complex is tetragonally distorted octahedral comprising two waters [CuO, 1.940(3) Å], two unidentate carboxylate oxygens [CuO, 1.942(2) Å] and two ether oxygens [CuO, 2.471(2) Å]. Two adducted [4-FPAH] acid molecules are linked to the un-coordinated oxygens of the acid ligands by hydrogen bonds [2.547(4) Å]. [Cu₂(4-FPA)₄(2-aminopyrimidine)₂] (2) is triclinic, space group P1 with Z = 1 in a cell of dimensions a = 12.688(2), b = 11.422(2), c = 7.951(1) Å, α = 78.74(1), β = 107.51(1), γ = 75.78(1)°, and was refined to a residual of 0.042 for 2683 ‘observed’ reflections. (2) is a centrosymmetric tetracarboxylate bridged dimer with four similar CuO (equatorial) distances [1.967–1.987 Å; 1.977(3) Å mean] and the axial position occupied by the hetero nitrogen of the 2-aminopyrimidine ligand [CuN, 2.176(3) Å]. The Cu---Cu separation is 2.710(1) Å. Crystal data are also presented which confirm the isostructurality of complex (2) with [Cu₂(phenoxyacetate)₄(2-aminopyrimidine)₂], the Co^II, Mg^II and Mn^II4-fluorophenoxyacetate complexes with their phenoxyacetic and 4-chlorophenoxyacetic acid analogues, and of Cd^II4-fluorophenoxyacetate with Cd^II and Zn^II phenoxyacetates.     

Synthesis,Structure, and Biological Activities of a New μ‐Oxamido‐Bridged Dicopper(II) Complex: The Influence of Hydrophobicity of Bridging Ligand on DNA Binding and Cytotoxic Activities

A new μ‐oxamido‐bridged dicopper(II) complex, [Cu₂(papo)(H₂O)‐ (phen)]Cl·CH₃OH·H₂O, where H₃papo and phen represent N‐(2‐hydroxyphenyl)‐N'‐(3‐aminopropyl)oxamide and 1,10‐phenanthroline, respectively, has been synthesized and characterized by elemental analysis, molar conductivity measurement, infrared and electronic spectra studies, and single‐crystal X‐ray diffraction. The complex crystallizes in the triclinic space group P‐1. Each copper(II) ion is located in a slightly distorted square‐pyramidal environment. The Cu···Cu distance through the oxamide bridge is 5.1848(7) Å. The three‐dimensional supramolecular structure is built‐up by hydrogen bonds and π–π stacking interactions. The dicopper(II) complex exhibits cytotoxic activity against the SMMC‐7721 and A549 cell lines. The reactivity toward herring sperm DNA and protein bovine serum albumin (BSA) reveals that the dicopper(II) complex can interact with the DNA by the intercalation mode, and effectively quench the intrinsic fluorescence of BSA via a static mechanism. The influence of hydrophobicity of the bridging ligand on DNA‐binding properties and in vitro cytotoxic activities of this kind of dicopper(II) complexes was investigated.