Spectroscopic identification of binding modes of anthracene probes and DNA sequence recognition

The binding properties of two anthracene derivatives with calf thymus DNA (CT DNA), poly(dA-dT), and poly(dG) x poly(dC) are reported. One contained bulky, cyclic cationic substituents at the 9 and 10 positions, and the other carried acylic, branched, cationic substituents. Binding of the probes to the DNA was examined by calorimetry, spectroscopy and helix melting studies. The cyclic derivative indicated exothermic binding, strong hypochromism, bathochromism, positive induced circular dichroism (CD, 300-400 nm), significant unwinding of the helix, large increases in the helix melting temperature, strong but negative linear dichroism (LD, 300-400 nm) and considerable stabilization of the helix. In contrast, the acyclic analog indicated thermoneutral binding, smaller hypochromism, no bathochromism, very weak induced CD, and no change in the helix melting temperature with any of the DNA polymers. A sharp distinction between the binding properties of the two probes is indicated, and both have intrinsic binding constants of approximately 10(6) M(-1) for the three polymers. However, when the ionic strength of the medium was lowered (10 mM NaCl), the absorption as well as CD spectral changes associated with the binding of the acyclic derivative corresponded with those of the cyclic derivative. The acyclic derivative showed large preference (10-fold) for poly(dG) x poly(dC) over poly(dA-dT), whereas the cyclic analog showed no preference. The characteristic spectroscopic signatures of the two distinct binding modes of these probes will be helpful in deciphering the interaction of other anthracene derivatives with DNA.     

Contributions of hydroxyethyl groups to the DNA binding affinities of anthracene probes

Contributions of hydroxyethyl functions to the DNA binding affinities of substituted anthracenes are evaluated by calorimetry and spectroscopy. Isothermal titration calorimetry indicated that binding of the ligands to calf thymus DNA (5 mM Tris buffer, 50 mM NaCl, pH 7.2, 25 degrees C) is exothermic. The binding constants increased from 1.5 x 10(4) to 1.7 x 10(6) M(-1) as a function of increase in the number of hydroxyethyl functions (0-4). DNA binding was accompanied by red-shifted absorption (approximately 630 cm(-1)), strong hypochromism (>65%), positive induced-circular dichroism bands, and negative linear dichroism signals. DNA binding, in general, increased the helix stabilities to a significant extent (DeltaT(m) approximately 7 degrees C, DeltaDeltaH approximately 3 kcal/mol, DeltaDeltaS approximately 6-20 cal/K.mol). The binding constants showed a strong correlation with the number of hydroxyethyl groups present on the anthracene ring system. Analysis of the binding data using the hydrophobicity parameter (Log P) showed a poor correlation between the binding affinity and hydrophobicity. This observation was also supported by a comparison of the affinities of probes carrying N-ethyl (Kb = 0.8 x 10(5) M(-1)) versus N-hydroxyethyl side chains (Kb = 5.5 x 10(5) M(-1)). These are the very first examples of a strong quantitative correlation between the DNA binding affinity of a probe and the number of hydroxyethyl groups present on the probe. These quantitative findings are useful in the rational design of new ligands for high-affinity binding to DNA.     

Construction and DNA Condensation of Cyclodextrin‐Coated Gold Nanoparticles with Anthryl Grafts

The condensation of DNA in a controlled manner is one of the key steps in gene delivery and gene therapy. For this purpose, a water‐soluble supramolecular nanostructure is constructed by coating 14 β‐cyclodextrins onto the surface of a gold nanoparticle, followed by the noncovalent association of different amounts of anthryl‐modified adamantanes with coated β‐cyclodextrins. The strong binding of β‐cyclodextrins with anthryl adamantanes (K_S=8.61×10⁴ M ^?1) efficiently stabilizes the supramolecular nanostructure. Spectrophotometric fluorescence spectra and microscopic studies demonstrated that, with many anthryl grafts that can intercalate in the outer space of the DNA double helix, this supramolecular nanostructure showed good condensation abilities to calf thymus DNA. Significantly, the condensation efficiency of supramolecular nanostructure towards DNA could be conveniently controlled by adjusting the ratio between gold nanoparticles and anthryl adamantane grafts, leading to the formation of DNA condensates of a size that are suitable for the endocytosis of hepatoma cells, which will make it potentially applicable in many fields of medicinal science and biotechnology.     

Multispectroscopic studies of the interaction of calf thymus DNA with the anti-viral drug, valacyclovir

The present study investigated the binding interaction between an antiviral drug, valacyclovir and calf thymus DNA (CT-DNA) using emission, absorption, circular dichroism, viscosity and DNA melting studies. In fluorimetric studies, thermodynamic enhancement constant (K(D)) and bimolecular enhancement constant (K(B)) were calculated at different temperatures and demonstrated that fluorescence enhancement is not initiated by a dynamic process, but instead by a static process that involves complex DNA formation in the ground state. Further, the enthalpy and entropy of the reaction between the drug and CT-DNA showed that the reaction is exothermic and enthalpy-favored. In addition, detectable changes in the circular dichroism spectrum of CT-DNA in the presence of valacyclovir indicated conformational changes in the DNA double helix following interaction with the drug. All these results prove that this antiviral drug interacts with CT-DNA via an intercalative mode of binding.     

Spectroscopic studies on the interaction of alpha‐eleostearic acid with calf thymus DNA

Interaction between alpha‐eleostearic acid (α‐ESA) and calf thymus DNA in Tris‐HCl buffer (pH = 7.4) using neutral red (NR) dye as a spectral probe was investigated using UV–Vis absorption and fluorescence spectroscopy. Spectral data matrix of the complexed reaction between α‐ESA and NR with DNA was processed with an alternative least‐squares (ALS) algorithm, the obtained concentration profiles and the corresponding pure spectra for species (NR, DNA–NR, and DNA–NR–ESA) demonstrated three kinds of reactions might occur in the system. The major groove binding between α‐ESA and DNA was further validated using circular dichroism, viscosity, DNA melting, and ionic strength effect measurements. Moreover, the calculated values of thermodynamic parameters, such as enthalpy (ΔH^θ, ?22.04 kJ/mol) and entropy change (ΔS^θ, 91.52 J K^?1 mol^?1), suggested binding between α‐ESA and DNA was mainly driven by hydrophobic interactions and hydrogen bonds without electrostatic force.     

Phospholipid-induced aggregation and anthracene excimer formation

The zinc complex of anthryl bis(dipicolylamine) (1) aggregates upon binding with long-chain aliphatic phosphates and displays anthracene excimer fluorescence, which provides a new strategy toward detection of the biologically important lysophosphatidic acid in aqueous solution.     

水溶性金属卟啉与DNA相互作用的微量热法研究

叶琳化合物以其对肿瘤组织的特殊亲和性和光动力学效应受到广泛的重视，国内外研究报导甚多·自D79年nel等人山证实水溶性四一K甲基毗陡基）叶咐及其金属配合物能嵌入＊＊A的碱基之间后，人们以这类水溶性叶琳为模型利用各种物理和化学手段研究它们与＊NA相互作用［2，3］．但用微量热法进行研究尚未见报导．我们曾报导用共振拉曼光谱研究图1所示的二个水溶性金属叶琳ru（＊A仰）」和卜i（N＊＊刊I同＊＊A的作用＊‘］，本文进一步报导用微量热法和紫外可见光谱研究的结果．1实验部分1．1试剂将小牛胸腺DN以华美生物工程公司产品）直接…     

Molecular aspects on the interaction of phenosafranine to deoxyribonucleic acid: Model for intercalative drug-DNA binding

The mode, mechanism and energetics of interaction of phenosafranine, the planar, cationic and rigid phenazium dye to calf thymus DNA was investigated from absorption, fluorescence, circular dichroism, isothermal titration calorimetry, thermal melting, and viscosity. The study revealed non-cooperative binding of the dye to DNA with an affinity in the range (3.81-4.22) × 10⁵ M⁻¹ as observed from diverse techniques and obeying neighbor exclusion principle. The stoichiometry of binding was characterized to be one phenosafranine molecule per two base pairs. The binding was characterized by strong stabilization of DNA against thermal strand separation, large intrinsic circular dichroic changes of DNA by itself and the generation of induced circular dichroism for the optically inactive phenosafranine molecules. Hydrodynamic and fluorescence quenching studies revealed strong evidence that the phenosafranine molecules are intercalated between every alternate base pairs of calf thymus DNA. Isothermal titration calorimetry studies suggested that the binding was exothermic and favoured by both negative enthalpy and positive entropy changes. This study for the first time presents the complete molecular aspects and energetics of phenosafranine complexation to DNA as model for intercalative drug-DNA interaction.     

A temperature-dependent interaction of neutral red with calf thymus DNA

Neutral red (NR) is used as a probe to study the temperature and concentration dependent interaction of a cationic dye with nucleic acid. A temperature-dependent interaction of NR with calf thymus DNA (CT DNA) has been studied by differential pulse voltammetry (DPV), UV-Visible absorption, circular dichroism (CD) and fluorescence spectroscopy. The experimental results of increasing peak current, changes in the UV-Visible absorption and fluorescence spectra of NR and decreasing the induced circular dichroism (ICD) intensity show that (i) the binding mode of NR molecules is changed from intercalating into DNA base pairs to aggregating along the DNA double helix and (ii) the orientation of NR chromophore in DNA double helix is also changed with the temperature.     

DNA-Binding and cytotoxicity of the cobalt(III) ethylenediamine pyrazole complex [Co(en)2(pyz)2]3+

The complex of cobalt(III) ethylenediamine was synthesized, isolated and characterized by UV-Vis, IR, and 1H NMR spectral methods. The binding of the complex with calf thymus DNA was investigated by absorption and emission spectroscopy, viscosity measurements, DNA melting and DNA photocleavage. The spectroscopic studies together with the viscosity measurements and DNA melting studies indicated that the complex binds to calf thymus DNA in a nonintercalative mode. This complex is found to promote photocleavage of the DNA plasmid pBR322 and shows a cytotoxic effect against CHO cells.     

Tuning the DNA binding modes of an anthracene derivative with salt

The DNA binding properties of an anthracene derivative with substituents at the 9 and 10 positions, carrying four positive charges, are examined in calorimetric, spectroscopic and photocleavage studies. Isothermal titration calorimetric data indicated exothermic binding of the ligand to calf thymus DNA with a binding constant of (1.4 ± 0.5) × 10⁵ M⁻¹ and this value is much greater than binding of similar monocationic derivatives. The values for the other binding parameters were, ΔH = −3.5 ± 0.4 kcal/mol; ΔS = 11.6 ± 1.6 cal/mol K, and a binding site size of ∼4 base pairs. Absorption spectral studies indicated small, but significant red shifts in the vibronic bands, and ∼70% of hypochromism. The binding plots indicated bi-phasic binding of the ligand. At higher ionic strengths, the red shifts in the absorption spectra were abolished but significant hypochromism persisted.Excitation and sensitized fluorescence spectral studies indicated weak energy transfer from the DNA bases to the ligand. Further more, energy transfer was reduced substantially at higher ionic strengths. Strong induced circular dichroism bands are noted, in the 300–400 nm region, and these are most likely dominated by the contributions from the groove bound form as well as the intercalated chromophore. Helix melting studies indicated improvement in the helix stability, and substantial increase in the melting temperature (ΔT_m > 17 °C). Differential scanning calorimetric data, on the other hand, indicated only minor improvements in the thermodynamic parameters. Irradiation of a mixture of the ligand (2 μM) and supercoiled pUC18 DNA (20 μM, @374 nm) resulted in the efficient formation of nicked circular DNA (>90%) in an hour. The data indicated at least two distinct binding modes, and one of these persisted at high ionic strengths (375 mM NaCl). Substitution at 9 and 10 positions of the anthracene ring system with positively charged residues resulted in multiple binding modes, and these are resolvable in ionic strength studies.     

BINDING OF ANTHRACENE TO CELLULAR MACROMOLECULES IN THE PRESENCE OF LIGHT

Ultraviolet radiation (δ > 295 nm) induced covalent binding of anthracene to DNA which increased with time and was not affected by oxygen. Irradiation in the presence of anthracene induced nicking of Col E, circular DNA and decreased the thermal denaturation temperature of calf thymus DNA. These effects were oxygen dependent, and were decreased by GMP. Irradiation of anthracene and human serum albumin resulted in covalent binding of the hydrocarbon to the protein accompanied by crosslinking of the protein. Protein crosslinking decreased under anaerobic conditions. Irradiation of anthracene bound to liposomes induced lipid peroxidation which was not affected by superoxide dismutase or catalase.     

Spectroscopic studies of the interaction between pirimicarb and calf thymus DNA

The interaction between pirimicarb and calf thymus DNA in physiological buffer (pH 7.4) was investigated with the use of Neutral Red (NR) dye as a spectral probe by UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy, as well as viscosity measurements and DNA melting techniques. The results revealed that an intercalation binding should be the interaction mode of pirimicarb to DNA. CD spectra indicated that pirimicarb induced conformational changes of DNA. The binding constants of pirimicarb with DNA were obtained by the fluorescence quenching method. The thermodynamic parameters, enthalpy change (ΔHθ) and entropy change (ΔSθ) were calculated to be -52.13±2.04 kJ mol(-1) and -108.8±6.72 J mol(-1) K(-1) according to the van't Hoff equation, which suggested that hydrogen bonds and van der Waals forces might play a major role in the binding of pirimicarb to DNA. Further, the alternative least squares (ALS) method was applied to resolve a complex two-way array of the absorption spectra data, which provided simultaneously the concentration information for the three reaction components, pirimicarb, NR and DNA-NR. This ALS analysis indicated that the intercalation of pirimicarb into the DNA by substituting for NR in the DNA-NR complex.     

2-Aza-1,3-butadiene derivatives featuring an anthracene or pyrene unit: highly selective colorimetric and fluorescent signaling of Cu2+ cation

[Structure: see text] A new probe based on an anthryl derivative bearing an azadiene side chain selectively senses Cu2+ in acetonitrile through two different channels: the yellow-to-orange color change and a remarkable enhancement of the fluorescence, whereas the pyrenyl analogous behaves as a fluorescent sensor for Cu2+ and Hg2+ in aqueous environment.     

1,4-二甲基-6,8-二甲氧基-9,10-蒽醌的合成及其与牛血清白蛋白和DNA的相互作用

合成了大黄素类蒽醌衍生物1,4-二甲基-6,8-二甲氧基-9,10-蒽醌(1)并应用紫外光谱、荧光光谱、圆二色谱等方法研究了其与牛血清白蛋白(BSA)和小牛胸腺DNA(ct-DNA)的相互作用.荧光光谱结果表明,化合物1与BSA的相互作用主要以静态猝灭方式使BSA的内源性荧光发生猝灭;圆二色谱表明,化合物1通过疏水作用及形成氢键破坏了α-螺旋结构,导致BSA分子中的α-螺旋含量下降.在pH 7.4时固定DNA的浓度,加入化合物1后,紫外光谱的最大吸收峰发生红移且吸光度加大.荧光光谱表明,化合物1与DNA-4S green NC的结合为竞争性抑制,并可使溶液体系荧光猝灭;圆二色谱表明,随着化合物1的加入,DNA碱基间作用能迅速减弱,表明化合物1与DNA之间为嵌插作用.此外,MTT方法的结果表明,化合物1对结肠癌细胞株HCT116增殖有明显的抑制作用.     

DNA Interaction with PtCl<Subscript>2</Subscript>(LL) (LL = Chelating Diamine Ligand: <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-Dimethyltrimethylendiamine) Complex

The [PtCl₂(LL)] complex, as a cisplatin derivative, which LL is diamine chelate ligand (N,N-dimethyltrimethylendiamine), was synthesized and characterized by elemental analysis (CHN) mass, ¹H, and ¹³C nuclear magnetic resonance techniques. Then the binding of this complex to calf thymus DNA was investigated by various physicochemical methods such as spectrophotometric, circular dichroism, spectrofluorometric, melting temperature, and viscosimetric techniques. Upon addition of the complex, important changes were observed in the characteristic UV–Vis bands (hypochromism) of calf thymus DNA, increase in melting temperature and some changes in specific viscosity. Also, the fluorescence spectral characteristics showed an increase in the fluorescence intensity of methylene blue–DNA solutions in the presence of increasing amounts of metal complex, indicating PtCl₂(LL) is able to displace the methylene blue bound to DNA but not as complete as intercalative molecules. The experimental results showed that the platinum complex is bound to DNA non-intercalatively, and an outside binding is the preferred mode of interaction.     

Synthesis, DNA intercalation and europium(III)-triggered DNA photocleavage by a bis-proflavine succinamide conjugate

We describe the synthesis of a bis-proflavine derivative containing a succinamide linking chain. Levels of pUC19 plasmid DNA photocleavage by this compound are significantly enhanced in the presence of Eu³⁺ (350 nm, 22 °C, pH 7.0). UV-visible spectrophotometric studies of the ligand with calf thymus DNA show bathochromic-shifts and hypochromicity in the major absorption bands of the bis-proflavine derivative. Viscosimetric analysis of the helical extension of sonicated calf thymus DNA agrees with a monofunctional intercalation process.     

Binding Gibbs energy of ionic liquids to calf thymus DNA: a fluorescence spectroscopy study

The binding constants and binding Gibbs energies of [C(n)mim]Br (n = 4, 6, 8, 10, 12) and [C(4)mim][BF(4)] to calf thymus DNA-D1501 have been determined by the fluorescence measurements of the pyrene probe. It was found that values of the binding Gibbs energy decrease linearly with the increase of alkyl chain length of the ILs. Based on this observation, Gibbs energies for both the interaction between DNA and -CH(2)- of the ILs and the interaction between DNA and the cationic head group of the ILs have been reported. The result suggests that electrostatic interaction between DNA and the cationic head group of the ILs is predominant for the binding of the ILs with DNA although contribution from the non-electrostatic interaction between DNA and the alkyl chain of the ILs increases with increasing alkyl chain length of the ILs. The information obtained here may have application in the design of novel ILs-based DNA extraction/separation systems.     

Synthesis and properties of anthracene-containing polybenzyls

A number of alternating copolymers containing anthryl and aryl units in the polymer chain have been prepared by Friedel-Crafts arylation of the anthracene (polymer type B) or by condensation of 9,10-bis(chloromethyl) anthracene with opportune aromatic substrates (polymer type A). Polymers of type A were all found to contain 9,10-disubstituted anthracene units, but polymers of type B were found to contain 1,4-disubstituted anthracene units. Structure of the polymers were established through their NMR and ultraviolet spectra, and through analogy with appropriate model compounds. It has been found that the inclusion of anthracene units in the polymer chain yields higher melting and more soluble materials with respect to polybenzyls containing only aryl units. Anthracene units introduce, also, some interesting fluorescence characteristics in the polymers, which show intense emission at about 440 mμ.