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An efficient method for a copper-catalyzed intramolecular C-C bond cleavage to construct 2-substituted quinazolinones has been developed. The C-C bond at the 2-position of 2,2-disubstituted-1,2,3,4-tetrahydroquinazolinone was selectively cleaved by a Cu/air catalytic system. The trend for the cleavage was dependent on the leaving group in the order of: alkyl > methyl > phenyl > substituted aryl. The process described herein provides an explanation for the mechanism of the reaction between substituted 2-halobenzamides and a-substituted arylmethanamines to construct 2-substituted quinazolinones, which were previously reported and limited to the construction of 2-arylquinazolinones.

The title compound of 3-benzothiazole-9-ethyl carbazole was synthesized by the reaction of 3-aldehyde-9-ethyl carbazole and 2-aminothiophenol. The compound was characterized by (1) H nuclear magnetic resonance (NMR) and mass spectrometry (MS). Its crystal structure was obtained and determined by single crystal X-ray diffraction. The results showed that the crystal belongs to the orthorhombic crystal system and the cell parameters of space group P2(1)2(1)2(1) were a = 5.6626 (12) Å, b = 12.606 (3) Å, c = 22.639 (5) Å, α = 90°, β = 90°, γ = 90°, V = 1616.0 (6) Å(3) , Z = 4, Dc = 1.350 mg/m(3) . The UV-vis and fluorescence spectra were also studied preliminarily. The fluorescence spectra of the title compound with bovine serum albumin (BSA) showed that BSA could be marked with the compound and the stability constant between them was 0.82 × 10(7) M(-1) . Meanwhile, the crystal and molecule were theoretically surveyed by density functional tight-binding (DFTB). The results showed that there was an orbital overlap for lowest unoccupied molecular orbital (LUMO) between the neighbouring molecules for the crystal, which is different from the molecule structure. It was also showed that the crystal structure is a non-conductor. Copyright © 2016 John WileySons, Ltd.

A supramolecular probe for visual detection of mercury (Hg) has been designed by using a cyanine dye and AS1411 G-quadruplexes, which exhibits an obvious color change from red to blue in response to an increased level of Hg(2+). The supramolecular probe exhibits high selectivity and sensitivity towards Hg(2+) and is promising for the detection of environmental samples with the naked eye.

The reaction tolerates a range of aryl and hetarylmethanamines and delivers the products in moderate to high yields.

Many organic ligands were synthesized to recognize G-quadruplexes. However, different kinds of G-quadruplexes (G4s) possess different structures and functions. Therefore, selective recognition of certain types of G4s is important for the study of G4s. In this paper, a novel cyanine dye, 3-(2-(4-vinylpyridine))-6-(2-((1-(4-sulfobutyl))-3,3-dimethyl-2-vinylbenz[e]indole)-9-ethyl-carbazole (9E PBIC), composed of benzindole and carbazole was designed and synthesised. The studies on UV-vis and fluorescence properties of the dye with different DNA forms showed that the dye exhibits almost no fluorescence under aqueous buffer conditions, but it increased over 100 fold in the presence of c-myc G4 and 10-30 fold in the presence of other G4s, while little in the presence of single/double-stranded DNA, indicating that it has excellent selectivity to c-myc 2345 G4. For the binding studies the dye is interacted with the c-myc 2345 G-quadruplex by using the end-stack binding model. It can be said that the dye is an excellent targeting fluorescent probe for c-myc G-quadruplexes.

Nucleic acid based molecular device is a developing research field which attracts great interests in material for building machinelike nanodevices. G-quadruplex, as a new type of DNA secondary structures, can be harnessed to construct molecular device owing to its rich structural polymorphism. Herein, we developed a switching system based on G-quadruplexes and methylazacalix[6]pyridine (MACP6). The induced circular dichroism (CD) signal of MACP6 was used to monitor the switch controlled by temperature or pH value. Furthermore, the CD titration, Job-plot, variable temperature CD and 1H-NMR experiments not only confirmed the binding mode between MACP6 and G-quadruplex, but also explained the difference switching effect of MACP6 and various G-quadruplexes. The established strategy has the potential to be used as the chiral probe for specific G-quadruplex recognition.

Double-stranded DNA (dsDNA) as a catalytic species has been applied in various key asymmetric reactions. Compared with dsDNA, G-quadruplex DNAs (G4DNAs) have unique conformational structures and versatile complexation properties, and act expectedly as hosts to recognize planar aromatic molecules through π–π stacking. Based on the specific recognition for small molecules, G4DNA-based catalysts have been used to assist the catalytic function, and have been applied in asymmetric organic reactions.

A novel optical transition for a hydrogel of polyacrylamide and poly(acrylic acid) random copolymer was observed. The poly(acrylamide-co-acrylic acid) hydrogel is opaque white at low temperature, while it will become transparent gradually or sharply on a fast or slow increase of temperature. Meanwhile, the hydrogel can swell or collapse with changing temperature. Both optical transition and volume swelling are reversible responding to temperature stimuli. The FT-IR, laser Raman, and 1H NMR spectroscopy demonstrated the driving force of optical and volume transition: formation and dissociation of hydrogen bonds in the hydrogel. The heterogeneity of the network results in these reversible transition responding to temperature stimuli. The effects of monomer, initiator, and cross-linker on the optical transition of the hydrogel were studied in detail. The formation and dissociation of hydrogen bonds in the limited domain of the hydrogel is related to the network structure. Because of the property of swelling...

Quercetin is a kind of flavonoid which has been proved to exhibit anti-tumor activity. The interaction modes of quercetins with monomeric and dimeric G-quadruplexes were studied by absorption, fluorescence, CD, and 1H NMR spectroscopies. The ligands were found to be stacked with terminal tetrads of monomeric G-quadruplexes by intercalation and bound to dimeric G-quadruplexes by groove binding.

Mononuclear copper phthalocyanine (CuPc) and binuclear copper phthalocyanine (Cu2Pc2) were synthesized by the phenylanhydride-urea route, and their catalytic oxidation activity on 2-mercaptoethanol was studied. Based on the experimental results, a catalytic mechanism of Cu2Pc2 on 2-mercaptoethanol has been proposed. Furthermore, the effects of pH, Cu2Pc2 concentration, and temperature on the catalytic oxidation activity were evaluated. The results showed that CuPc has no catalytic activity, while Cu2Pc2 has high catalytic oxidation activity towards 2-mercaptoethanol with the optimal activity at pH 11. The reaction can further be enhanced by increasing Cu2Pc2 concentration and temperature, due to its endothermic characteristics.

Unconventional fullerenes are those smaller than C(60) or those intermediate between C(60) and C(70), which are not stable in structure as none of the unconventional fullerene isomers satisfying the "isolated-pentagon-rule" (IPR). Below we report the synthesis of a stable unconventional fullerene derivative C(64)H(4) by introducing methane in the fullerene productions with the normal Krätschmer-Huffman method. We also applied various spectroscopic measurements such as mass spectrometry, (13)C NMR, IR, UV-vis absorption spectrometry, etc. to characterize the structural and electronic properties of this molecule, revealing an unprecedented fullerene cage with a triplet of directly fused pentagons in the framework of C(64)H(4). Four hydrogen atoms are added to the carbons at vertexes of fused pentagons to allow the bond angles at these sites close to the sp(3) tetrahedral angle, which essentially release the sp(2) bond strains on the abutting-pentagon sites of C(64). Ab initio calculations were performed to explore the electronic property and simulate the (13)C NMR and IR spectra of this fulleride, which reproduced well the experimental results and confirmed the structural assignment of the C(64)H(4).

Nanostructures with well-defined shape and highly monodisperse size were fabricated from model stilbazolium-like dyes with specific molecular structural and conformational characteristics. With the help of absorption and fluorescence optical spectroscopy, the correlated spectroscopy (COSY) and two- dimensional nuclear Overhauser effect spectroscopy (2D NOESY) techniques, along with X-ray diffraction (XRD) measurement, distinctively different aggregation processes of the model molecules are demonstrated. For model dye molecule with linear donor–π system–acceptor (D–π–A) structure, strong D–A pair, and planar conformation, specific intermolecular interaction was identified and special crystal structures as well as spectral properties were observed. For model dye molecules bearing nonlinear D–π–A–π–D structure, weak D–A pair but actual amphiphilic characteristics, a special aggregation process was confirmed and a focused size distribution of the produced nanostructures was obtained.

Novel peony-like as well as actinia-like mesostructures were prepared from a stilbazolium-like dye by changing the quality of the solvent. The architecture evolutions of these mesostructures at the earlier stages of their formation confirm that the mesostructures result from multistage aggregation processes. Combining the results obtained from the correlated spectroscopy (COSY) and two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) experiments with those from the UV/vis absorption and fluorescence spectra, as well as the XRD measurements, possible formation mechanism based on different intermolecular interactions were proposed.

With the view to developing new chiral molecular switches and logic gates, a new binaphthalene molecule with two spiropyran units (1) was synthesized and characterized. Absorption and 1H NMR spectral studies of 1 after reaction with acid/base indicate acidichromism can occur to compound 1. The synergistic actions of acid and UV light irradiation result in a remarkable change for the CD spectrum of the relatively dilute solution of 1, mimicking the behavior of a chiral "AND" gate, since the "ouput" is the CD signal. Furthermore, the optical rotation value of the relatively concentrated solution of 1 can be reversibly tuned after sequential reactions with acid and base, and thus a chiral molecular switch with nondestructive "output" signal is realized. The present results not only add a new example of chiral molecular switch with nondestructive readout but also provide a chiral "AND" gate based on the axial chiral binaphthalene to which switchable units are linked.

The effects of NaCl on the aggregation of two typical thiacarbocyanine dyes (3,3′-di(3-sulfopropyl)-4,5,4′,5′-dibenzo-9-phenyl-thiacarbocyanine triethyl ammonium salt (Dye 1) and 3,3′-di(3-sulfopropyl)-4,5,4′,5′-dibenzo-9-methyl-thiacarbocyanine triethyl ammonium salt (Dye 2)) in aqueous solution have been studied by using absorption spectroscopy, fluorescence spectroscopy, and 1H- and 23Na-NMR measurements. It is found that the J-aggregation of two dyes can be promoted by the addition of NaCl and that the effective coherence length of the J-aggregate is shorter than that obtained without NaCl. Fluorescence spectra demonstrate that the fluorescence intensities of the J-aggregates of two dyes are quenched by addition of NaCl. This is consistent with the decrease of the effective coherence length of J-aggregates of the two dyes in the presence of NaCl. 1H-NMR spectra of two dyes show that the Na+ ions penetrate into the J-aggregates and replace the counterion (triethylammonium ions) in two dyes. The measurements of the chemical shifts of 23Na nuclei provide further information about the interaction between the Na+ ions and dye anions in the J-aggregates of the two dyes. Due to this interaction, the electrostatic repulsion between the dye anions in the J-aggregates can be reduced and thus accelerate the aggregation of the two dyes in the presence of NaCl. The apparent association constants between Na+ ions and dye molecules in J-aggregates of Dye 1 and Dye 2 estimated from the measured chemical shifts of 23Na nuclei are about 2.38 M−1 and 1.35 M−1, respectively.

Carbazole and its derivatives have been widely utilized as a functional building block in the fabrication of the organic medicine, pesticides, materials, etc., because of their excellent solubility, stability and biological activity. In this paper, 1-(5-carboxypentyl)-4-(2-(N-ethyl-carbazole-3-yl) vinyl) pyridinium bromide with a large Stokes shift was synthesized and characterized by (1)H NMR and MS. The UV/vis absorption and fluorescence spectra in different solvents and at different pH values were investigated preliminarily. The photostability and thermostability were also studied and the results showed that the compound was stable. The compound was also used to label bovine serum albumin (BSA) and calf thymus (ct)DNA. The results showed that the fluorescence intensity is enhanced when labeling with BSA and the binding ability is stronger than ctDNA, making it may be used as a biological probe.

A copper-catalyzed approach for the synthesis of 2-aryl-quinazolinones through a domino reaction involving C–C bond cleavage is described. This protocol involves intramolecular C–C bond cleavage to construct 2-aryl-quinazolinones, which may offer an alternative method to prepare medically important quinazolinone derivatives and a new strategy for C–C bond cleavage. Besides C–C bond cleavage, this domino reaction includes N-arylation and benzylic C–H amidation.

The filming process of polystyrene nanolatex (NPS) particles was studied by a combination of various methods. For a constant annealing time of 1 h, the AFM images showed that the deformation and interdiffusion temperatures of NPS particles were ca. 90 and 100‐110 ◦ C, respectively. In spin-lattice relaxation measurements of solid state NMR, it is found that T1L, T1S, and PL increased significantly after annealing at 90 and 100 ◦ C for 1 h. DSC results showed that there was a exothermic peak near Tg after annealing for 1 h at the elected temperatures below 95 ◦ C; otherwise, the exothermic peak disappeared after annealing at 100 ◦ C or above. The apparent density of NPS increased suddenly in the temperature range of 90‐110 ◦ C. The results indicated that the macromolecules are highly constrained in NPS particles, leading to higher conformational energy, with more free volume and segments less restricted, which are the driving forces for the particles sintering at a lower temperature compared to the micro-PS particles with larger diameter. C � 2002 Elsevier Science (USA)

A novel Ag+ sensor has been designed based on the mechanism that i-motif formation induced by Ag+ was sensitively recognized by a cyanine dye. The sensor exhibited an over 130–16,000 fold selectivity toward Ag+ than that toward other metal ions. This research not only provides a step forward toward the development of Ag+ detection but also represents a new application for i-motif DNA.

A probe for colorimetric detecting lead ion (Pb2+) has been designed by using a newly synthesized clip-like cyanine dye and G-quadruplex. The unique structure of the clip-like cyanine dye endowed the probe with a high selectivity towards Pb2+. Significant changes in absorption spectra of the cyanine dye recognizing the Pb2+ -induced conformational transition of G-quadruplexes made the probe show a high sensitivity towards Pb2+ with a detection limit of 1 nM. The excellent performance enabled the probe to be practically applied in measuring the Pb2+ pollution in freshwater system. (C) 2015 Elsevier B.V. All rights reserved.

Filming process of polystyrene nano-latex (NPS) particles was studied by a combination of various methods. For a constant annealing time of 1 h, the AFM images showed that the deformation and sintering temperatures for NPS particles were ca. 90°C and 100°C respectively. In spin-lattice relaxation measurements of solid state NMR, it is found that T1L, T1S and I1I/I0 increased significantly after annealing at 90°C and above. DSC results showed that there was an exothermic peak near Tg after annealing for 1 h at the selected temperatures below 95°C; otherwise, the exothermic peak disappeared after annealing at 100°C or above. The apparent density of NPS increased suddenly in the temperature range. The results implied that the macromolecules in NPS particles are in a confined state with higher conformational energy and less cohensional interactions which are the drive force for the sintering at a lower temperature compared with the multichain PS particles and the bulk polymer.

mainlyfocusonscreeningmolecule(s)withknownstructure.However,uptonow,thescreeningofG-quadruplexligands from natural plant extracts, a complicated mixturesystem with multiform unknown chemical frames, has notbeenreported.Herein,weaddressanovelapproachforfastscreeningofG-quadruplex ligands from natural plant extracts. Thisapproach includes the following three steps: judging theexistence of G-quadruplex ligand(s) in the test extracts by

Silica gel column chromatography combined with high performance counter-current chromatography (HPCCC) was employed for the separation of potential anti-tumor compounds from a petroleum ether fraction of a crude extract of Zanthoxylum ailanthoides Sieb. & Zucc. This traditional Chinese medicine was recently found to display high inhibitory activity against A-549 human cancer cells in vitro and Lewis lung cancer in vivo. A 75% aqueous ethanol extract of the stem bark of Z. ailanthoides was fractionated with petroleum ether, ethyl acetate and n-butanol. In this paper, the petroleum ether fraction was pre-separated by silica gel column chromatography with a petroleum ether–ethyl acetate gradient. Two fractions were further separated and purified by HPCCC using n-hexane–ethyl acetate–methanol–water (3:1:2:1, v/v) and petroleum–ethyl acetate–methanol–water (8:6:7:7, v/v). Finally, coumarins and lignans including luvangetin, xanthyletin, hinokinin and asarinin were isolated and identified by MS, 1H and 13C NMR. In total, 56 mg of xanthyletin (1), 140 mg of hinokinin (2), 850 mg of luvangetin (3) and 74 mg of asarinin (4) were obtained from approximately 50 g of petroleum ether extract, in 96.0%, 94.0%, 99.0% and 94.0% purity, respectively, as determined by HPLC. The separation method proved to be efficient, especially for those minor components.

One of the most important carbohydrate-splitting enzymes is themaltase-glucoamylase which catalyzes the hydrolysis of alpha-glucosidic linkages. Maltase-glucoamylase inhibitors during the last few years have aroused medical interests in the treatment of diabetes. They contribute to a better understanding of the mechanism of maltase-glucoamylase. At present there are many different classes of maltase-glucoamylase inhibitors. This paper focuses on alkaloidal inhibitors of maltase-glucoamylase and structure-activity relationship (SAR) studies between them in order to discover some drugs with better efficiency and lower toxicity for treating diabetes.

Specific and sensitive identification of special G-quadruplex structures is an important issue and attracts increasing interest. In this paper, a novel, signal-amplified strategy is proposed for the specific detection of G-quadruplexes, which is very different from those currently-dominating methods based on single-molecular fluorescent probes. In this strategy, a ‘special designed’ cyanine dye loses the ability of self-assembly in solution but still keeps its assembly potential. When the G-quadruplex with a specific structure is present, the assembly potential of the dye is reactivated so that it can assemble to J-aggregates. Other DNA motifs without this specific structure cannot activate its assembly potential no matter if they are double-stranded or quadruplex DNA. Since the assembly is quite specific to structure, the induced procedure of the aggregates provides high specificity for this strategy. In addition, the attached aggregates exponentially amplify the signal due to the signal stacking of those monomers within the aggregates, which then significantly enhances the sensitivity of this strategy. As a result, this strategy exhibits a highly specific and sensitive detection ability for specific G-quadruplex structures both between quadruplexes and non-quadruplexes and among diverse quadruplex motifs.

A supramolecular probe is designed for visual detection of potassium based on a novel cyanine dye aggregate recognizing the motif transition of telomeric G-quadruplexes under the Na(+) background. The practical application for colorimetric measurement of urine potassium has been tested.

Telomeric DNA and C-myc22 are DNA G-quadruplex (G4)-forming sequences associated with tumorigenesis. Ligands that can facilitate the formation and increase the stabilization of G4 can halt tumor cell proliferation and have been regarded as potential anti-cancer drugs. In the present study, we have investigated the interaction of 11 natural alkaloids with G4 formed by telomeric DNA and C-myc22 sequences. Our results indicated that sanguinarine (San), palmatine (Pal), and berberine (Beb) of the first series (S1) can induce the formation of G4 as well as increase the stabilization ability. Daurisoline (S2-1), O-methyldauricine (S2-2), O-diacetyldaurisoline (S2-3), daurinoline (S2-4), dauricinoline (S2-5), N,N'-dimethyldauricine iodide (S2-6), and N,N'-dimethyldaurisoline iodide (S2-7) of the second series (S2) showed similar stabilization ability. We found that unsaturated ring C, N(+) positively charged centers, and conjugated aromatic rings are key factors to increase the stabilization ability of S1, and we gave some advice on structure modification to S2 through structure-activity study. Besides, we found San and Pal to be cell cycle blocker in G(1). San was speculated to bind to G4 through intercalation or end stacking.

Interaction between PEO-PPO-PEO copolymers and a hexapeptide, growth hormone releasing peptide-6 (GHRP-6), was investigated by NMR to study the potential use of the copolymers in peptide drug delivery. (1)H NMR and nuclear Overhauser effect spectroscopy (NOESY) measurements determined that PO methyl protons interacted with methyl protons of the Ala moiety, aromatic protons of the Trp moiety, and some of the Phe aromatic protons. The Lys moiety and part of the Phe moiety entered the hydrophilic EO environment via hydrogen bonding. PEO-PPO-PEO copolymers and the peptide formed a complex in 1:1 stoichiometry. Binding constants between copolymers and GHRP-6 were determined, and it was indicated that the copolymers containing more EO and PO units will lead to greater affinity with the peptide. Isothermal titration calorimetry (ITC) measurements confirmed the results of NMR experiments. This study indicates that PEO-PPO-PEO copolymers have great potential in delivering peptide drugs.

G-quadruplex structure is a four-stranded form of DNA, which is associated with cancer cell proliferation. G-quadruplex-stabilized ligands have the potential to interfere with telomere replication by blocking the elongation procedure catalyzed by telomerase, and therefore have the potential to be anti-cancer drugs. A considerable number of novel compounds capable of targeting G-quadruplex at high affinity and specificity have been reported. Among them, several G-quadruplex ligands have shown promising anti-cancer activity in tumor xenograft models, and entered phase II clinical trials on cancer patients. This review summarized recent developments of G-quadruplex ligands as anti-cancer drugs and several powerful strategies to discover novel G-quadruplex ligands as anti-cancer drug candidates by screening natural product extracts and structural optimization of previously identified typical compounds.

G-quadruplex DNA structure is considered to be a very attractive target for antitumor drug design due to its unique role in maintaining telomerase activities. Therefore, discovering ligands with high stability of G-quadruplex structure is of great interest. In this paper, high-performance liquid chromatography (HPLC) was used for fast screening of G-quadruplex ligands from the crude extract of Kalopanax septemlobus (Thunb.) Koidz, a traditional Chinese medicine. Four potent G-quadruplex ligands were firstly selected through HPLC by comparing the peak profiles and absorption intensity of the crude sample before and after interaction with G-quadruplex DNA. Then the target compounds were isolated and purified by high-speed countercurrent chromatography (HSCCC) for further confirmation of their stabilities of G-quadruplex by temperature-dependent circular dichroism (CD). Four compounds were isolated and identified as 2,4-dihydroxybenzoic acid (I), chlorogenic acid (II), caffeic acid (III) and 5-feruloylquinic acid (IV) each by MS and NMR. Finally, compound I, II, III were each proved to be potent G-quadruplex ligands by decreasing the peak intensity in HPLC chromatogram after complexation with G-quadruplex, which stabilize G-quadruplex by 7±2 °C, 10±2 °C, and 3±2 °C respectively, based on CD analyses. However, compound IV showed no G-quadruplex stability. The decrease of peak absorption intensity in HPLC chromatogram is the most important signal to find G-quadruplex ligands. This provides a very promising strategy for fast screening G-quadruplex ligands from natural plant extracts.

Transferrin has shown potential in the delivery of anticancer drugs into primarily proliferating malignant cells that over-express transferrin receptors. Constructing transferrin receptor targeted drug delivery system has been widespread concerned. In this study, whether transferrin could transport noncovalent binding drugs into cancer cells has been investigated. Two representative compounds, doxorubicin hydrochloride (Dox) and vanadocene dichloride (Cp 2 VCl 2 ), have been chosen to study the interactions with h-Tf and apo-Tf, and the influences in the presence of h-Tf and apo-Tf by using fluorescence spectroscopy, circular dichroism (CD) spectroscopy and MTT assay. The results have shown that both doxorubicin and Cp 2 VCl 2 could bind to h-Tf and apo-Tf but with different binding modes. The results of MTT assay demonstrate that the presence of both h-Tf and apo-Tf has enhanced the antiproliferative activity of Cp 2 VCl 2 . However, the anticancer activity of the mixture of doxorubicin and h-Tf is basically the same as that of doxorubicin does. Our studies indicate that transferrin plays an important role in the transport and targeted delivery of Cp 2 VCl 2 into cancer cells.

Both G-quadruplexes and natural polyamines are intimately associated with tumor growth and proliferation. The effect of the natural polyamines on telomeric and some oncogenic G-quadruplexes including bcl-2, c-kit, and c-myc G-quadruplexes has been studied by using absorption, fluorescence, CD, and NMR methods. The results exhibited an interesting dual-effect depending on polyamineś concentration. Polyamines promote and stabilize G-quadruplexes under a lower concentration (less than 1 mM) but denature G-quadruplexes under a higher concentration (more than 1 mM). Probably the electrostatic and hydrophobic effect of polyamines and the hydrogen-bonding interaction between guanines and polyamines were respectively responsible for the stabilizing and denaturing effect.

A scissors-shaped binaphthyl derivative (NPA) has been found to stabilize the G-quadruplex by intertwisting the whole G-quadruplex with two long chains, through the cooperation of the two functional groups: binaphthylene and the ethoxy chain. Moreover, NPA exhibits a good inhibitory effect of telomerase activity as well as excellent cytotoxic activity against HepG-2 human liver cancer cells.

The H-aggregates of a novel cyanine dye, 3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt (MTC), have been fabricated to verify hybrid/parallel intramolecular G-quadruplexes from linear duplex and single-strand DNAs under physiological conditions. The recognition is found to be successful both in solution and on Au film. These results have shown MTC H-aggregates, as a supramolecular system, may be used as a potential excellent probe for DNA structure, both in vitro and in vivo.

Human c-myc gene is a central regulator of cellular proliferation and cell growth, and G-quadruplexes have been proven to be the transcriptional controller of this gene. In this study, the interaction of bile acid-amino acid conjugate (BAA) with G-quadruplexes in c-myc was investigated by circular dichroism spectroscopy, nuclear magnetic resonance (NMR) measurement, and quantitative real-time polymerase chain reaction (PCR) assay. The experimental results indicated that BAA has the ability to selectively induce the formation of parallel G-quadruplexes in c-myc, which leads to down-regulation of c-myc transcription in the human breast cancer cell MCF-7.

The inducing abilities of two alkaloids, Sanguinarine (San) and Nitidine (Nit), to fold human telomeric DNA d[5'-TTGGG(TTAGGG)(3)A-3'] (H24A) into G-quadruplex structures has been investigated by using CD and (1)H NMR spectroscopy. It is found that, under salt-deficiency condition, San could induce H24A to fold into a normal anti-parallel G-quadruplex while Nit may induce hybrid or mixed-type G-quadruplex structures. In order to understand the structure of H24A induced by Nit, the interaction between Nit and existed hybrid G-quadruplex H24A in the presence of K(+) has been examined for comparison. The different behaviors of these two molecules interacted with DNA could be ascribed to distinct binding mode, which may be resulted from the steric hindrance of the molecular frame of these two alkaloids.

BACKGROUND: Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. METHODOLOGY: We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. CONCLUSIONS: This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking.

The micellization mechanism of PEO-PPO-PEO block copolymer in aqueous solutions was studied by two-dimensional correlation FTIR spectroscopy. The 1400-1000 cm(-1) region was investigated, involving the stretching vibrations of ether band, C-H wagging vibrations of EO methylene groups and C-H symmetric deformation vibrations of PO methyl groups. In the 2D correlated spectra, the hydrous and anhydrous state of the ether band, PO methyl groups, and the two conformations of EO methylene groups were observed. Molecules with different PO lengths and increasing molecular weight were investigated to determine the sequence of association of the separate groups. During temperature-induced micellization, the following changes were detected: firstly, EO methylene groups changed from a gauche state to a trans state; secondly, conformational transitions led to the dehydration of hydrated methyl groups; next, the hydrogen bonding between C-O band and water diminished; and finally, dehydrated groups approached to form hydrophobic cores, resulting in micelle formation. From this variation in the sequence of group associations, it is concluded that aggregates of unimers first formed, then hydrophobic cores formed through the hydrophobic interaction from dehydrated PPO blocks, and proper micelles eventually evolved. The temperature-induced conformational changes are suggested the reason for micellization. (C) 2010 Elsevier Inc. All rights reserved.

Using guanine (G)-quadruplexes to construct supramolecular systems receives great attention because G-quadruplexes possess peculiar structural and electronic properties. In this paper, a temperature-sensitive supramolecule self-assembled by G-quadruplexes has been reported, whose structure was demonstrated to be a hexagonal column with rod-shaped G-quadruplex aggregates bundling together.

The interaction between polyethylenimine (PEI) and telomeric DNA was studied. The results demonstrated that PEI could effectively induce, stabilize, and regulate intramolecular G-quadruplexes. The mechanism for these results has been discussed, and was estimated to be condensation effect of PEI.

Three small peptides (K4, K5, and K6) with different length were designed to induce the transformation of the assembled state and the chirality of cyanine dye supramolecule. The absorption and circular dichroism (CD) results indicated that, the peptides tend to induce cyanine dye to H-aggregation, competed with Na(+) in PBS, which would induce dye to J-aggregation. Meanwhile, all three peptides could influence the chirality of both J-aggregates induced by Na(+) and H-aggregates, among which K6 could induce chiral reversion of J-aggregates. Furthermore, molecular modeling and energy calculation results have shown that the peptides with different chain length have different conformations. This might be the reason for cyanine dye to form the different chiral assembly induced by these oligo-peptide templates.

Currently, there is a considerable interest in discovering G-quadruplex ligands. Plant-derived agents, because of their diversity in structure and bioactivity and low toxicity, may be a very diverse source of G-quadruplex ligands. However, up to now, the screening of G-quadruplex ligands from natural plant extract has not been reported. Herein, in order to develop a simple method for fast identifying G-quadruplex ligands from plant extract, we intended to substitute the spectral shift in the imino region ( δ 10–12) in 1 H NMR spectra of G-quadruplex for in vitro bioassay to judge the existence/nonexistence of G-quadruplex ligand(s) in plant extract, and then couple G-quadruplex recognition with NMR based structure elucidation to identify the structure of the ligand(s) without the need of prior separation. In this paper, we successfully screened a G-quadruplex ligand from a simulated plant extract using this approach. This research work provides a promising tactic to find new leading compounds from nature plant extract.

Bioactivity guided fractionation of the ethanolic extract of the whole plants of Lespedeza virgata (Thunb.) DC. resulted in the isolation of a novel flavonoid (1) along with five known compounds 2-6. The molecular and structural formula as well as the stereochemistry of compound 1 were determined using data obtained from (1)H and (13)C NMR spectra, DEPT135 and by 2D HSQC, HMBC, (1)H-(1)H correlated spectroscopy ((1)H-(1)H COSY), and nuclear overhauser effect spectroscopy (NOESY) experiments. The superoxide anion scavenging activities of all isolated compounds were evaluated by the hypoxanthine nitro blue tetrazolium and ESR methods and the new compound 1 showed the strongest antioxidative activity 95.79% (IC(50)=0.14 mg/ml).

By using a combination of 1H NMR spectroscopy, two-dimensional heteronuclear single-quantum coherence-resolved (1)H{(13)C} and homonuclear rotating-frame Overhauser enhancement NMR correlation experiments with diffusion ordered spectroscopy (DOSY), the location and distribution of a hydrophobic drug, paeonol, have been established with respect to the methyl groups of the poly(ethylene oxide)-poly(propylene oxide) -poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer. The interaction between them is adjustable according to the different temperature-dependent hydrophilicities or hydrophobicities of the triblock copolymer components. On the other hand, such interactions influence the self-assembly properties of the block copolymer amphiphiles in solution. The amount of anhydrous methyl groups of PPO segments shows an increase with increasing paeonol concentration. It was also demonstrated that the shell-crosslinking of the Pluronic polymer has an effect in increasing the amount of anhydrous methyl groups and thus increasing the hydrophobicity of Pluronic micelles. This might be the deeper reason underlying the increase in drug-loading capacity and prolongation in release time of Pluronic micelles for drug delivery after the shell-crosslinking. Changes in self-diffusion coefficients of paeonol with varying copolymer concentrations and types were also determined by the diffusion-based NMR DOSY technique, and values of K(a), DeltaG, and n were calculated.

The oil-induced aggregation behavior of PEO-PPO-PEO Pluronic P84 [(EO)19(PO)39(EO)19] in aqueous solutions has been systematically investigated by 1H NMR spectroscopy, freeze-fracture transmission electron microscopy (FF-TEM), and dynamic light scattering (DLS). The critical micellization temperature (CMT) for P84 in the presence of oils decreases with increasing oil concentration. The effectiveness of various oils in decreasing the CMT of block copolymer follows the order m-xylene (C(8)H(10))toluene (C(7)H(8))benzene (C(6)H(6))n-octane (C(8)H(18))n-hexane (C(6)H(14)) approximately cyclohexane (C(6)H(12)). It was found that the amount of anhydrous PO methyl groups increases whereas the amount of hydrated PO methyl groups decreases upon the addition of oils. At low oil concentration, the oil molecules are entrapped by the micellar core, but as the oil concentration increases above a certain value, the micellar core swells significantly as a result of the penetrated oil molecules, and much larger aggregates are formed. Intermolecular rotating-frame nuclear Overhauser effect (ROE) measurements between P84 and benzene were performed at 10 and 40 degrees C. The specific interaction between benzene and the methyl groups of PPO was determined, and it was observed that the interaction site remained unchanged as the temperature was increased.