Synthesis,characterization, molecular modeling,and DNA interaction studies of a Cu(II) complex containing drug of chronic hepatitis B: adefovir dipivoxil

A new copper(II) complex [Cu(adefovir)₂Cl₂], where adefovir = adefovir dipivoxil drug, was synthesized and characterized by using different physicochemical methods. Binding interaction of this complex with calf thymus DNA (ct-DNA) has been investigated by multi-spectroscopic techniques and molecular modeling study. The complex displays significant binding properties of ct-DNA. The results of fluorescence and UV–vis absorption spectroscopy indicated that, this complex interacted with ct-DNA in a groove-binding mode, and the binding constant was 4.3(±0.2) × 10⁴ M^?1. The fluorimeteric studies showed that the reaction between the complex and ct-DNA is exothermic (ΔH = 73.91 kJ M^?1; ΔS = 357.83 J M^?1 K^?1). Furthermore, the complex induces detectable changes in the CD spectrum of ct-DNA and slightly increases its viscosity which verified the groove-binding mode. The molecular modeling results illustrated that the complex strongly binds to the groove of DNA by relative binding energy of the docked structure ?5.74 kcal M^?1. All experimental and molecular modeling results showed that the Cu(II) complex binds to DNA by a groove-binding mode.     

Synthesis,characterization and in vitro DNA binding studies of a new copper(II) complex containing an antiviral drug,valganciclovir

A new complex, [Cu(valcyte)₂(NO₃)₂], in which valcyte served as a valganciclovir drug, was synthesized and characterized by different physicochemical methods. Optimization of ligand structures and their complexes with Cu²⁺ were performed by semi-empirical and DFT methods. Binding interaction of this complex with calf-thymus DNA (ct-DNA) was explored by emission, absorption, circular dichroism and viscosity techniques. Additionally, cell line targeting was studied and cytotoxic effects of [Cu(valcyte)₂(NO₃)₂] (0.0–160 μg) on AGS and MCF-7 cell lines were reported. Percentage of Cell Viability and Apoptotic Index were assessed. The complex displayed significant binding properties to ct-DNA. Undertaking fluorometric studies, the binding mode of the complex with ct-DNA was explored utilizing Hoechst as a fluorescence probe, indicating the binding to be of groove mode. The DNA viscosity altered slightly in presence of the complex. Enthalpy and entropy changes during the interaction showed that the process is endothermic, with the complex mainly bound to ct-DNA by hydrophobic attraction. Values of ΔG revealed a spontaneous reaction between DNA and the complex. Optimized docked model of DNA–complex mixture confirmed the experimental results. The results of MMFF94 calculations indicated stability of [Cu(valcyte)₂(NO₃)₂] after docking with the modeled DNA profile, as compared to the DNA profile and valganciclovir results before the docking process. Cytotoxicity studies showed that an increase in [Cu(valcyte)₂(NO₃)₂] may result in a significant decrease in cell viability and increase apoptosis index in the treated cells, as compared to valganciclovir treated cells (p < 0.05). The findings further showed that [Cu(valcyte)₂(NO₃)₂] has potential for use in cancer therapy.     

Synthesis,characterization and DNA interaction studies of a new platinum(II) complex containing caffeine and histidine ligands using instrumental and computational methods

A new Pt(II) complex, [Pt(Caff)(His)(Cl)] (Caff is Caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione) and His is l-Histidine), was synthesized and characterized using different physicochemical methods. The interaction of this complex with calf thymus DNA (ct-DNA) was investigated by absorption, emission, circular dichroism (CD), and viscosity measurements and molecular docking techniques. The calculated binding constant, K_b, was 5.3 × 10³ M^?1. In fluorimetric studies, the enthalpy and entropy of the reaction between the complex and ct-DNA showed that the reaction is exothermic (?H = ?184.07 kJ mol^?1, ?S = ?551.97 J mol^?1 K^?1). CD spectra of DNA in the presence of different amounts of the complex showed little changes in both the negative and positive band intensities, which imply a non-intercalative mode between the DNA and the platinum complex. Furthermore, the study of molecular docking also indicated that the complex binds to DNA via a groove binding mode.     

Synthesis,characterization, and DNA binding of two copper(II) complexes as DNA fluorescent probes

[Cu(DAPT)₂Cl]Cl·H₂O and [Cu(DBM)(DAPT)Cl] [DAPT = 2,4-diamine-6-(pyrazin-2-yl)-1,3,5-triazine] were synthesized and characterized by IR and UV spectroscopy, elemental analysis, TG–DTA, molar conductivity, and LC–MS. The interaction with calf thymus DNA (ct-DNA) of the two complexes has been studied using UV spectra, fluorescent spectra, cyclic voltammetry, and viscosity measurements. The complexes interact with ct-DNA through classical intercalation. Fluorescence intensity changes of 1 and 2 in the absence and presence of ct-DNA have been investigated for quantitative determination of ct-DNA with the limit of detection of 3.8 and 7.7 ng mL^?1, respectively. From the result, the two complexes are potentially sensitive DNA fluorescent probes.     

Kinetics and mechanism of the substitution reactions of some monofunctional Pt(II) complexes with heterocyclic nitrogen donor molecules. Crystal structure of [Pt(bpma)(pzBr)]Cl2·2H2O

Substitution reactions of [Pt(terpy)Cl]⁺ (terpy = 2,2′;6′,2′′-terpyridine), [Pt(bpma)Cl]⁺ (bpma = bis(2-pyridylmethyl)amine), [Pt(dien)Cl]⁺ (dien = diethylenetriamine or 1,5-diamino-3-azapentane) and [Pt(tpdm)Cl]⁺ (tpdm = tripyridinedimethane) with nitrogen donor heterocyclic molecules, such as 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr) and imidazole (Im), were studied in aqueous 0.10 M NaClO₄ in the presence of 10 mM NaCl using variable-temperature UV–vis spectrophotometry. The second-order rate constants k₂ indicate decrease in reactivity in the order [Pt(terpy)Cl]⁺ > [Pt(bpma)Cl]⁺ > [Pt(tpdm)Cl]⁺ > [Pt(dien)Cl]⁺. The most reactive nucleophile among the heterocyclic compounds is imidazole, while pzI shows slightly higher reactivity than pzBr. Activation parameters were also determined and the negative values for entropies of activation, ΔS^≠, support an associative mode of substitution for all substitution processes. Crystal structure of [Pt(bpma)(pzBr)]Cl₂·2H₂O was determined by single-crystal X-ray analysis. The coordination geometry of the complex is distorted square-planar while the bond distance Pt–N2(pzBr) is longer than the other three Pt–N distances.     

DNA binding and nuclease activity of a water-soluble sulfonated manganese(III) corrole

The interaction of a water-soluble sulfonated Mn(III) corrole Mn(tpfc)(SO₃Na)₂ [tpfc = 5,10,15-tris(pentafluorophenyl)corrole] with calf thymus DNA (ct-DNA) has been studied by spectroscopic methods, and the nuclease activity of this complex has also been examined by agarose gel electrophoresis. Mn(tpfc)(SO₃Na)₂ exhibits weak aggregation tendency in buffer solution and can bind to ct-DNA via an outside binding mode with a binding constant of 1.25 × 10⁴ M^?1. The observed increase in Stern–Volmer quenching constant with increasing temperature indicates that the competition of the manganese corrole and ethidium bromide with ct-DNA is a dynamic process. Moreover, the manganese corrole displays good chemical nuclease activity in the presence of hydrogen peroxide via oxidative cleavage of DNA.     

Synthesis,characterization, crystal structure,and DNA binding of two copper(II)–hydrazone complexes

Two new Cu(II)–hydrazone complexes, [Cu(L)(Hbpe)ClO₄]·ClO₄·[Cu(L)Cl] (1) and [Cu(HL)₂]·1.5ClO₄·0.5OH (2) (where HL?=?(E)-N′-(1-(pyridine-2-yl)ethylidene)benzohydrazide and bpe = trans-1-(2-pyridyl)-2-(4-pyridyl)ethylene), have been synthesized and characterized by physicochemical methods. The structures of the complexes have been established by single-crystal X-ray diffraction direct methods, which reveal that the metal ions have distorted square-pyramidal and square-planar geometries in 1, and a distorted octahedral geometry in 2. DNA binding of HL, 1, and 2, performed by UV–vis titration in tris-buffer medium, yielded binding constants, which are 9.5 × 10³, 1.88 × 10⁴, and 4.66 × 10⁴ M^?1, respectively. Viscosity measurements suggest a surface or groove-binding mode of interaction between CT-DNA with HL, 1, and 2.     

Synthesis,Characterization, and DNA Binding Studies of a New Pt(II) Complex Containing the Drug Levetiracetam: Combining Experimental and Computational Methods

The water-soluble platinum(II) complex, [Pt(LV)(dmso)Cl]Cl (LV is Levetiracetam an anti-epileptic drug belonging to the pyrrolidine family) was synthesized and characterized using physico-chemical, spectroscopic and computational methods. Multi-spectroscopic methods used to study the interaction of Pt(II) complex with calf thymus (ct-DNA) in Tris–HCl buffer solution (pH 7.4). The Pt(II) complex was found to be a minor groove binder with a preference for the A-T region compared to the G-C region. This was substantiated by displacement studies with Hoechst 33258, a known minor groove binder. The mean binding constant obtained from the spectroscopic techniques was 7?×?10⁴ M^?1. In comparison with the previous study, the binding constant of Pt(II) complex is 15 times greater than the corresponding value of levetiracetam. These results indicate that the binding affinity of Pt(II) complex is stronger than levetiracetam.     

DNA-interaction studies of a copper(II) complex containing ceftobiprole drug using molecular modeling and multispectroscopic methods

Abstract

The interaction of the [Cu(cef)(phen)Cl₂] complex with calf-thymus DNA (ct-DNA) at physiological pH was investigated by UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, circular dichroism spectroscopy, and molecular modeling. UV-vis spectra showed 5?nm bathochromic shift of the absorption band at 270?nm along with significant hypochromicity for the absorption band of the complex. The binding constant obtained of UV-vis (1?×?10⁵ M^?1) is more in keeping with intercalators and suggests this binding mode. Moreover, thermodynamic parameters indicated that hydrogen bond and van der Waals interactions play main roles in the binding of [Cu(cef)(phen)Cl₂] to ct-DNA. In addition, [Cu(cef)(phen)Cl₂]-DNA docked model is in approximate correlation with the experimental results.     

一种含吲哚咪唑基Ru(II)配合物的酸碱性质和与DNA相互作用的研究

合成了一个新的Ru(II)配合物[Ru(bpy)₂(H₂iip)](ClO₄)₂•5H₂O [bpy＝2,2'-联吡啶, H₂iip＝2-吲哚基-咪唑并[4,5-ƒ][1,10]-邻菲罗啉]. 通过酸碱滴定发射光谱测定了该配合物的表观电离常数; 用紫外可见光谱、荧光光谱、稳态荧光淬灭、溴化乙锭竞争键合、粘度测量和DNA裂解实验研究了配合物与DNA的相互作用性质. 结果表明配合物以经典的插入模式与DNA键合, 键合常数K_b＝(5.97±0.27)×10⁵ mol^－1•L (50 mmol/L NaCl).     

DNA-binding and cleavage studies of a novel porphyrin ruthenium mixed complex [MPyTPP—Ru(pip)2Cl]+

A novel porphyrin ruthenium mixed complex, [MPyTPP—Ru(pip)₂Cl]⁺, has been prepared and characterized by elemental analyses, ES-MS, u.v.–vis. and electrochemistry. The DNA binding properties of this complex have been investigated by absorption spectroscopy, fluorescence spectroscopy and by viscosity measurements. The results indicate that the complex may bind with DNA in a groove-binding mode. Upon irradiation with u.v. light, this complex has been found to promote cleavage of plasmid pBR 322 DNA from the supercoiled form I to the open circular form II.     

Synthesis,characterization and comparative DNA interaction studies of new copper(II) and nickel(II) complexes containing mesalamine drug using molecular modeling and multispectroscopic methods

Complexes of copper(II) and nickel(II) containing the drug mesalamine (5-ASA) have been synthesized and characterized by FT-IR, mass and UV–vis spectra, elemental analysis, and theoretical methods. The binding interactions between mesalamine and its Cu(II) and Ni(II) complexes with calf thymus DNA (ct-DNA) were investigated using absorption, fluorescence emission and circular dichroism (CD) spectroscopies, and viscosity measurements. Absorption spectra of 5-ASA, Cu(II) and Ni(II) complexes showed hypochromism. The calculated binding constants (K_b) obtained from UV–vis absorption studies were 1.27 × 10³, 1.6 × 10³, and 1.2 × 10⁴ M^?1 for 5-ASA, Cu(II) and Ni(II) complexes, respectively. The compounds induced detectable changes in the CD spectra of ct-DNA (B → A structural transition, B → C structural transition and stabilization of the right-handed B form, for mesalamine, Cu(II) and Ni(II) complexes, respectively). The competitive binding experiments with Hoechst 33258 indicated that 5-ASA and copper complex could interact as groove binders. Furthermore, Ni complex had no effect on the fluorescence intensity and peak position of MB-DNA system. Finally, the results obtained from experimental and molecular modeling showed that complexes bind to DNA via minor-groove binding.     

Inducement and stabilization of G-quadruplex DNA by a thiophene-containing dinuclear ruthenium(II) complex

G-quadruplex structures are attractive targets for the development of anticancer drugs, as their formation in human telomere could impair telomerase activity, thus inducing apoptosis in cancer cells. In this work, a thiophene-containing dinuclear ruthenium(II) complex, [Ru₂(bpy)₄(H₂bipt)]⁴⁺ {bpy = 2,2′-bipyridine, H₂bipt = 2,5-bis[1,10]phenanthrolin[4,5-f]-(imidazol-2-yl)thiophene}, was prepared and the interaction between the complex and human telomeric DNA oligomers 5′-G₃(T₂AG₃)₃-3′ (HTG21) has been investigated by UV-Vis, fluorescence and circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, fluorescent intercalator displacement (FID) titrations, Job plot and color reaction studies. The results indicate that the complex can well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA in the presence or absence of metal cations, and the ΔT_m value of the G-quadruplex DNA treated with the complex was obtained to be 12.8 °C even at levels of 50-fold molar of duplex DNA (calf-thymus DNA), suggesting that the complex exhibits higher G-quadruplex DNA selectivity over duplex DNA. The complex shows high interaction ability with G-quadruplex DNA at (1.17 ± 0.12) × 10⁷ M^?1 binding affinity using a 2:1 [complex]/[quadruplex] binding mode ratio. A novel visual method has been developed here for making a distinction between G-quadruplex DNA and duplex DNA by our ruthenium complex binding hemin to form the hemin-G-quadruplex DNAzyme.     

Kinetics and mechanism of the substitution reactions of some monofunctional Pd(II) complexes with different nitrogen-donor heterocycles

Substitution reactions of five monofunctional Pd(II) complexes, [Pd(terpy)Cl]⁺ (terpy = 2,2′;6′,2″-terpyridine), [Pd(bpma)Cl]⁺ (bpma = bis(2-pyridylmethyl)amine), [Pd(dien)Cl]⁺ (dien = diethylenetriamine or 1,5-diamino-3-azapentane), [Pd(Me₄dien)Cl]⁺ (Me₄dien = 1,1,7,7-tetramethyldiethylenetriamine), and [Pd(Et₄dien)Cl]⁺ (Et₄dien = 1,1,7,7-tetraethyldiethylenetriamine), with unsaturated N-heterocycles such as 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr), 1,2,4-triazole, pyrazole, pyrazine, and imidazole were investigated in aqueous 0.10 M NaClO₄ in the presence of 10 mM NaCl using variable-temperature stopped-flow spectrophotometry. The second-order rate constants k₂ indicate that the reactivity of the Pd(II) complexes decrease in the order [Pd(terpy)Cl]⁺ > [Pd(bpma)Cl]⁺ > [Pd(dien)Cl]⁺ > [Pd(Me₄dien)Cl]⁺ > [Pd(Et₄dien)Cl]⁺. The most reactive nucleophile of the heterocycles is pyrazine, while the slowest reactivity is with pyrazole. Activation parameters were determined for all reactions and negative entropies of activation, ΔS^≠, supporting an associative mode of substitution. The reactions between [Pd(bpma)Cl]⁺ and 1,2,4-triazole, pzI, and pzBr were also investigated by ¹H NMR to define the manner of coordination. These results could be useful for better explanation of structure-reactivity relationships of Pd(II) complexes as well as for the prediction of potential targets of Pd(II) complexes toward common N-heterocycles, constituents of biomolecules and different N-bonding pharmaceutical agents.     

A copper(II) complex of 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine and L-serinate: synthesis,crystal structure,DNA-binding and molecular docking studies

A water-soluble Cu(II) complex, [Cu(pzta)(L-Ser)(ClO₄)]·1.5H₂O (pzta = 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine; L-Ser = L-serinate), was synthesized and characterized by analytical and spectral techniques. In addition, the molecular structure of the complex was confirmed by single-crystal X-ray diffraction, revealing that the central Cu(II) atom was located in a six-coordinate distorted octahedral geometry. Multi-spectroscopic methods, viscosity measurements and thermal denaturation experiments revealed that the complex binds to DNA with apparent binding constant of 2.93 × 10³ M^?1 through a groove binding mode. The positive values of ΔH and ΔS obtained from isothermal titration calorimetry experiments indicated that hydrophobic interactions play an important role in the formation of the complex–DNA adduct. Molecular docking studies were carried out to better understand the binding mode of the complex with DNA.     

Synthesis,characterization and in vitro DNA binding studies of a new copper(II) complex containing antioxidant ferulic acid

A mononuclear Cu(II) complex, [Cu(FA)₂(NO₃)₂], in which FA is ferulic acid ((E)-3-(4-hydroxy-3-methoxy-phenyl)prop-2-enoic acid), was synthesized and characterized by spectroscopic methods. The main structures of the ligand and its complexes with Cu²⁺ were optimized by QM calculations. The calculations on the structures of the [Cu(FA)₂(NO₃)₂] complexes forms and the intercalating with DNA profile were undertaken by UHF/PM6 and MMFF94 methods, respectively. In vitro studies (UV-vis spectroscopy, emission titration, circular dichroism techniques, and viscometry) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) showed that the complex interacts with calf-thymus DNA (ct-DNA) via an intercalative binding mode. The thermodynamic parameters, enthalpy change (ΔH), and entropy change (ΔS) showed that the acting forces between Cu(II) complex and ct-DNA mainly included van der Waals interactions and hydrogen bonds. Methylene blue (MB) displacement studies revealed that Cu(II) complex can substitute MB probe in the MB-DNA complex which was indicative of intercalative binding. The theoretical data confirm the experimental results with respect to the mechanism of binding.     

Oxovanadium complex as potential nucleic acid binder

DNA binding study of a vanadium(V) complex, Oxo-chloro-bis-N-phenylbenzohydroxamto-vanadium(V), derived from N-phenylbenzohydroxamic acid(PBHA) form a violet color complex with vanadium (V) in presence of hydrochloric acid is performed using absorption, fluorescence and viscometric techniques. The binding parameters of the PBHA-V(V) complex using calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) have been determined. The complex shows the ability of cooperatively minor groove binding with ct-DNA as indicated by remarkable hyperchromicity and a blue shift of the absorption spectra. Quenching of metal complex calculation was carried out with Stern-Volmer equation and K_sv was found to be 2.32 ± 0.18 × 10⁴ M^?1, while in the case of t-RNA, enhancement is observed and that means the compound was not able to displace the Ethidium Bromide(EB)-t-RNA complex. Molecular docking was also applied to predict the mode of interaction of the hydroxamic acid with ct-DNA and t-RNA. DNA binding results of the complex are compared with those of the parent ligand.     

Synthesis,characterization, HSA interaction,and antibacterial activity of a new water-soluble Pt(II) complex containing the drug cephalexin

Abstract

A new water-soluble platinum(II) complex, [Pt(CEX)Cl(DMSO)]Cl (CEX is cephalexin), was synthesized and characterized by physicochemical, spectroscopic, and computational methods. Multispectroscopic techniques were used to investigate the interaction of Pt(II) complex with human serum albumin (HSA) under the physiological conditions. The results of fluorescence titration indicated that the binding of the Pt(II) complex to HSA induced fluorescence quenching through static quenching mechanism with binding constant of 1.24?×?10⁴?M^?1 at 298?K. The thermodynamic parameters at different temperatures indicated that van der Waals forces, hydrogen bonds, and electrostatic forces play major roles in the stability of Pt(II) complex–HSA association. The displacement experiments using the site probes warfarin and ibuprofen substantiated that Pt(II) complex could bind to both site I and II of HSA. Furthermore, UV–Vis and fluorescence spectra were used to investigate the conformational changes of HSA molecule with the addition of Pt(II) complex. The binding constant of Pt(II) complex is more than two orders of magnitude higher than the corresponding value of cephalexin. These results indicate that the binding affinity of Pt(II) complex is stronger than the free drug. In addition, the antibacterial study showed that the MIC of platinum complex of cephalexin for variety of organisms was lower than free cephalexin.     

Synthesis,characterization, DNA binding,topoisomerase I inhibition,and antiproliferation activities of (di-<Emphasis Type="Italic">tert</Emphasis>-butylbipyridine) platinum(II) complexes

Two mononuclear Pt(II) complexes, Pt(dbbpy)Cl₂ (1) and [Pt(dbbpy)₂](PF₆)₂ (2) (dbbpy?=?4,4′-ditertbutyl-2,2′-biyridine) were synthesized and characterized by single-crystal X-ray diffraction analysis, elemental analysis, ¹H NMR, and ESI–MS. Their binding affinities for both double-stranded (DS) calf thymus DNA (ct-DNA) and G-quadruplex DNA (HT21 and BCL-2) were investigated. In addition to structural differences, complex 1 displayed higher binding affinity for DS ct-DNA, whereas positively charged complex 2 was selective for binding to G-quadruplex DNA over DS DNA. The time-dependent cleavage of supercoiled circular plasmid pBR322 DNA by 1 was observed using agarose gel electrophoresis, whereas complex 2 hardly cleaved DS DNA. Stabilization of G-quadruplex HT21 DNA by both complexes was assessed by PCR stop assays. Both complexes exhibited moderate activities for inhibition of topoisomerase I as well as modest antiproliferation activities toward cancer cells in CKK-8 assays.     

磺酸咔咯及其镓(Ⅲ)配合物与DNA的相互作用和光核酸酶活性

本文用紫外-可见光谱、荧光光谱、圆二色光谱和粘度法研究了2,17-二(磺酸钠基)-5,10,15-三(五氟苯基)咔咯(1)及其镓配合物(1-Ga)与小牛胸腺DNA(ct-DNA)的相互作用。结果表明1和1-Ga通过外部结合的方式与ct-DNA相互作用,且结合能力1-Ga比1大。琼脂糖凝胶电泳实验显示1和1-Ga均具较好的光核酸酶活性,1-Ga光断裂DNA效果比1好,其光断裂机理与羟基自由基的产生有关。