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.     

真菌吸附铅锌的研究

正随着采矿业的迅速发展,越来越多的重金属通过多种途径进入土壤环境中,对生态环境造成了不可估量的破坏并严重威胁人类健康。铅锌在工业上具有非常重要的作用且其应用极为广泛,而他们具有的难去除、难迁移和生物累积等特性使得铅锌在环境中的污染尤为突出。通过微生物的生长代谢,有效降低土壤重金属毒性,是促进植物生长的重要步骤之一。同时也要求微生物自身具有抵抗重金属的功能,根际微生     

Transition metal-saccharide chemistry: d-glucose complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)

Metal complexes of d-glucose (d-Glc) from large cation containing dibromo-dichloro salts of dipositive metals [NEt₄]₂[MBr₂Cl₂] (M = Mn, Co, Ni, Cu and Zn) and the disodium salt of glucose were synthesized from a MeOH:MeCN mixture. The complexes were characterized by UV-vis absorption, circular dichroism, IR and proton magnetic resonance spectroscopies, and by elemental analysis, and were found to be Na[M(d-Glc)(OMe)Cl]. Cyclic voltammetric studies of these complexes, in the acidic to neutral pH range, indicated no dissociation, even in highly acidic conditions.This paper is dedicated to Professor Richard H. Holm (Harvard University) on the occasion of his 60th birthday.     

Enantiomeric Specificity of Biologically Significant Cu(II) and Zn(II) Chromone Complexes Towards DNA

Novel chiral Schiff base ligands (R)/(S)‐2‐amino‐3‐(((1‐hydroxypropan‐2‐yl)imino)methyl)‐4H‐chromen‐4‐one (L₁ and L₂) derived from 2‐amino‐3‐formylchromone and (R/S)‐2‐amino‐1‐propanol and their Cu(II)/Zn(II) complexes ( R1 , S1 , R2 , and S2 ) were synthesized. The complexes were characterized by elemental analysis, infrared (IR), hydrogen (¹H) and carbon (¹³C) nuclear magnetic resonance (NMR), electrospray ionization‐mass spectra (ESI‐MS), and molar conductance measurements. The DNA binding studies of the complexes with calf thymus were carried out by employing different biophysical methods and molecular docking studies that revealed that complexes R1 and S1 prefers the guanine–cytosine‐rich region, whereas R2 and S2 prefers the adenine–thymine residues in the major groove of DNA. The relative trend in K_b values followed the order R1 S1 R2 S2 . This observation together with the findings of circular dichroic and fluorescence studies revealed maximal potential of (R)‐enantiomeric form of complexes to bind DNA. Furthermore, the absorption studies with mononucleotides were also monitored to examine the base‐specific interactions of the complexes that revealed a higher propensity of Cu(II) complexes for guanosine‐5′‐monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to thymidine‐5′‐monophosphate disodium salt. The cleavage activity of R1 and R2 with pBR322 plasmid DNA was examined by gel electrophoresis that revealed that they are good DNA cleavage agents; nevertheless, R1 proved to show better DNA cleavage ability. Topoisomerase II inhibitory activity of complex R1 revealed that the complex inhibits topoisomerase II catalytic activity at a very low concentration (25 μM). Furthermore, in vitro antitumor activity of complexes R1 and S1 were screened against human carcinoma cell lines of different histological origin. Chirality 24:977–986, 2012. © 2012 Wiley Periodicals, Inc.     

Multispectroscopic studies on the interaction of a copper(ii) complex of ibuprofen drug with calf thymus DNA

The interaction of copper(II)–ibuprofenato complex with calf thymus DNA (ct-DNA) has been explored following, UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, and circular dichroism spectroscopy. In spectrophotometric studies of ct-DNA it was found that [Cu(ibp)₂]₂ can form a complex with double-helical DNA. The association constant of [Cu(ibp)₂]₂ with DNA from UV-Vis study was found to be 6.19 × 10⁴ L mol^?1. The values of K_f from fluorescence measurement clearly underscore the high affinity of [Cu(ibp)₂]₂ to DNA. The experimental results showed that the conformational changes in DNA helix induced by [Cu(ibp)₂]₂ are the reason for the fluorescence quenching of the DNA-Hoechst system. In addition, the fluorescence emission spectra of intercalated methylene blue (MB) with increasing concentrations of [Cu(ibp)₂]₂ represented a significant increase of MB intensity as to release MB from MB-DNA system. The results of circular dichroism (CD) suggested that copper(II)–ibuprofenato complex can change the conformation of DNA. In addition, the results of viscosity measurements suggest that copper(II)–ibuprofenato complex may bind with non-classical intercalative mode. From spectroscopic and hydrodynamic studies, it has been found that [Cu(ibp)₂]₂ interacts with DNA by partial intercalation mode which contains intercalation and groove properties.     

Intercalation of a Zn(II) complex containing ciprofloxacin drug between DNA base pairs

In this study, an attempt has been made to study the interaction of a Zn(II) complex containing an antibiotic drug, ciprofloxacin, with calf thymus DNA using spectroscopic methods. It was found that Zn(II) complex could bind with DNA via intercalation mode as evidenced by: hyperchromism in UV–Vis spectrum; these spectral characteristics suggest that the Zn(II) complex interacts with DNA most likely through a mode that involves a stacking interaction between the aromatic chromophore and the base pairs of DNA. DNA binding constant (K_b = 1.4 × 10⁴ M^?1) from spectrophotometric studies of the interaction of Zn(II) complex with DNA is comparable to those of some DNA intercalative polypyridyl Ru(II) complexes 1.0 ?4.8 × 10⁴ M^?1. CD study showed stabilization of the right-handed B form of DNA in the presence of Zn(II) complex as observed for the classical intercalator methylene blue. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and Van der Waals play main roles in this binding prose. Competitive fluorimetric studies with methylene blue (MB) dye have shown that Zn(II) complex exhibits the ability of this complex to displace with DNA-MB, indicating that it binds to DNA in strong competition with MB for the intercalation.     

Unusual dimeric Zn(II)-cytosine complexes: new models of the interaction of Zn(II) with DNA and RNA

Synthesis and crystal structure of two Zn(II) dimer complexes with 1-methylcytosine (1-MeC) are reported. In complex [Zn(2)Cl(4)(mu-1-MeC-O2,N3)(2)] (1), two 1-MeC ligands are bridging two ZnCl(2) moieties. In [Zn(2)(1-MeC-N3)(4)(mu-SO(4))(2)].2H(2)O (2), the sulfates act as bridging ligands and 1-MeC are linked via N3 to Zn(II) as terminal ligands. Both complexes represent the first examples of Zn(II)-pyrimidine dimers. The potential biological significance of 1 and 2 is discussed.     

Cu(II) and Zn(II) ions alter the dynamics and distribution of Mn(II) in cultured chick glial cells

Previous studies revealed that Mn(II) is accumulated in cultured glial cells to concentrations far above those present in whole brain or in culture medium. The data indicated that Mn(II) moves across the plasma membrane into the cytoplasm by facilitated diffusion or counter-ion transport with Ca(II), then into mitochondria by active transport. The fact that 1–10 M Mn(II) ions activate brain glutamine synthetase makes important the regulation of Mn(II) transport in the CNS. Since Cu(II) and Zn(II) caused significant changes in the accumulation of Mn(II) by glia, the mechanisms by which these ions alter the uptake and efflux of Mn(II) ions has been investigated systematically under chemically defined conditions. The kinetics of [⁵⁴MN]-Mn(II) uptake and efflux were determined and compared under four different sets of conditions: no adducts, Cu(II) or Zn(II) added externally, and with cells preloaded with Cu(II) or Zn(II) in the presence and absence of external added metal ions. Zn(II) ions inhibit the initial velocity of Mn(II) uptake, increase total Mn(II) accumulated, but do not alter the rate or extent Mn(II) efflux. Cu(II) ions increase both the initial velocity and the net Mn(II) accumulated by glia, with little effect on rate or extent of Mn(II) efflux. These results predict that increases in Cu(II) or Zn(II) levels may also increase the steady-state levels of Mn(II) in the cytoplasmic fraction of glial cells, which may in turn alter the activity of Mn(II)-sensitive enzymes in this cell compartment.     

Synthesis of a novel linear polymer of a macrocyclic polyamine copper (II) complex and its interaction with plasmid DNA

The novel linear polymer of a macrocyclic polyamine copper (II) complex, which has many cyclen groups linked by epichlorohydrin, has been synthesized as a DNA cleavage agent. The structure of the polymer 3 was identified by ¹HNMR and IR and its molecular weight was measured by GPC. The result of agarose gel electrophoresis assay showed that Cu-(II) complex 4 could act as a powerful catalyst for the cleavage of plasmid DNA under physiological conditions.     

DNA interaction of new copper(II) complexes with sulfonamides as ligands

New copper(II) complexes with sulfonamide ligands have been prepared and characterized. Sulfonamide ligands were prepared through a reaction between 8-aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the Cu(II) cation is between a square planar and a tetrahedral geometry, with stacking of the benzene rings of the sulfonyl ligands between neighbor molecules. Powder EPR spectra at room temperature gave rhombic spectra for the [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical nucleases that degrade DNA in the presence of sodium ascorbate. A study of the radical scavengers revealed that the ROS (reactive oxygen species) involved in the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.     

A new Schiff base copper (II) complex derived from estrone and d-glucosamine: Synthesis,characterization and its interaction with DNA

A novel copper (II) complex of Schiff base prepared through condensation between 2-formyl-17-deoxyestrone and d-glucosamine was synthesized and characterized. Fluorescence spectroscopy was conducted to assess their binding ability with CT-DNA. The results showed that the copper (II) complex could bind to DNA with a weak intercalative mode. The interaction between the copper (II) complex and DNA was also investigated by gel electrophoresis. Interestingly, we found that the complex could cleave plasmid DNA (pUC19) to nicked and linear forms through an oxidative mechanism without the use of exogenous agents.     

耐性真菌HA吸附铅、锌的影响因素及吸附机理研

【目的】从铅锌矿区分离筛选出耐铅锌性菌株,并研究其吸附铅、锌的影响因素及吸附机理,为重金属污染微生物修复提供参考。【方法】以从铅锌矿区筛选出的耐铅锌真菌HA作为试验菌株,考察影响其对铅、锌去除能力的主要因素(初始浓度、pH、接种量),同时通过等温吸附模型、动力学分析及红外光谱分析探讨其相关的吸附机理。【结果】经鉴定,从矿区筛选的对Pb2+、Zn2+有较强耐性的菌株HA为米曲霉(Aspergillus oryzae);在初始铅、锌浓度的实验范围内(100-800mg/L),HA对铅、锌离子的去除率随着其初始浓度增加而减小,25h后HA的生长进入平稳期,且对铅、锌离子的去除率趋于稳定。当铅、锌初始浓度为100mg/L、pH为5.0时,HA对铅、锌离子的去除率均达到最高,分别为97.8%、54.1%;当HA接种量为1mL时,其对铅、锌去除率的增长率达到最大。HA对铅、锌的吸附过程满足Langmuir吸附模型,其吸附以单层吸附为主。在动态吸附过程中,HA对Pb2+、Zn2+离子吸附性能与准二级动力学吸附方程的拟合程度更高,且对Pb2+的吸附效果明显高于Zn2+。红外光谱分析表明,HA细胞中羟基、烷基、酰胺基、羰基、磷酸基等参与了Pb2+、Zn2+的吸附过程。【结论】HA是一株对铅、锌有较强吸附能力的真菌,其吸附铅、锌影响因素及吸附机理研究结果将为重金属污染微生物修复提供指导。     

Studies on the formation of a complex of Cu(II) with sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate - An analogue of the core unit of anthracycline anticancer drugs and its interaction with calf thymus DNA

Copper(II) forms a complex with sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (sodium quinizarin-2-sulphonate, NaQSH₂), an analogue of the core unit of anthracycline antibiotics used in the treatment of cancer. The 1:2 metal-ligand complex is formed in aqueous solution at neutral and acidic pH while in alkaline pH both 1:1 and 1:2 species are formed. The effective stability constant of the 1:2 metal-ligand complex is 9.64 × 10¹⁶ while that of the 1:1 metal-ligand complex is 9.4 × 10⁹. The 1:2 complex Cu(NaQSH)₂(H₂O)₂ was synthesized and characterized by different techniques in solid state and in solution. The complex Cu(NaQSH)₂(H₂O)₂ interacts with calf thymus DNA which was studied by fluorescence spectroscopy. The binding constant and site size for the interaction with DNA were determined.     

Synthesis,characterization, DNA interaction,and cytotoxicity of novel Pd(II) and Pt(II) complexes

Four complexes [Pd(L)(bipy)Cl]·4H₂O (1), [Pd(L)(phen)Cl]·4H₂O (2), [Pt(L)(bipy)Cl]·4H₂O (3), and [Pt(L)(phen)Cl]·4H₂O (4), where L = quinolinic acid, bipy = 2,2’-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, ¹H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5?×?10⁴ M^?1, 3.9?×?10⁴ M^?1, 6.1?×?10⁴ M^?1, and 1.4?×?10⁵ M^?1, respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.     

Double-strand hydrolysis of DNA by a magnesium(II) complex with diethylenetriamine

The development of artificial nucleases that hydrolyze DNA or RNA is of great interest in molecular biology, biotechnology, and medicine. We now report that a magnesium(II) complex of diethylenetriamine (Mg-dien) can effectively promote the double-stranded cleavage of plasmid DNA and the dideoxynucleotide dApdA under physiological conditions of pH and temperature. Experiments performed in the presence of hydrogen peroxide, radical scavengers, or under rigorously anaerobic conditions indicate that DNA cleavage mediated by Mg-dien occurs via a hydrolytic path. Mg-dien efficiently hydrolyzes supercoiled pBR322 DNA and the pseudo-first-order rate constant at 37 degrees C and pH 8.0 is estimated to be 1.60 h(-1). The dinucleotide dApdA hydrolysis, with Mg-dien at 170 microM, shows a rate enhancement factor of ca. 5 x 10(8). 1H and 31P(1H) NMR studies show that Mg-dien effectively hydrolyzes 5'-dAMP to give deoxyadenosine and inorganic phosphate. While Mg2+ has been found at the catalytic sites of many natural nucleases, Mg-dien appears to be the first synthetic Mg2+-containing system capable of hydrolyzing dideoxynucleotides and DNA and thus may provide a simple model system to assist mechanistic studies of naturally occurring nucleases.     

Synthesis and photophysical properties of dansyl-based polyamine ligands and their Zn(II) complexes

The synthesis, potentiometric studies and photophysical properties of two new polyamine ligands (L1 and L2) possessing the dansyl chromophore were studied in aqueous 0.15 M NaCl. The compounds show the absorption and emissions bands characteristic of the dansylamide fluorophore and both present intramolecular excited state proton transfer at intermediate pH ranges. One of the ligands (L2) strongly coordinates Zn(II) leading to fluorescence quenching. A model compound (L3) of the dansyl moiety was also investigated.     

Comparative studies on the biospeciation of antidiabetic VO(IV) and Zn(II) complexes

The speciation of several insulin-mimetic/enhancing VO(IV) and Zn(II) complexes in human blood serum was studied and a comparison was made concerning the ability of the serum components to interact with the original metal complexes and the distribution of the metal ions between the low and the high molecular fractions of the serum. It was found that the low molecular mass components may play a larger role in transporting Zn(II) than in the case with VO(IV). Among the high molecular mass serum proteins, transferrin is the primary binder of VO(IV), and albumin is that of Zn(II). The results revealed that protein-ligand interactions may influence the metal ion distribution in the serum.     

Synthesis, structure and characterization of novel Cd(II) and Zn(II) complexes with the condensation product of 2-formylpyridine and selenosemicarbazide: Antiproliferative activity of the synthesized complexes and related selenosemicarbazone complexes

Two novel Cd(II) and Zn(II) complexes with the condensation product of 2-formylpyridine and selenosemicarbazide were synthesized. The structure of Cd(II) complex was determined by X-ray crystallography. The ligand is coordinated in a neutral form via pyridine and azomethine nitrogen atoms and the selenium donor. The cadmium ion completes its five-coordination by two chloride ligands, forming a square-pyramidal geometry. The structure of Zn(II) complex was established by analysis of spectroscopic data, which indicated coordination of the ligand as a bidentate via the selenium and the azomethine nitrogen atoms. The cytotoxic activity of the newly synthesized complexes, as well as if five structurally related complexes and the ligand evaluated against eight tumor cell lines. The new Cd(II) complex showed the highest activity similar to cisplatin with IC50 less than 10 μM for all cell lines. Cell cycle distribution and apoptosis study showed that Cd(II) complex and cisplatin might have some similarity in anticancer activity, which was not the case for cisplatin and other studied complexes. Effects of the complexes on matrix metalloproteinases (MMPs) MMP-9 and MMP-2 was also studied. Cd(II) and Zn(II) complexes and cisplatin increased MMP-2 activity in supernatants of tested cells, while Ni(II) complex with the same ligand decreased the activity, implying a possible activity in preventing tumor invasion and metastasis processes.     

Influence of Cr(III) and Cr(VI) on the interaction between sparfloxacin and calf thymus DNA

Cr(III) and Cr(VI) have different binding capacity with sparfloxacin, and have different combination modes with calf thymus DNA. Selecting these two different metal ions, the influence of them on the binding constants between sparfloxacin (SPFX) and calf thymus DNA, as well as the related mechanism has been studied by using absorption and fluorescence spectroscopy. The result shows that Cr(III) has weaker binding capacity to SPFX in the SPFX-Cr(III) binary system, but influences the binding between SPFX and DNA obviously in SPFX-DNA-Cr(III) ternary system. However, although Cr(VI) has a stronger binding capacity to SPFX, it has no effect on the binding between SPFX and DNA. Referring to the different modes of Cr(III) and Cr(VI) binding to DNA, the mechanism of the influence of metal ions on the binding between SPFX and DNA has been proposed. SPFX can directly bind to DNA by chelating DNA base sites. If a metal ion at certain concentration binds mainly to DNA bases, it can decrease the binding constants between SPFX and DNA through competing with SPFX. While if a metal ion at certain concentration mainly binds to phosphate groups of DNA, it can increase the binding constants by building a bridge between SPFX and DNA. If a metal ion at certain concentrations binds neither to bases nor phosphate groups in DNA, it will have no effect on the binding constant between SPFX and DNA. Our result supports Palumbo's conclusion that the binding between SPFX and the phosphata groups is the precondition for the combination between SPFX and DNA, which is stabilized through stacking interactions between the condensed rings of SPFX and DNA bases.     

Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt(II) and Pd(II) complexes of glycine derivatives with calf thymus DNA

Some amino acid derivatives, such as R-glycine, have been synthesized together with their full spectroscopic characterization. The sodium salts of these bidentate amino acid ligands have been interacted with [M(bpy)(H₂O)₂](NO₃)₂ giving the corresponding some new complexes with formula [M(bpy)(R-gly)]NO₃ (where M is Pt(II) or Pd(II), bpy is 2,2′-bipyridine and R-gly is butyl-, hexyl- and octyl-glycine). Due to less solubility of octyl derivatives, the biological activities of butyl and hexyl derivatives have been tested against chronic myelogenous leukemia cell line, K562. The interaction of these complexes with highly polymerized calf thymus DNA has been extensively studied by means of electronic absorption, fluorescence and other measurements. The experimental results suggest that these complexes positive cooperatively bind to DNA presumably via groove binding. Molecular dynamic results show that the DNA structure is largely maintained its native structure in hexylglycine derivative–water mixtures and at lower temperatures. The simulation data indicates that the more destabilizing effect of butylglycine is induced by preferential accumulation of these molecules around the DNA and due to their more negative free energy of binding via groove binding.