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SCA36 is a neurodegenerative disease mainly caused by the abnormal expansion of the GGGCCT repeat sequence in intron 1 of NOP56. The RNA sequences of this gene are expected to form large amounts of G-quadruplexes in the cytoplasm, which may be a potential intervention and detection target for SCA36. Here, we have developed a small-molecular compound named TCB-1, which shows good selectivity to the G-quadruplex structure, and its fluorescence can be enhanced by hundreds of folds. Interestingly, TCB-1 can avoid lysosome capture, evenly disperse in the cytoplasm, and selectively light up the cytoplasmic RNA G-quadruplexes. This property allows TCB-1 to sensitively detect the increased formation of cytoplasmic RNA G-quadruplexes in SCA36 model cells. This work not only provides new ideas for the design of small-molecule compounds targeting RNA G-quadruplexes in living cells, but also intuitively demonstrates the increased formation of RNA G-quadruplexes caused by NOP56 gene mutation, providing a possible tool for the detection of SCA36.

A highly selective and sensitive direct detection of potassium (K+) and lead (Pb2+) ions was developed by using the assembly and disassembly of a chiral cyanine dye/TBA complex. The dye DMSB (3-ethyl-2-[3-(3-ethyl-3H-benzoselenazol-2-ylidene)-2-methylprop-1-enyl] benzoselenazolium bromide) loses the ability of self-assembly, but it can be activated by thrombin-binding aptamer (TBA) G-quadruplex structure. And only the TBA G-quadruplex formed in the presence of K+, can strongly induce J-aggregate signals of DMSB. Because the Pb2+ ions can bind and stabilize the TBA G-quadruplex with much higher efficiency than K+, the J-aggregate signals of DMSB falls sharply when the Pb2+ is present. As a result, the assembly and disassembly of DMSB allows the selective detection of 10 μM K+ and 20 nM Pb2+ respectively, even the competitive sodium ion (Na+) was as high as 145 mM. The linear correlation existed between the J-aggregate intensity and the concentration of K+ and Pb2+ over the range of 0.5–5.0 mM and 200–2000 nM, respectively. Moreover, the concentration of K+ (∼3 mM) and Pb2+ (below 20 nM) in human blood serum samples were determined by the present method, which agreed well with inductively coupled plasma mass spectrometry (ICP-MS). This work not only opens a door for the further development of G-quadruplex-based aptasensor in complex real system, but also provides a simple and versatile sensing platform for ion detection in clinic.

Filamentous bacteria, particularly Microthrix parvicella, are mainly responsible for bulking or foaming of activated sludge. Based on the affinity of M. parvicella to the hydrophobic characteristics of long-chain fatty acids, a novel bisoctyl rhodamine B (BORB) and a novel fluorescence resonance energy transfer (FRET) complex probe were prepared herein to study their properties. When the FRET probe was used in in situ activated sludge, M. parvicella was clearly labeled at 20 nmol/L, which was a reduction of 50 times compared to that of the BORB (1 μmol/L) alone and 500 times compared to the carbazole–quinoline probe reported previously. Compared with fluorescence in situ hybridization, M. parvicella could be clearly labeled using BORB and the FRET probe in situ without requiring complicated pretreatments (i.e., shock and broken process, fixed sample, digestion, and lysozyme treatment). This study discusses the facile approach developed for labeling M. parvicella in early warning expansion, thereby inhibiting and controlling sludge bulking in situ.

Cyanine dyes have attracted more and more interest due to their controllable assembly and disassembly process with biomolecular templates. The self-assembly of cyanine dye not only depend on the environment, but also on their structures. Here, we report assembly and disassembly of two cyanine dyes, a dimeric cyaine dye (TC-P4) and its corresponding monomer (TC). In PBS, these dyes could form aggregates. The parallel c-myc G-quadruplex as a template causes the transformation of TC-P4 from H-aggregates to dimer and monomer; while duplex and single-stranded DNAs could not. The interaction between these DNAs motifs and TC could all induce the appearance of monomer band. Parallel c-myc G-quadruplex could enhance the fluorescence intensity of TC-P4 and TC. The self-assembly and disassembly of TC and TC-P4 could be regulated and used as probes for G-quadruplex recognition from duplex and single-stranded DNAs in solution.

Background G-quadruplex has been viewed as a promising therapeutic target in oncology due to its potentially important roles in physiological and pathological processes. Emerging evidence suggests that the biological functions of G-quadruplexes are closely related to the binding of some proteins. Insulin-like growth factor type I (IGF-1), as a significant modulator of cell growth and development, may serve as a quadruplex-binding protein. Methods The binding affinity and selectivity of IGF-1 to different DNA motifs in solution were measured by using fluorescence spectroscopy, Surface Plasmon Resonance (SPR), and force-induced remnant magnetization (FIRM). The effects of IGF-1 on the formation and stability of G-quadruplex structures were evaluated by circular dichroism (CD) and melting fluorescence resonance energy transfer (FRET) spectroscopy. The influence of quadruplex-specific ligands on the binding of G-quadruplexes with IGF-1 was determined by FIRM. Results IGF-1 shows a binding specificity for G-quadruplex structures, especially the G-quadruplex structure with a parallel topology. The quadruplex-specific ligands TMPyP4 and PDS (Pyridostatin) can inhibit the interaction between G-quadruplexes and proteins. Conclusions IGF-1 is demonstrated to selectively bind with G-quadruplex structures. The use of quadruplex-interactive ligands could modulate the binding of IGF-1 to G-quadruplexes. General significance This study provides us with a new perspective to understand the possible physiological relationship between IGF-1 and G-quadruplexes and also conveys a strategy to regulate the interaction between G-quadruplex DNA and proteins.

Mechanical biosensors can be used to quantitatively explore DNA-protein binding mechanisms by detecting targets at low concentrations or measuring force in single-molecule force spectroscopy. However, restrictions in single-molecule manipulation and labelling protocols have hindered the application for bulk analysis of label-free protein detection. Here, we present the integration of molecular force measurement and finely tunable detection of label-free proteins into one mechanical sensor. Regulatory-sequence force spectroscopy was obtained to investigate the binding force of DNA G-quadruplexes (GQ) and label-free protein. The dual control of regulatory sequences and mechanical forces induces the structure switching from DNA duplex to GQ/protein complex. It exhibits a synergistic effect, enabling the rational fine-tuning of the dynamic range for biosensing protein concentrations over eight orders of magnitude. Furthermore, this method was exploited to estimate the stability of the human telomeric DNA GQ by Ku protein and ligand methylpyridostatin. The results revealed that human telomeric GQ has two different binding sites for Ku protein and ligand. Force spectroscopy integrating label-free force measurement and tunable target detection holds great promise for use in biosensing, drug screening, targeted therapies, DNA nanotechnology, and fields in which GQ are of rapidly increasing importance.

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, pH-zone refining counter current chromatography (CCC) and preparative high performance liquid chromatography (HPLC) were employed for the separation of potent G-quadruplex ligands from the n-butanol fraction of the crude extract of Zanthoxylum ailanthoides, which is a traditional Chinese medicine recently found to display high inhibitory activity against several human cancer cells. The 75% aqueous ethanol extract of the stem bark of Z. ailanthoides and its fractions with petroleum ether, ethyl acetate and n-butanol displayed almost the same G-quadruplex stabilization ability. Here, pH-zone refining CCC was used for the separation of the alkaloids from the n-butanol fraction by a seldom used solvent system composed of dichloromethane-methanol-water (4:1:2.5) with 10mM TEA in the organic stationary phase as retainer and 10mM HCl in the aqueous mobile phase as eluter. Compounds I, II and III were obtained, with purity greater than 95%, in the quantities of 31.2, 94.0, and 26.4mg respectively from 300mg of lipophilic fraction within 80min, which were identified as three tetrahydroprotoberberines isolated for the first time in this plant. In addition, a phenylpropanoid glycoside compound IV (Syringin), an isoquinoline (Magnoflorine, V), and two lignin isomers (+)-lyoniresiol-3α-O-β-d-glucopyranoside (VI) and (-)-lyoniresinol -3α-O-β-D -glucopyranoside (VII) were isolated by traditional CCC together with preparative HPLC. Compounds IV, V, VI and VII were obtained, with purity greater than 95%, in the quantities of 4.0, 13.2, 6.7, and 6.5mg respectively from 960mg of hydrophilic fraction. Among the seven isolated compounds, tetrahydroprotoberberine I, II and III were found to display remarkable stabilization effects on G-quadruplex by increasing G-quadruplex's Tm approximately 10°C, which may be the most potent G-quadruplex ligands in Z. ailanthoides.

Mitochondrial autophagy (mitophagy) is critical to the quality and quantity control of mitochondria. Real-time monitoring of the occurrence of mitophagy is necessary for understanding mitochondrial metabolism and screening mitophagy-related therapeutic drugs. Here, we report a new type of fluorescence resonance energy transfer (FRET) switch constructed by the mixed assembly of two cyanine dyes. The FRET switch exhibits a highly selective fluorescence response to the G-quadruplex structure, and its fluorescence intensity decreases or increases correspondingly with the binding and separation of G-quadruplexes. This property enables the switch to track the progression and termination of mitophagy by identifying the G-quadruplex structures that enter the lysosome during autophagy. This work not only provides a new strategy for constructing non-covalent FRET probes, but also offers a reliable tool for tracking mitophagy.

The G-quadruplexes located in the P1 promoter of B-cell lymphoma-2 (Bcl-2) gene are implicated to regulate Bcl-2 expression. Here, we designed a new pyridostatin analog named PDF, which exhibited high specificity and stabilizing effect toward G-quadruplexes. The luciferase assay demonstrated that PDF could significantly suppress Bcl-2 transcriptional activation in human laryngeal squamous carcinoma cells (Hep-2) cells. Besides, PDF also induced cell apoptosis in vitro assays. These results provide an excellent G-quadruplex specific ligand as an efficient Bcl-2 inhibitor. These results also implicate that PDF may be a potential anticancer drug to head neck cancer.

There has been a big challenge in developing the Na(+) sensor that can be practically used in the physiological system with the interference of large amounts of K(+). In this research, a novel Na(+) sensor has been designed based on the G-quadruplex-conformation related DNAzyme activity. The sensor exhibits high selectivity and sensitivity with the detection limit of 0.6 μM, which enables the sensor to be practically used in determination of the Na(+) level in serum. The research not only provides a simple Na(+) sensor but also opens a new way for developing the detection technology of Na(+).

Owing to their chiral and self-assembly features, chiral supramolecules exhibit superior recognition and catalytic abilities. Here, we construct a chiral H-aggregates based on a cyanine dye, 3,3′-di(3-sulfopropyl)-4,5,4′5′-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt (MeCy), by spontaneous symmetry breaking in the presence of NaNO3. The chiral H-aggregates could specially recognize parallel DNA G-quadruplexes among other DNA types, probably by a three-step process, which comprises the amplified chiral induction, the disassembly of chiral H-aggregates and the binding of the MeCy monomer. The MeCy monomer binding to DNA parallel G-quadruplex led to a lighting-up fluorescence intensity obviously. Chiral supramolecules targeted to DNA G-quadruplex was proposed, and its transformation process was revealed, and thus potentially provided an excellent probe for DNA parallel G-quadruplexes.

It is found that G-quadruplexes have important functions in biological systems, such as gene expression. Molecules which can stabilize the G-quadruplex structure may have potential application in regulating the expression of gene. A series of methylazacalix[n]pyridine (n = 4, 6, 7, 8, 9) has been tested to stabilize the intermolecular human telomeric G-quadruplex (T12 and H12), intramolecular TBA, c-kit and bcl-2 G-quadruplex by CD denaturation experiments. The results showed that only methylazacalix[6] pyridine (MACP6) can stabilize the intermolecular G-quadruplex formed from the 12 bp human telomere. Further studies evidenced that the shape-complementary binding mode was what contributed to the interaction between MACP6 and T12 G-quadruplex. (C) 2015 Elsevier Ltd. All rights reserved.

The cyanine dyes are among the oldest classes of synthetic compounds but continue to find applications in a variety of fields. Compared to other organic molecules, diverse and controlled aggregate property is one most canonic feature of the cyanine dyes. With a primary focus on our own work, here we chose 3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-methyl-thiacarbo-cyanine triethylammonium salt as one model to discuss its controllable aggregates and its applications served as a chemosensor. Its H- and J-aggregates could be conversed mutually by the regulation of metal-salts or temperature or small peptides, presenting varied characteristic absorption spectra. And its J- or H-aggregates could be destroyed and converted to monomeric states, respectively by human serum albumin or G-quadruplex DNA. Furthermore, it was sensitive to the subtle conformer of G-quadruplex, and thus applied in detecting the Na+/K+ ratio or Pb2+ concentration in the solution samples as a chemosensor. (C) 2015 Elsevier Ltd. All rights reserved.

G-quadruplex as a therapeutic target to develop novel anti-cancer agents has attracted a growing interest. Among all the ligands of G-quadruplexes, pyridostatin derivatives play a very important role. Here, we first reported the recognition of the fundamental skeleton pyridostatin I, which was simply synthesized. Compared to pyridostatin II comprising terminal amino groups, pyridostatin I selectively stabilized intramolecular anti-parallel telomeric G-quadruplex by raising the melting temperature about 20 degrees C at 295 rim of H22, while pyridostatin II preferred to stabilize intermolecular parallel telomeric G-quadruplex by raising the melting temperature about 25 degrees C at 265 nm of H7, maybe due to the suited size measurements between G-quadruplex hosts and pyridostatin guests. MTT assays indicated that pyridostatin II had better cytotoxic effects against HCT-8 and A549 cell lines obviously, indicating positively charged side chains may be required for improving the water solubility and cellular uptake of the apolar central skeleton. (C) 2015 Published by Elsevier Ltd.

G-quadruplexes (G4s) play important roles in biological systems, such as telomere maintenance, replication, and transcription. Based on the DNA sequence, loop geometry, and the local environments, G4s can be classified into different conformations. It is important to detect different types of G4s to monitor the diseases related with G4s. Most ligands bind to G4s based on end-stacking modes, while rare ligands bind to G4s through groove binding modes. We have found that a cyanine dye DMSB interacts with parallel G4 by end-stacking and groove simultaneous binding mode. In this article, we found that DMSB could simply discriminate parallel G4s from other DNA motifs by using UV-vis spectrum. These results give some clues to develop high specificity G4 probes. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

The study of binding mechanisms and any associated conformational changes of human serum transferrin (Tf) on interaction with cyanine dye 3,3'-di(3-sulfopropy1)-4,5,4',5'-dibenzo-9-methyl-thiacarbocyanine triethylam-monium salt (MTC) are of great importance in the process of Tf targeting dye delivery into cancer cells. It is possible to lay theoretical foundations for cyanine dye as a potential photosensitizer to achieve the photodynamic therapy (PDT). The mechanisms of interaction between MTC and Tf were portrayed by means of fluorescence spectra, UV-vis absorption spectra, synchronous fluorescence spectra, circular dichroism (CD) and molecular dynamic docking. The data of fluorescence spectra displayed that the formation of MTC-Tf complex is a static quenching process through van der Waals forces and hydrogen bonds with a high affinity of 10(9) M-1. Binding distance between MTC and Tf substantiated that the non-radioactive energy transfer mechanism is also involved in the fluorescence quenching of protein. Furthermore, structural analysis indicated that MTC binding result in an increased of ce.-helix content and an increased hydrophobic around the tryptophan residues of Tf as well as a certain structural changes in Tf, which confirmed by the CD, synchronous fluorescence and UV-vis experiments. Additionally, the results of molecular dynamic docking elucidated that the dye was located in N-lobe of Tf. (C) 2015 Elsevier B.V. All rights reserved.

A novel method for achieving a copper(II)-catalyzed domino reaction for the construction of 2-aryl quinazolinones, without the addition of any ligand and additive, has been developed. The domino reaction achieved N-(alpha-substituted)benzylation, benzylic C-H amidation, and C-C (or C-H) bond cleavage. (C) 2014 Li-Xia Wang and Ya-Lin Tang. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.

Hydrogen bonding interaction as one type of non-covalent force has proven itself to be highly efficient for constructing structurally unique artificial secondary structures. Here, the structure of Naryl-substituted anthranilamide in solution is demonstrated by various NMR technique, the intramolecular hydrogen bonds between amide attached to arylamine of the same ring is proposed, which is supported by its crystal structure in the solid phase. The substituent on the nitrogen atom of arylamine plays an important role in forming the presence of intramolecular hydrogen bonds. The chemical shift of the Naryl-H downfield changes obviously, due to the formation of intramolecular hydrogen bonds and the deshielding effect of oxygen, and the neighboring C–H is activated and shows downfield protonic signal too. The presence of intramolecular hydrogen bonds probably provides the explanation for the transformation from Naryl-substituted anthranilamide to imine, which could be converted into 2-aryl quinazolinone finally.

Background A new G-quadruplex structure located in the B-cell CLL/lymphoma 2 (Bcl-2) P1 promoter and its physiological function related to Bcl-2 transcription have been studied to find a potential anticancer therapeutic target. Methods Absorption, polyacrylamide gel electrophoresis, fluorescence, circular dichroism, and nuclear magnetic resonance spectra have been employed to determine G-quadruplex structure and the interaction between G-quadruplex and phenanthrolin-dicarboxylate. Real time polymerase chain reaction and luciferase assay were done to assess the physiological function of the G-quadruplex structure. Results The UV-melting and polyacrylamide gel electrophoresis studies show that the p32 DNA sequence forms an intramolecular G-quadruplex structure. Circular dichroism and nuclear magnetic resonance spectra indicate that the G-quadruplex is a hybrid-type structure with four G-tetrads. Fluorescence spectra show that a phenanthroline derivative has a higher binding affinity for p32 G-quadruplex than duplex. Further circular dichroism and nuclear magnetic resonance studies indicate that the phenanthroline derivative can regulate p32 G-quadruplex conformation. Real time polymerase chain reaction and luciferase assays show that the phenanthroline derivative has down-modulated Bcl-2 transcription activity in a concentration-dependent manner. However, no such effect was observed when p32 G-quadruplex was denatured through base mutation. Conclusion The newly identified G-quadruplex located in the P1 promoter of Bcl-2 oncogene is intimately related with Bcl-2 transcription activity, which may be a promising anticancer therapeutic target. General significance The newly identified G-quadruplex in the Bcl-2 P1 promoter may be a novel anticancer therapeutic target.

Transferrin has been exploited as a potential drug carrier for targeted drug delivery into cancer cells, which express high levels of transferrin receptors. In the present study, we identified specific structural features in flavonoids that were critical for binding to transferrin. Flavanone naringenin and flavonoid apigenin, two flavonoids with characteristic flavonoid core structures were selected for the study of the effects of C2–C3 single bond in the C-ring on transferrin binding. We determined the binding affinities by fluorescence quenching experiments and investigated the binding modes by CD spectra and molecular modeling. Our results demonstrated that naringenin bound transferrin with an affinity almost 100 times higher than that of apigenin attributed to its higher structural flexibility and lower acidity compared with apigenin. Our docking study showed that naringenin had stronger van der Waals interactions with transferrin, which was believed to contribute to its higher binding affinity. We also found that naringenin-binding induced greater increase in the α-helix content in transferrin than apigenin, suggesting that transferrin became more compact upon association with naringenin. Our study demonstrated that naringenin was a ligand for transferrin with good affinity. The results reported herein can facilitate the design and development of drugs that bind transferrin with high affinity.

Inhibition of the α-glucosidase activity is a therapeutic approach for diabetes. In this study, an effective strategy for screening α-glucosidase inhibitors based on Nuclear magnetic resonance (NMR) techniques was developed to screen and identify α-glucosidase inhibitors from Mulberry leaf extract. As a result, deoxynojirimycin, as a potential α-glucosidase inhibitor, was found. The study suggested that our strategy was a powerful tool for screening and identification of α-glucosidase inhibitors in complex samples. Furthermore the interaction between α-glucosidase and its inhibitor was studied by NMR.

Screening G-quadruplex ligands from natural plants is important because the ligands may be potential antitumor drugs. A new screening strategy is proposed based on the combination of dialysis and G-quadruplex recognition technique which could separates G-quadruplex ligand from natural extracts and elucidate the structure of this ligand. This result offers a novel approach to obtain active antitumor compounds.

Human DNA sequences consisting of tandem guanine (G) nucleotides can fold into a four-stranded structure named G-quadruplex via Hoogsteen hydrogen bonding. As the sequences forming G-quadruplex exist in essential regions of eukaryotic chromosomes and are involved in many important biological processes, the study of their biological functions has currently become a hotspot. Compounds selectively binding and stabilizing G-quadruplex structures have the potential to inhibit telomerase activity or alter oncogene expression levels and thus may act as antitumor agents. Most of reported G-quadruplex ligands generally have planar structures which stabilize G-quadruplex by pi-pi stacking. However, based on a pharmacophore-based virtual screening two non-planar G-quadruplex ligands were found. These two ligands exhibit good capability for G-quadruplex stabilization and prefer binding to paralleled G-quadruplex rather than to duplex DNA. The binding of these ligands to G-quadruplex may result from groove binding at a 2:1 stoichiometry. These results have shown that planar structures are not essential for G-quadruplex stabilizers, which may represent a new class of G-quadruplex-targeted agents as potential antitumor drugs.

The studies on the interaction between HSA and drugs have been an interesting research field in life sciences, chemistry and clinical medicine. There are also many metal ions present in blood plasma, thus the research about the effect of metal ions on the interaction between drugs and plasma proteins is crucial. In this study, we have investigated the effect of a familiar metal ion-Cu 2+ on the interaction between an antitumor drug–mitoxantrone (MTO) and human serum albumin (HSA) by using fluorescence spectroscopy, ultraviolet–visible absorption spectroscopy and circular dichroism spectroscopy, for the first time. The results showed that the quenching efficiency of MTO to HSA is higher with Cu 2+ than that without Cu 2+ . In the presence of Cu 2+ , the secondary structure of HSA was changed and the α-helix content was increased. The apparent association constant ( K A ), the binding sites ( n ) and the spatial-distance ( r ) between MTO and HSA decreased. These results indicated that Cu 2+ could affect the interaction between MTO and HSA by altering HSA molecular conformation. Further calculation indicated that the binding mode of Cu 2+ in MTO–HSA system was likely to form Cu 2+ –HSA complex.

Aloe dihydroisocoumarin, one of new components isolated from Aloe vera, can scavenge reactive oxygen species. In order to explore the mechanism of drug action at a molecular level, the binding of Aloe dihydroisocoumarin with human serum albumin (HSA) has been investigated by using fluorescence, ultraviolet (UV), circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy, fluorescence dynamics, and molecular dynamic docking for the first time. We observed a quenching of fluorescence of HSA in the presence of Aloe dihydroisocoumarin and also analyzed the quenching results using the Stern–Volmer equation and obtained high affinity binding to HSA. An isoemissive point at 414 nm is seen, indicating that the quenching of HSA fluorescence depends on the formation of Aloe dihydroisocoumarin-HSA complex, which is further confirmed by fluorescence dynamic result. From the CD and FT-IR results, it is apparent that the interaction of Aloe dihydroisocoumarin with HSA causes a conformational change of the protein, with the gain of α-helix, β-sheet and random coil stability and the loss of β-turn content. Data obtained by fluorescence spectroscopy, fluorescence dynamics, CD, and FTIR experiments along with the docking studies suggest that Aloe dihydroisocoumarin binds to residues located in subdomain IIA of HSA.

Aloe dihydrocoumarin is an antioxidant and a candidate of immunomodulatory drug on the immune system and can balance physiological reactive oxygen species (ROS) levels which may be useful to maintain homeostasis. In order to explore the mechanism of drug action at a molecular level, the binding of Aloe dihydrocoumarin with human serum albumin (HSA) has been investigated by fluorescence, ultraviolet (UV), circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy, fluorescence dynamics, and molecular dynamic docking for the first time. We observed a quenching of fluorescence of HSA in the presence of Aloe dihydrocoumarin and also analyzed the quenching results using the Stern–Volmer equation and obtained high affinity binding to HSA. A Forster type fluorescence resonance energy transfer mechanism is involved in this quenching of Trp fluorescence by Aloe dihydrocoumarin. From the CD and FT-IR results, it is apparent that the interaction of Aloe dihydrocoumarin with HSA causes a conformational change of the protein, with the loss of α-helix stability and the gain of β-sheet and β-turn content. Data obtained by fluorescence spectroscopy, fluorescence dynamics, CD, and FT-IR experiments along with the docking studies suggest that Aloe dihydrocoumarin binds to residues located in subdomain IIA of HSA.

The interaction of a novel pesticide, NMD (spiro[(2 R ,3 R ,4 S )-4-benzyloxy-2,3-iso-propylidenedioxy-1-oxacyclopentane-5,5′-(2-nitromethylene-1,3-diazacyclohexane)]), with bovine serum albumin (BSA) has been investigated by using absorption, fluorescence, and circular dichroism (CD) spectroscopy methods. Quenching of the fluorescence of BSA has been observed in the presence of NMD. The binding parameters were determined using Stern–Volmer equation. From the thermodynamic parameters calculated according to the van’t Hoff equation, the enthalpy change Δ H , and entropy change Δ S were found to be −2.71 kJ mol −1 and 82.56 J mol −1 K −1 , respectively. These values suggested that, apart from an initial hydrophobic association, the complex is held together by van der Waals interactions and hydrogen bonding. These results provided a quantitative understanding of the binding of NMD to BSA, which is important in understanding its toxicity in vertebrates.

The effects of conformational changes to transferrin induced by the binding of flavonoids with different numbers and positions of hydroxyl groups were explored using spectroscopic and molecular modeling methods. The flavonoid hydroxyl group is not necessary for conformation changes of transferrin. However, the binding ability was found to increase with increasing numbers of hydroxyl groups and further conformational changes were observed. By molecular modeling calculations, intermolecular energy including van der Waals and electrostatic interactions, together with hydrogen bonding are found to have important roles in binding of flavonoids to transferrin. Additionally, the positions of the hydroxyl groups also affect the binding ability because they can alter the relative acidity of the hydroxyl groups, thereby changing the hydrogen bonding ability. Our results have indicated a mechanism for the interactions between flavonoids and transferrin, and provide information for possible flavonoid modification and design of methods to deliver drug molecules via transferrin to target tissues and cells effectively.

Single-crystal Sb doped ZnO nanowires were fabricated on Si (1 0 0) substrate by a chemical vapor deposition method. The photoluminescence properties of ZnO nanowires were studied with the temperature ranging from 81 to 306 K. At 81 K, the recombination of the acceptor-bound exciton was predominant in PL spectrum, which was attributed to the transition of the (SbZn–2VZn) complex bound exciton. The activation of A0X and the acceptor binding energy had been calculated to be 16.8 and 168 meV, respectively.

The J-aggregation behaviour of two cyanine dyes (3,3′-disulfopropyl-4,5,4′,5′-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt ( MTC ) and 3,3′-disulfopropyl-4,5,4′,5′-dibenzo-9-phenyl-thiacarbocyanine triethylammonium salt ( PTC )) has been investigated in the presence of dication chloride using absorption spectroscopy, 1 H and multinuclear NMR methods. The promotion efficiency on J-aggregation of the dye molecule and the magnitude of the effective coherence length of the J-aggregate were found to be dependent on the dyes' structure and their ability to coordinate with the metal ions. The interaction between the metal ions and the J-aggregates could be explained by the association between metal ions and J-aggregates, and the apparent association constants were obtained from the chemical shifts in NMR spectra of the metal ions.

The interaction between a novel promising drug (spiro[(2 R ,3 R ,4 S )-4-benzyloxy-2,3-isopropylidene-dioxy-1-oxa-cyclopentane-5,5′-(2-benzoylmethylene-1,3-diaza-cyclohexane)] (SBDC)) and human serum albumin (HSA) under physiological conditions has been investigated by using fluorescence, absorption, and circular dichroism (CD) spectroscopic techniques in combination with protein–ligand docking study. It was observed that SBDC has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The association constants of SBDC with HSA were determined at different temperatures based on fluorescence quenching results. The negative Δ H and positive Δ S values in case of SBDC–HSA complex showed that apart from an initial hydrophobic association, both van der Waals interactions and hydrogen bonding play a vital role in the binding of SBDC to HSA. The quantitative analysis data of CD spectra showed that the binding of SBDC to HSA induced conformational changes in HSA and the α-helix of 52.1% in free HSA increased to 55.7% in HSA–SBDC complex. The distance between donor (HSA) and acceptor (SBDC) was obtained according to the Forster's theory of non-radiation energy transfer. Data obtained by spectroscopic techniques and protein–ligand docking study suggested that SBDC binds to residues located in subdomain IIA of HSA.

The action mechanism of vanadocene dichloride, Cp2VCl2 (Cp=eta5-C5H5), has been investigated by interaction with human serum transferrin for its promising antitumor activities. Our results have shown that Cp2VCl2 binds to transferrin and form a new complex, and the calculated apparent association constant is 1.37 x 10(5)M(-1) from the fluorescence quenching. Simultaneously, the variation of the secondary structure of transferrin occurs, most probably due to the coordination of the amino residues of protein with VIV. It was evidenced that Cp is released free in solution after VIV binding to transferrin by 1H NMR measurements. These results have shown that Cp2VCl2 forms a complex with transferrin, which may provide a possible pathway in the transport and targeted delivery of the antitumor agent.

H-1 nuclear magnetic resonance (NMR) spectroscopy has been applied to study the temperature and concentration-induced micellization of a poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) triblock copolymer, Pluronic P105, in D2O solutions in the temperature range from 5 to 45 degrees C and the concentration range from 0.01 to 15% (w/v). The intrinsic probes, the chemical shift, and the half-height width of the PO -CH3 signal are very sensitive to the local environment and can be used to characterize the temperature and concentration-dependent aggregation process. When the temperature approaches the critical micellization temperature or the polymer concentration reaches the critical micellization concentration, the chemical shift of the PO -CH3 signal moves toward lower ppm values and the half-height width of the PO -CH3 signal shows a sudden increase. It indicates that the methyl groups are experiencing a progressively less polar environment and transferring from water to the hydrophobic micellar core. The hydrodynamic radius of the unimers and the micelles are determined as be 1.8 and 5.0 nm by means of pulsed-field gradient spin-echo (PGSE) NMR. They were independent of temperature and concentration. The drastic shortening of spin-lattice relaxation time T-1 for the PO -CH3/-CH2- protons in the transition region suggested that the PPO blocks are located in a "liquid-like" micellar core, whereas the exponential increase of T-1 for the PEO -CH2- protons implied that the PEO blocks are still keeping in contact with surrounding water. Thermodynamics analysis according to a closed association model shows that the micellization process is entropy-driven and has an endothermic micellization enthalpy. (c) 2007 Elsevier Inc. All rights reserved.

The interactions of three cyanine dyes, which exhibit different meso substituent in polymethine chain, with human serum albumin (HSA) have been investigated by the means of absorption, fluorescence and circular dichroism (CD) spectra. In phosphate buffer solution (PBS), the mentioned dyes exist not as isolated monomers but rather in the formation of J-aggregation. In the presence of HSA, the absorption and fluorescence emission spectra indicated that the J-aggregation was decomposed to monomer because of the strong affinity between dye molecules and HSA. Besides the association of cyanine dyes with HSA, binding to HSA gave rise to the J-aggregation CD signals. The meso substituent in the polymethine plays an important role in the interaction of HSA and the J-aggregation. Spectral studies showed that the dye bound with HSA in a 1:1 formation. The apparent constant (K(a)) value was roughly identified by analysis of the corresponding fluorescence data at various HSA concentrations. The higher affinity of the molecule with meso phenyl towards HSA with respect to molecules with meso ethyl or methyl can be attributed to the arrangement of molecules in J-aggregation and the hydrophobic force between the molecules and HSA.

The effects of three diosgenyl saponins isolated from Paris polyphylla on the immuno-stimulating activity in relation to phagocytosis, respiratory burst, and nitric oxide production in mouse macrophage cells RAW 264.7 have been investigated. Our results showed that all three diosgenyl saponins significantly enhanced phagocytic activity that increased with the concentration of saponins to reach a maximum, and then tended to decrease with higher concentrations. Saponins with sugar moiety directly induced respiratory burst response in RAW 264.7 cells that increased with the concentrations and reached a maximum, then decreased with higher concentrations after 2-h incubations, however, diosgenin had no PMA-triggered respiratory burst response. Treatment of RAW 264.7 cells with saponins with sugar moiety for 24-h caused a significant increase in the production of nitric oxide, while diosgenin had no effect at all. Consequently, relationship between molecular structures of three diosgenyl saponins and their immunomodulatory activities was discussed, and a possible mechanism of immuno-stimulating function of diosgenyl saponins was accordingly explored.

Sinomenine, an herbal ingredient isolated from Sinomenium acutum, is used for the amelioration of arthritis. It has been found that this molecule could bind to human serum transferrin (Tf), the iron (III) transport protein in the blood, by using fluorescence, circular dichroism (CD) spectroscopy, and molecular modeling methods. The results provide possible usage of transferrin to transport sinomenine.

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.

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.

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.

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)

The crystal growth and defects in cubic zirconia grown by the skull melting method have been investigated. The distribution coefficients of stabilizers Y 2 O 3 and CaO in the crystal were greater than 1 and less than 1 respectively. By preparing materials with 10–12 mol% Y 2 O 3 as stabilizer, it is easy to get nearly colourless transparent large cubic zirconia single crystals. The substances which influence the uniformity of the cubic zirconia crystal are not only the inclusions, but also growth striae and mosaics. The results of the observation and analysis on the inclusions by scanning electron microscopy, show that Si, Ca, Mg, Y, etc. occur mainly at the ends and in the centre of the crystal.